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Melanoma pp 791-817 | Cite as

Evolving Role of the Oncology Nurse in the Care of Patients with Melanoma

  • Krista M. RubinEmail author
Reference work entry

Abstract

Over the past several years, treatment for melanoma has undergone a revolutionary change. A virtual explosion of scientific knowledge has given rise to a plethora of novel therapies as evidenced by the FDA approval of 14 new drugs and/or combinations since 2011. Patients have derived tremendous benefit from this, and the survival statistics have beneficially changed transforming a once uniformly fatal disease to one with the hope of sustained control, possibly even cure. However, the complex nature of melanoma makes it one of the most challenging malignancies to treat, and it is recognized that patients with melanoma have considerable unmet needs. This chapter will describe the evolving role of oncology nursing in the patient’s journey through the melanoma disease spectrum. The various components of the nursing role will be illustrated in the context of the disease trajectory including that of communicator, patient advocate, educator, coordinator, and often as a coach for the patient and caregiver/family. Furthermore, the value of nursing presence on the interdisciplinary care team will be highlighted, as well as the ever-important role of toxicity management.

Keywords

Metastatic melanoma Disease spectrum Evolving role Nursing care Nursing role Oncology nurse Immune checkpoints Immune toxicity Multidisciplinary 

Introduction

Melanoma is a notoriously aggressive cancer that can metastasize even at the earliest stages. It is a malignancy resistant to traditional anticancer therapies such as chemotherapy and radiotherapy. Fortunately, about 90% of melanomas are diagnosed as primary tumors without any evidence of metastasis (Garbe et al. 2016) and are likely cured with surgical intervention only. Decades of research have led to breakthroughs in treatment as the result of increased understanding of the underlying biology of melanoma and role of the immune system and cancer. This has resulted in the development of novel therapies dramatically improving the treatment landscape including the introduction of immune checkpoint inhibitors (ICIs) and molecularly targeted agents. As the field advances, there is excitement among the melanoma community. These novel therapies offer the promise of hope. Improved disease and survival outcomes are a reality, and the momentum of successes is driving the field forward. However, toxicities associated with these agents not only differ among class but differ from traditional chemotherapy, and management is often complex and time-consuming, with some patients requiring significant support (Lomax et al. 2017).

Despite the historic paradigm change, melanoma remains a challenging malignancy. Heterogenous in nature and complex in behavior, the clinical management of an individual with advanced melanoma often presents a clinical conundrum for treating physicians. Only a subset of patients will derive long-term benefit from ICIs, and for patients eligible for targeted therapy, the benefit does not continue beyond a year or two (Ugurel et al. 2017). Unanswered questions remain about ideal patient selection, sequencing, and best treatment approaches, notably whether all stage III or M1a patients should receive adjuvant therapy (Dimitriou et al. 2018). Predictive biomarkers have yet to be established. As such, a multidisciplinary approach to patient care is recommended, wherein individual patients are discussed among diverse specialists and a consensus decision regarding management is reached (Dummer et al. 2017).

Nurses are an essential member of the multidisciplinary team. They are often the most accessible, play a variety of roles, and provide support beyond care directly related to the illness (Cooper and de Lord 2018). Nurses play a unique role in the care and management of patients with cancer, one of the most important is providing knowledge and assistance, since patients can become overwhelmed by the care and information they receive. Thus, patients and families must be supported in times of their vulnerabilities (Cooper and de Lord 2018: Tariman et al. 2016). Furthermore, with the emergence of new and novel treatments including ICIs and targeted therapies, it is essential that oncology nurses are knowledgeable and skilled in assessing toxicities and following agreed pathways in order to manage the complexity of various toxicities, leading to improved outcomes

Diagnosis

A diagnosis of melanoma is devastating. For most individuals, such a diagnosis unleashes a vast array of emotions. It is important to recognize approximately 30% of all patients diagnosed with melanoma, including long-term survivors, report levels of psychological distress, notably anxiety and depression (Vogel et al. 2017; Kasparian et al. 2009; Beesley et al. 2015; Tan et al. 2014). A sense of uncertainty frequently accompanies a diagnosis, not only for the patient but also the family and/or caregiver(s) as they face unfamiliar, complex, and potentially life-threatening experiences (Kasparian et al. 2016; Stamataki et al. 2015). It is not uncommon for multiple providers of various specialties to be involved in the care of patients with melanoma (e.g., dermatology, surgical oncology, medical oncology, radiation oncology, and occasionally plastic surgery). Each provider has a distinct role in the care; nonetheless, individual care is often uncoordinated, and it is easy for patients to become confused and overwhelmed if left to navigate a highly specialized but fragmented care system.

A component of the oncology nurse role is coordination among various providers. In addition, nurses support and assist patients as they learn to navigate the healthcare system, offer reassurance, answer questions, address concerns, and ensure patients’ needs are met (Tariman et al. 2016). Every interaction provides an exchange of information which enables the nurse to get to know a patient and their caregiver(s) via assessment of their physical and emotional state, past health history, health practices, and beliefs. This exchange begins the formation of the ever-important therapeutic relationship establishing the foundation from which patient-centered care evolves .

Treatment of Melanoma

Surgery

Surgery is the most common treatment for melanoma and spans the spectrum from wide excision of a primary lesion with curative intent to palliative resection. It is the preferred treatment for local and regional melanoma. Fortunately for most patients presenting with a primary tumor, surgical resection will represent definitive treatment without the need for any further treatment. Despite a favorable prognosis, it is imperative providers be cognizant of the emotional, social, and psychological consequences that may result from cancer surgery. Findings from multiple qualitative studies reveal dissatisfaction with scar appearance of (Vogel et al. 2017; Kasparian et al. 2009; Tan et al. 2014), especially among patients who underwent resections on the head or neck as the scars prove more difficult to disguise with clothing (Vogel et al. 2017; Kasparian et al. 2009). The visible nature of cancer, associated scarring and/or disfigurement, and altered body image that may occur are identified as significant concerns expressed by melanoma patients (Tan et al. 2014; Oliveria et al. 2011). Stamataki et al. (2015) describe how, for some patients, altered body image was linked to a disparity in the pre- and postsurgery expectations of scar appearance. Respondents felt they had not been fully prepared for the reality of the scar appearance despite speaking to health professionals beforehand. Furthermore, the authors highlight disparity between doctors’ perceptions of a healing scar and the language used to describe it, compared to patients’ perceptions of their healing scar and language they (the patient) would use to describe it (Stamataki et al. 2015).

Nurses with awareness of these findings can minimize distress in the postsurgical setting by anticipating such concerns and importantly setting expectations about the scar and other physical sequelae. Including family/caregivers in these discussions improves communication and patient/caregiver satisfaction. Interventions such as showing photos or thoroughly describing the process of wound healing can decrease distress about scar appearance (Cassileth et al. 1983). Anticipatory guidance about postoperative expectations for pain; need for medications, drain, and/or wound care; and recognizing complications are important information to provide for both patients and caregivers (Tan et al. 2014). Tailored information should be provided about what patients can expect in terms of functional capacity, limitations, or restrictions on activity (Tan et al. 2014) such as driving; lifting; ability to weight-bear; ability to work, drive, and care for children; etc. as these may negatively affect recovery if patients are not adequately prepared.

For patients whom sentinel lymph node biopsy (SLNB) is advised, reiterate that the procedure is a staging procedure and will involve a team of providers from both nuclear medicine and surgery. Some patients may benefit from a detailed description of how the procedure is performed, while others may want only minimal information; discussions should be tailored accordingly. It is essential, however, to ensure all patients understand the procedure objectives and rationale, and what to expect postoperatively, including when pathology results may be available and what they mean. Providing as much information as possible and setting expectations will minimize anxiety.

Historically, patients with a positive SLNB were advised to proceed with immediate completion lymph node dissection (CLND). Despite significant associated morbidity, the procedure was recommended because it provided increased regional disease control and additional prognostic information (Faries et al. 2017) such as number and extent of nodal involvement. However, recent evidence demonstrates a lack of a survival advantage with immediate CLND (Faries et al. 2017; Leiter et al. 2016). Findings from the Multicenter Selective Lymphadenectomy Trial (MSLT-II) (Faries et al. 2017) and from German Dermatologic Cooperative Oncology Group (DeCOG) (Leiter et al. 2016) demonstrate similar survival outcomes whether nodal dissection is immediate or when/if a nodal relapse is detected. These findings provide unequivocal evidence that not all patients with a positive sentinel node biopsy require CLND. These findings support a change in practice, not proceeding immediately to CLND but, instead, following closely with the aid of frequent nodal ultrasound, reserving nodal dissection for patients in whom clinically detected nodal recurrence had developed (Faries et al. 2017). Such practice spares those patients who do not relapse from a morbid (and unnecessary) surgery, and for those that do relapse, performing LND at that time of relapse does not negatively impact survival. Moreover, in the current era of effective adjuvant therapies (discussed below), foregoing immediate CLND facilitates earlier commencement of adjuvant systemic, augmenting the potential for long-term benefit.

For some patients, the idea of not pursuing CLND despite a positive sentinel node biopsy may be a difficult concept to grasp. Nurses must be prepared to provide support to patients and families through education and counseling, despite the prognostic significance of having an involved sentinel node(s). Preparing patients for potential outcomes through anticipatory guidance provided prior to the sentinel node biopsy procedure sets expectations. Early education prepares patients for what may be advised postoperatively; thus patients are better able to understand the recommendation for a “watch-and-wait” approach despite involved sentinel node(s). Reiterating the rationale for avoiding CLND to spare a potentially morbid surgery should be emphasized. Nurses should also stress the importance and rationale for ongoing patient self-examination as well as follow-up visits including the need for regular imaging (ultrasound to evaluate the nodal basin as well as systemic imaging to evaluate for distant relapse). For patients who do need lymph node dissection (LND), it is important they are prepared for the potential outcomes given the procedure can be associated with significant morbidities including development of seroma, infection, wound dehiscence, bleeding, deep vein thrombosis, and, notably, lymphedema (Ahmed et al. 2013).

