This study aims to evaluate the long-term skin-related patient-reported outcomes (PROs) of a randomized controlled trial (RCT) comparing Mepitel Film (MF) to standard of care (SOC) for the prevention of acute radiation dermatitis (ARD) in breast cancer patients undergoing radiation therapy (RT). Patients were contacted via telephone at 6 months, 12 months, and 24 months post-RT to complete the Skin Symptom Assessment (SSA) and Radiation-induced Skin Reaction Assessment Scale (RISRAS). SSA and RISRAS scores at follow-up visits were compared to baseline using a generalized estimation equation with Poisson distribution and log link function. To account for multiple testing, the Bonferroni-adjusted p-value of < 0.001 was considered statistically significant. From April 2020 to August 2024, 376 patients were included in the modified intention-to-treat analysis and followed at the pre-specified time points. When comparing MF and SOC, no significant differences were captured longitudinally regardless of the severity of ARD (Common Terminology Criteria for Adverse Events grade [G] 0–1 versus G2-3). Comparing to the baseline scores, patients reported worse pruritis at 6 months and pigmentation at 6 months, 12 months, and 24 months (p < 0.001) for the SSA. For the RISRAS, tenderness/discomfort/pain, itchiness and burning sensation were worse at 6 months (p < 0.001), but only itchiness was worse at 12 and 24 months (p = 0.0007, p < 0.001, respectively) compared to baseline. In the subgroup analysis of patients based on the severity of ARD, pigmentation was worse at all follow-up visits (p < 0.001) in both G0-1 and G2-3 cohorts. PROs returned to baseline at 6 months to 2 years after RT, except pigmentation and pruritis that persist regardless of the severity of ARD, necessitating confirmation with physical signs and further research to understand the pathophysiology of these chronic symptoms to guide preventative strategies. No long-term issues were identified in patients treated with MF, confirming it as a safe and effective strategy for the prevention of ARD.

BACKGROUND:A "symptom cluster" is commonly known as two or more symptoms that occur concurrently. Patients with breast cancer often experience multiple symptoms simultaneously. The purpose of this study was to investigate acute radiation dermatitis symptom clusters in breast cancer patients using Mepitel film (MF) versus standard of care (SOC) aqueous cream during radiation therapy (RT). METHODS:A secondary analysis was performed of the MF versus SOC randomized control trial (n = 376) for the prophylaxis of radiation dermatitis in patients undergoing breast cancer radiation treatment. To identify potential symptom clusters, a principal component analysis (PCA) with varimax rotation was performed on patient-reported Skin Symptom Assessment (SSA) items at baseline and at the 2-week and 3-month follow-ups. RESULTS:Symptom clusters varied based on time point and treatment arm. Two to three symptom clusters were identified for both treatment arms at each follow-up. Patients in the MF arm had the item "trouble fitting brassieres" clustered with "edema" and/or "pain/soreness" at each time point. The items "blistering/peeling" and "erythema," as well as the items "pruritus," "pain/soreness," and "pigmentation," were clustered together at both follow-ups. Patients in the SOC arm had items "erythema" and "pruritus" commonly clustering together across time points. The item "edema" was often clustered with "trouble fitting brassieres" or "pain/soreness." CONCLUSION:Symptom clusters should be managed together to optimize improvement in patients. Further research using the SSA or other skin-symptom questionnaires is required to build upon the symptom clusters found in the present study, as well as to compare how symptoms differ between treatment methods.

