Current Oncology Reports

, 20:102 | Cite as

Treatment of Rectal Cancer in Older Adults

  • Ayesha R. SheikhEmail author
  • Hassan Yameen
  • Kevan Hartshorn
Geriatric Oncology (AR MacKenzie, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Geriatric Oncology


Purpose of Review

Rectal cancer is predominantly a disease of older adults but current guidelines do not incorporate the associated specific challenges leading to wide variation in the delivery of cancer care to this subset of population. Here, we will review the current data available regarding the management of rectal cancer in older adults.

Recent Findings

The greatest challenge arises in the management of stage II/III disease as it involves tri-modality treatment that can be harder to tolerate by frail older patients. Response to neoadjuvant treatment is being used as a new marker to tailor further therapy and possibly avoid surgery. Oxaliplatin can be omitted from the adjuvant treatment without compromising outcomes.


Physicians should perform geriatric assessment utilizing many validated tools available to help predict treatment tolerability and outcomes in older adults that can help personalize subsequent management. Most older adults can undergo standard therapy for stages I, II, or III rectal cancer with curative intent. Increasing evidence suggests that patients with a clinical complete response to neoadjuvant treatment may be observed closely with the possibility of avoiding surgery. Studies are evaluating alternate systemic treatments for advanced metastatic disease with the hope of maintaining quality of life without compromising cancer outcomes.


Rectal cancer Older adults Neoadjuvant chemoradiation Watch and wait Pre-treatment risk assessment Rectal cancer surgery 