Lymphedema is a significant health issue for cancer survivors with a considerable impact on patients’ health-related quality of life (Tan et al. 2014). The amount of edema can range from mild to severe and when left untreated can lead to skin changes, impaired function, loss of normal sensation, discomfort, pain, and chronic infections that affect the quality of life (Chang and Cormier 2013). Complete decongestive therapy (CDT) is the mainstay treatment for lymphedema and should only be performed by certified lymphedema therapist (Chang and Cormier 2013). Oncology nurses play a vital role in the prevention and management of this disorder by assessing for early signs and symptoms of lymphedema and prospectively identifying high-risk individuals. Early diagnosis is important because lymphedema is most successfully treated and complications minimized when therapies are introduced early (Chang and Cormier 2013). For example, patients who undergo inguinal LND are at greater risk of developing lymphedema compared with those who undergo axillary LND (Ahmed et al. 2013). Other factors contribute to increased risk including prior radiation to a lymphatic basin, development of a postoperative infection or seroma, and obesity (Ridner 2013). Obtaining preoperative limb measurements for high-risk individuals in comparing to postoperative measurements promotes early identification of lymphedema. Patients should be instructed to self-monitor for physical signs of lymphedema including noting the presence of edema during exercise, changes in skin texture, change in range of motion or skin tone, as well as sensation changes such as limb heaviness or numbness. During follow-up visits, query patients about “heaviness” or swelling area near resection site or if clothing or jewelry has become tighter (Ridner 2013). A positive response to the above inquiries should trigger a prompt referral to specialty care with a dedicated lymphedema specialist.

High-Risk Melanoma

The concept of “recurrence risk” is difficult for many patients to comprehend because they are disease-free but are being treated for a future statistical possibility of recurrence and death. Patients considered high risk include those with stage II and III disease. For patients with stage IIB/C disease [American Joint Committee on Cancer (AJCC) 8th edition] (between 2.0 and 4.0 mm with ulceration or >4.0 mm regardless of ulceration status), discussions regarding recurrence risk may be particularly difficult as they are often focused on the notion that “the cancer was removed, and there was no spread to lymph nodes” but are then surprised to hear about the underlying risk of relapse and death despite uninvolved nodes. Stage III disease represents a vastly heterogenous population encompassing resected nodal disease, as well as non-nodal locoregional sites (e.g., microsatellites, satellites, and in-transit metastases). Five-year survival rates vary greatly, from 93% for stage IIIA to 32% for IIID (Gershenwald et al. 2017). Treatment recommendations are based on stage and associated prognosis; thus patients may be faced with the decision to pursue adjuvant therapy, a difficult decision for many patients as they are unintentionally confronted with facing their own mortality.

Increasingly there has been a swing toward more active patient involvement in their own treatment making decisions. Stacey et al. (2010) found improved outcomes when patients were actively engaged in the decision-making process about cancer screening and treatment. This collaborative approach is known as “shared decision-making” (SDM). It is described by Tariman et al. (2016) as “the process of choosing between treatment alternatives or multiple treatment options. It is a complex process in which data are gathered and evaluated, information is exchanged between patients and clinicians, and a decision is mutually agreed upon.” This approach implies that not only should patients be provided with the necessary information to make informed decisions about their healthcare but incorporates understanding about those factors that influence an individual’s preferences and view on treatment based on their personal situation (Jansen et al. 2004). In other words, understanding the values of each individual patient enables providers to assess risk for that individual. To best support patients through this process, Jansen et al. (2004) emphasize the importance of getting to know patients by taking the time to explore their willingness to accept side effects for a given therapy or to forego benefits of an alternative treatment. This decides the relative strength of their treatment preference. Each patient has a sense of what risk-benefit ratio is acceptable to them, and the threshold at which risk outweighs benefit will vary among individual patients as well as providers. Patients need information about what they can realistically expect in terms of toxicity, how it is managed, and how the treatment will impact his or her everyday life, as well as caregivers/family (Tariman and Szubski 2015). Case in point is the decision to pursue postoperative radiation in the setting of bulky, matted nodes noted upon LND. Weighing the risk of lymphedema against the benefit of increased local control may be a straightforward choice, but it needs to be clear to patients that the risk of systemic relapse is not reduced. Concern for disfigurement if a local relapse were to occur may influence one patient’s decision to proceed with the radiation, while another patient may choose to forgo radiation due to the risk of lymphedema. Knowing a patient, encouraging that individual to take an active role in their own care, and advocating for their treatment preference will improve the quality of decision-making (Tariman and Szubski 2015). Shared decision-making contributes to shaping the patient experience. Cooper and de Lord (2018) call attention to the cancer patient experience being reported as on a par with clinical effectiveness [of treatment] in terms of importance.

Adjuvant Treatment

The landscape of adjuvant therapy has recently undergone a revolutionary transformation with results from two pivotal phase III clinical trials revealing practice-changing results (Eggermont and Dummer 2017). There has been a shift to PD-1 inhibitor therapy as the mainstay treatment for all patients, and for those with an identified v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, treatment options may also include BRAF inhibitor-based therapy (with or without mitogen-activated protein kinase (MEK) inhibition (Eggermont and Dummer 2017)). The role of local therapy such as radiation or isolated limb perfusion/infusion remains unclear but may be appropriate in select instances. Adjuvant ipilimumab, on the other hand, has most certainly been replaced by nivolumab based on superior efficacy and an improved toxicity profile (Eggermont and Dummer 2017). Interferon too has also fallen out of form and will have little to no role in the adjuvant arena. Its utility should be limited to patients with ulcerated primary melanomas only, and this may remain the mainstay treatment in countries without access to the novel therapies (Eggermont and Dummer 2017). As the landscape continues to evolve, it is important that nurses remain knowledgeable about these therapies to appropriately counsel and support patients during their decision-making process. A brief review of currently available therapies will be discussed along with nursing considerations.

Locally Directed Therapy

Radiation

Adjuvant radiation may be recommended in select situations, for instance, in the treatment of patients with recurrent, in-transit, or nodal metastatic melanoma needing local control (Dimitriou et al. 2018; Garbe et al. 2016). Nurses provide support by ensuring patients and their family understand the goal of treatment and risks involved such as lymphedema and perform ongoing assessments of patient and caregiver coping. If applicable, nurses may facilitate referrals to the appropriate provider(s) such as to physical therapy for lymphedema management or to social work or other resources if a need has been identified by the patient or nurse. Nurses also aid in coordinating care among various providers, counsel patients, and family about proper skin care during radiotherapy and provide anticipatory guidance about treatment.

Limb Perfusion and Infusion

Isolated limb perfusion and isolated limb infusion (a simpler and less invasive procedure) are therapies available for treatment of new or recurrent in-transit disease of an extremity. Both are highly specialized surgical procedures providing intravascular delivery of chemotherapy, most commonly melphalan, occasionally combined with tumor necrosis factor. These procedures are available only at select facilities with trained staff. For the most part, the direct care of patients receiving limb perfusion is delivered by peri-anesthesia and surgical nurses; however, oncology nurses should possess general knowledge and understanding of the procedures to provide support and anticipatory guidance before and after the procedure (Ashton 2012).

Systemic Therapy

Interferon

At present, there remains little to no role for use of adjuvant interferon . Instead, it has been replaced by more effective therapies such as anti-PD-1 agents and molecularly targeted therapies. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma where the benefit is felt to be greatest (Eggermont and Dummer 2017).

Ipilimumab

Ipilimumab is a human IgG1 monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4) and was approved by the FDA in late 2015 for use in the adjuvant setting. Known as an immune checkpoint inhibitor (ICI), ipilimumab is a novel therapy with a novel toxicity profile completely unlike traditional anticancer therapies. The unique mechanism of action directly leads to a characteristic and vast toxicity spectrum almost exclusively auto-immune-based referred to as immune-mediated adverse events (imAEs) or immune-related adverse events (irAEs). The dose of ipilimumab in the adjuvant setting (10 mg/kg) is higher than that approved in the metastatic setting (3 mg/kg). In the phase III trial, nearly half of the participants experienced severe (grade 3–4) toxicity and five deaths occurred from drug-related causes (Eggermont 2016) [Detailed discussion of specific ICI-related toxicity is discussed below in the section on checkpoints in metastatic disease.].

Nivolumab and Pembrolizumab

Nivolumab and pembrolizumab are human IgG4 monoclonal antibodies against programmed death 1 (PD-1). Like ipilimumab, nivolumab and pembrolizumab are known as immune checkpoint inhibitors (ICIs). Nivolumab was approved by the FDA in late 2017 for use in the adjuvant setting. The approval of nivolumab was based on data showing improved RFS and, notably, a lower rate of grade 3 or 4 adverse events when compared to adjuvant ipilimumab (Dimitriou et al. 2018; Eggermont and Dummer 2017). Checkmate 054, is a phase III trial enrolling patients with resected stage IIIA (limited to those with sentinel node tumor volume >1 mm) IIIB, IIIC, or IV and compared pembrolizumab to placebo. Findings demonstrated improved RFS, with a similar toxicity profile to that of nivolumab and no new toxicities (Eggermont et al. 2018). Based on these results reported in May 2018, pembrolizumab is expected to gain FDA approval sometime in the next year.

While generally well tolerated, the risk of severe and/or permanent toxicity makes the decision to recommend adjuvant immunotherapy a challenging one, a decision that should be reached together with the patient and family. It remains to be seen whether it is best to treat patients in the adjuvant setting versus waiting to see if relapse occurs. Data suggests that due to the primed immune system, toxicities may be greater in the adjuvant setting than in advanced disease setting (Napolitano et al. 2018). Conversely, a major advantage of adjuvant immunotherapy is the possibility to discontinue treatment and maintain antitumor responses. The immunological “memory” induced by the immunotherapy agent offers the potential for long-lasting, lifelong, therapeutic responses (Napolitano et al. 2018).

As with any adjuvant discussion, it must be made clear to patients that surgical resection alone may be curative. Adjuvant therapy recommendations are based on a risk: risk of relapse, notably risk of systemic (visceral) relapse. Local relapse can be managed, for the most part, with additional surgical resection, but when the relapse is a systemic, management becomes complex. Each risk/benefit discussion must be based on the estimated individualized risk for a specific patient and should consider comorbidities or other related factors that may influence treatment outcomes (age, prior treatment, psychosocial issues, etc.) carefully weighed against the risk of both short- and long-term adverse events associated with PD-1 blockade (discussed in detail in the metastatic treatment section).

Given the lack of predictive and prognostic biomarkers or other means of ideal patient selection, questions will remain regarding best treatment approach. Until that time is reached, patients must be encouraged to be active participants in their care and treatment decisions and to partner with their oncology team to make decisions that are best for them. The process of shared decision-making is discussed in more detail below.

