Excision of a Large Gastrointestinal Stromal Tumour Following 16 Months of Neoadjuvant Therapy with Imatinib (Case Report)
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Although the standard treatment for stromal tumours is surgery, in locally advanced forms, it is often necessary to achieve tumour downstaging to improve surgical outcomes. Neoadjuvant treatment in gastrointestinal stromal tumours (GISTs) with tyrosine kinase inhibitors, including imatinib, has been shown to be effective in several studies, but the duration of this treatment is still a subject of debate.
We report a case of a large GIST of the stomach in a 51-year-old patient with atypical presentation that was initially unresectable. Neoadjuvant treatment with imatinib for 16 months resulted in a good response, allowing secondary surgical excision.
Imatinib in neoadjuvant therapy should be continued as long as there is a good response and tolerance to the medication to obtain tumour downsizing compatible with carcinologic excision.
KeywordsGIST Imatinib Neoadjuvant therapy Surgery
Gastrointestinal stromal tumour
Cluster of differentiation
Tyrosine protein kinase cKIT
Platelet-derived growth factor receptor α
Positron emission tomography
European Organisation for Research and Treatment of Cancer
Radiation Therapy Oncology Group
European Society for Medical Oncology
Key Summary Points
The duration of neoadjuvant treatment of GISTs with imatinib remains a subject of debate
Some authors recommend not to exceed 12 months. But there is no scientific basis for this delay
Through this clinical case, the authors report a good tolerance and a good tumour response after 16 months of neoadjuvant treatment with imatinib, allowing the excision of a large gastric stromal tumour, and discuss the criteria to determine the duration of the neoadjuvant treatment
The authors suggest, in the context of neoadjuvant therapy, to continue treatment as long as there is good tumour response and tolerance allowing carcinologic excision
Gastrointestinal stromal tumours (GISTs) are tumours that are derived from Cajal cells or their precursors. These are the most frequent mesenchymal tumours of the digestive tract . They represent 0.1–3% of all gastrointestinal tumours, and gastric localisation is the most frequent . Although the standard of care is surgery, the prognosis of these tumours has been improved by tyrosine kinase inhibitors, which have increased overall and disease-free survival rates [3, 4, 5, 6, 7]. GISTs may sometimes be diagnosed at a locally advanced stage, and the use of these inhibitors may be necessary to obtain tumour downsizing before surgery . Neoadjuvant treatment in GISTs has been shown to be effective in several studies, but the duration of this treatment has been the subject of debate. We report a good response after 16 months of neoadjuvant therapy with imatinib in a large atypical stomach GIST, allowing secondary surgical excision
The authors received consent to both publish and participate from the patient. This case also received approval from the head of the Surgery Department of the Sylvanus Olympio University Hospital (Ref. N06/2019/DCS/CHUSO) to be reported and published.
Surgery remains the curative treatment of GISTs to this day . However, the surgical option may be reconsidered in the case of a large tumour, which, via its extension to neighbouring organs, may potentially impose organ sacrifice with the risk of not obtaining a negative margin , thus posing the problem of resectability. The case we reported fits into this situation, with an unusual predominant mix of aerobic and cystic components, creating additional diagnostic difficulties related to its confusion with gastric duplication. Indeed, the exploration tools at our disposal did not allow us to make a diagnosis, and the predominant cystic component of the tumour increased the risk of tumour rupture in the event of a percutaneous biopsy. Hence, our first laparotomy, the main goal of which was clearly surgical excision for a histological diagnosis on the surgical specimen. The limitation of our objective to perform an exclusively diagnostic procedure in view of the operative findings during this first operation supports the need for a histological diagnosis to plan the management of our patient as well as the need for neoadjuvant therapy for large tumours to obtain downstaging for a better carcinologic result.
The introduction of targeted therapy, including imatinib, whose administration is well codified in adjuvant therapy, has improved patient prognosis . Targeted therapy has provided neoadjuvant perspectives for large tumours with a high risk of malignancy. The preoperative use of imatinib in locally advanced GISTs is based on the assumption that in neoadjuvant therapy, imatinib could reduce the risk of tumour rupture and incomplete resections as well as minimise the intraperitoneal dissemination of tumour cells and thus the recurrence rate . In fact, the preoperative use of imatinib is becoming more common, but the duration of this neoadjuvant treatment, which varies from one study to another, remains a point of controversy. Blanke  proposed a duration of 3–6 months in a randomized trial. In 2009, the ESMO recommended a duration of 3–12 months until a maximum response was obtained . However, for most studies, the median duration of neoadjuvant treatment is between 6 and 8 weeks and generally does not exceed 1 year [11, 12, 13, 14, 15, 16, 17]. These studies remained within these limits based on the idea that the optimal response would be achieved between 4 and 12 months, with a low risk of developing secondary resistance and a better surgical outcome .