Compliance with Ethical Standards

Conflict of Interest

Ayesha R. Sheikh, Hassan Yameen, and Kevan Hartshorn declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Howlader N, Noone A, Krapcho M, et al. Cancer Statistics Review, 1975-2014 - SEER Statistics, National Cancer Institute. In: SEER Cancer Stat. Rev. 1975–2014. 2016.Google Scholar
  2. 2.
    Extermann M, Boler I, Reich R, Lyman GH, Brown RH, DeFelice J, et al. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score: Design and validation. J Clin Oncol. 2010.Google Scholar
  3. 3.
    Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011.
  4. 4.
    •• McCleary, NJ, Hubbard J, Mahoney MR, Meyerhardt JA, Sargent D, Venook A, Grothey A. Challenges of conducting a prospective clinical trial for older patients: Lessons learned from NCCTG N0949 (alliance). J Geriatr Oncol. 2018. A phase III trial, to evaluate treatment outcome differences in older adults (70 and above) accrued only 32 patients of the projected 380. Reasons for the poor accrual included discomfort with randomizing older adults to regimens of varying intensity without considering their fitness, as well as concerns about bevacizumab use in older adults.
  5. 5.
    Bohac GC, Guaqueta D, Cheng DM, Aschengrau A, Hartshorn KL. Disparity in the use of combined modality therapy for rectal cancer in the older adult. J Geriatr Oncol. 2013.
  6. 6.
    Babaei M, Jansen L, Balavarca Y, et al. Neoadjuvant Therapy in Rectal Cancer Patients With Clinical Stage II to III Across European Countries: Variations and Outcomes. Clin Colorectal Cancer. 2018; 17:e129–42. Available from:
  7. 7.
    Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, O’Mahony MS, Maughan TS, Parmar M, Langley RE. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): An open-label, randomised factorial trial. Lancet. 2011.
  8. 8.
    Dao D, Zemla T, Jatoi A, et al. Is there a role for older-patient-specific cancer clinical trials? A pooled analysis of 2277 older patients in adjuvant breast cancer trials (Alliance A151715). J Clin Oncol. 2018;36:10034.CrossRefGoogle Scholar
  9. 9.
    Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, et al. Prognostic and predictive relevance of primary tumor location in patients with ras wild-type metastatic colorectal cancer retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2017.
  10. 10.
    AJCC. Implementation of the AJCC 8 th Edition Cancer Staging System. 2016. In:
  11. 11.
    Group MS. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006.
  12. 12.
    Personalized treatment of elderly patients with rectal cancer. A position paper by the SIOG- surgical task force, ESSO, ESCP and OSTRiCh Consortium collaborative group | SIOG. Available at:
  13. 13.
    Mohile SG, Dale W, Somerfield MR, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. J Clin Oncol. 2018.
  14. 14.
    Wieland D, Hirth V. Comprehensive geriatric assessment. Cancer Control. 2003.Google Scholar
  15. 15.
    Hurria A, Mohile S, Gajra A, et al. Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer. J Clin Oncol. 2016.
  16. 16.
    • Cancer and Aging Research Group - Chemo Toxicity Calculator. Accessed 12 Aug 2018. Online tool helps estimate the overall risk of grade 3 to 5 chemotherapy toxicity in patients aged 65+ with a solid tumor or lymphoma starting a new chemotherapy regimen.
  17. 17.
    Moffitt Cancer Center. Accessed 12 Aug 2018 Online tool provides estimates for risk of grade 3 hematologic and grade 3 to 4 nonhematologic toxicity.
  18. 18.
    Rodríguez-Mañas L, Féart C, Mann G, et al. Searching for an operational definition of frailty: A delphi method based consensus statement. the frailty operative definition-consensus conference project. J Gerontol - Ser A Biol Sci Med Sci. 2013.
  19. 19.
    Tan KY, Kawamura YJ, Tokomitsu A, Tang T. Assessment for frailty is useful for predicting morbidity in elderly patients undergoing colorectal cancer resection whose comorbidities are already optimized. Am J Surg. 2012.
  20. 20.
    Driver JA, Viswanathan AN. Frailty measure is more predictive of outcomes after curative therapy for endometrial cancer than traditional risk factors in women 60 and older. Gynecol Oncol. 2017.
  21. 21.
    Tian Y, Xu B, Yu G, Li Y, Liu H. Age-adjusted charlson comorbidity index score as predictor of prolonged postoperative ileus in patients with colorectal cancer who underwent surgical resection. Oncotarget. 2017.
  22. 22.
    Park J-H, Kim D-H, Kim B-R, Kim Y-W. The American Society of Anesthesiologists score influences on postoperative complications and total hospital charges after laparoscopic colorectal cancer surgery. Medicine (Baltimore). 2018;97:e0653. Available from:
