596 Background: The 21-gene Oncotype DX Breast Recurrence Score assay is well established for determining use of adjuvant chemotherapy in hormone receptor (HR)-positive, HER2-negative breast cancer patients. However, the role of the 21-gene assay in the neoadjuvant setting has yet to be established. We previously reported the impact of the 21-gene assay in the neoadjuvant setting in node-negative breast cancer patients, which led to a reduction in the recommendation of chemotherapy in about one-third of patients. Here, we report the impact of the assay on neoadjuvant treatment pathways including surgery, endocrine therapy, and chemotherapy, in addition to overall costs. Methods: We performed a multicentre, prospective observational trial of HR-positive, HER2-negative breast cancer patients with T2-T3 disease and clinically negative axillary lymph nodes. Physicians completed questionnaires prior to and after Recurrence Score (RS) results, indicating their treatment choice for neoadjuvant endocrine or chemotherapy, or upfront surgery. Data was also collected at 6 months after initiation of therapy, to verify treatment received. The primary and secondary objectives were to evaluate impact of RS results on physician’s treatment decisions and on drug (anti-emetics and pre-medication), and nursing (counselling and infusion time) costs, respectively. Results: A total of 70 patients were enrolled in the study as part of five hospital centers of the McPeak Sirois Group in the province of Quebec from 2018-2021. Feasibility of the 21-gene assay from core biopsy samples was 98.6%. At 6-month follow-up, the 21-gene assay led to a change in treatment decision in 52.2% of patients, including de-escalation from neoadjuvant chemotherapy to either upfront surgery in 21.7%, or to neoadjuvant endocrine therapy in a further 21.7%. The use of upfront surgery changed from 10.0% at baseline to 33.3% at 6-month follow-up ( p = 0.0004). Use of neoadjuvant endocrine therapy also changed from 12.9% to 29.0% ( p = 0.02). Among patients treated with upfront surgery or neoadjuvant endocrine therapy, 52.2% and 55.0% of patients, respectively, had a RS≥16. At baseline, for all patients, total chemotherapy-associated drug costs were $190,656 CAD, and nursing-associated costs were $96,918 CAD. RS-guided treatment recommendation reduced chemotherapy-associated drug costs by 32.3% and nursing resource utilization by 44.1%. Conclusions: The use of the 21-gene assay reclassified treatment pathways in 52.2% of patients, including shifting patients from neoadjuvant chemotherapy toward upfront surgery or neoadjuvant endocrine therapy, while reducing chemotherapy-related resource utilisation. These data support the use of the 21-gene assay as a clinical decision-making tool in the neoadjuvant setting. Additional information: Coauthor André Robidoux, MD, died in July 2020.
Background The Peritoneal Cancer Index recorded at laparotomy is based on visual and palpable inspection of peritoneal surfaces for disease. This study aimed to analyze interobserver variation in assigning the lesion score (LS) and morphologic term (MT) to characterize peritoneal lesions (PL) and predict the probability of malignancy (POM) among surgeons with expertise in cytoreductive surgery (CRS) for peritoneal malignancies. Methods The study selected 80 intraoperative images of PLs depicting different morphologic appearances of PLs arising from different primary tumors in various peritoneal regions. In the study, 50 expert peritoneal malignancy surgeons were asked to assign an LS to the region in question, select the MT or MTs to describe the PL, and predict the POM. Information on the presence of disease on histopathology was not provided at this point. Inter-observer reliability was evaluated using Krippendorff's alpha (alpha). A consensus was reached if any option received more than 75% of the votes. Results The study participants comprised 41 (82%) of 50 experts. Consensus on LS was achieved for 18 images (22.5%), with low agreement (alpha = 0.174). For MTs, a consensus was reached for 21 images (26.5%; alpha = 0.0902, denoting low and unreliable agreement. Of these 21 images, the MT used was "tumor nodule" for 90.4% of the images (p < 0.001). The POM was accurately predicted in 52.5% of the cases (alpha = 0.155). Administration of neoadjuvant chemotherapy had no impact on the surgeons' assessment of the three parameters. Conclusions Even the most experienced CRS surgeons showed high interobserver variation and unreliable agreement in the description and accurate characterization of PLs on pictorial records. A Delphi consensus to standardize the MT used and scoring of PL could reduce discordance.
