Survival of patients with ruptured gastrointestinal stromal tumour treated with adjuvant imatinib in a randomised trial.

BACKGROUND: Patients with ruptured gastrointestinal stromal tumour (GIST) have poor prognosis. Little information is available about how adjuvant imatinib influences survival. METHODS: We explored recurrence-free survival (RFS) and overall survival (OS) of patients with ruptured GIST who participated in a randomised trial (SSG XVIII/AIO), where 400 patients with high-risk GIST were allocated to adjuvant imatinib for either 1 year or 3 years after surgery. Of the 358 patients with confirmed localised GIST, 73 (20%) had rupture reported. The ruptures were classified retrospectively using the Oslo criteria. RESULTS: Most ruptures were major, four reported ruptures were reclassified unruptured. The 69 patients with rupture had inferior RFS and OS compared with 289 patients with unruptured GIST (10-year RFS 21% vs. 55%, OS 59% vs. 78%, respectively). Three-year adjuvant imatinib did not significantly improve RFS or OS of the patients with rupture compared with 1-year treatment, but in the largest mutational subset with KIT exon 11 deletion/indel mutation OS was higher in the 3-year group than in the 1-year group (10-year OS 94% vs. 54%). CONCLUSIONS: About one-fifth of ruptured GISTs treated with adjuvant imatinib did not recur during the first decade of follow-up. Relatively high OS rates were achieved despite rupture. CLINICAL TRIAL REGISTRATION: NCT00116935.

Long-term outcome after surgical resection of non-high-risk gastrointestinal stromal tumours without adjuvant therapy.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common intra-abdominal sarcoma. Risk classification systems, commonly the modified National Institutes of Health consensus criteria, identify tumour properties relating to patient outcomes. However, owing to limited long-term evidence, most guidelines recommend up to 10-year follow-up for all risk groups except very low-risk GIST. METHODS: This retrospective multicentre study included patients who had complete resection of primary, non-metastatic GIST from three Scandinavian sarcoma centres: Gothenburg (2004-2020), Stockholm (2000-2019), and Oslo (2000-2017). Medical records were reviewed for clinical details regarding diagnosis, treatment, and follow-up, and recurrence-free and disease-specific survival evaluated. RESULTS: The total cohort consisted of 1213 patients with GIST. High-risk patients and those treated with tyrosine kinase inhibitors were excluded. The remaining 649 patients were included in the present analysis: 118 with very low-, 381 with low-, and 150 with intermediate-risk GISTs. Five-year recurrence-free survival rates were 100, 98.5, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.246). Disease-specific survival rates 10 years after surgery were 100, 98.4, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.262). CONCLUSION: Patients with completely resected non-high-risk GISTs have an excellent long-term outcome, irrespective of risk group. Follow-up programmes to detect disease recurrences in these patients are probably not indicated.

Gastrointestinal stromal tumours (GISTs) originate from the muscle layer of the gastrointestinal tract. They are divided into risk groups according to size, location, and how quickly they grow. Patients with GIST, regardless of risk group, have been followed with imaging for several years after their tumour has been successfully removed with an operation. The aim of this study was to evaluate whether follow-up is necessary for patients in the lower-risk groups. Six hundred and forty-nine patients with GISTs from the lower-risk groups were followed for 5 years (median). Only 1.2 per cent of the patients experienced a recurrence of their cancer. It was concluded that patients with GIST in the lower-risk groups do not need follow-up with imaging after a successful operation.

Palliative resection of the primary tumour improves survival in incurable metastatic colorectal cancer.

BACKGROUND: Studies show conflicting results on whether primary tumour resection (PTR) in metastatic colorectal cancer (mCRC) prolongs survival. The aim of this study was to analyse prognostic factors and the effects of PTR on overall survival (OS) in mCRC patients. METHODS: In this population-based cohort study, factors associated with PTR and OS were assessed in 188 mCRC patients with mCRC treated with palliative chemotherapy between 2008 and 2019. The Chi-square test and Mann-Whitney U-test were used to assess factors associated with PTR. The log-rank test was used to compare Kaplan-Meier estimates for OS. Cox regression was used to identify factors predicting OS. RESULTS: Patients undergoing PTR had significantly better performance status, fewer metastatic sites, lower CEA levels, and more often had left-sided CRC than patients not undergoing PTR. OS was longer in palliative mCRC patients undergoing PTR (P < 0.01) and PTR was an independent variable in the Cox regression analysis (P < 0.05). Median OS was 22.9 ± 1.9 months for the PTR group and 14.5 ± 1.5 months for the non-operated group. Poor performance status and liver metastases were significantly associated with poor prognosis. CONCLUSION: This study shows that PTR had a positive effect on OS and may be considered in patients suitable for surgery. PTR was offered to palliative mCRC patients with prognostic factors associated with better prognosis.

Targeted Therapy in the Palliative Setting of Colorectal Cancer-Survival and Medical Costs.

(1) Background: Targeted therapy is used alone or together with chemotherapy in metastatic colorectal cancer. The aim of this study was to assess overall survival and medical costs in a cohort of patients with metastatic colorectal cancer. (2) Methods: Demographic and clinical characteristics of 337 patients and pathological data of colorectal tumors were retrospectively collected in this population-based study. The overall survival and medical costs for patients receiving chemotherapy plus targeted therapy were compared with those for patients receiving chemotherapy only. (3) Results: Patients administered chemotherapy plus targeted therapy were less frail and had more often RAS wild-type tumors but had higher CEA levels than patients receiving chemotherapy only. No prolonged overall survival could be observed in patients receiving palliative targeted therapy. The medical costs for patients undergoing treatment with targeted therapy were significantly higher than for patients treated only with chemotherapy; they were especially higher in the group receiving targeted therapy early than late in the palliative setting. (4) Conclusions: The use of targeted therapy in metastatic colorectal cancer leads to significantly higher medical costs when used early in the palliative setting. No positive effects of the use of targeted therapy could be observed in this study; therefore, we suggest that targeted therapy be used in later lines of palliative therapy in metastatic colorectal cancer.

