Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

Improvement of perioperative outcomes of gastric gastrointestinal stromal tumour (GIST) resections and the influence of minimal invasive surgery.

BACKGROUND: Safety of minimally invasive surgery (MIS) for gastrointestinal stromal tumours (GISTs) is still under debate since it might increase the risk of tumour rupture, especially in larger tumours. The aim of this study was to investigate trends in treatment and perioperative outcomes of patients undergoing resections of gastric GISTs over time. METHODS: This was a multicentre retrospective study of consecutive patients who underwent wedge resection or partial gastrectomy for localized gastric GIST at five GIST reference centres between January 2009 and January 2022. To evaluate changes in treatment and perioperative outcomes over time, patients were divided into four equal periods. Perioperative outcomes were analysed separately and as a novel composite measure textbook outcome (TO). RESULTS: In total 385 patients were included. Patient and tumour characteristics did not change over time, except for median age (62-65-68-68 years, p = 0.002). The proportion of MIS increased (4.0%-9.8%-37.4%-53.0 %, p < 0.001). Postoperative complications (Clavien Dindo ≥2; 22%-15%-11%-10 %, p = 0.146), duration of admission (6-6-5-4 days, p < 0.001) and operating time (92-94-77-73 min, p = 0.007) decreased over time while TO increased (54.0%- 52.7%-65.9%-76.0 %, p < 0.001). No change was seen in perioperative ruptures (6.0%- 3.6%-1.6%-3.0 %, p = 0.499). MIS was correlated with less CD ≥ 2 complications (p = 0.006), shorter duration of admission (p < 0.001) and more TO (p < 0.001). Similar results were observed in tumours ≤5 cm and >5 cm. CONCLUSION: A larger percentage of gastric GIST were treated with MIS over time. MIS was correlated with less complications, shorter duration of admission and more TO. Tumour rupture rates remained low over time.

Inflammatory polyp of the ileum causing small bowel intussusception: A case report.

Adult intussusception is rare, and an underlying benign or malignant aetiology is often found. Inflammatory fibroid polyp, a benign neoplastic polyp that can arise anywhere in the gastrointestinal tract is a rare cause of intussusception of the small bowel. Clinical presentation differs depending on the location of the lesion in the gastrointestinal tract. Diagnosis may be confirmed on a computed tomography scan or ultrasound. Definite diagnosis is based on histopathology and immunocytochemistry. We present the case of a 58-year-old lady with an inflammatory fibroid polyp who presented with microcytic anaemia and chronic abdominal pain due to recurrent intussusception.

The Sarcoma Assessment Measure (SAM): Preliminary Psychometric Validation of a Novel Patient-Reported Outcome Measure.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13 to 82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the global quality of life scale and 18% of the Toronto Extremity Salvage Scale (TESS); so psychometrically, it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

A gist on an obscure neoplasm in Ghana: gastrointestinal stromal tumours.

BACKGROUND: Gastrointestinal Stromal Tumour is a rare but potentially curable tumour of the gastrointestinal tract accounting for up to 1% of all gastrointestinal tumours. The discovery of Imatinib mesylate, a novel tyrosine kinase inhibitor has improved the chances even for unresectable, recurrent, or metastatic diseases. METHODS: This study sought to document the clinical and pathological characteristics of GISTs from two tertiary hospitals in Ghana that have undergone immunohistochemistry confirmation between 2014 and 2021. RESULTS: The median age of the subjects was 50 years with most of them (28.0%) being above 61 years. There were more females than males (64.0% vs. 36.0%). Abdominal mass and abdominal pain made up the majority of the clinical presentations. The majority of the subjects had partial gastrectomy (32.0%) which was followed by wedge resection (28.0%). Appendectomy and sleeve gastrectomy were the least performed procedures (8% each). Four of the 25 patients (16.0%) had resections of involved contiguous organs done with splenectomy being the most common procedure. The majority of GISTs were found in the stomach (68.0%) followed by the appendix (12.0%) and small bowel (12.0%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most reported symptoms. Free resection margins were observed in 84.0% of the subjects and only 3/25 (12.0%) experienced tumour recurrence. CONCLUSION: GIST is a potentially curable tumour that once was obscure but currently gaining popularity. Surgical resection offers the hope of a cure for localized disease while targeted therapies is a viable option for recurrent, metastatic, or unresectable tumours.