BACKGROUND:Changes in patient-reported outcomes may be statistically significant, but not necessarily clinically significant. This study determined the minimal clinically important differences (MCIDs) in the Skin Symptom Assessment (SSA) questionnaire for the Mepitel film (MF) versus standard of care (SOC) randomized controlled trial for the prevention of radiation dermatitis (RD) in breast cancer patients. MCIDs are the smallest changes in patient-reported outcome measures (PROMs) that hold meaningful significance for patients and justify a change in clinical management. METHODS:A secondary analysis was conducted on the MF vs SOC phase III randomized controlled trial (n = 376) aimed at preventing breast cancer radiation dermatitis. Anchor- and distribution-based methods were used to determine MCIDs, with worst CTCAE grade as the anchor. MCIDs were determined between baseline and the 2-week follow-up, as well as between the 2-week follow-up and the 3-, 6-, 12-, and 24-month follow-ups. RESULTS:MCIDs were determined for total patients, MF patients, and SOC patients. Between baseline and the 2-week follow-up, the MCIDs for deterioration in MF patients ranged from 0.11 (edema) to 0.76 units (erythema). MCIDs for SOC patients ranged from 0.29 (edema) to 1.21 units (pigmentation). The MCIDs for the other time points ranged from 0.12 units (edema) in MF patients to 1.13 units (erythema) in SOC patients. MCIDs at all time-points and in all patient subgroups were closest to 0.5 standard deviation. CONCLUSION:Determining MCIDs can help HCPs determine when treatments meaningfully improve patient QoL. MCIDs may also guide decisions to introduce alternative or additional treatments.

The Eastern Canadian Gastrointestinal Cancer Consensus Conference was an annual meeting that was held in St. John’s, Newfoundland and Labrador, from 26 to 28 September 2024. This included experts in medical oncology, radiation oncology, surgical oncology, nuclear medicine, and general practitioners in oncology (GPO) from across the eastern Canadian provinces who are involved in the management of patients with gastrointestinal malignancies. This consensus statement generated by the conference addresses multiple topics, including the management of localized rectal cancer, liver-limited colorectal cancer, systemic therapy for advanced biliary tract cancers, radioligand therapy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), systemic therapy for pancreatic and midgut well-differentiated NETs, and systemic therapy for HER2-positive gastroesophageal cancers.