Background:Gastrojejunocolic fistulas (GJCFs) are rare complications following gastrojejunostomy and Roux-en-Y procedures, most often in the context of peptic ulcer disease. Case Report:A 42-year-old woman, with a history of cocaine addiction, underwent an gastrojejunostomy, a transgastric closure of the gastric pylorus, and a Graham patch for a perforated duodenal ulcer. She then presented with a dehisced gastrojejunal anastomosis. Resection of the dehisced anastomosis and Roux-en-Y reconstruction was performed. Eight months later, the patient returned to the hospital with a GJCF. A one-stage en-bloc GJCF resection with redo Roux-en-Y was performed. Six months later, a scan demonstrated a recurrent GJCF. Antrectomy and bilateral truncal vagotomy were performed to avoid recurrent gastric acid secretion. Resection of the dehisced gastrojejunal anastomosis and the segment of fistulized transverse colon was performed. A third Roux-en-Y reconstruction was fashioned. The patient evolved well and showed no signs of recurrent disease. Discussion:The cornerstone treatment of GJCF is the administration of parenteral nutrition, followed by a single-stage en-bloc procedure. Some factors that can contribute to recurrent GJCF are retained gastric antrum syndrome, incomplete vagotomy, and noncompliance with oral antacid therapy. Despite the significant leaps in the medical management of peptic ulcer disease in recent years, surgical strategies that reduce excess gastric acid secretion should be considered in select cases. Conclusion:This case highlights that gastric antrectomy and bilateral vagotomy have not been rendered obsolete in the 21st century, particularly in patients who cannot be compliant with oral proton pump inhibitors.
BACKGROUND:Peritoneal metastases from colorectal cancer (pmCRC) are associated with poor prognosis. Neoadjuvant chemotherapy followed by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival in these patients. However, few studies have evaluated the influence of radiological and pathological responses on overall survival (OS) and recurrence-free survival (RFS) in this population. OBJECTIVE:The objective of this study was to assess these prognostic markers in patients with pmCRC who received neoadjuvant chemotherapy followed by CRS-HIPEC at our institution. METHODS:A total of 121 patients with pmCRC treated with neoadjuvant chemotherapy followed by CRS-HIPEC from 2012 to 2023 were included. Demographic, clinical, and oncological data were extracted from medical records. OS and RFS were obtained using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were done. RESULTS:After a median follow-up of 44.6 months, median OS was 47.1 months (95% confidence interval [CI] 32.4-61.6) and RFS was 21.8 months (95% CI 13.7-29.9). No significant difference in OS was observed among patients who achieved a partial response on imaging compared with non-responders (hazard ratio [HR] 0.9; 95% CI 0.5-1.5; p = 0.725). Patients who did not achieve a complete pathological response showed a significant difference in OS, with worse OS (HR 3.4; 95% CI 1.3-8.9; p = 0.012). OS was significantly lower in patients with a peritoneal carcinomatosis index >15 (HR 4.1; 95% CI 1.1-15; p = 0.033). CONCLUSIONS:Radiological response after neoadjuvant chemotherapy does not significantly affect the OS or RFS of patients with pmCRC. Complete pathological response is a significant prognostic marker for both OS and RFS.