The extension of this duration to 16 months in our patient was justified by the good clinical response illustrated by the progressive and regular disappearance of the mass on palpation and by an objective response to the control on the CT scan. According to a study by Chaoyong Shen , one patient remained sensitive to imatinib after 57 months of treatment, suggesting that the optimal duration of preoperative treatment may vary from one individual to another. Recent data on the tumour response to imatinib based on the molecular profile of GISTs seem to confirm this interindividual difference in the treatment response by showing a better response of KIT exon 11 and 13 mutations, while KIT exon 9 mutations and PDGFRA gene mutations are associated with a poor response . Furthermore, by comparing the median duration of the neoadjuvant treatments of several series, it appears that a longer duration is associated with a higher resectability rate and, consequently, a better tumour response [11, 12, 13, 14, 15, 17].
It can be concluded from the above results that the response to treatment varies from one individual to another and that the longer the duration of neoadjuvant treatment is, the better the tumour response. Regarding the expectation of surgical excision, we believe that the duration of optimal treatment should depend on the tumour response to treatment and be the option that provides better tumour reduction for carcinologic excision.
For very large tumours, the duration of treatment must therefore be extended as long as the tumour responds to treatment, as in our patient, for whom 16 months were necessary. In our opinion, the regular monitoring and, if possible, molecular typing of GISTs are decisive criteria that should be considered in the neoadjuvant treatment of GISTs. Indeed, one of the objectives of follow-up is to identify adverse side effects that may lead to a reconsideration of imatinib dosage, as was the case in our patient. In the context of neoadjuvant therapy, the main objective of follow-up is to assess the response to imatinib therapy, which should be key in decision making to continue or not continue treatment, especially in the absence of molecular typing to predict a tumour response. This response can be evaluated with a CT or PET scan . However, according to the ESMO’s recommendations in 2014 , PET scans show high sensitivity in the early assessment of the tumour response and could therefore be very useful in neoadjuvant treatment where response prediction is particularly important. However, for regular monitoring, CT is most commonly used because it provides more anatomical information . We based our follow-up essentially on the clinic because of the difficult accessibility of the CT scan under our working conditions and performed a CT scan only when the mass disappeared after abdominal palpation.
The 16-month neoadjuvant treatment thus allowed tumour removal in two stages. Despite tumour reduction, the persistence of infiltration in the splenic hilum and inferior side of the left lobe indicated splenectomy, and a notch in the left lobe suggested a potential gain in organ preservation if treatment had continued.
For technical reasons, the molecular profile used to determine the type of mutation involved was not performed, although this had little impact on the management of our patient.
Neoadjuvant treatment is necessary in patients with large GISTs to achieve tumour downsizing before surgery. The treatment should be continued as long as there is a good tumour response and tolerance to the medication to obtain tumour downsizing compatible with carcinologic excision.
We thank the patient for giving us permission to report this clinical case. We would also like to thank Mr. Liloudini Arouna for the free English translation of the manuscript.
No funding or sponsorship was received for this study or publication of this article.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Fousséni Alassani was responsible for the design of the study and data collection and wrote the manuscript. Boyodi Tchangai, Aklesso Bagny, Ablavi A. Adani-Ife and Kossigan A. Amavi participated in the data collection and reading and redaction of the manuscript. Tchin Darre and Komla Attipou were responsible for overall scientific management and manuscript preparation.
Fousséni Alassani, Boyodi Tchangai, Aklesso Bagny, Ablavi A Adani-Ife, Kossigan A Amavi, Tchin Darre and Komla Attipou declare that they have no competing interest.
Compliance with Ethical Guidelines
We received consent to both publish and participate from the patient. This case also received approval from the head of the Surgery Department of the Sylvanus Olympio University Hospital (Ref. N°06/2019/DCS/CHUSO) to be reported and published.
All data generated or analyzed during this study are included in this published article/as supplementary information files.
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