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Background In order to determine the optimal combination of perioperative chemotherapy and chemoradiotherapy for Western patients with advanced resectable gastric cancer, the international multicentre CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated. In this trial, patients with resectable gastric cancer were randomised before start of treatment between adjuvant chemotherapy or adjuvant chemoradiotherapy following neoadjuvant chemotherapy plus gastric cancer resection. The purpose of this study was to report on surgical morbidity and mortality in this trial, and to identify factors associated with surgical morbidity. Methods Patients who underwent a gastrectomy with curative intent were selected. Logistic regression analyses were used to assess risk factors for developing postoperative complications. Results Between 2007 and 2015, 788 patients were included in the CRITICS trial, of whom 636 patients were eligible for current analyses. Complications occurred in 296 patients (47%). Postoperative mortality was 2.2% (n = 14). Complications due to anastomotic leakage was cause of death in 5 patients. Failure to complete preoperative chemotherapy (OR = 2.09, P = 0.004), splenectomy (OR = 2.82, P = 0.012), and male sex (OR = 1.55, P = 0.020) were associated with a greater risk for postoperative complications. Total gastrectomy and oesophago-cardia resection were associated with greater risk for morbidity compared with subtotal gastrectomy (OR = 1.88, P = 0.001 and OR = 1.89, P = 0.038). Conclusion Compared to other Western studies, surgical morbidity in the CRITICS trial was slightly higher whereas mortality was low. Complications following anastomotic leakage was the most important factor for postoperative mortality. Important proxies for developing postoperative complications were failure to complete preoperative chemotherapy, splenectomy, male sex, total gastrectomy, and oesophago-cardia resection. [ABSTRACT FROM AUTHOR]

Purpose In the adjuvant setting, specific adverse events (AEs) such as vasomotor symptoms (VMS) and musculoskeletal AEs are associated with relapse-free survival in aromatase inhibitor (AI)-treated patients. In the neoadjuvant setting, specific AEs may be associated with tumor response to AIs as well. Methods Between 2007 and 2012, 107 patients participated in the prospective TEAMIIA trial, a prospective, phase II trial investigating 6 months of neoadjuvant exemestane in patients with strongly ER-positive breast cancer. Radiological response (≥30% decrease in tumor size) was studied in relation to VMSs and MSAEs. Pearson's Chi-Square tests and multivariate logistic regression analyses were used to evaluate of statistical significance (p < 0.05). Results Out of 102 patients 26 patients (25.4%) experienced at least one episode of VMS and 27 patients (26.4%) experienced MSAE. Out of 240 reported adverse events, 71 were specific AEs (40 MSAEs, 31 VMSs). Radiological response was greater in patients who reported VMSs compared to patients who did not (70.8% vs. 49.3%, multivariate OR 2.91, 95% C.I. 1.03–8.26, P = 0.045). No significant advantage towards better response was observed in patients who experienced MSAEs (60.0% vs. 53.3%, univariate OR 1.33, 95% C.I. 0.53–3.38, P = 0.545). Conclusion VMSs are associated with tumor response to neoadjuvant exemestane and may be useful for predicting treatment outcomes of AI treatment at an early stage in patients treated with neoadjuvant AIs. [ABSTRACT FROM AUTHOR]