  23. 23.
    • Yeom S-S, Park IJ, Jung SW, et al. Outcomes of patients with abdominoperineal resection (APR) and low anterior resection (LAR) who had very low rectal cancer. Medicine (Baltimore). 2017. Study comparing APR vs sphincter-saving resection (SSR) for very low rectal cancer (3cm from anal verge) showing no statistical difference in recurrence-free survival between the 2 groups regardless of neoadjuvant chemoradiotherapy administration.
  24. 24.
    Sauer R, Becker H, Hohenberger W, et al. Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. N Engl J Med. 2004.
  25. 25.
    Liu W-Y, Jin J, Tang Y, et al. Can fit elderly patients evaluated by comprehensive geriatric assessment with intermediate or locally advanced rectal cancer receive preoperative chemoradiotherapy? An interim analysis of a multicenter phase II trial. J Clin Oncol. 2018;36:e15688. Available from:
  26. 26.
    • Wan J, Zhu J, Li G, Sun W, Zhang Z. Implications for determining the optimal treatment for locally advanced rectal cancer in elderly patients aged 75 years and older. Oncotarget. 2015. This retrospective study specifically looked at older adults 75 and above who received 4 different treatment modalities (surgery only, RT only, neoadjuvant RT with surgery, and surgery with adjvuant RT.) The best outcomes were associated with neoadjuvant RT with surgery a 5-year cancer specific survival of 60.4%.
  27. 27.
    Margalit DN, Mamon HJ, Ancukiewicz M, Kobayashi W, Ryan DP, Blaszkowsky LS, et al. Tolerability of combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Int J Radiat Oncol Biol Phys. 2011.
  28. 28.
    Tougeron D, Roullet B, Paillot B, Hamidou H, Tourani JM, Bensadoun RJ, et al. Safety and outcome of chemoradiotherapy in elderly patients with rectal cancer: Results from two French tertiary centres. Dig Liver Dis. 2012.
  29. 29.
    Gérard JP, Azria D, Gourgou-Bourgade S, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012.
  30. 30.
    Schmoll H-J, Haustermans K, Price TJ, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine +/- oxaliplatin in locally advanced rectal cancer: Final results of PETACC-6. J Clin Oncol. 2018;36:3500. Available from: http://
  31. 31.
    Deng Y, Chi P, Lan P, et al. Modified FOLFOX6 with or without radiation in neoadjuvant treatment of locally advanced rectal cancer: Final results of the Chinese FOWARC multicenter randomized trial. J Clin Oncol. 2018;36:3502 Available from:
  32. 32.
    Garcia-Aguilar J, Chow OS, Smith DD, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: A multicentre, phase 2 trial. Lancet Oncol. 2015.
  33. 33.
    NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Rectal Cancer. In: Version 2.2016. 2016.Google Scholar
  34. 34.
    • Wiltink LM, Marijnen, CAM, Kranenbarg, EMK, Van De Velde, CJH, Nout RA. A comprehensive longitudinal overview of health-related quality of life and symptoms after treatment for rectal cancer in the TME trial. Acta Oncol (Madr). 2016. A longitudinal analysis comparing adverse events related to TME alone vs neoadjuvant XRT with TME. General symptoms between both groups were similar but increased in older adults with the XRT arm reporting more bowel dysfunction including fecal incontinence.
  35. 35.
    Ngan SY, Burmeister B, Fisher RJ, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group Trial 01.04. J Clin Oncol. 2012.
  36. 36.
    Hoendervangers S, Couwenberg AM, Intven MPW, van Grevenstein WMU, Verkooijen HM. Comparison of pathological complete response rates after neoadjuvant short-course radiotherapy or chemoradiation followed by delayed surgery in locally advanced rectal cancer. Eur J Surg Oncol. 2018.
  37. 37.
    • Dattani M, Heald RJ, Goussous G, Broadhurst J, São Julião GP, Habr-Gama A, Oliva Perez R, Moran BJ. Oncological and Survival Outcomes in Watch and Wait Patients With a Clinical Complete Response After Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Systematic Review and Pooled Analysis. Ann Surg. 2018. Systematic review of literature of 17 studies on the “Watch and Wait” strategy showed that a clinical complete response after neoadjuvant chemotherapy when combined with robust surveillance allows early detection of recurrence and a high rate of successful salvage surgery (93% R0 resection) with no adverse effects on 3-year overall survival (93.5%).
  38. 38.
    Yeo HL, O’Mahoney PRA, Lachs M, Michelassi F, Mao J, Finlayson E, et al. Surgical oncology outcomes in the aging US population. J Surg Res. 2016.
  39. 39.