Dabrafenib and Trametinib

In April 2018, the FDA approved the combination of dabrafenib and trametinib (D/T) for the adjuvant treatment of patients with BRAF V600E- or V600 K-positive stage III melanoma following complete resection. This approval is the first oral molecularly targeted agents available as an adjuvant treatment option. The approval was based on results from the COMBI-AD trial, a phase III trial comparing D/T to placebo. Results demonstrate improved RFS without concern for additional toxicity than is seen in patients with unresectable stage III or stage IV (Long et al. 2017). Additional details and the nursing role in the care of patients receiving these agents will be discussed in the metastatic section below.

Future Considerations

Checkmate 915 is a phase III clinical trial, currently underway, comparing the combination of nivolumab plus ipilimumab versus nivolumab monotherapy in the adjuvant setting. The study enrolls patients after complete resection of stage IIIB/IIIC/IIID or stage IV melanoma, based on the AJCC 8th edition staging criteria. The rationale for this trial stems from the observation reported by Wolchok et al. (2017) that combination of CTLA-4 with PD-1 blockade augments the immune response when compared with each agent alone in metastatic melanoma (Dimitriou et al. 2018).

Follow-Up/Surveillance

Upon completion of definitive treatment (surgical or medical), recommendations for follow-up should be outlined and discussed with patients and their families. Nurses must be able to effectively convey the main objectives of follow-up care: early detection of relapse and identification of additional primary melanomas (Kurtz et al. 2017; Mrazek and Chao 2014; Garbe et al. 2016). An estimated 50% of recurrences in stages II and III melanoma are identified by clinical examination alone including physician detection, patient detection, or symptoms that prompt further testing (Kurtz et al. 2017). Of the relapses, approximately 50% recur in regional lymph nodes, 20% recur locally, and 30% recur at distant site(s) (Rueth et al. 2015). Ninety percent of relapses occur within 5 years (Garbe et al. 2016), with most relapses occurring within 2–3 years from diagnosis (Rueth et al. 2015; Kurtz et al. 2017). Early detection of recurrence is important as surgical resection of metastatic disease can provide a survival benefit in addition to the survival benefit of effective modern systemic therapy (Kurtz et al. 2017).

The survival advantage from early detection of relapses underscores the importance of patient education and establishing a strong patient-nurse relationship. Anticipatory guidance about what to expect at follow-up visits should be provided. Patients should know that a detailed history and review of symptoms is performed at every visit to identify early symptoms that may be suggestive of relapse. For the same reason, patients should be instructed to report any new symptoms that may develop in between visits. Instruction on skin and lymph node self-examination should be provided as well as counseling about proper UV/sun protection (Garbe et al. 2016; Mrazek and Chao 2014). Nurses are the ideal member of the oncology team to provide this type of education. Nursing assessment of patient learning will help define best counseling methods and may include demonstration, video or web-based educational tools, or other strategies that best fit the patients’ learning need. In addition, barriers to learning should be identified and addressed. Subsequent visits allow the nurse to reassess self-exam technique, and the visit also provides an opportunity for assessment of patient coping and their willingness to engage in self-care and evaluate adherence to follow-up recommendations.

In addition to history and physical exam, the use of surveillance imaging has an evolving role in management. Approximately 50% of asymptomatic recurrences are detected via imaging (Kurtz et al. 2017); however, there is controversy in defining optimal follow-up strategies (Kurtz et al. 2017; Garbe et al. 2016). Hence the frequency and intensity of follow-up should be determined based on estimated individual risk along with other factors, if present including history of multiple primary melanomas, the presence of clinically atypical nevi, family history of melanoma, patient anxiety, and the patient’s awareness and ability to detect early signs and symptoms of disease (Garbe et al. 2016).

The period of follow-up, referred to by some as a time of “watch and wait,” is often enormously challenging for patients (Boyle 2003) and family members. The so-called “active therapy” such as surgical resection or adjuvant therapy has been completed, and many patients report significant anxiety as they feel they are “waiting for the other shoe to drop.” Numerous qualitative studies examining the supportive care needs of patients with melanoma demonstrate a consistent need for disease-specific information for both the patient and their caregivers, provided in a timely and easy to understand language (Beesley et al. 2015; Kasparian et al. 2016; Stamataki et al. 2015). Findings also reveal concerns including anxiety, fear of relapse, and what to expect if recurrence occurs (Stamataki et al. 2015; Beesley et al. 2015). Emotional support for physical symptoms (e.g., lymphedema, pain, fatigue) was also identified as important to respondents. Setting expectations, providing anticipatory guidance, and simply “being present” improve the understanding of disease management. It is also a time to clarify patient or family misunderstandings or misconceptions regarding diagnosis, prognosis, or treatment plans. Through active listening and encouraging patients to express underlying fears, concerns, and worries, nurses can assess patient coping level of distress and, when necessary, refer for emotional or psychological supports. As reported by Stamataki et al. (2015), patients describe improved outcomes when provided with an opportunity to meet individually for 1 h with a melanoma nurse specialist. Patients valued the time spent, reported feeling better informed, and experienced decreased stress and anxiety.

Recurrent Melanoma

Recurrent melanoma is devastating and may be accompanied by anxiety, fear, and, once again, uncertainty for the future. When a recurrence is suspected or confirmed, additional diagnostic and/or genomic testing may be required to ascertain the extent of the relapse and determine treatment options. The primary role of the oncology nurse is supportive: ensuring patients understand why certain testing is being performed, what results mean, and assessing the psychosocial impact. Tariman et al. (2016) emphasize that many patients are facing life-changing illness; are often overwhelmed and overburdened with the diagnosis, treatment decisions, and overall healthcare system; and thus should be supported in times of their vulnerabilities. Nurses ensure patients’ needs are met, their concerns addressed, and their questions answered (Tariman et al. 2016).

Treatment of Metastatic Melanoma

Chemotherapy

Up until recently, a diagnosis of metastatic melanoma equated a dismal survival of less than 1 year and was considered an incurable malignancy without effective treatments. Various chemotherapy regimens have been tried including dacarbazine, temozolomide, and carboplatin/paclitaxel among others. Responses are marginal at best, typically short-lived, and without demonstrated survival advantage. Combination regimens have slightly better responses but with increased toxicity. In the current arena, chemotherapy may be considered in second and third line in patients with resistance to immunotherapy and targeted therapy (Garbe et al. 2016). In the rare instance chemotherapy is used, the primary nursing role is providing support and education regarding expectations of treatment and toxicity management.

Interleukin-2

Interleukin-2 (IL-2), a cytokine, received FDA approval in 1998 for the treatment of unresectable or metastatic melanoma. It is historically one of the few treatments that could produce complete responses (CRs) that were often durable for decades without further therapy (Atkins et al. 1999). However, only highly selected patients with excellent organ function and performance status are candidates for treatment (Atkins et al. 1999) which entails 2 near-week-long inpatient admissions. Treatment is associated with significant toxicity often requiring intensive care level of support, and for that reason, availability is limited to specialized centers with highly trained staff expert in administration and management (Atkins et al. 1999). Given the historical lack of effective treatments for advanced melanoma, oncology nurses may have little experience in caring for this patient population. Instead, the experience may be limited to nurses in academic medical centers or institutions heavily involved in clinical research. In the community setting, care may be limited to patients receiving salvage chemotherapy and/or palliative/supportive care.

Immune Checkpoint Inhibitors

The integration of ICIs into clinical practice has led to a dramatic change in practice with the contemporary melanoma clinic strikingly different than a few years ago. The anti-CTLA-4 antibody ipilimumab and the PD-1 antibodies pembrolizumab and nivolumab are now what should be considered standard of care treatments. Their use either as monotherapy or in combination has redefined the meaning of long-term survival for a population of patients with little to no effective therapies. As the field continues to advance with newer therapies and combination approaches evolving, the ability to tailor treatment and improve quality of life continues to expand. As a group, oncologists tend to direct efforts to risk-benefit assessment and the ultimate treatment goal of improved overall and disease-free survival. Yet they caution that less attention directed toward safety assessments and delayed recognition of symptoms can lead to increased morbidity, prolonged hospitalizations, nonadherence, premature termination of treatment, and potentially lethal outcomes (Gordon et al. 2017; Kirkwood and Ribas 2017).

In what has now been deemed an era of immunotherapy, oncology nurses in a variety of settings are more likely to be involved in the care of patients with metastatic melanoma receiving ICIs. Early identification and management of toxicity are essential to achieving all treatment outcomes (Kirkwood and Ribas 2017). Dummer et al. (2017) foresee oncology nurses increasingly being integrated into the treatment processes and be given major responsibilities, especially in keeping regular contact with patients regarding irAEs. The authors also highlight that many patients feel more comfortable and are more likely to call a nurse than the physician; hence, nurses could provide open and easy contact with the treatment team. As such, nurses must possess a thorough understanding of how ICIs work and truly comprehend how distinctly different these agents are from traditional chemotherapy. Insight into when certain toxicities are more likely to appear, and which patients are at greater risk, will maximize prompt diagnosis. Published algorithms and consensus on guidelines for management of irAEs are available from organizations including European Society of Medical Oncology, Society for Immunotherapy of Cancer, and American Society of Clinical Oncology-National Comprehensive Cancer Network. Nursing-specific information is available through the Oncology Nursing Society and the Society for Immunotherapy of Cancer, and an entire nurse-centric educational initiative was developed by the Melanoma Nursing Initiative. Nurses should be familiar with these valuable multimodality resources which offer tools, strategies, and interventions to maximize patient care, including best practices for telephone triage, a critical skill for nurses caring for these patients.

Nurses cognizant of the wide spectrum of toxicities associated with ICIs will anticipate and recognize subtle signs and facilitate appropriate intervention. Due diligence warrants thoughtful assessment of symptoms. Once an irAE has been identified, a suitable intervention will depend on the severity, or grade, as defined by the most current version of Common Toxicity Criteria for Adverse Events (CTCAE). This process allows for interpretation of subjective symptoms in an objective manner (Rubin 2017a) by employing a grading system from 1 (mild) to 5 (death) to represent symptoms defined by specific parameters based on the organ system involved (National Cancer Institute (NCI) 2017). Interventions are based on the assigned grade; therefore, nurses must be able to identify and grade symptoms. A key strategy is establishing and documenting patients’ “baseline” health. It must be made clear to patients how important it is to report any change in baseline health, no matter how subtle or seemingly insignificant (McGettigan and Rubin 2017). It is imperative patients understand toxicity from ICIs can be atypical in presentation and easily overlooked. While most toxicities occur within the first 4 months of therapy, they can occur at any time, including during and after completion of therapy (Puzanov et al. 2017; Weber et al. 2015).