Background: We proposed adjunctive statistical standardization of quantitated ER and PgR to improve inter-laboratory comparability of biomarker results and therapeutic management of breast cancer. Adjunctive statistical standardization of quantitated HER2 is used here; we also examined the effects on outcome of ultra-low HER2 and very low statistically standardized HER2. Methods: We utilized CCTG MA.27 (NCT00066573), an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER+ and/or PgR+ tumors. IHC HER2 HSCORE and % positivity (%+) were centrally assessed by machine image quantitation, and statistically standardized to mean of 0, standard deviationn (SD) of 1 followig Box-Cox variance stabilization transformations of 1.) natural logarithm (ln with addition of 0.1 to 0 HSCOREs and 0 %+), 2. square root. Additionally, centrally assessed FISH HER2 and CEP17 values were used to define ASCO/CAP categorizatiion. Post hoc, the effects of ultra-low HER2 , IHC 0 with (0,10%] 1+ stain, were examined. The primary endpoint was distant disease-free survival (DDFS) at the longest trial follow-up of median 4.1 years. Survival was described with Kaplan-Meier plots and tested with the univariate Wilcoxon (Peto-Prentice) test statistic. We examined cut-points at standard deviations about mean of 0 (<-1; (-1,0]; (0,1]; >1). Cox multivariant regressions were adjusted for age, T and N stage, grade, lymphovascular invasion, treatment, baseline patient demographics, ER and PgR; 2-sided Wald tests had nominal significance if p<0.05. Results: Of 7576 women accrued to MA.27, 2900 women had ER, 2726 had PgR, and 2680 had HER2 results; 2325 had all three biomarkers for multivariant investigations. Twenty-five women received received herceptin with only one experiencng a DDFS event. ASCO/CAP categorization significantly differentiated univariate DDFS (p=0.01). Image analysis identified 57% of IHC 0 to have ultra-low HER2. Five-year DDFS for IHC 0 without stain was 92% [95% CI (90,95); N=864] which was similar to that for ultra-low HER2 of 96% [95% CI (94,97); N=1143]. Statistical standardization did not significantly differentiate univariate DDFS (p=0.08-0.27). DDFS for ln standardized values <-1.0 (HSCORE, or %+ <0.1) was similar to that with standardized values >1.0 (HSCORE >19, or %+ >14): for HSCORE <1.0, 5-year DDFS was 92% [95% CI (85.98); N=88] vs for >1.0, 92% [95% CI (89,95); N=577]; for %+, 5-year DDFS was 91% [95% CI (85,98); N=102] vs >1.0, 92% [95% CI (89,95); N=613].In multivariant assessments with ASCO/CAP guideline and statistically standardized data, both ER (p=0.65-0.94) and HER2 (p=0.20-0.97) were not significantly associated with the DDFS primary endpoint in models with PgR; while higher PgR had significantly better DDFS (p<.003) in models with ER and HER2. Conclusions: ASCO/CAP HER2 guidelines significantly differentiated univariate DDFS although not values of IHC 0 and ultra-low HER2, with <10% weak stain. Statistical standardization did not differentiate univariate DDFS. Image quantitation identified very small numbers of 1+/2+/3+ intensity stained nuclei. DDFS was similar for any intensity of low ln(HER2) stain (<1 SD below the mean) compared to any intensity of higher HER2 stain (>1 SD above the mean), although we offer caution in assessment of ultra-low, or very low, HER2 stain due to the dynamic range of the HER2 assay. Neither ASCO/CAP nor standardized HER2 had multivariant significance in these hormone receptor rich patient tumors. The adjunctive statistical standardization of ER, PgR, and HER2 performed here is similar to that mandated for clinical practice by the World Health Organization for BMD. Citation Format: Judith-Anne Chapman, Jane Bayani, Sandip SenGupta, John M.S. Bartlett, Tammy Piper, Mary Anne Quintayo, Shakeel Virk, Paul E. Goss, James N. Ingle, Matthew J. Ellis, George W. Sledge, G. Thomas Budd, Manuela Rabaglio, Rafat H. Ansari, Richard Tozer, David P. D'Souza, Haji Chalchal, Silvana Spadafora, Vered Stearns, Edith A. Perez, Karen A. Gelmon, Timothy J. Whelan, Catherine Elliott, Lois E. Shepherd, Bingshu E. Chen, Karen J. Taylor. Adjunctive statistical standardization of quantitated adjuvant HER2 and very low statistically standardized HER2 in CCTG MA.27 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-07-06.

PURPOSE ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes. METHODS MA.27 (ClinicalTrials.gov identifier: NCT00066573 ) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤–1; (–1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05. RESULTS Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS ( P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated ( P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS ( P = .001) in models with ER. CONCLUSION Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤–1.