CLINICOPATHOLOGICAL AND IMMUNO-HISTOCHEMICAL CHARACTERIZATION OF GASTROINTESTINAL STROMAL TUMOUR AT FOUR TERTIARY HEALTH CENTERS IN NIGERIA USING CD117, DOG1, AND HER-2 BIOMARKERS.

Introduction: Gastrointestinal stromal tumours (GISTs) are neoplastic lesions that primarily affect the digestive tract and develop from interstitial cells of Cajal. Due to their malignant potential and personalized treatment, these lesions require histopathologic and immunohistochemical characterization. In this investigation, the sex, age, lesional sites of origin, histopathologic types, the prevalence of HER-2 expression, prognostic indices (based on tumour size and mitotic figures), expression of CD117 and DOG1, and characteristics of patients with GIST were all characterized. Methodology: This is a retrospective cross-sectional analysis of GIST cases seen at four tertiary healthcare centers in Nigeria over ten years (2008 to 2017) and investigated utilizing histopathological and immunohistochemical (CD117, DOG1, and HER-2) methods. Result: In this study, there were twenty GIST cases. Notably, the majority (40%) of the cases had tumours with sizes between 7.0 and 8.0, the stomach was the most frequent site (70%) and the spindle cell type of GIST was the most prevalent (80%) histopathological type. Additionally, the stomach was significantly associated with GIST as an origin site (with a P value of 0.001), and 100% and 50% of these tumours were immunoreactive with CD117 and DOG1 respectively. Finally, HER-2 immunoreactivity was negatively stained with GIST tumour. Conclusion: In our study, GISTs most frequently develop in the stomach, and CD117& DOG1 are essential for correctly diagnosing these tumours. However, HER-2 immunoreactivity is a predictive marker of survival for personalized care.

Impact of tumour rupture risk on the oncological rationale for the surgical treatment choice of gastrointestinal stromal tumours.

Tumour rupture of gastrointestinal stromal tumours (GISTs) has been considered to be a remarkable risk factor because of its unfavourable impact on the oncological outcome. Although tumour rupture has not yet been included in the current tumor-node-metastasis classification of GISTs as a prognostic factor, it may change the natural history of a low-risk GIST to a high-risk GIST. Originally, tumour rupture was defined as the spillage or fracture of a tumour into a body cavity, but recently, new definitions have been proposed. These definitions distinguished from the prognostic point of view between the major defects of tumour integrity, which are considered tumour rupture, and the minor defects of tumour integrity, which are not considered tumour rupture. Moreover, it has been demonstrated that the risk of disease recurrence in R1 patients is largely modulated by the presence of tumour rupture. Therefore, after excluding tumour rupture, R1 may not be an unfavourable prognostic factor for GISTs. Additionally, after the standard adjuvant treatment of imatinib for GIST with rupture, a high recurrence rate persists. This review highlights the prognostic value of tumour rupture in GISTs and emphasizes the need to carefully take into account and minimize the risk of tumour rupture when choosing surgical strategies for GISTs.

Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study.

PURPOSE: In the INTRIGUE trial, ripretinib showed no significant difference versus sunitinib in progression-free survival for patients with advanced gastrointestinal stromal tumour (GIST) previously treated with imatinib. We compared the impact of these treatments on health-related quality of life (HRQoL). PATIENTS AND METHODS: Patients were randomised 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off). Patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer-30 (EORTC QLQ-C30) questionnaire at day (D)1, and D29 of all cycles until treatment discontinuation. Change from baseline was calculated. Time without symptoms or toxicity (TWiST) was estimated as the mean number of days without progression, death, or grade ≥3 treatment-emergent adverse events per patient over 1 year of follow-up. RESULTS: Questionnaire completion at baseline was 88.1% (199/226) for ripretinib and 87.7% (199/227) for sunitinib and remained high for enrolled patients throughout treatment. Patients receiving sunitinib demonstrated within-cycle variation in self-reported HRQoL, corresponding to the on/off dosing regimen. Patients receiving ripretinib reported better HRQoL at D29 assessments than patients receiving sunitinib on all scales except constipation. HRQoL was similar between treatments at D1 assessments, following 2 weeks without treatment for sunitinib patients. TWiST was greater for ripretinib patients (173 versus 126 days). CONCLUSION: Patients receiving ripretinib experienced better HRQoL than patients receiving sunitinib during the dosing period and similar HRQoL to patients who had not received sunitinib for 2 weeks for all QLQ-C30 domains except constipation. Ripretinib may provide clinically meaningful benefit to patients with advanced GIST previously treated with imatinib.

