Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile / Características clínicas y pronóstico de los tumores malignos de intestino delgado: experiencia en un hospital universitario de Chile

Background Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America.AimTo describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs.MethodsRetrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile.ResultsA total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1–99.2), 82.2% (95%CI: 57.6–93.3), 40.0% (95%CI: 16.5–82.8) and 25.9% (95%CI: 4.5–55.7%), respectively. NET (HR 6.1; 95%CI: 2.1–17.2) and GIST (HR 24.4; 95%CI: 3.0–19.8) were independently associated with higher survival compared to AC, adjusted for age and sex.ConclusionsMalignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes. (AU)

Introducción Los tumores del intestino delgado (TID) son infrecuentes y la información sobre ellos es escasa en Latinoamérica.ObjetivoDescribir la epidemiología, características clínicas, métodos diagnósticos y supervivencia de los TID malignos.MétodosEstudio observacional retrospectivo de pacientes adultos con diagnóstico histopatológico de TID entre 2007-2021 en un hospital universitario de Chile.ResultadosSe observaron 104 pacientes (51,9% hombres; edad media 57 años) con TID. El tipo histológico fue tumor neuroendocrino (TNE) (43,7%, n=38), tumor estromal gastrointestinal (GIST) (21,8%, n=19), linfoma (17,2%, n=15) y adenocarcinoma (AC) (11,5%, n=10). Los GIST fueron más frecuentes en el duodeno (50%; n=12) y los TNE en el íleon (65,8%; n=25). Hubo 17 casos de metástasis, más comúnmente de colon y melanoma. Las náuseas y los vómitos se observaron con mayor frecuencia en AC (p=0,035), así como el sangrado gastrointestinal en GIST (p=0,007). Las herramientas de valoración más comunes fueron TC y enteroclisis por TC con un rendimiento diagnóstico alto (86% y 94%, respectivamente). La supervivencia a cinco años de los GIST, TNE, linfoma y AC fue 94,7% (intervalo de confianza [IC] 95%: 68,1-99,2), 82,2% (IC 95%: 57,6-93,3), 40,0% (IC 95%: 16,5-82,8) y 25,9% (IC 95%: 4,5-55,7), respectivamente. Los TNE (hazard ratio [HR] 6,1; IC 95%: 2,1-17,2) y GIST (HR 24,4; IC 95%: 3,0-19,8) se asociaron de forma independiente con una mayor supervivencia en comparación con AC, ajustado por edad y sexo.ConclusionesLos TID malignos son enfermedades poco frecuentes y los TNE son el subtipo histológico más común. La presentación clínica en el momento del diagnóstico, localización o complicaciones pueden sugerir un dictamen más probable. Los GIST y TNE se asocian a una mejor supervivencia en comparación con otros subtipos malignos. (AU)

How do others cope? Extracting coping strategies for adverse drug events from social media.

Patients advise their peers on how to cope with their illness in daily life on online support groups. To date, no efforts have been made to automatically extract recommended coping strategies from online patient discussion groups. We introduce this new task, which poses a number of challenges including complex, long entities, a large long-tailed label space, and cross-document relations. We present an initial ontology for coping strategies as a starting point for future research on coping strategies, and the first end-to-end pipeline for extracting coping strategies for side effects. We also compared two possible computational solutions for this novel and highly challenging task; multi-label classification and named entity recognition (NER) with entity linking (EL). We evaluated our methods on the discussion forum from the Facebook group of the worldwide patient support organization 'GIST support international' (GSI); GIST support international donated the data to us. We found that coping strategy extraction is difficult and both methods attain limited performance (measured with F1 score) on held out test sets; multi-label classification outperforms NER+EL (F1=0.220 vs F1=0.155). An inspection of the multi-label classification output revealed that for some of the incorrect predictions, the reference label is close to the predicted label in the ontology (e.g. the predicted label 'juice' instead of the more specific reference label 'grapefruit juice'). Performance increased to F1=0.498 when we evaluated at a coarser level of the ontology. We conclude that our pipeline can be used in a semi-automatic setting, in interaction with domain experts to discover coping strategies for side effects from a patient forum. For example, we found that patients recommend ginger tea for nausea and magnesium and potassium supplements for cramps. This information can be used as input for patient surveys or clinical studies.