Abstract Background: Adjuvant breast cancer therapy is informed by whether a tumour is positive or negative for the biomarkers ER, PgR, and HER2, often without regard to level of positivity. Quantitation has been proposed to improve therapeutic management. Adjunctive statistical standardization has been proposed to improve inter-laboratory comparability of biomarkers results. Methods: This primary report utilized adjunctive statistical standardization of machine-quantitated image analysis biomarker assessments. CCTG MA.27 (NCT00066573) is an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER+ and/or PgR+ tumours. IHC ER, PgR, and HER2 were centrally assessed, with FISH (HER2;HER2/CEP17) determinations for equivocal IHC HER2. HSCOREs were statistically standardized to a mean of 0, standard deviation of 1 following Box-Cox variance stabilization transformations of square for ER and natural logarithm for PgR (0.1 was added to 0 HSCOREs). The primary endpoint was STEEP distant disease-free survival (DDFS) at the longest trial follow-up of median 4.1 years. Survival was described with Kaplan-Meier plots. The univariate Wilcoxon (Peto-Prentice) test statistic was used with usual designation of negative/positive (0; >0), and standardized cut-points at standard deviations about mean of 0(<-1; (-1,0]; (0,1]; >1). Cox multivariate regressions adjusted for age, T and N stage, grade, lymphovascular invasion, treatment, and baseline patient demographics, utilized likelihood ratio tests. Nominal significance was p=0.05. Results: Of the 7576 women accrued, 3048 had machine-quantitated image analysis results: 2900 (95%) for ER; 2726 (89%) for PgR. Only 8 women were ASCO/CAP ER- (HSCORE 0); PgR HSCORE was 0 for 533. Statistically standardized units differentiated DDFS ER levels (p< 0.001) and PgR levels (p< 0.001). In adjusted multivariate analyses, higher ER HSCORE was associated with better DDFS (p=0.05) with weak evidence of an association (p=0.11) for standardized HSCORE, and no significant association (respectively, p=0.28, p=0.54) in models with PgR. Higher PgR was associated with better DDFS (p=0.001) in all multivariate assessments, including those with ER. Conclusions: DDFS was superior for patients with higher ER and PgR standardized units compared with those with HSCOREs <-1. Adjunctive statistical standardization, similar to that mandated for clinical practice by the World Health Organization for BMD, should improve inter-laboratory comparability of biomarker results for similar patient populations. Biomarker N DDFS DDFS 5-year (%) 95% CI ER total 2900 ER <-1 506 86 (82, 91) ER (-1, 0] 934 94 (92, 96) ER ( 0, 1] 919 94 (92, 96) ER >1 541 96 (93, 98) PgR total 2726 PgR <-1 734 89 (86, 92) PgR (-1, 0] 439 92 (89, 95) PgR ( 0, 1] 967 95 (93, 96) PgR >1.0 586 98 (97,100) Citation Format: Judy-Anne Chapman, Jane Bayani, Sandip SenGupta, John MS Bartlett, Tammy Piper, Mary Anne Quintayo, Shakeel Virk, Paul Goss, James Ingle, Matthew Ellis, George Sledge Jr, George Budd, Manuela Rabaglio, Rafat Ansari, Richard Tozer, David D'Souza, Haji Chalchal, Silvana Spadafora, Vered Stearns, Edith A. Perez, Karen Gelmon, Timothy Whelan, Catherine Elliott, Lois Shepherd, Bingshu Chen, Karen Taylor. Adjunctive statistical standardization of quantitated machine image analysis of Estrogen and Progesterone Receptors: CCTG MA.27 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-27-10.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

BACKGROUND AND PURPOSE:Clinicians use the CTCAE scale to grade radiation dermatitis (RD) based on edema, erythema, and desquamation. The purpose of this study was to correlate the CTCAE scores with the severity of patient-reported symptoms using a skin symptom assessment (SSA) and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS). MATERIALS AND METHODS:This is a secondary analysis of a randomized controlled trial involving 376 patients receiving Mepitel Film or standard-of-care for RD prophylaxis. The highest symptom categories for SSA and patient-component RISRAS assessments were selected from all time points, and a summary analysis and Spearman correlation coefficient was calculated for patients with CTCAE Grades 0, 1, 2, 3, and Grade 2/3, respectively. Analyses were conducted across all patients, within each treatment arm, and between arms in patients with only Grade 2 or 3 toxicity. RESULTS:Weak correlations between CTCAE scores and all patient-reported skin symptoms were found across the entire cohort and each treatment arm (p < 0.05). Patients with Grade 2 (n = 72) and Grade 3 RD (n = 24) reported similar rates of patient-reported moderate-to-severe skin symptoms (11-72% vs 14-79%), with no significant difference in rates of individual moderate-to-severe symptom between these cohorts (p > 0.05). Between treatment arms, rates of patient-reported moderate-to-severe scores were similar for most symptoms. CONCLUSION:CTCAE RD scores are weakly correlated with patient-reported skin symptoms and cannot distinguish between patients with severe patient-reported outcomes. Clinicians should consider the limitations of CTCAE grading and incorporate patient-reported outcomes within clinical practice.