Background Studies suggest that MRI is an accurate means for assessing tumor size after neoadjuvant chemotherapy (NAC). However, accuracy might be dependent on the receptor status of tumors. MRI accuracy for response assessment after homogenous NAC in a relative large group of patients with stage II/III HER2-negative breast cancer has not been reported before. Methods 250 patients from 26 hospitals received NAC (docetaxel, adriamycin and cyclophosphamide) in the context of the NEOZOTAC trial. MRI was done after 3 cycles and post-NAC. Imaging (RECIST 1.1) and pathological (Miller and Payne) responses were recorded. Accuracy measures were calculated and MRI and pathologically assessed tumor sizes were correlated. Tumor size over- and underestimation were quantified. Results Accuracy of MRI for determining pathological complete response (pCR) was 76%. The ROC-curve of MRI response and pCR had an area under the curve value of 0.63 (95% C.I. 0.52–0.74). The correlation coefficient of MRI and histopathological tumor measurements was 0.46 ( p < 0.001). Correlations were different for ER-positive ( r = 0.40, p < 0.001) and ER-negative ( r = 0.76, p < 0.001) breast tumors. MRI under- and overestimated the tumor size in 47% and 40% of all patients. In cases of substantial tumor size underestimation (>2 cm), surgical margins were more often tumor positive compared to the rest of the patients (33% vs.12%, p = 0.005). Conclusion MRI measurements correlated moderately with tumor size on the surgical specimen. Only in ER-negative breast tumors, MRI tumor sizes correlated sufficiently with residual tumor size on the pathological specimen. Therefore, post-NAC MRI should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Abstract: Background: The last decade there has been an increased awareness of the problem of anastomotic leakage after low anterior resection for rectal cancer, which may have led to more defunctioning stomas. In this study, current use of defunctioning stomas was assessed and compared to the use of defunctioning stomas at the time of the TME-trial together with associated outcomes. Methods: Eligible patients with rectal cancer undergoing low anterior resection were selected from the Dutch Surgical Colorectal Audit (DSCA, n = 988). Similar patients were selected from the TME-trial (n = 891). The percentages of patients with a defunctioning stoma, anastomotic leakage and postoperative mortality rates were studied. Multivariable models were used to study possible confounding on the outcomes. Results: At the time of the TME-trial, 57% of patients received a defunctioning stoma. At the time of the DSCA, 70% of all patients received a defunctioning stoma (p < 0.001). Anastomotic leakage rates were similar (11.4% and 12.1%; p = 0.640). The postoperative mortality rate differed (3.9% in the TME-trial vs. 1.1% in the DSCA; p < 0.001), but was not associated with a more frequent use of a stoma (OR 1.80, 95% CI 0.91–3.58). Conclusion: In current surgical practice, 70% of patients undergoing LAR for rectal cancer receives a defunctioning stomas. This percentage seems increased when compared to data from the TME-trial. Clinically relevant anastomotic leakage rates remained similar. Therefore, current routine use of defunctioning stomas should be questioned. [Copyright &y& Elsevier]

Abstract: Aims: The aim of this study was to investigate non-compliance to aromatase inhibitors and factors associated with early treatment discontinuation in the extended adjuvant setting. Methods: The IDEAL trial is a prospective, open-label phase-III trial comparing 2.5 with 5 years of extended adjuvant letrozole (LET) in hormone receptor positive (HR+) postmenopausal early breast-cancer patients after 5 years of adjuvant endocrine therapy (ET). The purpose of this study was to assess non-compliance in the first 2.5 years of extended adjuvant therapy. Non-compliance was defined as early discontinuation of LET for all reasons, excluding death or recurrence. Results: At 2.5 years, 1215 patients were included in the analysis. Overall non-compliance probability was 18.4%, of which 85.1% discontinued due to toxicities. Analyses showed that patients with prior sequential therapy were less likely to discontinue treatment than when treated with AI or TAM upfront (logrank p = 0.004). Longer treatment-free intervals also predicted more non-compliance (logrank p = 0.011). Age was not predictive of non-compliance (p = 0.571). Prior surgery (mastectomy vs breast conserving surgery), both with or without radiotherapy and/or chemotherapy were also not associated with early treatment discontinuation (p = 0.228 and p = 0.585 respectively). Although having fewer than four positive lymph nodes predicted more non-compliance (logrank p = 0.050), age, tumor type and locoregional treatment did not. Conclusions: High non-compliance to extended ET was confirmed. Toxicities were the major reason for discontinuation, and this was not influenced by age. Longer treatment-free intervals and fewer positive lymph nodes predicted more non-compliance. Patients who underwent sequential therapy were least likely to discontinue extended adjuvant ET. [Copyright &y& Elsevier]

Abstract: Purpose: After total mesorectal excision (TME) for rectal cancer, pathology is standardized with margin status as a predictor for recurrence. This has yet to be implemented after transanal endoscopic microsurgery (TEM) and was investigated prospectively for T1 rectal adenocarcinomas. Patients and methods: Eighty patients after TEM were compared to 75 patients after TME. The study protocol included standardized pathology. TEM patients were eligible when excision margins were negative. Results: TEM was safer than TME as reflected by operating time, blood loss, hospital stay, morbidity, re-operation rate and stoma formation (all P <0.001). Mortality after TEM was 0% and after TME 4%. At 5 years after TEM and TME, both overall survival (TEM 75% versus TME 77%, P =0.9) and cancer-specific survival (TEM 90% versus TME 87%, P =0.5) were comparable. Local recurrence rate after TEM was 24% and after TME 0% (HR 79.266, 95% CI, 1.208 to 5202, P <0.0001). Conclusion: For T1 rectal adenocarcinomas TEM is much saver than TME and survival is comparable. After TEM local recurrence rate is substantial, despite negative excision margins. [Copyright &y& Elsevier]