Linear and circular stapled gastrojejunal anastomoses in Roux-en-Y gastric bypass: stomal diameter at onset and at long-term follow-up.

BACKGROUND: In the laparoscopic Roux-en-Y gastric bypass procedure, the gastrojejunal stoma is constructed with either a circular (CSD) or a linear stapling device (LSD). The diameter of the stoma following stapling with the 21 mm CSD is expected to be approximately 12 mm (diameter of the anvil). Measuring the stoma diameter after linear stapling is a little more complex since the remaining opening in the linear anastomosis is closed by hand. The aim of this prospective randomized study was to follow up on changes in the diameter of gastrojejunal stomata after laparoscopic Roux-en-Y gastric bypass using either a CSD or an LSD between that at construction and at a long-term follow-up of 12-72 months later. METHODS: Twenty patients were randomly assigned to gastrojejunostomy with either a 21 mm CSD or a 45 mm LSD. Directly after completion of the surgery, the diameter of the gastrojejunal stoma was measured using a Fogarty occlusion catheter and again at follow-up 12-72 months later. RESULTS: Five patients were lost for follow-up, and 15 patients remained. The mean diameter of the CSD stomata at construction was 19.3 ± 5.3 mm (mean ± SD) and increased to 26.4 ± 6.6 mm at follow-up after a mean of 46 months (P = 0.02). The corresponding figures for the LSD stomata were 26.2 ± 4.1 mm, increasing to 32.7 ± 3.0 mm also after a mean follow-up of 46 months (P = 0.03). CONCLUSIONS: The mean diameter of the circular stapled gastrojejunostomy stomata at construction was 20 mm, that is, considerably larger than the 12 mm expected. After a mean of 5 years, the mean diameter had increased by 37%. The mean diameter of the linear stapled stomata increased by 25%.

Monitoring Circulating Tumor DNA During Surgical Treatment in Patients with Gastrointestinal Stromal Tumors.

The majority of patients diagnosed with advanced gastrointestinal stromal tumors (GISTs) are successfully treated with a combination of surgery and tyrosine kinase inhibitors (TKIs). However, it remains challenging to monitor treatment efficacy and identify relapse early. Here, we utilized a sequencing strategy based on molecular barcodes and developed a GIST-specific panel to monitor tumor-specific and TKI resistance mutations in cell-free DNA and applied the approach to patients undergoing surgical treatment. Thirty-two patients with GISTs were included, and 161 blood plasma samples were collected and analyzed at routine visits before and after surgery and at the beginning, during, and after surgery. Patients were included regardless of their risk category. Our GIST-specific sequencing approach allowed detection of tumor-specific mutations and TKI resistance mutations with mutant allele frequency < 0.1%. Circulating tumor DNA (ctDNA) was detected in at least one timepoint in nine of 32 patients, ranging from 0.04% to 93% in mutant allele frequency. High-risk patients were more often ctDNA positive than other risk groups (P < 0.05). Patients with detectable ctDNA also displayed higher tumor cell proliferation rates (P < 0.01) and larger tumor sizes (P < 0.01). All patients who were ctDNA positive during surgery became negative after surgery. Finally, in two patients who progressed on TKI treatment, we detected multiple resistance mutations. Our data show that ctDNA may become a clinically useful biomarker in monitoring treatment efficacy in patients with high-risk GISTs and can assist in treatment decision making.

Quality of life and gastric acid-suppression medication 20 years after laparoscopic fundoplication.

BACKGROUND: Laparoscopic fundoplication is an effective treatment for gastro-oesophageal reflux disease (GERD). We aimed to assess quality of life (QoL), long-term residual symptoms, patient satisfaction and use of acid-suppression medication at 5, 10 and 20 years after surgery. METHODS: We identified a cohort of 100 patients who underwent laparoscopic fundoplication between 1993 and 1998. The validated QoL questionnaires Short Form health survey (SF-36), and Quality-of-Life in Reflux and Dyspepsia (QOLRAD), as well as a specific questionnaire regarding post-fundoplication symptoms, were sent to the patients at 5, 10 and 20 years after surgery. Furthermore, patients who reported using the acid-suppression medication after 20 years were interviewed by telephone regarding their reason for taking it. RESULTS: Eighty-eight percent of the patients responded at 5 and 10 years post-surgery. Twenty years following fundoplication, 68 (84% of those still alive) patients completed the questionnaires. The patients had equivalent health-related QoL scores in both the QOLRAD and SF-36 questionnaires after 10 and 20 years, and those scores were in line with a Swedish age-matched population. After 20 years, 87% were satisfied with the results, and 84% of the patients would recommend reflux surgery to a relative or a friend. At the telephone interview, 32% (22/68) confirmed using acid-suppression medication, but only half (11/68) used it because of reflux symptoms. CONCLUSION: The long-term, satisfying outcomes in GERD symptoms and QoL 5 and 10 years after surgery were maintained at a 20-year follow-up. Half of the patients used acid-suppression medication for reasons other than GERD symptoms.