Measuring Tumour Imatinib Concentrations in Gastrointestinal Stromal Tumours: Relevant or Redundant?

Imatinib plasma trough concentrations are associated with efficacy for patients treated for advanced or metastatic KIT-positive gastrointestinal stromal tumours (GISTs). This relationship has not been studied for patients treated in the neoadjuvant setting, let alone its correlation with tumour drug concentrations. In this exploratory study we aimed to determine the correlation between plasma and tumour imatinib concentrations in the neoadjuvant setting, investigate tumour imatinib distribution patterns within GISTs, and analyse its correlation with pathological response. Imatinib concentrations were measured in both plasma and in three regions of the resected primary tumour: the core, middle part, and periphery. Twenty-four tumour samples derived from the primary tumours of eight patients were included in the analyses. Imatinib tumour concentrations were higher compared to plasma concentrations. No correlation was observed between plasma and tumour concentrations. Interpatient variability in tumour concentrations was high compared to interindividual variability in plasma concentrations. Although imatinib accumulates in tumour tissue, no distribution pattern of imatinib in tumour tissue could be identified. There was no correlation between imatinib concentrations in tumour tissue and pathological treatment response.

Radiomics in gastrointestinal stromal tumours: an up-to-date review.

Gastrointestinal stromal tumours are rare mesenchymal neoplasms originating from the Cajal cells and represent the most common sarcomas in the gastroenteric tract. Symptoms may be absent or non-specific, ranging from fatigue and weight loss to acute abdomen. Nowadays endoscopy, echoendoscopy, contrast-enhanced computed tomography, magnetic resonance imaging and positron emission tomography are the main methods for diagnosis. Because of their rarity, these neoplasms may not be included immediately in the differential diagnosis of a solitary abdominal mass. Radiomics is an emerging technique that can extract medical imaging information, not visible to the human eye, transforming it into quantitative data. The purpose of this review is to demonstrate how radiomics can improve the already known imaging techniques by providing useful tools for the diagnosis, treatment, and prognosis of these tumours.

Psychological and social challenges of patients with locally advanced and metastatic gastrointestinal stromal tumours (GIST) on long-term treatment with tyrosine kinase inhibitors: a qualitative study with patients and medical oncologists.

PURPOSE: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of locally advanced and metastatic gastrointestinal stromal tumours (GISTs). Patients are experiencing prolonged survival but often at the expense of their health-related quality of life. It is not only the physical side effects that impact GIST patients' daily lives but also the psychological and social challenges they have to deal with. This qualitative study aimed to explore the psychological and social life challenges of GIST patients with locally advanced and metastatic disease on ≥ 5 years TKI treatment. METHODS: Semi-structured interviews with 15 locally advanced and/or metastatic GIST patients and 10 medical oncologists with experience of delivering care to this specific patient group were conducted. Thematic analysis was used to interpret the data. RESULTS: Psychological challenges expressed by participants concerned fears, scanxiety, negative change in emotion and mood, doubts about their treatment and follow-up, living with uncertainty, lack of understanding from others or healthcare professionals, and constantly being reminded of their illness. Challenges regarding social health included financial difficulties, challenges in relationships, concerns about fertility and parenting, work, and impact on social activities. CONCLUSION: The reported psychological and social challenges can significantly hamper the overall quality of life of GIST patients. Some challenges were clearly underreported and hardly recognized by medical oncologist, as they may tend to focus on the physical side effects and clinical outcomes of treatment. Therefore, it is essential to take the patient's perspective into account in research and clinical practice to ensure optimal care for this patient group.