Ten-Year Survivorship in Patients with Metastatic Gastrointestinal Stromal Tumors.

INTRODUCTION: Patients developing metastatic gastrointestinal stromal tumors (mGIST) have heterogenous disease biology and oncologic outcomes; prognostic factors are incompletely characterized. We sought to evaluate predictors of 10-year metastatic survivorship in the era of tyrosine kinase inhibitor (TKI) therapy. METHODS: We reviewed patients with mGIST treated at our Comprehensive Cancer Center from 2003 to 2019, including only patients with either mortality or 10 years of follow-up. Ten-year survivorship was evaluated with logistic regression. RESULTS: We identified 109 patients with a median age of 57 years at mGIST diagnosis. Synchronous disease was present in 57% (n = 62) of patients; liver (n = 48, 44%), peritoneum (n = 40, 37%), and liver + peritoneum (n = 18, 17%) were the most common sites. Forty-six (42%) patients were 10-year mGIST survivors. Following mGIST diagnosis, radiographic progression occurred within 2 years in 53% (n = 58) of patients, 2-5 years in 16% (n = 17), and 5-10 years in 16% (n = 17), with median survival of 32, 76, and 173 months, respectively. Seventeen (16%) patients had not progressed by 10 years. Fifty-two (47%) patients underwent metastasectomy, which was associated with improved progression-free survival (hazard ratio 0.63, p = 0.04). In patients experiencing progression, factors independently associated with 10-year survivorship were age (odds ratio [OR] 0.96, p = 0.03) and time to progression (OR 1.71/year, p < 0.001). CONCLUSIONS: Ten-year survivorship is achievable in mGIST in the era of TKIs and is associated with younger age and longer time to first progression, while metastasectomy is associated with longer time to first progression. The role of metastasectomy in the management of patients with disease progression receiving TKI therapy merits further study.

GIST presenting as refractory iron-deficiency anaemia in paediatric patient.

Gastrointestinal stromal tumours (GISTs) are very rare gastrointestinal (GI) mesenchymal tumours affecting only 0.02 children/million/year below the age of 14 years. We reported a 9-year-old girl presented to emergency department with pallor and haemoglobin of 50 g/L. Extensive workup for anaemia suggested iron-deficiency anaemia secondary to GI loss. Ultimately after blood transfusion of packed cells, she was discharged with a haemoglobin of 92 g/L with iron supplementation. Upper endoscopy showed incidental antral nodularity with biopsy proven helicobacter gastritis and an isolate 3-4 cm suspicious mass in the lesser curvature. Abdomen imaging confirmed the gastric mass in addition to two lesions, one retroperitoneal and one paraspinal. She undergone open laparotomy with complete surgical resection of the gastric and retroperitoneal masses with histological confirmation of GIST and paraganglioma. This case emphasises the importance of proper examination of the stomach at endoscopy and to illustrate that although anaemia is common in paediatric age group it may be reflect serious medical condition even in normal looking child.

A proposed risk assessment score for gastrointestinal stromal tumors based on evaluation of 19,030 cases from the National Cancer Database.

BACKGROUND: Standard risk assessment algorithms for gastrointestinal stromal tumor (GIST) are based on anatomic and histopathological variables with arbitrarily defined subcategories. Our goal was to improve risk assessment for GIST through retrospective analysis of patient data. METHODS: The National Cancer Database (NCDB) was queried for patients with GIST; the final cohort consisted of 19,030 cases. Main outcomes were metastasis at presentation and overall survival. A test dataset was used to reevaluate risk stratification parameters in multivariate regression models. A novel risk assessment system was applied to the validation dataset and compared to other currently used risk assessment schemes. RESULTS: Analysis of observed prevalence of metastases at presentation suggested 7 cm and mitotic rates > 10 per 5 mm2 as optimal threshold values. A proposed risk stratification score showed statistical superiority compared to the National Comprehensive Cancer Network, American Joint Committee on Cancer, and modified National Institute of Health classifications in predicting probability of presentation with metastasis at diagnosis and 4-year overall survival after accounting for important covariables including patient age and comorbidities, year of diagnosis, and surgical/systemic therapeutic regimen. CONCLUSIONS: Reexamination of prognostic factors for GIST demonstrated that current threshold values for tumor size and mitotic rate are suboptimal. A risk stratification score based on revised categorization of these factors outperformed currently used risk assessment algorithms.