The most common irAEs affect the skin (rash, pruritus), gastrointestinal organs (diarrhea, colitis), endocrine, and hepatic systems; these are discussed below. Neurologic events occur with less frequency (Friedman et al. 2016) but may have dire consequences if not identified. Toxicity from ipilimumab appears to be dose related (Michot et al. 2016; Weber et al. 2015). Notably, the approved dose of ipilimumab in the metastatic setting is 3 mg/kg, while the approved dose in the adjuvant setting is 10 mg/kg. Nurses must be mindful of the differences in doses when educating patients and families regarding treatment and when assessing for toxicity. It is not unusual to see an earlier onset of toxicity with higher [10 mg/kg] doses of ipilimumab (Madden and Hoffner 2017). Importantly, nurses must keep in mind the incidence of irAEs is higher with combination of ipilimumab plus nivolumab with either agent alone (Wolchok et al. 2017).

Unlike traditional cancer therapies, dose reductions are not strategies employed as management of ICIs. Generally, mild irAEs are managed conservatively without the need for treatment interruption; however, close monitoring is necessary to assess for increasing severity. Persistent mild or moderate toxicity requires initiation of oral corticosteroids and a hold of the immunotherapy and, for the most part, should be manageable on an outpatient basis (Friedman et al. 2016; Weber et al. 2015). Severe or life-threatening irAEs require immediate hospitalization, in some cases intensive care, and prompt initiation of high-dose intravenous (IV) corticosteroids and permanent discontinuation of the immunotherapy. In rare instances, toxicities such hepatitis or colitis not responding to IV steroids after 3–5 days require additional immunosuppression such as mycophenolate mofetil or infliximab (Weber et al. 2015; Friedman et al. 2016). For many of the common toxicities, algorithms have been developed with detailed management guidelines to help clinicians manage and treat the most common irAEs. The key management strategies employed by oncology nurses include ongoing assessment and vigilant toxicity screening. Bottom-line, prompt intervention is crucial as outcomes depend on how quickly irAEs are recognized, reported, and treated.

The potential for toxicity underscores the importance of open communication among the patient, family, and treating oncology team. Patient education is paramount. Ideally, every patient has a pretreatment comprehensive education session with the nurse or nurse practitioner. This session would be dedicated to the provision of ICI-specific education tailored to individual patients including a discussion of safe sexual practices, pregnancy avoidance, and fertility preservation for appropriate patients with referral to a fertility specialist as necessary prior to starting treatment. Toxicity-specific counseling includes direction about when patients should call, how to call (e.g., how to contact the provider outside of office hours), and specifically what to say when they call. This is of particular importance if on-call providers are not familiar with ICI toxicity. Further complicating such a scenario is if patients are not taught to correctly refer to treatment by the drug name or as “immunotherapy” and instead refer to it as “chemotherapy.” Interventions for “chemotherapy-related diarrhea” vastly differ from interventions for “ipilimumab-related diarrhea.” Such detail is not trivial.

The pretreatment visit also offers opportunity for nurses to assess patients’ understanding of their disease, recommended treatment, and goals of care and whether they demonstrate a clear understanding of risks and benefits of treatment, including the risk of serious toxicity. It is also a chance for nurses to identify potential barriers to treatment or adherence (e.g., lack of physical resources such as transportation or telephone) (Madden and Hoffner 2017) and to identify comorbid conditions that may negatively affect treatment outcomes (e.g., current or prior history of serious mental illness, cognitive deficit, substance abuse, underlying autoimmune disease).

Specific irAEs

Skin-related adverse events are the most common and typically the earliest to develop (Puzanov et al. 2017; Weber et al. 2015; Friedman et al. 2016). Nurses must educate patients about cutaneous irAEs, implement self-care strategies for at-risk individuals, and minimize the severity of irAEs that do develop (Madden and Hoffner 2017). Rash and/or pruritus are seen in approximately half the patients (Weber et al. 2015) and are typically mild to moderate in severity. Symptoms are managed conservatively with over-the-counter moisturizers, antihistamines, and topical corticosteroids. Pruritus is managed conservatively with moisturizers and antipruritus medications as the mainstay. However, pruritus can be very distressing and therefore requires prompt intervention and aggressive management even in the absence of rash. Grade 3 dermatitis requires oral or IV systemic corticosteroids, and grade 4 symptoms require hospitalization with the initiation of intravenous (IV) corticosteroids.

Nurses should encourage patients to employ proactive prevention strategies including skin hygiene with regular use of a gentle skin cleanser (non-soap), moisturizing once or twice daily with nonsteroidal emollients or creams, vigilant sun protection, and treating existing xerosis (McGettigan and Rubin 2017). In some cases, providing a prescription for a topical corticosteroid can expedite treatment but will require specific instructions for use. Ongoing assessment of cutaneous toxicity is necessary as serious events have been reported including Stevens-Johnson syndrome and toxic epidermal necrolysis (Puzanov et al. 2017; Friedman et al. 2016). Nurses play a crucial role in counseling patients, providing individualized interventions, assessing patient and caregiver understanding, assessing treatment adherence and barriers to treatment, and assessing skin integrity. Dermatologic toxicities can have a detrimental impact on quality of life. Pruritus can be incredibly distressing and be distracting to patients (McGettigan and Rubin 2017); therefore proactive and aggressive management of cutaneous toxicity including early referral to dermatology will improve outcomes.

Gastrointestinal (GI) effects are associated with ICIs. Diarrhea is one of the most common GI presentations. Abdominal pain, when accompanied by the presence of mucus and/or blood in the stool, is suggestive of colitis (Madden and Hoffner 2017). Recognizing symptoms early is critical to minimize the risk of bowel obstruction and/or perforation or other grave complications. Awareness that colitis is commonly seen 4–6 weeks from treatment start and is more likely in patients receiving ipilimumab (Weber et al. 2015) enables nurses to individualize assessments and education. Establishing patients’ baseline bowel pattern is crucial as a change from baseline may be indicative of evolving toxicity. Therefore, patients should be queried about change in bowel pattern, consistency or frequency, and/or other symptoms that may be indicative of evolving GI toxicity such as reflux, chance in appetite, abdominal pain, or cramping. A focused and detailed review of systems should include assessing for a recent change in diet, recent travel, and taking the time to fully review and reconcile each patient’s medication list. Patients should be queried about all medications including prescription, over the counter, vitamins, minerals, herbals, and any type of supplement both current and recent. Due diligence warrants thoughtful assessment of symptoms and can sometimes reveal simple etiology of seemingly big problems. Case in point: a patient receiving anti-PD-1 monotherapy calls shortly after the second infusion to report diarrhea for 2 days. Via directed questioning and ROS, it was apparent the symptoms were a result of overuse of laxative stool softeners resulting in symptoms mimicking colitis. The patient had not mentioned he was taking the bowel agents as he did not consider them “medications.”

Autoimmune hepatitis is a less common but notable toxicity because the majority of clinical presentations are characterized by asymptomatic elevations in liver function tests (LFTs) including aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and may or may not include elevations in bilirubin (Puzanov et al. 2017; Friedman et al. 2016; Weber et al. 2012). Rarely, patients may report nonspecific symptoms such as fever, fatigue, nausea, and abdominal pain making a prompt diagnosis more challenging. However, the knowledge that median onset of hepatitis is approximately 6–14 weeks after starting therapy and is most commonly seen in patients receiving combined anti-CTLA-4 and anti-PD-1 provides insight (Puzanov et al. 2017; Friedman et al. 2016) and enables nurses to facilitate expedited work-up by narrowing down vague symptoms. Nurses should ensure baseline LFTs are obtained before starting ICI therapy and reassessed prior to each cycle. Recognition of even mild increases from baseline, when low grade, should prompt intervention such as querying patients more in-depth about alcohol intake and use of hepatoxic medications (Friedman et al. 2016; Madden and Hoffner, 2017). As applicable, patients should be instructed to abstain from alcohol, avoid or minimize acetaminophen, and consider withholding statin. Repeating LFTs a few days later to determine trajectory is recommended. Higher-grade elevations require withholding the ICI and corticosteroids started. Abdominal imaging and/or liver biopsy may be warranted in certain instances (Puzanov et al. 2017; Weber et al. 2012), and referral to hepatologist or GI specialist may be beneficial (Madden and Hoffner 2017; McGettigan and Rubin 2017).

Pneumonitis is a rare but potentially fatal irAE seen with ICIs that can be fatal if not recognized early (Friedman et al. 2016; Puzanov et al. 2017). It is more prevalent with PD-1 inhibitors than with ipilimumab, but it is most likely to occur with combination of CTLA-4 and PD-1 inhibition (Friedman et al. 2016). Onset tends to be later than other irAEs, occurring several months after the start of treatment, though it may occur at any time (Friedman et al. 2016; Madden and Hoffner 2017). Presentations vary; symptoms include dyspnea, dry cough, tachypnea, tachycardia, fatigue, or less commonly fevers and chills (Puzanov et al. 2017; Friedman et al. 2016; Weber et al. 2015). When pneumonitis is suspected, a chest CT scan is indicated (Friedman et al. 2016; Michot et al. 2016). Importantly, clinical and radiographic findings may closely mimic pneumonia or disease progression (Puzanov et al. 2017) which may lead to improper treatment. Findings may be described as “ground-glass opacities” or “multifocal consolidation.” Any new findings suggestive of an infiltrative process predominately in the lower lobes (Michot et al. 2016; Friedman et al. 2016) should be presumed to be pneumonitis in patients receiving (or having received) ICIs.

Treatment for pneumonitis is based on severity and includes oral or IV corticosteroids. ICI will be held. In some cases, bronchoscopy with or without lung biopsy may be performed to exclude infectious etiologies before starting immunosuppression. In severe cases, patients should be hospitalized, and treatment with high-dose corticosteroids (e.g., methylprednisolone 2–4 mg/kg/d) should be initiated. For refractory cases, additional immunosuppression, including mycophenolate mofetil, cyclophosphamide, and infliximab, can be administered. Severe cases require permanent discontinuation of ICIs (Friedman et al. 2016; Michot et al. 2016; Weber et al. 2015).