Preoperative colonoscopy is recommended for colorectal cancers to exclude synchronous tumors. However, data are lacking regarding this recommendation for appendiceal mucinous neoplasms. This study evaluated whether preoperative colonoscopy in patients with appendiceal mucinous lesions would reveal a significant finding, modify the operative plan, or be associated with adverse events. This mixed-methods retrospective cohort study included all mucinous appendiceal neoplasms between 2017 and 2024 at a tertiary care hospital. Overall, 100 patients were included: 15
INTRODUCTION:Despite advances in systemic therapy, metastatic gastric cancer is associated with a poor prognosis. As peritoneal disease is common, several studies looked at the potential benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) in this context, with encouraging results. However, no Canadian data currently exists on the subject. MATERIALS AND METHODS:This study aims to report characteristics and outcomes of Canadian patients who underwent cytoreductive surgery and HIPEC (CRS-HIPEC) for gastric cancer associated with peritoneal disease or positive peritoneal cytology. This multicenter retrospective study included patients 18 years or older with gastric cancer associated with isolated peritoneal involvement who underwent CRS-HIPEC in five tertiary centers from 2016 to 2022. RESULTS:CRS-HIPEC was performed on 20 patients aged 34-69 years old, most of whom presented with poorly differentiated (90 %) adenocarcinoma, with synchronous peritoneal disease (95 %). Median PCI was 3 (0-13). The associated 90-day morbidity rate, defined as Clavien-Dindo grade III and above complications, was 10 %. At a mean follow-up of 23.3 months (range 4-48), 25 % of patients remained disease-free, with an estimated median overall survival of 24.2 months. CONCLUSION:CRS-HIPEC for gastric cancer can achieve longer term survival in highly selected patients with low-burden peritoneal disease or positive cytology. Ongoing randomized trials will further clarify patients' selection criteria and benefits of this approach.
Goals: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival in patients with peritoneal metastases (PM). While mitomycin-C (MMC) and oxaliplatin are the primary HIPEC agents for colorectal and appendiceal PM, previous studies comparing both agents relied on outdated low-dose MMC regimens. This study evaluates the safety of high-dose 35 mg/m(2) mitomycin C vs 460 mg/m(2) oxaliplatin. Methods: This retrospective cohort study analyzed all patients with appendiceal and colorectal PM treated at a tertiary-care hospital from 2014 to 2024. Results: Among 282 patients, 48 (17.0 %) received high-dose MMC and 234 (83.0 %) received oxaliplatin. Patient demographics and oncological characteristics were similar (p > 0.05). High-dose MMC had significantly more toxic events (35.4 % vs 14.1 %, p < 0.001), greater CTCAE median toxicity grade (2 vs 1, p < 0.001), higher hepatic cytolysis (2.1 % vs 0.0 %, p = 0.027), increased neutropenia (27.1 % vs 4.3 %, p < 0.001), more gastric perforations (4.2 % vs 0 %, p = 0.002) as well as one case of HIPEC toxicity-related death due to neutropenic enterocolitis (2.1 % vs 0.0 %, p = 0.380). Oxaliplatin resulted in more hematomas (12.0 % vs 2.1 %, p = 0.040), higher need for parenteral nutrition (94.0 % vs 83.3 %, p = 0.012), and longer duration of nutritional support (12.3d vs 8.6d, p = 0.020). High-dose MMC had higher abdominal sepsis rates (6.3 % vs 1.3 %, p = 0.030). Severe complications, reintervention, ICU transfers, and 90-day mortality were similar (p > 0.05). Length of stay was shorter for high-dose MMC (14.7d vs 17.7d, p = 0.031). Conclusion: High-dose MMC was associated with increased HIPEC toxicity, primarily neutropenia-related. Clinicians must balance the benefits and drawbacks of high-dose MMC and oxaliplatin to provide an optimal and individualized treatment.
BACKGROUND Malignant peritoneal mesothelioma (MPM) is a rare subtype of malignant mesothelioma (MM) that arises from mesothelial/serosal surfaces of the peritoneal lining and carries a poor prognosis. Given the rarity of this disease, many expert groups such as the Peritoneal Surface Oncology Group International (PSOGI) and the National Comprehensive Cancer Network (NCCN) have developed recommendations to guide the optimal treatment for MPM. Currently, the standard of care for resectable MPM is a combination of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). There are no clear guidelines for treatment of inoperable malignant mesothelioma, but several studies have demonstrated a benefit of incorporating immunotherapy in the treatment plan. CASE REPORT We present a case of a 63-year-old woman who sought medical attention for several months of persistent vague abdominal discomfort, weight loss, and night sweats. Laboratory workup and diagnostic imaging led to the diagnosis of borderline/unresectable MPM. A multidisciplinary tumor board discussion based on the published literature and guidelines on malignant mesothelioma (MM) was undertaken, and the decision was made to treat the patient with nivolumab-ipilimumab in the perioperative period. The patient had a positive clinical response allowing for subsequent CRS and HIPEC. She remains disease free 30 months following her surgery, with the intention to continue the immunotherapy. CONCLUSIONS This case report contributes to the current literature demonstrating a potential role for perioperative immunotherapy in the treatment of aggressive subtype or borderline resectable/unresectable MPM and a bridge to consolidative CRS/HIPEC.