Imatinib-resistant gastrointestinal stromal tumors in the era of second- and third-line tyrosine kinase inhibitors: Does surgical resection have a role?

BACKGROUND: Imatinib resistance is associated with a poor prognosis in patients with gastrointestinal stromal tumors. Although novel tyrosine kinase inhibitors have improved outcomes in imatinib-resistant gastrointestinal stromal tumors, the role of resection remains unclear. We sought to investigate factors predictive of overall and progression-free survival in patients with imatinib-resistant gastrointestinal stromal tumors. METHODS: A query of our prospectively maintained Comprehensive Cancer Center registry was performed from 2003 to 2019 for patients with imatinib-resistant gastrointestinal stromal tumors. Clinicopathologic characteristics and medical and surgical treatments were collected; overall survival and progression-free survival after imatinib-resistance were analyzed with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: A total of 84 patients developed imatinib resistance at a median age of 59 years. Median time to imatinib resistance after diagnosis and overall survival after imatinib resistance was 50 and 51 months, respectively. After being diagnosed with imatinib resistance, 17 (20%) patients underwent resection. On multivariable analysis, resection after imatinib resistance was independently associated with improved progression-free survival (hazard ratio 0.50; P = .027) but not overall survival (hazard ratio 0.62; P = .215). Similar findings were found on subgroup analysis of patients treated with second-line sunitinib (n = 71). CONCLUSION: Long-term survival can be achieved in patients who develop imatinib-resistant gastrointestinal stromal tumors. Surgical resection of imatinib-resistant gastrointestinal stromal tumors is associated with improved progression-free survival and should be considered in selected patients.

National Utilization of Imatinib in the Management of Resected Gastrointestinal Stromal Tumors.

BACKGROUND: Imatinib decreases recurrence risk and improves overall survival (OS) in localized gastrointestinal stromal tumors (GISTs); however, the extent to which patients receive appropriate treatment in the US has not been well characterized. METHODS: Patients with non-metastatic, resectable GIST were included in this study (National Cancer Database, 2010-2015). Those with a low-risk of recurrence were classified as receiving overtreatment or guideline-concordant treatment, while those with a high-risk of recurrence were classified as receiving undertreatment or guideline-concordant treatment. Multivariable logistic regression was used to determine factors associated with non-concordant treatment. The association between non-concordant treatment and OS was evaluated using multivariable Cox regression and propensity score matching. RESULTS: Among 3088 patients with high-risk GIST, 41% were undertreated, and among 3908 patients with low-risk GIST, 18.8% were overtreated. For patients with high-risk GIST, age > 60 years, African American race, and treatment at a community or comprehensive cancer program were associated with undertreatment. Among low-risk patients, small bowel primary, tumor size > 2 cm, and tumors with > 1 mitotic figure per 50 high-power fields were more likely to be overtreated. After propensity score matching, guideline-concordant therapy was associated with an 8.8% improvement in 5-year OS (81.9% vs. 73.1%, p = 0.002) for those with high-risk GIST and decreased risk of death (hazard ratio 0.63, 95% confidence interval 0.47-0.84). There was no statistically significant difference in survival for patients with low-risk GIST with the addition of imatinib overtreatment (overtreatment 93.9% vs. 89.6%, p = 0.053). CONCLUSIONS: Nearly 30% of GIST patients do not receive guideline-concordant treatment and future work is needed to understand the factors driving non-concordant treatment.

[Molecular mechanism study of Shouhui Tongbian Capsules on promoting energy metabolism of gastrointestinal stromal cells].

Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 µg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.

[Safety and feasibility of laparoscopic double-flap technique in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction tumors larger than 5 cm].