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how “incremental cost-effectiveness ratios” (ICERs) based on measures such as gains in “quality-adjusted life-years” (QALYs) may be used to determine a drug’s value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.

The study evaluated the concordance between patient-reported outcomes (PRO) and clinician-reported outcomes (CRO) of acute radiation dermatitis (RD) symptoms following adjuvant radiotherapy for early-stage and locally advanced breast cancer. This is a secondary analysis of a multi-center randomized phase 3 trial (376 patients). Ordinal logistic regression analysis was used to compare the Skin Symptom Assessment (SSA) independently reported by both patients and clinicians. Concordance between patient- and clinician-reported SSAs for RD symptoms was measured by percent concordance, concordance index (C-statistic), and Cohen’s Kappa. Analyses were performed across all patients in the original modified intention-to-treat analysis and those with only grade 2–3 (CTCAE) RD. PROs were significantly more severe than CROs across all RD symptoms (Odds Ratio [OR] > 1; p < 0.0001). Pigmentation (OR 5.4), blistering/peeling (OR 4.0), and pain/soreness (OR 3.9) were the most differentially reported symptoms. Poor-to-low concordance was noted between patient- and clinician-reported SSAs for all RD symptoms for the entire cohort (percent concordance < 50

PURPOSE:Radiation dermatitis (RD) is common in patients undergoing breast radiotherapy. Mepitel film (MF) can reduce RD, but the results from two randomized controlled trials are conflicting. We aimed to conduct a confirmatory randomized controlled trial in patients at risk of RD.METHODS:Patients were randomly assigned to receive MF or standard care (2:1 ratio). Patients with large breasts after lumpectomy (bra size ≥ 36 inches or cup size ≥ C) or after mastectomy were eligible. Stratification factors included surgery type, dose fractionation, and administration of boost/bolus. The primary end point was grade (G) 2 or 3 RD using the Common Terminology Criteria for Adverse Events v5.0. Secondary end points included patient- and clinician-reported outcomes.RESULTS:Between January 2020 and May 2022, 376 patients were included in the modified intention-to-treat analysis. The incidence of G2 or 3 RD was significantly lower in MF patients compared with standard care (n = 39/251, 15.5%; 95% CI, 11.3 to 20.6% v n = 57/125, 45.6%; 95% CI, 36.7 to 54.8% respectively, odds ratio (OR): 0.20, P < .0001). Benefits of MF remained significant in patients who developed G 3 RD (n = 7, 2.8%; 95% CI, 1.1 to 5.7% v n = 17, 13.6%; 95% CI, 8.1 to 20.9%, OR: 0.19) and moist desquamation (n = 20, 8.0%; 95% CI, 4.9 to 12.0% v n = 24, 19.2%; 95% CI, 12.7 to 27.1%, OR: 0.36). When evaluating the combined patient and health care provider score using Radiation-Induced Skin Reaction Assessment Scale, the MF arm had significantly lower scores (P < .0001). Individual items on the Radiation-Induced Skin Reaction Assessment Scale also favored the MF for both patient- and clinician-reported outcomes. Blistering/peeling, erythema, pigmentation, and edema were significantly reduced in the MF arm. Three patients removed the film prematurely because of rash (n = 2) and excessive pruritus (n = 1).CONCLUSION:MF significantly reduces RD in patients undergoing breast radiotherapy.

# 01. Operative classification of ventral abdominal hernias: new and practical classification {#article-title-2} Ventral hernias of the abdomen are defined as a noninguinal, nonhiatal defect in the fascia of the abdominal wall. Unfortunately, there is not currently a universal classification system

The government of Canada now plans to bring into force new federal drug pricing regulations on 1 July 2022. We do not take issue with the goal of medication affordability, which is vital in healthcare the world over. Our concern is that the new guidelines are being implemented without due consideration for three major unintended consequences: regulatory changes will lower the number of clinical trials for new medications in Canada, fewer clinical trials will mean lower research and development investments, and changes will reduce patients’ access to new medications. Access to effective medications is a cornerstone of healthcare for Canadian patients. As physicians, our duty to patient care demands that we tell the government to protect the right of Canadians to timely access to life-changing medicines.