BACKGROUND:ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC.MATERIALS AND METHODS:Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site.RESULTS:A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2.CONCLUSION:The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.
PurposeBreast cancer (BC) is the most frequently diagnosed cancer among women. Approximately 40% of BC survivors are diagnosed during the peak years of their professional career. Women face numerous obstacles when returning to work (RTW) after BC. Their decision-making process and self-efficacy to overcome these barriers may undergo alterations. The objective of this study was to validate the Return-to-work Obstacles and Self-Efficacy Scale (ROSES) for BC survivors, with a focus on three psychometric properties: construct validity, test-retest reliability, and predictive validity.MethodsThis prospective study consists of three phases: Phase 1 (baseline, during sick leave) was conducted to evaluate construct validity, Phase 2 (2 weeks later) assessed test-retest reliability, and Phase 3 (6-month follow-up, RTW or not) aimed to evaluate predictive validity. A total of 153 BC survivors participated in Phase 1 of the study, where they completed the 10 dimensions of the ROSES (e.g., fear of relapse, cognitive difficulties). Confirmatory factor analyses (CFA), Pearson correlations, and Cox regressions were performed, with respect to each phase.ResultsThe mean duration for RTW with the same employer was 62.7 weeks. CFAs confirmed the ROSES structure, which had previously been established for other health conditions, showing satisfactory coefficients. Significant Pearson correlation coefficients were observed between the ROSES dimensions from Phase 1 to Phase 2, ranging from 0.66 to 0.88. When considering various confounding variables, chemotherapy treatment and cognitive difficulties (ROSES dimension) emerged as the only significant predictors of RTW.ConclusionThese findings support the utilization of the ROSES in clinical and research settings for BC survivors to improve their successful RTW. After an initial screening using the ROSES, occupational health professionals can further conduct a focused and thorough evaluation of specific dimensions, such as cognitive difficulties. Additional research and information are required to assist BC survivors in dealing with cognitive impairments induced by chemotherapy when they return to work.
BACKGROUND:A novel approach using single-fraction preoperative partial breast irradiation (PBI) for low-risk breast cancer is under study. We sought to investigate the rate of pathologic response (pR), toxicities and cosmetic results related to this new treatment strategy. METHODS:Women of 65 years or older with stage I unifocal luminal A breast cancer were eligible for inclusion in this phase I prospective trial. Patients received a single 20 Gy dose of PBI followed by breast-conserving surgery (BCS) 3 months later. The primary endpoint was the pR rate, and the secondary endpoints were radiation therapy-related toxicity and cosmetic results. RESULTS:Thirteen patients were treated, with a median age of 71. Eleven patients (84.6 %) had pR with a median residual cellularity of 1 % (range: 0-10 %). At median follow-up of 48.5 months, no recurrences or cancer-related deaths were recorded. Acute radiation therapy-related toxicity were limited to grade 1 dermatitis and breast pain. At the 1-year follow-up, there were one grade 2 fat necrosis and two grade 3 toxicities (wound infection and hematoma). Only grade 1 toxicities remained at 2 years, but one grade 2 toxicity (fibrosis/induration) developed by the 3-year follow-up. Three-year patient-reported cosmetic outcomes were good or excellent in 60 % of patients. CONCLUSIONS:Single-fraction preoperative PBI preceding BCS for low-risk breast cancer is feasible, relatively well tolerated and leads to a high level of pR. The 3-month interval after PBI seems to place surgery in a post-radiation inflammatory phase. Further delay between PBI and surgery could improve pR and cosmetic outcome. NCT03917498.