Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts.

BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.

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.

Postoperative Complications After Neoadjuvant Chemotherapy Versus Upfront Surgery in Gastric Adenocarcinoma: A Population-Based Nationwide Study in Finland.

BACKGROUND: To date, no large population-based studies have compared complications and short-term outcomes between neoadjuvant chemotherapy and upfront surgery in gastric cancer. More nationwide studies with standardized reporting on complications are needed to enable international comparison between studies. This study aimed to compare postoperative complications between neoadjuvant therapy and upfront surgery after gastrectomy for gastric adenocarcinoma in a population-based setting. METHODS: This population-based study based on the Finnish National Esophago-Gastric Cancer Cohort included all patients 18 years of age or older undergoing gastrectomy for gastric adenocarcinoma in Finland during 2005-2016. Logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), both crude and adjusted for key confounders. Different types of complications were graded based on the Esophagectomy Complications Consensus Group definitions, and major complications were assessed by the Clavien-Dindo scale. RESULTS: This study analyzed 769 patients. Neoadjuvant chemotherapy did not increase major postoperative complications after gastrectomy for gastric cancer compared with upfront surgery (OR, 1.12; 95% CI 0.81-1.56). Furthermore, it did not increase pneumonia, anastomotic complications, wound complications, or other complications. CONCLUSIONS: Neoadjuvant therapy is not associated with increased postoperative complications, reoperations, or short-term mortality compared with upfront surgery in gastric adenocarcinoma.

Comparison of Postoperative Complications After Gastrectomy for Gastric Cancer with Antecolic Versus Retrocolic Reconstruction: A Population-Based Study.

BACKGROUND: The purpose of this study was to examine the rates of 90-day anastomotic complications and other postoperative complications after total or partial gastrectomy with antecolic versus retrocolic reconstruction in a population-based setting. METHODS: This population-based nationwide retrospective cohort study included all patients undergoing total or partial gastrectomy for gastric adenocarcinoma in Finland in 2005-2016, with follow-up until 31 December 2019. Logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs) of 90-day mortality. Results were adjusted for age, sex, year of the surgery, comorbidities, tumor locations, pathological stage, and neoadjuvant therapy. RESULTS: A total of 2063 patients having gastrectomy with antecolic (n = 814) or retrocolic (n = 1249) reconstruction were identified from the registries. The anastomotic complication rate was 3.8% with antecolic reconstruction and 5.0% with retrocolic reconstruction. Antecolic reconstruction was not associated with a higher risk of anastomotic complications compared with retrocolic reconstruction in the adjusted analysis (OR 0.69, 95% CI 0.44-1.09) of the whole cohort or in the predefined subgroups. The reoperation rate was 8.2% with antecolic reconstruction and 7.7% with retrocolic reconstruction, without statistical significance. In subgroup analysis of total gastrectomy patients, the risk of major complications was lower with antecolic reconstruction compared with retrocolic reconstruction (OR 0.62, 95% CI 0.45-0.86). CONCLUSIONS: The rate of anastomotic complications did not differ after antecolic versus retrocolic reconstruction after total or partial gastrectomy. In total gastrectomies, the risk of major complications was lower after antecolic compared with retrocolic reconstruction.

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study).

BACKGROUND AND PURPOSE: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. MATERIALS AND METHODS: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. RESULTS: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. INTERPRETATION: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.

Five-year Survival after McKeown Compared to Ivor-Lewis Esophagectomy for Esophageal Cancer: A Population-based Nationwide Study in Finland.