Abstract: Background: In the Netherlands, standardised limited D1 and extended D2 lymph node dissections in the treatment of resectable gastric cancer were introduced nationwide within the framework of the Dutch D1–D2 Gastric Cancer Trial between 1989 and 1993. In a population-based study, we evaluated whether the survival of patients with resectable gastric cancer improved over time on a regional level. Methods: We compared 5-year overall and relative survival of patients with curatively resected non-cardia gastric cancer in the regional cancer registry of the Comprehensive Cancer Centre West in the Netherlands before the Dutch D1–D2 trial (1986 to mid 1989; n =273), during the trial period (mid 1989 to mid 1993; n =255), and after the trial (mid 1993 to 1999; n =219), adjusting for prognostic variables. Results: Unadjusted survival was highest in the post-trial period: 5-year overall and relative survival were 42% and 52%, respectively, compared to 34% and 41% in the pre-trial period, and 39% and 46% in the trial period (p =0.31 and p =0.06, respectively). After adjustment for age, gender, tumour site, pT-stage, nodal status and hospital volume, the effect of period on survival was more apparent (p =0.009). Compared to the pre-trial period, the hazard ratio was 0.83 (95% confidence interval, 0.68–1.02) for the trial period, and 0.72 (0.58–0.89) after the trial. Less than 1% of the patients received adjuvant therapy. Conclusion: Survival of patients with curatively resected non-cardia gastric cancer has improved. Standardisation and surgical training in D1 and D2 lymph node dissection are the most likely explanation for this improvement. [Copyright &y& Elsevier]

B Background: b In breast cancer, the tumour-stroma ratio (TSR) has shown to be a strong prognosticator, portraying that patients with stroma-low tumours have better survival outcomes than patients with stroma-high tumours. B Conclusions: b Stroma-low tumours, determined on pre-treatment biopsies, are associated with higher MP scores and pCR rates after neoadjuvant treatment than stroma-high tumours. [Extracted from the article]

Abstract: Background: Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship. Method: Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n =1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0ng/ml. Results: Normal pre-operative CEA values were present in 63% (CEA<5.0) and 39% (CEA<2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA<5.0), 50% (CEA<2.5) and in 60% with both threshold values when the last measurement was done within 3months before recurrent disease was diagnosed. Conclusion: A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA. [Copyright &y& Elsevier]

B Background: b The advantage of nipple sparing mastectomy (NSM) over traditional skin sparing mastectomy (SSM) is the radical removal of all breast tissue while preserving native breast integrity and the nipple-areola complex (NAC), which improves cosmetic outcome. B Results: b Between February 2016 and January 2019, 677 patients were recruited by 29 centres from 18 countries and a total of 804 breast operations were performed (545 for BC and 247 for RR). In the BC group, 74% of patients filled in the pre-surgery EORTC QLQ-C30 and 64% of patients filled in the pre-surgery QLQ-BR23. [Extracted from the article]

B Background: b Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. All patients in the experimental arm received 5x5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed preoperative chemotherapy courses. [Extracted from the article]

B Background: b The aim of this study is to describe patterns of recurrence in patients with resectable gastric cancer treated with preoperative chemotherapy, surgery, and postoperative chemotherapy or chemoradiotherapy in the international multicenter randomized phase III CRITICS trial. B Results: b Of the 788 patients (393 in the CT and 395 in the CRT arm) included between 2007 and 2015, 636 (81%) patients (310 in the CT and 326 in the CRT arm) underwent surgery with curative intent, and 478 (61%) patients (233 in the CT and 245 in the CRT arm) started postoperative treatment. Median follow-up was 6.1 years at the time of analysis and 488 patients experienced an event (240 patients in the CT arm and 248 patients in the CRT arm). [Extracted from the article]