Current status of and future prospects for the treatment of unresectable or metastatic gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GISTs) are soft-tissue sarcomas of the gastrointestinal tract. Surgery is the standard treatment for localised disease, but the risk of relapse and progression to more advanced disease is substantial. Following the discovery of the molecular mechanisms underlying GISTs, targeted therapies for advanced GIST were developed, with the first being the tyrosine kinase inhibitor (TKI) imatinib. Imatinib is recommended in international guidelines as first-line therapy to reduce the risk of GIST relapse in high-risk patients, and for locally advanced, inoperable and metastatic disease. Unfortunately, imatinib resistance frequently occurs and, therefore, second-line (sunitinib) and third-line (regorafenib) TKIs have been developed. Treatment options are limited for patients with GIST that has progressed despite these therapies. A number of other TKIs for advanced/metastatic GIST have been approved in some countries. Ripretinib is approved as fourth-line treatment of GIST and avapritinib is approved for GIST harbouring specific genetic mutations, while larotrectinib and entrectinib are approved for solid tumours (including GIST) with specific genetic mutations. In Japan, pimitespib, a heat shock protein 90 (HSP90) inhibitor, is now available as a fourth-line therapy for GIST. Clinical studies of pimitespib have indicated that it has good efficacy and tolerability, importantly not displaying the ocular toxicity of previously developed HSP90 inhibitors. Additional approaches for advanced GIST have been investigated, including alternative uses of currently available TKIs (such as combination therapy), novel TKIs, antibody-drug conjugates, and immunotherapies. Given the poor prognosis of advanced GIST, the development of new therapies remains an important goal.

Endoscopic full­thickness resection with clip­ and snare­assisted traction for gastric submucosal tumours in the fundus: A single­centre case series.

Exposed endoscopic full-thickness resection (Eo-EFTR) has been recognized as a feasible therapy for gastrointestinal submucosal tumours (SMTs) originating deep in the muscularis propria layer; however, Eo-EFTR is difficult to perform in a retroflexed fashion in the gastric fundus. As a supportive technique, clip- and snare-assisted traction may help expose the surgical field and shorten the operation time in endoscopic resection of difficult regions. However, the application of clip- and snare-assisted traction in Eo-EFTR of SMTs in the gastric fundus is limited. Between April 2018 and December 2021, Eo-EFTR with clip- and snare-assisted traction was performed in 20 patients with SMTs in the gastric fundus at The First Affiliated Hospital of Soochow University. The relevant clinical data were collected retrospectively for all of the patients and analysed. All 20 patients underwent Eo-EFTR successfully without conversion to open surgery or severe adverse events. The en bloc resection rate and R0 resection rate were both 100%. Two patients had abdominal pain and fever after the operation, and five patients had fever, which recovered with medical therapy. No complications, such as delayed bleeding or delayed perforation, were observed. The postoperative pathology indicated that 19 cases were gastrointestinal stromal tumours and one case was leiomyoma. During the follow-up, no residual tumour, local recurrence or distant metastasis was detected by endoscopy or abdominal computed tomography. In conclusion, Eo-EFTR with clip- and snare-assisted traction appears to be a relatively safe and effective treatment for gastric SMTs in the fundus. However, prospective studies on a larger sample size are required to verify the effect of the clip- and snare-assisted traction in Eo-EFTR.

Gastrointestinal Stromal Tumour with Liver Metastasis Presenting as Gastric Cancer.

Gastrointestinal stromal tumour (GIST) is a malignant tumour of the gastrointestinal lobe tissue, which mostly occurs in the gastrointestinal tract. Clinical manifestations can range from being benign to malignant. It mainly occurs in the gastric and small intestine. It may also develop in the colon, oesophagus, and bowel membranes, or outside the gastrointestinal tract and intestines. The pathological diagnosis of GIST depends on morphological measurements and immunohistochemistry. We report an interesting case in which the patient's gastroscopy indicated gastric malignant tumours, and the results of the contrast-enhanced computed tomography (CT) of the upper abdomen showed malignant stomach tumour accompanied by liver metastasis. After the patient knew about this diagnosis, she wanted to give up treatment. Finally, the gastric biopsy suggested positive CD34, CD117, DOG1, and Ki-67, which supported the diagnosis of GIST. We hope that, through this case, we could improve clinicians' understanding of GIST and improve its diagnosis and treatment.

Query2: Query over queries for improving gastrointestinal stromal tumour detection in an endoscopic ultrasound.