OBJECTIVE: The aim of study was to compare overall 5-year survival of esophageal cancer patients undergoing transthoracic esophagectomy with either neck or intrathoracic anastomosis, that is, McKeown and Ivor-Lewis esophagectomy. BACKGROUND: No national studies comparing long-term survival after McKeown and ivor-Lewis esophagectomies in the West exist. METHODS: This population-based nationwide study included all curatively intended transthoracic esophagectomies for esophageal adenocarcinoma or squamous cell carcinoma in Finland in 1987 to 2016, with follow-up until December 31, 2019. Cox proportional hazard models provided hazard ratios (HR) with 95% confidence intervals (ci) of all-cause 5-year mortality. The results were adjusted for age, sex, year of the operation, comorbidities, histology, stage, and neoadjuvant treatment. Adjusted model 2 included also tumor location and lymph node yield. RESULTS: A total of 990 patients underwent McKeown (n = 278) or Ivor-Lewis (n = 712) esophagectomy The observed overall 5-year survival was 43.1% after McKeown, and 45.9% after Ivor-Lewis esophagectomy. McKeown esophagectomy was not associated with the overall 5-year mortality (adjusted HR 1.11, 95% CI: 0.89-1.38), compared to Ivor-Lewis esophagectomy. Additional adjustment for tumor location and lymphadenectomy further attenuated the point estimate (HR 1.06, 95% CI: 0.85-1.33). Surgical approach was not associated with 90-day mortality rate (adjusted HR 1.15, 95% CI: 0.67-1.97). CONCLUSIONS: This population-based nationwide study suggests that overall 5-year survival or 90-day survival with McKeown and Ivor-Lewis esopha-gectomy for esophageal cancer are comparable.

Impact of cholangitis on survival of patients with malignant biliary obstruction treated with percutaneous transhepatic biliary drainage.

PURPOSE: To evaluate the impact of cholangitis on survival of patients with gastrointestinal cancer and malignant biliary obstruction treated with percutaneous transhepatic biliary drainage (PTBD). METHODS: A retrospective registry study was performed at a tertiary center from 2000 to 2016 in Northern Finland. RESULTS: The study included 588 patients, 258 (43.9%) patients with pancreatic cancer, 222 (37.7%) with biliary tract cancer, and 108 (18.4%) with metastasis from gastrointestinal cancers. Patient mean age was 70 years, range 26 - 93 years. There were 288 [49.0%] women. The 30-day mortality rate was 30.8% for 156 patients with cholangitis before PTBD, 19.5% for 215 patients with cholangitis after PTBD and 25.8% for 217 patients without cholangitis (P = 0.039). The median survival was 1.8 months for patients with cholangitis before PTBD, 3.0 months for patients with cholangitis after PTBD, and 3.2 months for patients without cholangitis (P = 0.002). The hazard ratio (HR) for 1-year mortality for patients with cholangitis before PTBD was 1.3 (95% CI 1.06 - 1.67, P = 0.015) compared to patients with cholangitis after PTBD. After successful PTBD, 54 out of 291 patients received chemotherapy; the median survival was 5.2 months with cholangitis before PTBD, 9.4 months with cholangitis after PTBD and 15.3 months without cholangitis. CONCLUSION: In gastrointestinal cancers with malignant biliary obstruction, survival is poorer if cholangitis occurs before PTBD compared to cholangitis after PTBD. An oncologist's consultation is essential for assessing the possibility of chemotherapy in successfully treated PTBD patients, because of the notable survival benefit.

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study.

BACKGROUND: Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. METHODS: This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. RESULTS: Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. CONCLUSIONS: There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status. CLINICAL TRIAL REGISTRATION: NCT01531621/EudraCT2011-003158-24.

Long-Term Survival After Transhiatal Versus Transthoracic Esophagectomy: A Population-Based Nationwide Study in Finland.

BACKGROUND: No population-based studies comparing long-term survival after transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) exist. This study aimed to compare the 5-year survival of esophageal cancer patients undergoing THE or TTE in a population-based nationwide setting. METHODS: This study included all curatively intended THE and TTE for esophageal cancer in Finland during 1987-2016, with follow-up evaluation until 31 December 2019. Cox proportional hazard models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of 5-year and 90-day mortality. The results were adjusted for age, sex, year of operation, comorbidities, histology, neoadjuvant treatment, and pathologic stage. RESULTS: A total of 1338 patients underwent THE (n = 323) or TTE (n = 1015). The observed 5-year survival rate was 39.3% after THE and 45.0% after TTE (p = 0.072). In adjusted model 1, THE was not associated with greater 5-year mortality (HR 0.99; 95% CI 0.82-1.20) than TTE. In adjusted model 2, including T stage instead of pathologic stage, the 5-year mortality hazard rates after THE (HR 0.87, 95% CI 0.72-1.05) and TTE were comparable. The 90-day mortality rate for THE was higher than for TTE (adjusted HR 0.72; 95% CI 0.45-1.14). In subgroup analyses, no differences between THE and TTE were observed in Siewert II gastroesophageal junction cancers, esophageal cancers, or pN0 tumors, nor in the comparison of THE and TTE with two-field lymphadenectomy. The sensitivity analysis, including patients with missing patient records, who underwent surgery during 1996-2016 mirrored the main analysis. CONCLUSIONS: This Finnish population-based nationwide study suggests no difference in 5-year or 90-day mortality after THE and TTE for esophageal cancer.