Objective: To investigate the safety and feasibility of laparoscopic double-flap technique (Kamikawa) in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction (EGJ) leiomyoma and gastrointestinal stromal tumor (GIST) with the maximum diameter >5 cm. Methods: A descriptive case-series study was used to retrospectively analyze the data of patients with EGJ leiomyoma and GIST undergoing laparoscopic-assisted proximal gastrectomy and double-flap technique (Kamikawa) at the Department of Gastrointestinal Surgery, Guangdong Hospital of Traditional Chinese Medicine from September 2017 to March 2019. All the tumors invaded the cardia dentate line, and the maximum diameter was >5 cm. After the exclusion of patients requiring emergency surgery and complicating with severe cardiopulmonary diseases, a total of 4 patients, including 3 males and 1 female with age of 29-49 years, were included in this study. After laparoscopic-assisted proximal gastrectomy, the residual stomach was pulled out of the abdominal cavity and marked with methylene blue at the proximal end 3~4 cm from the anterior wall of the residual stomach in the shape of "H". The gastric wall plasma muscular layer was cut along the "H" shape, and the space between the submucosa and the muscular layer was separated to both sides along the longitudinal incision line to make the seromuscular flap. The residual stomach was put back into the abdominal cavity. Under laparoscopy, 4 stitches were intermittently sutured at the upside of "H" shape and 4-5 cm from the posterior wall of the esophageal stump. The stump of the esophagus was cut open, and the submucosa and mucosa were cut under the "H" shape to enter the gastric cavity. The posterior wall of the esophageal stump was sutured continuously with the gastric stump mucosa and submucosa under laparoscopy. The anterior wall of the esophageal stump was sutured continuously with the whole layer of the residual stomach. The anterior wall of the stomach was sutured to cover the esophagus. The anterior gastric muscle flap was sutured and embedded in the esophagus to complete the reconstruction of digestive tract. The morbidity of intraoperative complications and postoperative reflux esophagitis and anastomosis-related complications were observed. Results: All the 4 patients completed the operation successfully, and there was no conversion to laparotomy. The median operative time was 239 (192-261) minutes, the median Kamikawa anastomosis time was 149 (102-163) minutes, and the median intraoperative blood loss was 35 (20-200) ml. The abdominal drainage tube and gastric tube were removed, and the fluid diet was resumed on the first day after surgery in all the 4 patients. The median postoperative hospitalization time was 6 (6-8) days. Postoperative pathology revealed 3 leiomyomas and 1 GIST. There were no postoperative complications such as anastomotic leakage or stenosis, and no reflux symptoms were observed. The median follow-up time was 22 (11-29) months after the operation, and no reflux esophagitis occurred in any of the 4 patients by gastroscopy. Conclusion: For >5 cm EGJ leiomyoma or GIST, double-flap technique (Kamikawa) used for digestive tract reconstruction after proximal gastrectomy is safe and feasible.

Imatinib and nutritional support can make successful treatment for a case of huge liver metastasis of duodenal gastrointestinal stromal tumor that initially showed jaundice and cachexia.

It is very difficult to treat patients with liver metastasis presenting with jaundice or cachexia. We herein report a successfully treated case of huge liver metastasis of gastrointestinal stromal tumor (GIST) that initially showed jaundice and cachexia. The patient was a woman in her early 40 s. She had a history of duodenal GIST 4 years before this admission. She was admitted to our hospital for abdominal fullness and anorexia. Abdominal computed tomography revealed huge liver metastasis of GIST. She showed jaundice and cancer cachexia with a modified Glasgow Prognostic Score of 2. After applying nutritional support, 400 mg of imatinib was administered. Although leg edema transiently worsened, the withdrawal of imatinib and administration of diuretics improved it. Imatinib was re-administered, and nutritional support was continued. The total bilirubin level decreased, and the serum albumin level increased. The tumor gradually decreased in size. Finally, she received surgical resection after 16 months of treatment with imatinib. Although adjuvant imatinib administration was continued after surgery, and no recurrence was observed as of 18 months after surgery.