Patient outcomes are influenced by vigilant nursing assessment as early management is associated with improved prognosis and reduced morbidity and mortality (Gordon et al. 2017). Baseline oxygen saturation should be documented and reassessed at every visit. Hypoxia (pulse oximetry <90%) is reported as a presenting symptom of pneumonitis (Weber et al. 2015; Friedman et al. 2016); however, nurses with knowledge of the spectrum of irAEs with ICIs would heed subtleties such as a slight decrease in oxygen saturation (rather than a decrease to <90%) resulting in diagnosis when low grade. Knowing patients allows nurses to identify a patient report of only being able to play a 9-hole round of golf rather than his usual 18 holes as a red flag, once again, possibly identifying pneumonitis when low grade. The ongoing, directed, and focused questioning as part of a nursing assessment allows for identification of seemingly innocuous signs and symptoms suggestive of evolving toxicity that otherwise would be easily overlooked. The key is maintaining a high index of clinical suspicion in any patient treated with ICIs (Gordon et al. 2017; McGettigan and Rubin, 2017) and the realization that attention to detail cannot be underestimated.

Endocrine-related toxicities, or endocrinopathies, tend to appear after the sixth or seventh week of treatment, with a median time to onset of 7–20 weeks (González-Rodríguez and Rodríguez-Eberu 2016). They occur in up to 1/3 of patients treated with ICIs (Alessandrino et al. 2018) and include thyroid dysfunction, hypophysitis, primary adrenal insufficiency (AI), and autoimmune diabetes mellitus (DM). Awareness is key. Endocrinopathy is outside of the typical side-effect profile of chemotherapies. If not identified early and promptly treated, endocrinopathies can progress and pose serious, possibly life-threatening consequences as in the case of adrenal insufficiency or adrenal crisis. However, nurses with awareness and understanding of these distinct toxicities can mitigate risk through vigilant screening, triage, and ready strategies to facilitate expedited work-up ensuring correct diagnosis and management. The result is decreased morbidity and increased likelihood of patients staying on treatment (Madden and Hoffner 2017; González-Rodríguez and Rodríguez-Eberu 2016).

Hypophysitis and thyroid dysfunction are the most common of the endocrinopathies (Alessandro et al. 2018). Nurses are frequently the primary and constant contact for patients (Sznol et al. 2017); therefore nurses must be mindful as hypophysitis can be challenging to recognize as signs and symptoms are often subtle, nonspecific in presentation (Alessandro et al. 2018), and can mimic symptoms common to patients with advanced cancer such as headaches, fatigue, nausea, and/or vomiting. It is most common in older males and in patients treated with combination of anti-CTLA-4 plus anti-PD-1. Incidence with anti-CTLA-4 is dose dependent; a higher incidence is seen in doses >3 mg/kg (Alessandro et al., 2018; González-Rodríguez and Rodríguez-Abreu 2016). Hypophysitis is rare with PD-1 monotherapy. If suspected, nurses should ensure treatment is held and facilitate obtaining proper labs and magnetic resonance imaging (MRI) with pituitary cuts. Results of hormone studies and MRI will confirm the diagnosis. Adrenal insufficiency or crisis is a potentially life-threatening condition. Patients require immediate intervention with stress-dose corticosteroids (e.g., hydrocortisone 100 mg IV immediately, followed by 50–100 mg every 8 h), hydration, and supportive care (Gordon et al. 2017; Sznol et al. 2017).

Management of hypophysitis includes decreasing the pituitary inflammation with steroids, which are then slowly tapered; and at the same time, hormone replacement of affected hypothalamic-pituitary axes should be started when a deficiency is present (cortisol, thyroxine, and testosterone/estradiol) (Iglesias 2018). For the most part, once side effects are controlled, and steroids are tapered to <10 mg prednisone or equivalent per day, ICI therapy may be restarted (Iglesias, 2018; González-Rodríguez and Rodríguez-Abreu, 2016). These patients are usually followed by endocrinology with oncology nurses serving as a liaison between the patients, oncologists, and various specialty providers (Sznol et al. 2017). Patients and their families may require a great deal of support during this time given the often complex nature of endocrine toxicity and need for specialty involvement. Nurses provide emotional support, assess patient understanding and coping, and provide anticipatory guidance regarding disease and toxicity management.

Thyroid dysfunction or thyroiditis is seen more frequently with PD-1 antibodies than ipilimumab and more commonly in women (González-Rodríguez and Rodríguez-Abreu 2016; Alessandro et al. 2018). However, the incidence is highest in patients receiving combination of anti-CTLA-4 plus anti-PD-1. Thyroiditis manifests most commonly as hypothyroidism and less commonly hyperthyroidism. Median onset of hypothyroidism ranges from 1 to 5 months sometimes following a brief period of hyperthyroidism. Treatment involves replacing thyroid hormone (e.g., levothyroxine), while hyperthyroidism is treated with β-blockers in symptomatic cases, followed by levothyroxine for hypothyroidism that develops later (Sznol et al. 2017).

Type 1 diabetes results from complete insulin deficiency caused by autoimmune destruction of pancreatic beta cells (González-Rodríguez and Rodríguez-Abreu 2016). It has been reported in patients receiving PD-1 inhibitors as well as in patients receiving combination of anti-CTLA-4 plus anti-PD-1 (Iglesias 2018). Management requires insulin therapy. Nurses should ensure baseline glucose level is obtained and repeated regularly. Typically, these patients are referred to endocrinology or to a diabetes specialty provider (Madden and Hoffner 2017).

Unique from other irAEs, endocrinopathies typically do not resolve because the function of the gland rarely recovers. Lifelong hormone replacement is therefore required (Iglesias 2018; Sznol et al. 2017). Patient counseling must be provided regarding “sick-day rules” of steroid dosing for medical procedures or acute illness (fever or cases of nausea, vomiting, and diarrhea), and patients should be encouraged to obtain a medical alert necklace or bracelet (Sznol et al. 2017). In some cases, providing patients with a prescription and instructions for use of hydrocortisone emergency injections may be beneficial (González-Rodríguez and Rodríguez-Abreu 2016). It is also prudent to assess for barriers to medication adherence (e.g., inability to take oral medication, cognitive dysfunction, lack of caregiver resource, financial problems that may impact inability to afford medication). Due to the risk of adrenal crisis, medication adherence is critical (González-Rodríguez and Rodríguez-Abreu 2016).

Arthralgias and inflammatory arthritis are reported by approximately 10% of patients receiving ICIs, particularly PD-1 inhibitors, and those receiving combination of PD-1 and anti-CTLA-4 inhibition (Madden and Hoffner 2017). A thorough medical history and review of symptoms will highlight patients at greater risk including those with underlying joint inflammation from prior injury or overuse (tendonitis, bursitis) or those with underlying rheumatologic disorders such as polymyalgia rheumatica or rheumatoid arthritis. For example, a patient with a history of a rotator cuff injury, even decades prior, may develop recrudescence of tenderness, pain, or discomfort during treatment with ICIs. Since delayed diagnosis and treatment can lead to long-term disability, and disorders may become chronic and require ongoing immunosuppressive/immunomodulatory therapy, it is important to understand typical symptom presentation and recommended management (Puzanov et al. 2017).

Treatment is directed at managing the inflammation with resultant pain, maintaining or improving physical functioning and ability to perform activities of daily living (ADLs), and decreasing the impact on quality of life (Madden and Hoffner 2017; McGettigan and Rubin 2017; Puzanov et al. 2017). Most patients will find conservative management strategies effective; nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, or topical diclofenac gel applied to localized or limited sore joints, or for those who cannot tolerate NSAIDs (Madden and Hoffner 2017; McGettigan and Rubin 2017). In some cases, low doses of prednisone may be necessary (Michot et al. 2016).

Rheumatologic consultation should be initiated for patients in whom symptoms do not improve with conservative management or for those where mobility or quality of life is impaired. Nurses should assess patients at risk of fall and implement safety strategies. Low-intensity physical activity should be encouraged to improve physical conditioning and sleep and decrease pain perception (Madden and Hoffner 2017; McGettigan and Rubin 2017).

Xerostomia and mucositis are less common rheumatologic irAEs seen with ICIs. Sicca syndrome with severe eye and mouth dryness and parotitis (Puzanov et al. 2017) and Sjögren’s syndrome have been reported (Michot et al. 2016). Importantly, even mild symptoms may have a negative impact on quality of life and affect day-to-day functioning such as eating. Even mild symptoms can lead to more serious sequelae such as decreased oral intake, weight loss, or aspiration. Withholding the ICI may be indicated and will be determined on an individual basis. Prior to starting treatment, nurses should screen patients for preexisting symptoms, notably xerostomia, from prior surgery such as parotid dissection or parotid radiation. Review of medication list may reveal patients at risk including those with concomitant medications known to cause or contribute to xerostomia such as antihistamines. Because of the impact on quality of life, proactive and aggressive symptom management should be instituted by nurses. For dry eyes, lubricating eye drop (Michot et al. 2016) should be encouraged and consideration should be given to ophthalmological consultation if symptoms are impacting vision or for patients who wear contact lenses. Xerostomia and mucositis treatments may overlap and include oral moisturizing agents such as saliva substitutes or synthetic saliva and/or secretagogues both non-pharmacologic (sugarless gum, sour candies). If ineffective, nurses may advocate for pharmacologic agents (pilocarpine, cevimeline hydrochloride) depending on the severity of symptoms (Michot et al. 2016; Madden and Hoffner 2017; McGettigan and Rubin 2017). Patient education includes counseling regarding vigilant oral hygiene: increasing frequency of brushing to every 4 hours and at bedtime using a soft toothbrush, daily flossing, avoidance of alcohol-based mouthwashes, proper fit of dentures (if applicable), and regular dental exams. For patients unable to tolerate brushing, chlorhexidine gluconate 0.12% or sodium bicarbonate rinses (1 teaspoon baking soda in 8 ounces of water or 1/2 tsp. salt and 2 tablespoons sodium bicarbonate dissolved in 4 cups of water) can be effective. Encourage patients to sip cool water or crushed ice. Soft, bland, nonacidic foods are better tolerated. Advocate for use of pharmacologic agents for appropriate patients (Gelclair® and Zilactin®, 2% viscous lidocaine applied to lesions 15 minutes prior to meals, 2% morphine mouthwash, and 0.5% doxepin mouthwash or “miracle mouthwash” of diphenhydramine, lidocaine, and simethicone may be effective). Corticosteroid rinse (dexamethasone oral solution) can also be effective but will require prophylactic treatment for candidiasis such as weekly fluconazole (Madden and Hoffner 2017; McGettigan and Rubin 2017).