Selective internal radiation therapy (SIRT) as treatment for hepatic metastases of uveal melanoma: a Finnish nation-wide retrospective experience.

BACKGROUND: In Finland, selective internal radiation therapy (SIRT) is at present the preferred first-line loco-regional therapy for uveal melanoma patients with hepatic metastases not suitable for surgery. We retrospectively evaluate the outcome and safety of SIRT in this group of patients. MATERIAL AND METHODS: Yttrium-90 microspheres were delivered via the hepatic artery into the circulation of metastases from uveal melanoma in 18 patients with a predicted life expectancy of more than three months in three Finnish tertiary referral centers between November 2010 and December 2015. Progression-free survival (PFS), toxicity and overall survival (OS) were evaluated. Patients with historical uveal melanoma without extrahepatic metastases, who had received systemic chemotherapy as first-line treatment for their hepatic metastases at the Helsinki University Hospital between January 2006 and May 2010, were used as a historical control group. RESULTS: Partial response and stable disease were observed in three (17%) and eight (44%) patients, respectively; one patient was not evaluable for response. Median PFS after SIRT was 5.6 (range, 1.3-40.8) months. Median OS after SIRT was 13.5 (range, 3.6-44.8) months compared with 10.5 (range, 3.0-16.5; p = .047) months for the historical chemotherapy group. Among patients who received SIRT as first-line treatment, the median OS was 18.7 (range, 8.2-44.8) months, significantly longer than that of the chemotherapy group (10.5 months, p = .017). There were no treatment-related deaths. Toxicity was mainly WHO grade 1-2 and self-limited. CONCLUSION: SIRT is a feasible and safe treatment for liver metastases in patients with uveal melanoma.

Is Palliative Percutaneous Drainage for Malignant Biliary Obstruction Useful?

BACKGROUND: Malignant biliary obstruction is a challenging problem for cancer patients. Here we evaluate predictive factors for survival following percutaneous drainage for malignant biliary obstruction in patients in whom endoscopic drainage was unsuccessful or insufficient. METHODS: A retrospective register study in a tertiary-level university hospital. RESULTS: A total of 643 cancer patients (317 females and 326 males) with malignant biliary obstruction were treated with percutaneous drainage at our hospital between 1999 and 2016. Their median overall survival rate was 2.6 months, with a 95% confidence interval (CI) of 2.2-3.0. Independent factors predicting poor outcome were metastatic cancer, with a hazard ratio (HR) of 2.2 (95% CI 1.8-2.7); Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 (HR 2.3; 95% CI 1.8-2.8); ECOG PS of 3-4 (HR 3.5; 95% CI 2.8-4.4), American Society of Anesthesiologists physical status classification (ASA) of 4 (HR 2.1; 95% CI 1.5-2.9); and bilirubin of ≥60.0 µmol/L within 30 days post-drainage (HR 1.3; 95% CI 1.1-1.6). During the time periods 1999-2004 and 2005-2010, patients had poorer outcomes (HR 1.4; 95% CI 1.1-1.7 and HR 1.4; 95% CI 1.2-1.8) than during the last period 2011-2016. CONCLUSION: Patients with cancer who underwent percutaneous biliary drainage for biliary obstruction had a poor median overall survival. The usefulness of biliary drainage, especially in patients with metastatic cancer, poor ECOG PS, and high ASA class, should be critically considered.

Impact of splenectomy on long-term outcomes after gastrectomy for gastric cancer: a population-based study.

