Clinical Outcome After Rectal Replacement With Side-to-End, Colon-J-Pouch, or Straight Colorectal Anastomosis Following Total Mesorectal Excision: A Swiss Prospective, Randomized, Multicenter Trial (SAKK 40/04).

OBJECTIVE: To compare, in a phase 3, prospective, randomized, multi-center clinical trial functional outcome of reconstruction procedures following total mesorectal excision (TME). SUMMARY BACKGROUND DATA: Intestinal continuity reconstruction following TME is accompanied by postoperative defecation dysfunctions known as "anterior resection syndrome." Commonly used reconstruction techniques are straight colorectal anastomosis (SCA), colon J -pouch (CJP), and side-to-end anastomosis (SEA). Comparison of their functional outcomes in prospective, randomized, multi-center studies, including long-term assessments, is lacking. METHODS: Patients requiring TME for histologically proven rectal tumor, with or without neoadjuvant treatment, age ≥ 18 years, normal sphincter function without history of incontinence, any pretreatment staging or adenoma, expected R0-resection, were randomized for standardized SCA, CJP, or SEA procedures. Primary endpoint was comparison of composite evacuation scores 12 months after TME. Comparison of composite evacuation and incontinence scores at 6, 18 and 24 months after surgery, morbidity, and overall survival represented secondary endpoints. Analysis was based on "per protocol" (PP) population, fully complying with trial requirements, and intention-to treat (ITT) population. RESULTS: Three hundred thirty-six patients from 15 hospitals were randomized. PP population included 257 patients (JCP = 63; SEA = 95; SCA = 99). Composite evacuation scores of PP and ITT populations did not show statistically significant differences among the 3 groups at any time point. Similarly, composite incontinence scores for PP and ITT populations showed no statistically significant difference among the 3 trial arms at any time point. CONCLUSIONS: Within boundaries of investigated procedures, surgeons in charge may continue to perform reconstruction of intestinal continuity following TME at their technical preference.

Quality of Life After Total Mesorectal Excision and Rectal Replacement: Comparing Side-to-End, Colon J-Pouch and Straight Colorectal Reconstruction in a Randomized, Phase III Trial (SAKK 40/04).

BACKGROUND: Functional outcomes of different reconstruction techniques have an impact on patients' quality of life (QoL), but information on long-term QoL is lacking. We compared QoL among three reconstruction techniques after total mesorectal excision (TME). METHODS: Quality of life was assessed within a randomized, multicenter trial comparing rectal surgery using side-to-end anastomosis (SEA), colon J-pouch (CJP), and straight colorectal anastomosis (SCA) by the Functional Assessment of Cancer Therapy-Colorectal scale (FACT-C) before randomization and every 6 months up to 2 years post-TME. The primary QoL endpoint was the change in the Trial Outcome Index (TOI), including the FACT-C subscales of physical and functional well-being and colorectal cancer symptoms (CSS), from baseline to month 12. Pair-wise comparisons of changes from baseline (presurgery) to each timepoint between the three arms were analyzed by Mann-Whitney tests. RESULTS: For the QoL analysis, 257 of 336 randomized patients were in the per protocol evaluation (SEA = 95; CJP = 63; SCA = 99). Significant differences between the reconstruction techniques were found for selected QoL scales up to 12 months, all in favor of CJP. Patients with SEA or SCA reported a clinically relevant deterioration for TOI and CSS at 6 months, those with SCA for CSS also at 12 months after TME. Patients with CJP remained stable. CONCLUSIONS: Although the three reconstruction techniques differ in their effects on QoL at months 6 and 12, these differences did not persist over the whole observation period of 24 months. Patients with a colon J-pouch may benefit with respect to QoL in the short-term.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

Cetuximab monotherapy and cetuximab plus capecitabine as first-line treatment in older patients with RAS- and BRAF wild-type metastatic colorectal cancer. Results of the multicenter phase II trial SAKK 41/10.

INTRODUCTION: While the anti-VEGF antibody bevacizumab was studied repeatedly as part of low-intensity regimens in less fit elderly patients with metastatic colorectal cancer (mCRC), anti-EGFR antibodies as upfront treatment modality have been scarcely investigated. MATERIAL AND METHODS: In SAKK 41/10, the benefit of cetuximab, either alone or in combination with capecitabine, was evaluated in vulnerable elderly patients with RAS/BRAF-wild-type mCRC. RESULTS AND DISCUSSION: The trial was stopped prematurely due to slow accrual after the inclusion of 24 patients (11 in the monotherapy arm, 13 in the combination arm). Median patient age was 80 years (range 71-89), median CIRS-G score 7 (range 2-13), and median IADL score 7 (range 3-8). At week 12, 6 of 11 patients (55%) were progression-free in the cetuximab monotherapy arm and 9 of 13 patients (69%) in the combination arm. Response rate was 9% in the monotherapy arm and 38% combination arm. The 6 patients with right-sided primary tumors were not responsive to cetuximab. NGS revealed additional mutations affecting the RAS/RAF/MAP kinase pathway in 5 patients; 4 of these patients showed early disease progression. Cetuximab was generally well tolerated and a trend toward an improvement of symptom-related QoL was observed. In the combination arm, a higher incidence of toxicities and treatment stoppings was observed. In conclusion, trial recruitment - requiring both geriatric as well as molecular eligibility criteria - proved more difficult than expected. Bearing in mind the very small sample size, upfront cetuximab treatment appeared tolerable and showed promising activity in left-sided tumors in both treatment arms.