Neurologic toxicity is rare but can be seen with both anti-CTLA-4 and anti-PD-1. A range of neurologic conditions has been reported including Guillain-Barré syndrome, myasthenia gravis, encephalitis, motor dysfunction, meningitis, demyelination, neuropathy, and nerve paresis (Michot et al. 2016; Friedman et al. 2016; Weber et al. 2015; Puzanov et al. 2017). Because symptoms can be subtle, overlap, or be misinterpreted by patients, nurses should perform focused assessments and direct questioning at every visit to evaluate for changes from baseline neurologic functioning. Prompt referral to a neuromuscular specialist is indicated as accurate diagnosis can be delayed if not identified early leading to poorer outcomes (Madden and Hoffner 2017). Depending on presentation, patients may require neuroimaging, nerve conduction studies, and, potentially, nerve or muscle biopsy to arrive at a diagnosis (Puzanov et al. 2017). Once again, the key to prompt recognition of possibly early toxicity is maintaining a high index of clinical suspicion in any patient treated with ICIs (Gordon et al. 2017; McGettigan and Rubin 2017).

Nephritis , another rare toxicity, should be considered with an increase in creatinine. Nurses should ensure baseline renal function is documented and take note of change from baseline and notify the treating provider. Vigilant nursing assessment can reveal subtle changes in renal function enabling early intervention to minimize the risk of high-grade toxicity. Focused and detailed nursing assessment may reveal modifiable risks such as the use of NSAIDs or inadequate oral hydration around the time of routine scans. Appropriate counseling and intervention may mitigate such risks, thus optimizing treatment. However, a 1.5-fold increase from baseline creatinine or development of proteinuria requires further evaluation, referral to nephrology, and consideration of renal biopsy (Puzanov et al. 2017). Nurses should anticipate the use of high-dose corticosteroids to prevent late damage to the kidneys, need for IV hydration, and avoidance or modification(s) to nephrotoxic medications and contrast media (Madden and Hoffner 2017; McGettigan and Rubin 2017).

Ocular and orbital toxicity includes uveitis most commonly, and others include conjunctivitis, blepharitis, iritis, keratitis, scleritis, episcleritis, vitritis, choroiditis, and serous retinal detachment (Michot et al. 2016; Puzanov et al. 2017; Madden and Hoffner 2017). Symptoms include eye pain, redness, photophobia, excessive tearing, floaters, and decreased visual acuity (Gordon et al. 2017). Awareness that ocular toxicities are frequently accompanied by irAEs in other systems, especially colitis (Puzanov et al., 2017), improves vigilance. Prompt ophthalmologic evaluation is required.

Cardiotoxicity includes myocardial fibrosis, pericarditis, cardiomyopathy, heart block, and myocarditis. Though exceedingly rare, several cases of fatal myocarditis have been reported in patients treated with ICIs. Data reveals incidence and severity is greatest in patients who received combination ipilimumab and nivolumab (Mahood et al. 2018; Varricchi et al. 2017; Johnson et al. 2016) compared with monotherapy regimens. Overall incidence is reported from <1% (Johnson et al. 2016; Puzanov et al. 2017) to 2.4% with anti-PD-1/anti-CTLA-4 combined therapy (Mahood et al. 2018). However, Johnson et al. (2016) assert the true incidence of early and late cardiotoxicity is unknown and likely underestimated because routine cardiac monitoring with EKG and/or assessing troponin levels was not routinely performed in most of the immunotherapy trials (Varricchi et al. 2017).

Findings reported by Mahmood and colleagues (2018) provide important clinical feature clinicians to be aware with regard to myocarditis. These include time to onset of myocarditis from first ICI was 34 days, 81% of patients presented with 3 months of starting therapy, nearly all cases of myocarditis (94%) had an elevated troponin, and 89% had an abnormal ECG, both of which were normal prior to starting therapy. Furthermore, they also emphasize of the 51% of patients with myocarditis, LVEF was normal. Based on these findings, the authors do not recommend pretreatment screening EKG or ECHO; however, they do advise obtaining baseline troponin. Nurses, therefore, anticipate and ensure baseline troponin levels are obtained as part of the pretreatment laboratory assessment on all patients commencing ICI-based therapy.

Clinical suspicion must be maintained by nurses when patients report vague symptoms such as fatigue, weakness, muscle pain, or syncope, with higher suspicion with reports of more typical cardiac symptoms such as chest pain, shortness of breath, lower extremity edema, or palpitations. Patients with underlying cardiac dysfunction require careful monitoring as do patients with evidence of myocarditis, vasculitis, or myositis. Weights should be monitored. For patients presenting with symptoms or concern for evolving cardiotoxicity, nurses should anticipate obtaining N-terminal pro-B-type natriuretic peptide (NT pro-BNP), troponin, and EKG and assisting in the prompt referral to specialty care (Johnson et al. 2016; Madden and Hoffner 2017). Cardiac MRI and/or cardiac biopsy may be requested. The ICI will likely be withheld and, more likely, will be permanently discontinued depending on the severity.

Molecularly Targeted Therapies

The integration of molecularly targeted agents into the therapeutic landscape for melanoma has contributed to the successes seen not only in metastatic disease but also now in the adjuvant setting. Combination BRAF/MEK is now considered a standard treatment option for patients with unresectable metastatic melanoma with an identified BRAF V600E or V600 K mutation (Daud and Tsai 2017). At this time there are two combination regimens approved by the FDA: dabrafenib/trametinib and vemurafenib/cobimetinib. A third combination, encorafenib/binimetinib, has completed phase III trials with results demonstrating improved ORR and PFS as well as what appears to be a more favorable toxicity profile (Dummer et al. 2017; Daud and Tsai 2017; Flaherty 2017). Data is currently being evaluated by the FDA and is expected to be approved in summer 2018.

As with every cancer therapy, patient education is a fundamental component of the oncology nurse role. With targeted therapy, however, the need for counseling starts way before a treatment plan has been formulated. Anticipatory guidance about targeted therapies includes conveying the guiding principle of this treatment: the presence of a BRAF mutation. Identification of a BRAF mutation within the tumor by an FDA-approved test is critical to ensuring a patient is receiving appropriate therapy and education begins with this concept. It should also be made clear that a BRAF mutation is an acquired mutation, not somatic, as many patients fear a positive BRAF result implies increased risk to offspring.

There are currently two approved mutation tests: cobas® 4800 BRAF V600 which identifies V600E mutations (for vemurafenib plus cobimetinib) and THxID™ which identifies both V600E and V600K (for dabrafenib plus trametinib). Some institutions may use other assays based on sequencing methods due to improved sensitivity and ability to analyze multiple genes; however, insurance coverage may vary. Because BRAFi are contraindicated in patients with wild-type tumors as they may promote tumor growth by activating MAPK pathway signaling (Czupryn and Cisneros 2017; Rubin 2017b), nurses must be prepared to field questions regarding testing. Nurses are in key positions to anticipate and expedite specific BRAF testing (or retesting), necessary for intended treatment (Czupryn and Cisneros 2017). This is especially important for patients with aggressive disease or those with a heavy symptom burden who need to begin therapy as soon as possible. Minimizing delays may be a matter of life or death and is therefore of the utmost importance.

Targeted agents are administered until disease progression or unacceptable toxicity. The goal of treatment is to prolong survival with minimal impairment of quality of life; therefore, drug-related AEs require prompt management to ensure patients derive optimal benefit from therapy (Daud and Tsai 2017). BRAF and MEK inhibitors are generally very well tolerated. Several AEs associated with BRAFi or MEKi (e.g., fatigue, nausea, diarrhea) are common with other cancer treatments and have well-reported management strategies; however, there are distinct, class-specific AEs of BRAF inhibitors, MEK inhibitors, as well as characteristic AEs seen with combination BRAFi/MEKi (Czupryn and Cisneros 2017; Daud and Tsai 2017; Rubin 2017b). Anticipating, continuously assessing, promptly recognizing, and managing AEs are a key role of oncology nurses and require a comprehensive understanding of the MOA and etiology of AEs. Nurses with in-depth knowledge of the AE profiles and a thorough understanding of which AEs are most likely attributed to the BRAFi or MEKi possess skills necessary for early identification of AE prompt intervention, thus resultant improved outcomes as well as patient satisfaction.

Targeted therapies are oral agents, thus offering more convenient administration compared with injectable therapies. Furthermore, oral delivery allows alterations in treatment – interruptions and dose reductions – to be made readily (Flaherty 2017). Nonetheless oral delivery has its own challenges that may hamper appropriate use (Czupryn and Cisneros 2017), most notably patient adherence. Nurses improve outcomes by simply anticipating, assessing, and addressing both real and perceived barriers that may influence proper administration and dosing. Barriers include delays in accessing drugs from specialty pharmacies, high copays, difficulties following complex dosing regimens, lack of social supports, reluctance to report AEs, and challenges associated with managing AEs (Kottschade and Reed 2017). When educating patients, nurses must include counseling on proper dosing and administration and drug and food interactions and provide anticipatory guidance about AEs. Counseling about safe sexual practices including pregnancy avoidance for appropriate patients should be a component of the education. Importantly, dabrafenib can interact with hormonal contraceptives (oral pills, injections, or patches); thus when necessary, patients should be referred to their primary care physician or to an obstetrician/gynecologist when necessary. Furthermore, nurses should be prepared to discuss fertility preservation options and/or provide referred to a fertility specialist as necessary prior to initiating therapy (Kottschade and Reed 2017).

Of the novel AEs associated with targeted therapies, pyrexia, by far, is identified as a characteristic and challenging AE associated with BRAFi-based therapy, primarily seen with combination dabrafenib/trametinib. Long et al. (2017) reported 5-year safety and efficacy outcomes for patients enrolled on the landmark BRF113220 phase II study. Pyrexia was the most commonly reported AE with the incidence of 69%. It was also the most frequent cause of treatment discontinuation. These findings were similar to those reported by Robert and colleagues (2015) in the COMBI-v trial, comparing combination dabrafenib plus trametinib with vemurafenib. In this study, pyrexia was the most commonly reported AE with combination D/T, and pyrexia was the most common reason for dose interruption or reduction, as well as most common reason for treatment discontinuation. Conversely, results from the COLUMBUS trial demonstrate a low frequency of pyrexia seen with encorafenib monotherapy, as well as when encorafenib was combined with binimetinib (Dummer et al. 2018; Flaherty 2017). The low rate of pyrexia seen with encorafenib and binimetinib (enco/bini) distinguishes this combination from the other combination targeted therapies and will likely have significant clinical implications.