Gastrointestinal stromal tumour (GIST) lesions are mesenchymal neoplasms commonly found in the upper gastrointestinal tract, but non-invasive GIST detection during an endoscopy remains challenging because their ultrasonic images resemble several benign lesions. Techniques for automatic GIST detection and other lesions from endoscopic ultrasound (EUS) images offer great potential to advance the precision and automation of traditional endoscopy and treatment procedures. However, GIST recognition faces several intrinsic challenges, including the input restriction of a single image modality and the mismatch between tasks and models. To address these challenges, we propose a novel Query2 (Query over Queries) framework to identify GISTs from ultrasound images. The proposed Query2 framework applies an anatomical location embedding layer to break the single image modality. A cross-attention module is then applied to query the queries generated from the basic detection head. Moreover, a single-object restricted detection head is applied to infer the lesion categories. Meanwhile, to drive this network, we present GIST514-DB, a GIST dataset that will be made publicly available, which includes the ultrasound images, bounding boxes, categories and anatomical locations from 514 cases. Extensive experiments on the GIST514-DB demonstrate that the proposed Query2 outperforms most of the state-of-the-art methods.

Imatinib plasma levels in patients with gastrointestinal stromal tumour under routine clinical practice conditions.

OBJECTIVES: Imatinib is the first therapeutic option for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Previous studies have shown an improvement in patient survival rates following the use of imatinib. Nevertheless, adequate plasma concentrations of imatinib are necessary to achieve such improvement in survival and limit the toxicity of the drug. This study aims to analyse the influence of imatinib plasma concentrations on efficacy and safety in the treatment of gastrointestinal stromal tumour. MATERIALS AND METHODS: This descriptive, multicentre study analysed plasma levels of imatinib in patients diagnosed with gastrointestinal stromal tumour in the period 2019-2020. An optimal therapeutic range of 750-1500 ng/mL was established for the patient stratification based on their minimum plasma concentrations measured at the steady state. RESULTS: This study included 11 patients with metastatic disease in total, among whom only 54.5% (n = 6) had a minimum plasma concentrations measured at the steady state value within the therapeutic range. A median progression-free survival of 7.0 months was recorded for those patients with minimum plasma concentrations measured at the steady state < 750 ng/mL, while that median progression-free survival value remained unachieved for the group with minimum plasma concentrations measured at the steady state > 750 ng/mL (p = 0.005). The toxicity rate was 25% and 14.3% for patients with minimum plasma concentrations measured at the steady state > 1500 ng/mL and minimum plasma concentrations measured at the steady state ≤1500 ng/mL, respectively (p = 0.66). CONCLUSIONS: The present study aims to describe the correlation between the toxicity and effectiveness of imatinib as a function of minimum plasma concentrations measured at the steady state under routine clinical practice conditions. The results described here show the usefulness of imatinib plasma concentrations monitoring as part of the standard daily routine in our hospitals.

An unusual and life-threatening presentation of a large GIST.

INTRODUCTION: Gastrointestinal stromal tumours (GIST's) are rare tumours of the alimentary tract. They are often discovered incidentally during imaging or intra-operatively. In rare instances, they present acutely with life threatening gastrointestinal (GI) bleeding requiring emergency surgical intervention. CASE PRESENTATION: A 47-year-old gentleman, who is an ex-smoker with normal body mass index (BMI), presented with acute onset of epigastric pain, dizziness, and multiple episodes of melaena. The patient deteriorated rapidly and urgent endoscopy revealed active retrograde bleeding from beyond the duodenojejunal junction. Computed tomography angiography (CTA) suggested a highly vascular ileal exophytic mass resembling a GIST. Emergency exploratory laparotomy was conducted where hemostasis was achieved via segmental enterectomy of the mass that was unexpectedly jejunal in origin. During recovery, he encountered post-operative complications that were managed conservatively and eventually was discharged with a referral to the national cancer centre. CLINICAL DISCUSSION: The clinical presentation of GIST is based on its size and location. Definitive diagnosis of GIST relies on histopathological findings although the clinical presentation and imaging, in particular CTA, can aid in its diagnosis. Management of GIST differs depending on the clinical presentation, size, location and whether metastasis is present. Surgical resection is the standard of treatment; however, Imatinib could be used for non-resectable tumours as well as in cases of recurrence, metastasis or as an adjuvant chemotherapy. CONCLUSION: It is important to acknowledge that small GISTs are often asymptomatic while larger ones may present with non-specific symptoms which can be misleading. This could potentially delay the diagnosis and thus treatment of GIST which can be detrimental in acute cases as illustrated here. It is important to have GIST as one of the differentials when faced with a patient presenting with non-specific GI symptoms.