BACKGROUND: No national studies comparing long-term survival after total or partial gastrectomy with splenectomy due to injury or oncologic reasons or spleen preservation exist. This study aimed to examine the 5-year overall survival (OS) of patients with gastric adenocarcinoma who underwent total or partial gastrectomy with splenectomy due to injury or oncologic reasons or spleen preservation in a population-based nationwide setting. METHODS: This study included all patients undergoing total or partial gastrectomy with splenectomy or spleen preservation for gastric adenocarcinoma in Finland from 2005 to 2016, with follow-up until December 31, 2019. A total of 2196 patients with gastric cancer diagnosis and total or partial gastrectomy were identified in the registries. Of these patients, 2118 were applicable for this study. Cox proportional hazard models provided hazard ratios (HRs) with 95% CIs of 5-year OS. The results were adjusted for age, sex, year of operation, comorbidities, tumor location, pathologic stage, and neoadjuvant therapy. RESULTS: The observed 5-year OS rates were 38.7% in patients with no or minor spleen injury, 39.7% in patients with splenectomy due to injury, and 30.8% in patients with splenectomy due to oncologic reasons (P = .032). Patients who underwent R0 gastrectomy with splenectomy due to oncologic reasons had higher 5-year mortality (the adjusted model HR, 1.26; 95% CI, 1.01-1.56) than patients who underwent spleen preservation. CONCLUSION: The OS was worst in patients who underwent gastrectomy with splenectomy due to oncologic reasons, highlighting the poor prognosis in patients with advanced gastric cancer. Splenectomy due to injury does not compromise the prognosis.

Stapled vs handsewn anastomosis and anastomotic leaks in gastric cancer surgery-a population-based nationwide study in Finland.

BACKGROUND: There is a lack of evidence regarding anastomotic technique and postoperative complications in gastric cancer surgery. This study aimed to evaluate whether there are differences between stapled and handsewn anastomosis and anastomotic leaks. METHODS: This was a population-based, retrospective, nationwide cohort study in Finland using the Finnish National Esophago-Gastric Cancer Cohort. Patients undergoing gastrectomy with available postoperative complication data were included. Logistic regression analysis was used to calculate the odds ratios with 95% CIs, adjusted for calendar period of surgery, age at surgery, sex, comorbidity, tumor stage, neoadjuvant therapy, minimally invasive surgery, type of gastrectomy, radical resection, and type of anastomosis. RESULTS: Of the 2164 patients, 472 of all patients (21.8%) had handsewn anastomosis and 1692 of all patients (78.2%) had stapled anastomosis. In the unadjusted analysis, anastomotic leaks were significantly lower in the handsewn group (hazard ratio [HR], 0.42; 95% CI, 0.22-0.79) than the stapled group, but after adjustment for known prognostic factors, this association was no longer significant (HR, 0.57; 95% CI, 0.27-1.21). In the analysis stratified by gastrectomy type (distal or total), no differences in anastomotic leaks were observed between anastomotic techniques. CONCLUSION: In this population-based nationwide study, anastomotic technique (stapled or handsewn) was not associated with anastomotic leaks in any, distal or total, gastrectomy.

Postoperative delayed emptying after total, subtotal, or distal gastrectomy for gastric cancer: a population-based study.

BACKGROUND: This study aimed to examine the rate of delayed emptying and other 90-day postoperative complications after total, subtotal, and distal gastrectomies for gastric adenocarcinoma in a population-based setting. METHODS: This study included all patients who underwent total, subtotal, or distal gastrectomy for gastric cancer in Finland in 2005-2016, with follow-up until December 31, 2019. Logistic regression provided the odds ratios with 95% CIs of 90-day mortality. The results were adjusted for age, sex, year of surgery, comorbidities, pathologic stage, and neoadjuvant therapy. RESULTS: A total of 2058 patients underwent total (n = 1227), subtotal (n = 450), or distal (n = 381) gastrectomy. In the total, subtotal, and distal gastrectomy groups, the rates of 90-day delayed emptying were 1.7%, 1.3%, and 2.1% in the whole cohort and 1.6%, 1.8%, and 3.5% in the subgroup analysis of R0 resections, respectively. The resection type was not associated with the risk of delayed emptying. Subtotal gastrectomy was associated with a lower risk of major complications and reoperations, whereas distal gastrectomy was associated with a lower risk of anastomotic complications. CONCLUSION: The extent of resection did not affect delayed emptying, whereas fewer postoperative complications were observed after subtotal or distal gastrectomy than after total gastrectomy.

Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study).

The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL.

KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial.

PURPOSE: Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib. PATIENTS AND METHODS: The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses. RESULTS: During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15-0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31-0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib. CONCLUSIONS: Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.

Population-based nationwide incidence of complications after gastrectomy for gastric adenocarcinoma in Finland.

BACKGROUND: The incidence of postoperative complications after gastrectomy for gastric cancer is not well known. More population-based studies using established complication classifications are needed for international comparison. The aim of this study was to evaluate the population-based incidence of postoperative complications after gastrectomy for gastric cancer. METHODS: This population-based study based on the Finnish National Esophago-Gastric Cancer Cohort included all patients at least 18 years of age undergoing gastrectomy for gastric adenocarcinoma in Finland during 2005-2016. The occurrence of complications 30 and 90 days after surgery was graded based on the Esophagectomy Complications Consensus Group definitions and the severity of complications was assessed using the Clavien-Dindo scale. RESULTS: This study included a total of 2196 patients. Postoperative complications occurred in 906 (41.3 per cent) of patients during 30 days after surgery and in 946 (43.1 per cent) during 90 days after surgery. Clavien-Dindo grade III or higher complications occurred in 375 (17.1 per cent) of patients. The most common complications 90 days after surgery by Esophagectomy Complications Consensus Group upper-level categories were gastrointestinal (n = 438; 19.9 per cent), including anastomotic leak, infectious (n = 377; 17.2 per cent) and pulmonary (n = 335; 15.3 per cent) complications. Postoperative mortality rate was occurred in 72 (3.3 per cent) patients within 30 days and in 161 (7.3 per cent) patients within 90 days after surgery. The median duration of postoperative hospital stay was 9 days (interquartile range 4-14). CONCLUSIONS: Postoperative complications are common across all types of gastrectomy and the majority occur during the first 30 postoperative days. This study informs the patients and caregivers of the expected outcomes of gastrectomy.

Preoperative Esophageal Stenting and 5-Year Survival in Patients Undergoing Esophagectomy for Esophageal Cancer: a Population-Based Nationwide Study from Finland.

BACKGROUND: Preoperative esophageal stenting is proposed to have a negative effect on outcomes. The aim was to compare a 5-year survival in patients undergoing esophagectomy for esophageal cancer with and without preoperative esophageal stent in a population-based nationwide cohort from Finland. The secondary outcome was 90-day mortality. METHODS: This study included curatively intended esophagectomies for esophageal cancer in Finland between 1999 and 2016, with follow-up until December 31, 2019. Cox proportional hazards models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of overall 5-year and 90-day mortality. Model 1 was adjusted for age, sex, year of the surgery, comorbidities, histology, pathological stage, and neoadjuvant therapy. Model 2 included also albumin level and BMI. RESULT: Of 1064 patients, a total of 134 patients underwent preoperative stenting and 930 did not. In both adjusted models 1 and 2, higher 5-year mortality was seen in patients with preoperative stent with HRs of 1.29 (95% CI 1.00-1.65) and 1.25 (95% CI 0.97-1.62), respectively, compared to no stenting. The adjusted HR of 90-day mortality was 2.49 (95% CI 1.27-4.87) in model 1 and 2.49 (95% CI 1.25-4.99) in model 2. When including only neoadjuvant-treated patients, those with preoperative stent had a 5-year survival of 39.2% compared to 46.4% without stent (adjusted HR 1.34, 95% CI 1.00-1.80), and a 90-day mortality rate of 8.5% and 2.5% (adjusted HR 3.99, 95% CI 1.51-10.50). DISCUSSION: This nationwide study reports worse 5-year and 90-day outcomes in patients with preoperative esophageal stent. Since residual confounding remains possible, observed difference could be only an association rather than the cause.