Defined by oral temperature >38.5 °C (101.3 °F) in the absence of clinical or microbiologic evidence of infection (Rubin 2017b), the etiology of pyrexia is not well understood and does not appear to correlate with any predictive baseline characteristics or be predictive of clinical outcome or response to treatment (Daud and Tsai 2017). Some patients will often identify a prodrome prior to the development of fever or significant symptoms of pyrexia, and if this occurs, management should be the same as for established pyrexia syndrome (Atkinson et al. 2016). Management guidelines vary in the literature, but most agree on withholding both dabrafenib and trametinib (Daud and Tsai 2017) and restarting at the same dose once afebrile for 24 hours. Additional recommendations include the use of antipyretics (such as acetaminophen and/or nonsteroidal anti-inflammatories), supportive care strategies such as maintaining hydration, and ensuring patients are adhering to treatment recommendations, particularly those concerning treatment holds or dose adjustments (Czupryn and Cisneros 2017; Rubin 2017b). For recurrent episodes, scheduled administration of antipyretics continued upon reinitiating the targeted therapy can be effective. For patients with persistent pyrexia, a short course of corticosteroids (e.g., prednisone 10 mg daily for 5 days) may be considered. Alternatively, an intermittent dosing schedule can be effective employing full doses of medications. Expert opinion suggests that intermittent dosing is an effective management strategy that is unlikely to impact efficacy and is preferable to dose reduction although randomized clinical trial evidence is lacking (Atkinson et al. 2016; Daud and Tsai 2017). The authors provide an example: if a patient experiences pyrexia syndrome every 2–3 weeks, consider treating for 12 days followed by a 2-day break. Atkinson and colleagues also suggest considering prophylactic corticosteroids (e.g., prednisone 10–25 mg/day), with plans to taper if/when the patient has remained pyrexia free for at least 1 month. Dose reductions should be considered only if intermittent dosing and corticosteroid prophylaxis have failed, with an attempt to escalate doses as tolerated (Daud and Tsai 2017).

Experience may influence how patients are managed. Nonetheless, effective management requires significant clinical support, commonly provided by nurses. This often involves daily phone calls for symptom assessment and management. In addition, frequent clinic visits may be necessary for assessment and/or supportive care (such as IV hydration), not to mention the psychosocial support patients and families should be provided through education and anticipatory guidance. Throughout the process, nurses should be managing expectations and assess coping to minimize anxiety. This level and degree of care is resource and time intensive and require nurses with knowledge, skill, and experience to manage this unique toxicity. The arduous clinical management makes the safety profile of encorafenib/binimetinib a particularly attractive treatment options given the low incidence of associated pyrexia.

Arthralgias are a common AE more common with BRAFi monotherapy and less so with combination BRAF/ MEKi (Rubin 2017b). Management depends on severity; therefore patient education requires reporting of symptoms including severity and how impactful symptoms are on quality of life. NSAIDs and/or acetaminophen is advised for mild to moderate symptoms, while more severe symptoms may require a dose interruption until symptoms improve and dose reduction when restarting. For recurrent pain, low-dose prednisone can be very effective (Rubin 2017b).

Cutaneous AEs are associated with the available BRAF/MEKi and include rash, pruritus, and photosensitivity (Daud and Tsai 2017). The photosensitivity associated with vemurafenib is of particular clinical significance as it can be seen with even short sun exposures and therefore requires dedicated significant patient education and intervention to minimize UV. Notably results from the COLUMBUS trial (Dummer et al. 2018) demonstrated low incidence of photosensitivity with enco/bini. This finding represents yet another distinctive clinical advantage of enco/bini compared to other available combinations in the same class; specifically, it provides a safer option for patients at greater risk of photosensitivity or unwilling to adhere to UV protection.

Nurses should be familiar with rash and pruritus management including generalized skin care strategies: avoidance of harsh soaps, use of tepid (not hot) water for bathing, and daily use of moisturizers to minimize irritation. Anti-itch interventions include adding menthol to moisturizers, cool cloths to focal areas of pruritus, antihistamines, and steroids (topical or oral). Patients should be counseled to avoid direct sun or ultraviolet (UV) exposure. Use of protective clothing and/or sunscreen should be employed to minimize UV exposure. Use of physical sunscreens is preferred over chemical sunscreens as they are less irritating and work as soon as they are applied avoiding the need to apply in advance of UV exposure (Rubin 2017b). Hyperproliferative skin disorders such as keratoacanthoma (KA) and KA-like squamous cell carcinomas (SCCs) are a class effect of BRAFi resulting from paradoxical activation of the MAPK pathway by BRAFi in BRAF wild-type cells. For this reason, it is important to counsel patients to report any new or changing skin lesions, and routine full-body skin examinations (including oral and genitalia) by a dermatology provider are advised. Some skin lesions may resolve without intervention. Other management modalities include excision, cryotherapy, and curettage (Czupryn and Cisneros 2017; Rubin 2017b).

Other AEs are associated with BRAF/MEKi requiring awareness by nurses. Ocular and cardiac effects are rare but warrant awareness to ensure signs and symptoms are recognized and managed appropriately. Guidelines for management are available and should be familiar to nurses. Uveitis and retinal disorders are associated with BRAFi and MEKi, respectively. Ophthalmologic screening is recommended at regular intervals for patients treated with MEKi with or without BRAFi, and patients should be counseled to report any visual symptoms including blurred or double vision, redness of the eyes, or any type of eye pain (Czupryn and Cisneros 2017; Rubin 2017b). Cardiac effects associated with BRAFi include QT prolongation, and with MEKi ventricular dysfunction can be seen. Nurses should ensure baseline EKG and cardiac echocardiogram are obtained pretreatment and repeated at various intervals. Patients with an asymptomatic decrease in LVEF of 10% or greater from baseline require withholding the MEKi. If improvement is seen, agents can be restarted with appropriate dose reduction. If no improvement is seen, MEKi should be permanently discontinued (Daud and Tsai 2017). Anticipatory guidance regarding management of toxicity is essential to minimize patient dissatisfaction. Patients must understand the rationale for management and how it will impact overall treatment goals.

Oncolytic Viruses

Talimogene laherparepvec (TVEC) is first-in-class oncolytic virus derived from a herpes simplex virus-1 (HSV-1). It received FDA approval in October 2015 for local treatment of unresectable cutaneous, subcutaneous, and nodal melanoma metastases (Seery 2017; Rehman et al. 2016). TVEC is a live, attenuated virus, which has been modified to replicate specifically within tumor cells resulting in cell destruction (Seery 2017). The approval of TVEC offers a unique treatment option for a select subset of patients.

The logistics of TVEC administration requires a coordinated effort among multiple departments and personnel. While technically feasible for nurses to administer, at the centers currently offering this therapy, oncologists (medical or surgical) or advanced practice providers (APPs) tend to be the ones administering TVEC (personal communication with V. Seery; personal communication with H. Kaufman). Select nursing staff at various centers have been involved in coordinating and implementing TVEC into their institution and subsequently providing patient (and staff) education.

Providers who are pregnant or immunocompromised should not prepare or administer TVEC, touch a patient injection site(s) or dressing, or encounter any bodily fluids (Seery 2017). Treatment is contraindicated in pregnant or immunocompromised patients, in patients with clinical or laboratory evidence of an active herpetic infection, or in patients who require daily antiviral therapy such as acyclovir (Rehman et al. 2016). Patient education should include a description of treatment logistics, side effects, and postinjection care. The first injection consists of a lower concentration and is given initially to allow all patients to seroconvert if not previously exposed to HSV-1. The second injection is administered 3 weeks later at a higher concentration as are all subsequent injections. Treatment continues every 2 weeks, depending on treatment response and patient tolerability (Seery 2017; Rehman et al. 2016). An occlusive dressing is applied to the injection site(s), and patients should be instructed to keep site(s) covered for at least the first week after each treatment visit or longer if the injection site is weeping or oozing and to replace the dressing if it falls off. Patients should be instructed to avoid touching or scratching the injection sites, even if covered, to prevent the transfer of TVEC, and should be counseled to avoid kissing close contacts if either has an open mouth sore and to use condoms when engaging in sexual activity (Amgen 2017).

Adverse reactions are generally mild and resolve within 2–3 days. Common side effects include fatigue, chills, fever, nausea/vomiting, arthralgias and/or myalgias, and injection site pain (Seery 2017; Amgen 2017). Premedication with acetaminophen and/or nonsteroidal anti-inflammatories can prevent or minimize symptoms (Seery 2017); local anesthetics are not required but may be used if a patient has previously experienced significant pain during the injections (Rehman et al. 2016). In rare instances, cellulitis may develop at an injection site; therefore any reports of persistent or worsening erythema or edema or for a fever that persists beyond 48 h warrant evaluation (Seery 2017).

Central Nervous System Metastases

Approximately 50% of patients with stage IV melanoma will develop brain metastases (Olivia et al. 2017; Venur et al. 2017b; Flanigan et al. 2013) and up to 75% of patients in autopsy series (Olivia et al. 2017). The presence of BRAF or NRAS mutations increases the risk of CNS metastases in patients with advanced melanoma by 24% and 23%, respectively, compared with a 12% rate in wild-type tumors (Venur et al. 2017b). Common clinical manifestations include headache, neurologic deficits, cognitive impairment, and seizure, yet many patients will be asymptomatic with metastases identified on routine imaging. Though an individual clinical course is difficult to predict, certain prognostic indicators determine survival and thus guide treatment/management decisions. These include age, performance status, comorbidities, extent of systemic (extracranial) disease, number and location of CNS metastases, time from primary tumor diagnosis, the presence of neurologic symptoms, and elevated lactate dehydrogenase (Venur et al. 2017a; Flanigan et al. 2013).

Management strategies are broadly divided into supportive and therapeutic (Venur et al. 2017a). Supportive treatments include corticosteroids to reduce peritumoral edema, antiepileptics for seizure control, and medications to preserve cognitive function. Traditionally, therapeutic strategies focused on local treatment, including surgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS) and often a combination. Novel treatment approaches are being investigated, and early clinical trials with immunotherapy have shown encouraging intracranial activity in patients with asymptomatic brain metastases as have trials with BRAF-directed targeted therapies (Venur et al. 2017b). Combination of radiation and systemic therapy may be used to improve local control.