Safety and feasibility of laparoscopic double-flap technique in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction tumors larger than 5 cm / 中华胃肠外科杂志

Objective: To investigate the safety and feasibility of laparoscopic double-flap technique (Kamikawa) in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction (EGJ) leiomyoma and gastrointestinal stromal tumor (GIST) with the maximum diameter >5 cm. Methods: A descriptive case-series study was used to retrospectively analyze the data of patients with EGJ leiomyoma and GIST undergoing laparoscopic-assisted proximal gastrectomy and double-flap technique (Kamikawa) at the Department of Gastrointestinal Surgery, Guangdong Hospital of Traditional Chinese Medicine from September 2017 to March 2019. All the tumors invaded the cardia dentate line, and the maximum diameter was >5 cm. After the exclusion of patients requiring emergency surgery and complicating with severe cardiopulmonary diseases, a total of 4 patients, including 3 males and 1 female with age of 29-49 years, were included in this study. After laparoscopic-assisted proximal gastrectomy, the residual stomach was pulled out of the abdominal cavity and marked with methylene blue at the proximal end 3~4 cm from the anterior wall of the residual stomach in the shape of "H". The gastric wall plasma muscular layer was cut along the "H" shape, and the space between the submucosa and the muscular layer was separated to both sides along the longitudinal incision line to make the seromuscular flap. The residual stomach was put back into the abdominal cavity. Under laparoscopy, 4 stitches were intermittently sutured at the upside of "H" shape and 4-5 cm from the posterior wall of the esophageal stump. The stump of the esophagus was cut open, and the submucosa and mucosa were cut under the "H" shape to enter the gastric cavity. The posterior wall of the esophageal stump was sutured continuously with the gastric stump mucosa and submucosa under laparoscopy. The anterior wall of the esophageal stump was sutured continuously with the whole layer of the residual stomach. The anterior wall of the stomach was sutured to cover the esophagus. The anterior gastric muscle flap was sutured and embedded in the esophagus to complete the reconstruction of digestive tract. The morbidity of intraoperative complications and postoperative reflux esophagitis and anastomosis-related complications were observed. Results: All the 4 patients completed the operation successfully, and there was no conversion to laparotomy. The median operative time was 239 (192-261) minutes, the median Kamikawa anastomosis time was 149 (102-163) minutes, and the median intraoperative blood loss was 35 (20-200) ml. The abdominal drainage tube and gastric tube were removed, and the fluid diet was resumed on the first day after surgery in all the 4 patients. The median postoperative hospitalization time was 6 (6-8) days. Postoperative pathology revealed 3 leiomyomas and 1 GIST. There were no postoperative complications such as anastomotic leakage or stenosis, and no reflux symptoms were observed. The median follow-up time was 22 (11-29) months after the operation, and no reflux esophagitis occurred in any of the 4 patients by gastroscopy. Conclusion: For >5 cm EGJ leiomyoma or GIST, double-flap technique (Kamikawa) used for digestive tract reconstruction after proximal gastrectomy is safe and feasible.

Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumor: A Systematic Review.

Background: The introduction of tyrosine kinase inhibitor (TKI) therapy has dramatically improved the clinical effectiveness of patients with locally advanced and/or metastatic gastrointestinal stromal tumors (GIST), and this systematic review was conducted aiming at the cost-effectiveness analysis of TKIs in GIST. Methods: A thorough literature search of online databases was performed, using appropriate terms such as "gastrointestinal stromal tumor or GIST," "cost-effectiveness," and "economic evaluation." Data extraction was conducted independently by two authors, and completeness of reporting and quality of the evaluation were assessed. The systematic review was conducted following the PRISMA statement. Results: Published between 2005 and 2020, 15 articles were incorporated into the systematic review. For advanced GIST, imatinib followed by sunitinib was considered cost-effective, and regorafenib was cost-effective compared with imatinib re-challenge therapy in the third-line treatment. For resectable GIST, 3-year adjuvant imatinib therapy represented a cost-effective treatment option. The precision medicine-assisted imatinib treatment was cost-effective compared with empirical treatment. Conclusion: Although identified studies varied in predicted costs and quality-adjusted life years, there was general agreement in study conclusions. More cost-effectiveness analysis should be conducted regarding more TKIs that have been approved for the treatment of GIST. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO: CRD42021225253.