Gastric Schwannoma, a benign neoplasm hiding as gastrointestinal stromal tumour.

Gastric Schwannomas are rare, submucosal mesenchymal tumours arising from the nerve plexus of the Gut wall. They have an incidence rate of 0.2% of all Gastric tumours. They are mostly asymptomatic, but can present with vague gastrointestinal symptoms and the fact that histopathologically, they are similar to Gastrointestinal stromal tumours, so they are most often misinterpreted as Gastrointestinal stromal tumours. We present a case, which was also hiding as GIST (Gastrointestinal stromal tumours) preoperatively, on the basis of Endoscopic and Radiological investigations. The diagnosis was then confirmed as Gastric Schwannoma, postoperatively by immunohistochemical analysis. Hence, it is important to diagnose correctly to make appropriate treatment decisions. The findings presented here can may be helpful for a clinician for diagnosing a Gastric Schwannoma.

Naples prognostic score, a novel prognostic score for patients with high- and intermediate-risk gastrointestinal stromal tumours after surgical resection.

BACKGROUND: A novel multidimensional inflammatory and nutritional assessment system named the Naples prognostic score could serve as an independent prognostic indicator. However, its significance in patients with high- and intermediate-risk gastrointestinal stromal tumours remains unclear. METHODS: We performed this retrospective cohort study based on a prospectively collected database of gastrointestinal stromal tumours (GISTs) between March 2010 and December 2019. The Kaplan-Meier method and log-rank test were used for survival analyses. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression analysis was used for univariate and multivariate analyses. Time-dependent receiver operating characteristic curves were generated to evaluate the discriminatory ability of the prognostic scoring systems. Differences in the areas under the curve were further compared. RESULTS: A total of 405 patients with regular follow-up were included and analysed in this study. Significant differences in progression-free survival and overall survival were observed between the groups (P < 0.001). Multivariate analysis demonstrated that the NPS was a significant predictor of poor progression-free survival (1 vs 0, HR = 4.622, P = 0.001; 2 vs 0, HR = 12.770, P < 0.001) and overall survival (2 vs 0, HR = 5.535, P = 0.002). Furthermore, time-dependent AUC analyses showed that the NPS was more accurate than other haematologic prognostic systems. CONCLUSIONS: The present study demonstrates that the NPS could independently predict disease progression and survival among patients with high- and intermediate-risk GISTs. The NPS might be regarded and applied as one of the most convenient and effective preoperative risk stratification tools in the future, which should be validated by large-scale multicentre prospective cohort studies.

Symptoms reported by gastrointestinal stromal tumour (GIST) patients on imatinib treatment: combining questionnaire and forum data.

PURPOSE: Treatment with the tyrosine kinase inhibitor (TKI) imatinib in patients with gastrointestinal stromal tumours (GIST) causes symptoms that could negatively impact health-related quality of life (HRQoL). Treatment-related symptoms are usually clinician-reported and little is known about patient reports. We used survey and online patient forum data to investigate (1) prevalence of patient-reported symptoms; (2) coverage of symptoms mentioned on the forum by existing HRQoL questionnaires; and (3) priorities of prevalent symptoms in HRQoL assessment. METHODS: In the cross-sectional population-based survey study, Dutch GIST patients completed items from the EORTC QLQ-C30 and Symptom-Based Questionnaire (SBQ). In the forum study, machine learning algorithms were used to extract TKI side-effects from English messages on an international online forum for GIST patients. Prevalence of symptoms related to imatinib treatment in both sources was calculated and exploratively compared. RESULTS: Fatigue and muscle pain or cramps were reported most frequently. Seven out of 10 most reported symptoms (i.e. fatigue, muscle pain or cramps, facial swelling, joint pain, skin problems, diarrhoea, and oedema) overlapped between the two sources. Alopecia was frequently mentioned on the forum, but not in the survey. Four out of 10 most reported symptoms on the online forum are covered by the EORTC QLQ-C30. The EORTC-SBQ and EORTC Item Library cover 9 and 10 symptoms, respectively. CONCLUSION: This first overview of patient-reported imatinib-related symptoms from two data sources helps to determine coverage of items in existing questionnaires, and prioritize HRQoL issues. Combining cancer-generic instruments with treatment-specific item lists will improve future HRQoL assessment in care and research in GIST patients using TKI.