Caring for patients with CNS involvement is challenging and requires insight and experience by the nursing team. A clinical course for patients with CNS involvement varies considerably, and patients and families require much support. Nursing care must be comprehensive: meeting both the direct physical needs of patients and families (e.g., managing symptoms) while at the same time addressing the psychosocial and emotional responses to and spiritual aspects of cancer.

Palliative Care/End of Life

Immunotherapy brings with it the promise of meaningful benefit. However, despite advances that have dramatically improved outcomes for so many, there remain a significant number of patients who will not benefit from contemporary therapies and will die of melanoma. When treatment(s) fails, or if risks outweigh perceived benefits of treatment, patients must be informed. Nevidjon and Mayer (2012) advise frank, open, and ongoing discussions to ensure patients, their family/caregivers, and providers are all on the same page and goals of care are clearly described. They go on to explain if a patient does not have an honest picture of the prognosis, a realistic conversation can’t even begin about end-of-life care. When it does, concerns about the financial impact of end-of-life care for the individual and his or her family, differences between patient and family wishes, and fears of abandonment from the healthcare providers can overshadow the quality-of-life desires of the individual. These conversations are difficult to conduct in a brief office or inpatient visit, especially if the health of the patient is deteriorating (Nevidjon and Mayer 2012). Ideally, these types of discussions are explored with patients prior to when answers are needed. Within the confines of a therapeutic nurse-patient relationship, nurses should be prepared to bring up difficult topics (Nevidjon and Mayer 2012) such as code status; preference for dying at home, hospital, or hospice house; and exploring the emotional and psychosocial implications of transitioning care from a disease focus to symptom focus.

Nurses provide support though simply listening and encouraging patients to identify what is important to them, correcting any misconceptions they may have about the process of dying, and inquiring about any religious, spiritual, and cultural aspects of care that are important to the patients and should advocate for inclusion into the plan of care. In knowing a patient, the nurse can provide or facilitate care tailored to the needs of the patient. This may include interfacing with family or other caregivers when needed and acting as an advocate for other healthcare providers.

Fundamental to the nursing role is symptom management. Unlike most other malignancies, melanoma commonly metastasizes to the skin, subcutaneous tissue, and lymph nodes. Malignant wounds often develop which can be intensely painful disfiguring tumors that are both physically and psychologically devastating to not only the patient but to caregivers/family (Young 2017). These lesions may weep and bleed and, due to necrosis, often have a terrible odor that causes intense distress and embarrassment. Often the care of the malignant wound takes over the lives of the individuals and their caregivers (Young 2017). Healing is often not a therapeutic reality, instead, the goal wound care with symptom control what Young (2017) calls “palliative wound care. ” This requires palliative care to be combined with effective wound management with priority given to symptom management and the relief/prevention of pain along with psychological, spiritual, and emotional support. Oncology nurses are ideally positioned to spearhead this type of effort through facilitating interdisciplinary collaboration among palliative care provider(s) and individuals providing wound care, whether that be as part of a home care team such as hospice or visiting nurse service. Goals of wound care must be defined with various providers on the same page regarding management strategies for both physical care and psychological support. When appropriate, oncology nurses provide guidance during the transition to the end of life care. Young (2017) emphasizes how even at the end of life, combining a palliative model of care with effective wound management can significantly enhance the patient’s quality of life.

Survivorship

Cancer survivorship is a term that has gained popularity over the past few decades. It began with the establishment of the National Coalition of Cancer Survivors (NCCS) in 1986 and then later evolved to the Office of Cancer Survivorship at the National Cancer Institute (NCI). The primary intent was recognition of cancer survivors as a unique population with unique needs. Survivorship is defined by the NCI as “the health and life of a person with cancer post treatment until the end of life. It covers the physical, psychosocial, and economic issues of cancer, beyond the diagnosis and treatment phases.” To formalize care, the Institute of Medicine defined four major components of survivorship care models: prevention, surveillance, interventions, and coordination.

There is a paucity of data in the literature about melanoma-specific survivorship. The available evidence is analogous to the components identified by IOM and, for the most part, is already included in standard melanoma follow-up care. It is worth mentioning that the term “survivor” has a different meaning to different people (Smith et al. 2015). Oliveria et al. (2011) conducted a series of focus groups with stages I–III melanoma patients diagnosed 1–10 years prior; none were receiving treatment. The respondents varied in how they perceived their diagnosis. Those who did not consider themselves to be a survivor provided reasons such as not a “real” cancer, nor was it as serious as other cancers. One respondent remarked she did not consider herself a survivor as it [the melanoma] was on “the outside of the body, never inside”; therefore it was not interpreted as serious. Another respondent provided a similar reason, stating because it was not metastatic, it was not “real.” Some felt the label “survivor” should be reserved for individuals who received chemotherapy, radiation, or other extensive treatment. Another believed that one was not considered a survivor until reaching the 5-year mark from diagnosis (Oliveria et al. 2011; Vogel et al. 2017). Knowing how individuals see themselves influences follow-up care.

Prevention is a critical component of melanoma survivorship due to the higher risk of secondary melanoma and other skin cancers as discussed previously. Through assessment of existing knowledge, nurses can provide tailored education on proper use and application of sunscreens, use of UV protective clothing and hats, and eye protection. Education also includes strategies to reduce ambient and recreational sun exposure: seeking shade when possible, avoiding sunburns and tanning bed usage, and other safe sun practices (Mrazek and Chao 2014). Interestingly, Oliveria et al. (2011) found many survivors become less stringent with UV protection with pasting time, the reason being the desire to “live life” normally by going outdoors, and felt barriers to sun protection presented by lack of convenience. Regular and ongoing nursing assessment identifies those at risk and allows for tailored strategies aimed at increasing independence adherence.

Hereditary forms of melanoma (those with germline mutations in CDKN2A or CDK4) are rare. However, these patients have a high risk of developing multiple primary melanomas as well as increased risk of additional malignancies including pancreatic, breast, and lung (Soura et al. 2016). These individuals are best managed by a multidisciplinary team to address all required subspecialty care and screenings. Nurses should facilitate any appropriate referrals and ensure patients understand the rationale for ongoing follow-up.

Surveillance is an important aspect of follow-up and stems from higher risk of additional skin cancer development (Kasparian et al. 2016; Mrazek and Chao 2014). If not already, patients should be referred to a pigmented lesion clinic or to a dermatology provider skilled in high-risk skin cancer assessment for ongoing surveillance. Patient education should include instructions on skin and lymph node self-examination. Ongoing assessment and reinforcement of proper technique will identify any barriers to adherence. It is also helpful to clarify when and why patients should contact their primary care provider versus oncologist provider (Grant et al. 2010). Interventions focus on symptom management or education for long-term effects of cancer and cancer treatments. Grant et al. (2010) illustrate how interventions can be organized in relation to four domains of quality of life: physical, psychological, social, and spiritual.

Physical interventions are directed at management of symptoms such as lymphedema, pain, or decreased range of motion or addressing physical consequences from disease or treatment such as scar or other body image issues identified (Tan et al. 2014; Oliveria et al. 2011).

Psychological support has been identified as a priority need among individuals with melanoma (Tan et al. 2014; Mrazek and Chao 2014). In a systematic review of published studies, Kasparian et al. (2009) found approximately 30% of patients diagnosed with melanoma, including long-term survivors, and 20–30% of cancer caregivers reported levels of psychological distress report indicative of the need for clinical intervention. Anxiety and depression are the most commonly reported emotions experienced by melanoma patients (Mrazek and Chao 2014). Despite limited data, results of multiple studies highlight the psychological challenges faced by individuals with or a survivor of melanoma.

The primary goal of melanoma follow-up care is early detection of recurrent disease or new primary melanoma (Mrazek and Chao 2014); however, best practice would suggest that psychological care and support be incorporated into standard follow-up. Interventions include ongoing screening for psychological distress at various time points throughout care, facilitating access to specialty care when necessary (e.g., social work, psycho-oncology, local mental health provider), and promoting effective communication between patients, family members, and healthcare professionals (Wouters et al. 2018).

A melanoma diagnosis and subsequent treatment can affect social supports and family dynamics, often adversely affecting patients and their caregivers. Caregivers may benefit from receiving information/support interventions to address caregiver burden resulting from new roles and responsibilities. Such interventions help caregivers maintain their own psychosocial well-being (Tan et al. 2014). Support groups are another means of effective social support. Group programs are cost-effective and provide a safe environment for patients and caregivers to meet to support each other, feel a sense of belonging, develop friendships, and share ideas and thoughts (Tan et al. 2014).

Religion and/or spiritual beliefs are a tremendous source of support for patients and families and can help them cope with cancer (Vogel et al. 2017; Tan et al. 2014). Religious and spiritual preferences should be incorporated into comprehensive care. Churches, synagogues, and other religious institutions are often sources of community support, and efforts should be made to facilitate inclusion into plans of care as appropriate.

Coordination

Oncology care does not end when treatment ends. Nurses have a significant role in the dissemination and coordination of information between the patient and other healthcare providers (Grant et al. 2010). Simple interventions such as ensuring visit notes are being sent to relevant providers will enhance effective communication. Helping patients to prioritize their health needs and navigate the healthcare system will reduce stress and assisting patients to coordinate appointments among the multiple providers.

Conclusion

The arsenal of effective treatments for melanoma is expected to expand as result of ongoing research into various combinations and as new agents become available. As treatment options for melanoma expand, so does the role of oncology nurses. Nurses are on the front lines of patient care, play an important role in the multidisciplinary team, and influence treatment adherence and completion of therapy yielding more successful outcomes across the entire disease spectrum. Quintessential to providing effective patient-centered care is taking the time to build a therapeutic nurse-patient relationship. This relationship affords the framework for care and is necessary to provide individualized care that meets the needs of patients and their families.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for MelanomaMassachusetts General Hospital Cancer CenterBostonUSA

Section editors and affiliations

  • Keith T. Flaherty
    • 1
  • Boris C. Bastian
    • 2
  • Hensin Tsao
    • 3
    • 4
  • F. Stephen Hodi
    • 5
    • 6
  1. 1.Henri and Belinda Termeer Center for Targeted TherapiesMGH Cancer CenterCambridgeUSA
  2. 2.Departments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer CenterUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.AuburndaleUSA
  4. 4.Harvard-MIT Health Sciences and TechnologyCambridgeUSA
  5. 5.FraminghamUSA
  6. 6.Department of Medicine, Brigham and Women's HospitalDana-Farber Cancer InstituteBostonUSA

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