    •• Aquina CT, Mohile SG, Tejani MA, et al. The impact of age on complications, survival, and cause of death following colon cancer surgery. Br J Cancer. 2017. Retrospective study of over 24,000 patients who underwent colon cancer surgery showing that older adults had higher complication rates and higher risk of colon cancer specific death (HR 2.57 for age 75 and older).
  40. 40.
    Couwenberg AM, de Beer FSA, Intven MPW, et al. The impact of postoperative complications on health-related quality of life in older patients with rectal cancer; a prospective cohort study. J Geriatr Oncol. 2017.
  41. 41.
    Stevenson ARL, Solomon MJ, Brown CSB, et al. Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial. Ann Surg Publish Ah. 9000.Google Scholar
  42. 42.
    Jayne D, Pigazzi A, Marshall H, et al. Effect of robotic-assisted vs conventional laparoscopic surgery on risk of conversion to open laparotomy among patients undergoing resection for rectal cancer the rolarr randomized clinical trial. JAMA - J Am Med Assoc. 2017.
  43. 43.
    Knol J, Chadi SA. Transanal total mesorectal excision: technical aspects of approaching the mesorectal plane from below. Minim Invasive Ther Allied Technol. 2016.
  44. 44.
    Kosinski L. Shifting Concepts in Rectal Cancer Management. CA Cancer J Clin. 2012.
  45. 45.
    Patel UB, Brown G, Rutten H, et al. Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer. Ann Surg Oncol. 2012.
  46. 46.
    Bhoday J, Smith F, Siddiqui MR, Balyasnikova S, Swift RI, Perez R, et al. Magnetic Resonance Tumor Regression Grade and Residual Mucosal Abnormality as Predictors for Pathological Complete Response in Rectal Cancer Postneoadjuvant Chemoradiotherapy. Dis Colon Rectum. 2016.
  47. 47.
    Lambregts DMJ, Vandecaveye V, Barbaro B, Bakers FCH, Lambrecht M, Maas M, et al. Diffusion-weighted MRI for selection of complete responders after chemoradiation for locally advanced rectal cancer: A multicenter study. Ann Surg Oncol. 2011.
  48. 48.
    • Sun X, Huang T, Cheng F, et al. Monitoring colorectal cancer following surgery using plasma circulating tumor DNA. Oncol Lett. 2018. Small study assessing the mutational landscape with circulating tumor DNA of 11 patients after colorectal cancer surgery showed evidence that suggests tDNA has high specificity and sensitivity compared to CEA measurement in terms of prognosis.
  49. 49.
    Murray D, Young GP, Pedersen SK, Rabbitt P, Byrne SE, Cornthwaite KJ, Roy A, Karapetis C, Symonds EL. A prospective cohort study in colorectal cancer assessing the relationship between post-surgery detection of methylated BCAT1 or IKZF1 ctDNA and risk for residual disease and survival. J Clin Oncol. 2018;36:3596. Available from:
  50. 50.
    Habr-Gama A, Gama-Rodrigues J, São Julião GP, Proscurshim I, Sabbagh C, Lynn PB, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: Impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014.
  51. 51.
    Smith FM, Rao C, Oliva Perez R, Bujko K, Athanasiou T, Habr-Gama A, et al. Avoiding radical surgery improves early survival in elderly patients with rectal cancer, demonstrating complete clinical response after neoadjuvant therapy: results of a decision-analytic model. Dis Colon Rectum. 2015.
  52. 52.
    Garcia-Aguilar J, Renfro LA, Chow OS, et al. Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): Results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol. 2015.
  53. 53.
    Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001.
  54. 54.
    Tournigand C, André T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: Subgroup analyses of the multicenter international study of oxaliplatin, fluorouracil, and leucovorin in the adjuvant tre. J Clin Oncol. 2012.
  55. 55.
    Yothers G, O’Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, et al. Oxaliplatin As Adjuvant Therapy for Colon Cancer: Updated Results of NSABP C-07 Trial, Including Survival and Subset Analyses. J Clin Oncol. 2011;29:3768–74.CrossRefGoogle Scholar
  56. 56.
    •• Huang X-Z, Gao P, Song Y-X, Sun J-X, Chen X-W, Zhao J-H, Ma B, Wang J, Wang Z-N. Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. Oncotarget. 2016. Retrospective study on adding oxaliplatin the adjuvant setting showed no survival benefit in patients aged 73 or older regardless of ypN status.
  57. 57.
    Hong YS, Kim SY, Lee JS, et al. Long-term results of the ADORE trial: Adjuvant oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) versus 5-fluorouracil and leucovorin (FL) after preoperative chemoradiotherapy and surgery for locally advanced rectal cancer. J Clin Oncol. 2018;36:3501. Available from:
  58. 58.
    Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer. J Clin Oncol. 2011;29:1465–71.CrossRefGoogle Scholar
  59. 59.