Financial Implications of Avapritinib for Treatment of Unresectable Gastrointestinal Stromal Tumors in Patients With a PDGFRA Exon 18 Variant or After 3 Previous Therapies in a Hypothetical US Health Plan.

Importance: With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 variant, including PDGFRA D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget. Objective: To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a PDGFRA exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan. Design, Setting, and Participants: For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased PDGFRA testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic PDGFRA exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%. Exposures: The model compared scenarios with and without avapritinib in a formulary. Main Outcomes and Measures: Annual, total, and per member per month (PMPM) budget impact. Results: In a hypothetical 1-million member plan, fewer than 0.1 new patients with a PDGFRA exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a PDGFRA exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3. Conclusions and Relevance: These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.

"I Have Everything to Win and Nothing to Lose": Patient Experiences of Mobilization Out of Bed Immediately After Abdominal Surgery.

OBJECTIVE: Early mobilization is advocated for patients going through abdominal surgery; however, little is known about the patient experience of being mobilized immediately after surgery. The purpose of this study was to explore patient experiences of mobilization immediately after elective abdominal cancer surgery. METHODS: This interview study used qualitative content analysis. With the use of purposeful sampling, a total of 23 participants who had been mobilized immediately after abdominal surgery were recruited at a university hospital in Stockholm, Sweden. Individual face-to-face interviews were conducted within 1 to 4 days after surgery and took place at the surgical ward where the participants were treated. A semi-structured guide was used. All interviews were audio recorded and transcribed verbatim. RESULTS: The content analysis revealed 3 categories that emerged into 1 overarching theme: "to do whatever it takes to get home earlier." The participants experienced that mobilization out of bed had an impact on their physical and mental well-being. Motivation and the experiences of themselves and others were factors that affected patient attitudes toward early mobilization. Preparation and competent caregivers were emphasized as important factors that enabled the patient to feel safe and confident during mobilization. CONCLUSIONS: Patients experienced mobilization as an important part of the care that had an impact on recovery and well-being, physically as well as mentally, both immediately and over time. IMPACT: As this is the first study to our knowledge to investigate patient experiences of mobilization immediately after abdominal surgery, this information can be used to support the development of early mobilization protocols in hospital settings.

[Clinical diagnosis and treatment of gastrointestinal stromal tumor: matching technological breakthrough with patient care].

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract. Although GIST has only been recognized as a separate entity for several decades, management strategies for GIST have changed dramatically over time. Advances in treatment have yielded dramatic successes in improving prognosis of patients with GIST. However, the meaningful progress also brings escalating social and economic burdens. There is a long distance between technological breakthroughs and its real benefits of society. Due to the rapid development in a short period, successful experience in disease diagnosis and treatment and the accompanying problems have appeared in a more concentrated and obvious manner. Any medical science exploration and practice initially aim to have the essence of humanism. As practitioners of medical technology, doctors should treat patients as a whole "human" in the process of diagnosis and treatment instead of just focusing on the technology itself. Moreover, doctors should comprehensively consider patients' physical, psychological and social attributes, pay attention to their physical, mental and social needs, find and try to solve problems, so as to promote the developement of medical science in the correct direction.

[Updates and interpretations of the NCCN Clinical Practice Guidelines (2019 6th version) on gastrointestinal stromal tumor].

The diagnosis and treatment of gastrointestinal stromal tumor (GIST) is getting more and more standardized. In the last two decades, due to the elucidation of molecular mechanism of tumorigenesis, as well as the effectiveness of tyrosine kinase inhibitors, GIST has become well-known as one of the most classical models of targeted therapy on solid tumors in the precision medicine era. The National Comprehensive Cancer Network (NCCN) issued the latest version of clinical practice guideline on soft tissue sarcoma in February 2020. Compared with previous versions, the new version of the guideline highlighted the treatment recommendations of avapritinib, which further promoted the precise targeted treatment of GIST.

Thermal ablation versus hepatic resection for the treatment of liver metastases from gastrointestinal stromal tumors: a retrospective study.

Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs).Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors.Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p = .875). The 1-, 3- and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3- and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p = .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p = .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p = .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p = .001) in the ablation group.Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.

[Analysis of imatinib trough concentration at steady state in adjuvant therapy of patients with high risk gastrointestinal stromal tumor].

Objective: To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 µg/L influences the efficacy of adjuvant therapy. Methods: A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 µg/L group and ≥1100 µg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis. Results: Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m(2) and body surface area was (1.6±0.2) m(2). Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) µg/L, and there were 32 patients with plasma concentration <1100 µg/L and 53 patients with plasma concentration ≥1100 µg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow-up time was 30 (range 4-49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 µg/L and two with plasma concentration ≥1100 µg/L. One recurrent patient with plasma concentration <1100 µg/L was detected to harbor c-Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 µg/L were both detected to harbor c-Kit exon 9 mutation. The 3-year relapse-free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 µg/L, and 96.6% in patients with plasma concentration ≥1100 µg/L. No significant difference in relapse-free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration <1100 µg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022-2.637, P=0.242). Conclusions: IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 µg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.

Phase I Study of Rapid Alternation of Sunitinib and Regorafenib for the Treatment of Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors.

PURPOSE: Polyclonal emergence of KIT secondary mutations is a main mechanism of imatinib progression in gastrointestinal stromal tumor (GIST). Approved KIT inhibitors sunitinib and regorafenib have complementary activity against KIT resistance mutations. Preclinical evidence suggests that rapid alternation of sunitinib and regorafenib broadens the spectrum of imatinib-resistant subclones targeted. PATIENTS AND METHODS: Phase Ib study investigating continuous treatment with cycles of sunitinib (3 days) followed by regorafenib (4 days) in patients with tyrosine kinase inhibitor (TKI)-refractory GIST. A 3+3 dosing schema was utilized to determine the recommended phase II dose (RP2D). Plasma samples were analyzed for pharmacokinetics and circulating tumor DNA (ctDNA) studies using targeted error correction sequencing (TEC-seq) and droplet digital PCR (ddPCR). RESULTS: Of the 14 patients enrolled, 2 experienced dose-limiting toxicities at dose level 2 (asymptomatic grade 3 hypophosphatemia). Sunitinib 37.5 mg/day and regorafenib 120 mg/day was the RP2D. Treatment was well-tolerated and no unexpected toxicities resulted from the combination. Stable disease was the best response in 4 patients, and median progression-free survival was 1.9 months. Combined assessment of ctDNA with TEC-seq and ddPCR detected plasma mutations in 11 of 12 patients (92%). ctDNA studies showed that KIT secondary mutations remain the main mechanism of resistance in TKI-refractory GIST, revealing effective suppression of KIT-mutant subpopulations in patients benefiting from the combination. CONCLUSIONS: Sunitinib and regorafenib combination is feasible and tolerable. Rapid alternation of TKIs with complementary activity might be effective when combining drugs with favorable pharmacokinetics, potentially allowing active doses while minimizing adverse events. Serial monitoring with ctDNA may guide treatment in patients with GIST.

Imaging surveillance of gastrointestinal stromal tumour: current recommendation by National Comprehensive Cancer Network and European Society of Medical Oncology-European Reference Network for rare adult solid cancers.

Imaging plays an active role in the surveillance of gastrointestinal stromal tumours (GISTs). Risk stratification schemes, based on size, mitotic count, and anatomical site of origin of the GIST, help in planning preoperative and postoperative imaging strategies especially in determining the frequency and duration of surveillance; however, there is no clear consensus on the optimal imaging strategies in patients with GISTs who are completely cured by surgery and patients who are at risk of recurrence. In addition, current surveillance protocols depend on the resectability of the primary tumour and presence of metastatic disease. The objective of this article is to provide a comprehensive review of the role of the different imaging methods for surveillance of GISTs, focusing on the guidelines recommended by National Comprehensive Cancer Network and European Society of Medical Oncology - European Network for Rare adult solid Cancers, and to propose practical guidelines for surveillance of GISTs for various risk categories.