    Venook AP. Advances in Adjuvant Therapy for Colon Cancer: P value or Practical Value. J Clin Oncol. 2018;36:1461–2.CrossRefGoogle Scholar
  60. 60.
    Zhang J, Hu H, Cai Y, Chen D, Xiao J, Ling J, et al. Total neoadjuvant treatment versus chemoradiotherapy in locally advanced rectal cancer: A propensity score analysis from two prospective phase II clinical trials. J Clin Oncol. 2018;36:3600.CrossRefGoogle Scholar
  61. 61.
    Abbott S, Eglinton TW, Ma Y, Stevenson C, Robertson GM, Frizelle FA. Predictors of outcome in palliative colonic stent placement for malignant obstruction. Br J Surg. 2014.
  62. 62.
    Zhao XD, Cai BB, Cao RS, Shi RH. Palliative treatment for incurable malignant colorectal obstructions: A meta-analysis. World J Gastroenterol. 2013.
  63. 63.
    Arnold D, Lueza B, Douillard JY, et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol. 2017.
  64. 64.
    Hurwitz HI, Tebbutt NC, Kabbinavar F, Giantonio BJ, Guan Z-Z, Mitchell L, et al. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013.
  65. 65.
    Landre T, Maillard E, Taleb C, Ghebriou D, Des GG, Zelek L, et al. Impact of the addition of bevacizumab, oxaliplatin, or irinotecan to fluoropyrimidin in the first-line treatment of metastatic colorectal cancer in elderly patients. Int J Colorectal Dis. 2018.
  66. 66.
    Simkens LHJ, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015.
  67. 67.
    Breadner D, Vincent MD, Jonker D, et al. Health related quality of life in older or frail patients with advanced colorectal cancer treated with dose reduced capecitabine. J Geriatr Oncol. 2018.
  68. 68.
    Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012.
  69. 69.
    Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): A randomised, double-blin. Lancet Oncol. 2015.
  70. 70.
    Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013.
  71. 71.
    Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer. N Engl J Med. 2015.
  72. 72.
    Petrioli R, Chirra M, Messuti L, Fiaschi AI, Savelli V, Martellucci I, et al. Efficacy and Safety of Regorafenib With 2/1 Schedule for Patients ≥ 75 Years With Metastatic Colorectal Cancer (mCRC) After Failure of 2 Lines of Chemotherapy. Clin Colorectal Cancer. 2018.
  73. 73.
    Tsuji Y, Shitara K, Yamanaka T, et al. REVERCE: Randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin, and irinotecan—Biomarker analysis. J Clin Oncol. 2018;36:3510. Available from:
  74. 74.
    Chen X, Li P, Sun J, Wang B, Lin P, Cai X, Han X, Gu Y. Apatinib as a salvage treatment for refractory metastatic colorectal cancer. J Clin Oncol. 2018;36:3556. Available from:
  75. 75.
    Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015.
  76. 76.
    Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017.
  77. 77.
    Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000.
  78. 78.
    Franke AJ, Skelton WP, Gaffar M, et al. Differences in the characteristics of younger and older MSI-H colorectal cancer (CRC) as determined by universal reflex testing. J Clin Oncol. 2018;36:3593.CrossRefGoogle Scholar
  79. 79.
    Overman MJ. Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results. ASCO. 2016.
  80. 80.
    • Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O. Efficacy of PD-1 & PD-L1 inhibitors in older adults: A meta-analysis. J Immunother Cancer. 2018. Systematic review looking at the efficacy of immune checkpoint inhibitors in younger (<65) vs older adults (65 and older) showed similar results for both groups in terms of both death and progression.
  81. 81.
    Elias R, Karantanos T, Sira E, Hartshorn KL. Immunotherapy comes of age: Immune aging & checkpoint inhibitors. J Geriatr Oncol. 2017.
  82. 82.
    Weber J, Mandala M, Del Vecchio M, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017.
  83. 83.
    Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018.
  84. 84.
    George TJ, Yothers G, Lee JJ, Jacobs SA, Deutsch M, Allegra CJ, et al. NSABP FR-2: Phase II study of durvalumab following neoadjuvant chemotherapy (NAC) in stage II-IV rectal cancer. J Clin Oncol. 2018;36:TPS3624.CrossRefGoogle Scholar
  85. 85.
    Fernandez-Martos C, Pericay C, Losa F, et al. RIA: Randomized phase II study comparing induction (I) mFOLFOX6 with or without aflibercept followed by chemoradiation (CRT) and total mesorectal excision (TME) in high risk-rectal cancer. GEMCAD 14-02 trial. J Clin Oncol. 2018;36:3518. Available from:
  86. 86.
    Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ayesha R. Sheikh
    • 1
    Email author
  • Hassan Yameen
    • 1
  • Kevan Hartshorn
    • 1
  1. 1.Section of Hematology/OncologyBoston University Medical CenterBostonUSA

Personalised recommendations