124 Background: Cancer patients undergoing surgical resection of their tumor are hypercoagulable beyond the period of hospitalization. Preclinical studies demonstrate that the postoperative hypercoagulable state promotes metastases, an effect that is abrogated by administration of perioperative low molecular-weight heparin (LMWH). Methods: We conducted a randomized, open label clinical trial to determine if extended duration thromboprophylaxis using subcutaneous LMWH (tinzaparin 4,500 IU daily), beginning at decision to operate and continuing for 56 days postoperatively, compared to inpatient postoperative thromboprophylaxis only, increased the 3-year disease-free survival (DSF) in patients undergoing resection for colorectal cancer. Secondary outcomes included 5-year overall survival (OS), postoperative bleeding and venous thromboembolism (VTE). Results: Trial recruitment was stopped prematurely after 614 of the planned 1075 patients were registered, following a pre-defined interim analysis for futility. The intention-to-treat analysis included 602 patients with demographics in the table. The 3-year DFS was 78.9% (63/299 recurrences) in the tinzaparin group and 80.5% (59/303 recurrences) in the control group (hazard ratio (HR) 1.09; [95% CI 0.91,1.31; p=0.3]). The 5-year OS was 91.3% in the tinzaparin group and 92.4% in the control group (HR 1.08; [95% CI 0.66,1.79; p=0.1]). The incidence of postoperative VTE was 1.7% and 1.3% in the tinzaparin and control groups, respectively (HR 1.3; [95% CI 0.30,5.69; p=0.7]. The incidence of major bleeding in the first postoperative week was 0.3% and 2% in the tinzaparin and control groups, respectively (HR 0.16; [95% CI 0.02,1.15; p=0.07]. Conclusions: Extended duration perioperative anticoagulation with tinzaparin did not improve DFS or OS in colorectal cancer patients undergoing surgical resection. The incidences of postoperative bleeding and VTE were low. Funded by Canadian Institute of Health Research and Leo Pharma Clinical trial information: NCT01455831. [Table: see text]

OBJECTIVE:To determine the efficacy and safety of extended duration perioperative thromboprophylaxis by low molecular weight heparin when assessing disease-free survival in patients undergoing resection for colorectal cancer.DESIGN:Multicentre, open label, randomised controlled trial.SETTINGS:12 hospitals in Quebec and Ontario, Canada, between 25 October 2011 and 31 December 2020.PARTICIPANTS:614 adults (age ≥18 years) were eligible with pathologically confirmed invasive adenocarcinoma of the colon or rectum, no evidence of metastatic disease, a haemoglobin concentration of ≥8 g/dL, and were scheduled to undergo surgical resection.INTERVENTIONS:Random assignment to extended duration thromboprophylaxis using daily subcutaneous tinzaparin at 4500 IU, beginning at decision to operate and continuing for 56 days postoperatively, compared with in-patient postoperative thromboprophylaxis only.MAIN OUTCOME MEASURES:Primary outcome was disease-free survival at three years, defined as survival without locoregional recurrence, distant metastases, second primary (same cancer), second primary (other cancer), or death. Secondary outcomes included venous thromboembolism, postoperative major bleeding complications, and five year overall survival. Analyses were done in the intention-to-treat population.RESULTS:The trial stopped recruitment prematurely after the interim analysis for futility. The primary outcome occurred in 235 (77%) of 307 patients in the extended duration group and in 243 (79%) of 307 patients in the in-hospital thromboprophylaxis group (hazard ratio 1.1, 95% confidence interval 0.90 to 1.33; P=0.4). Postoperative venous thromboembolism occurred in five patients (2%) in the extended duration group and in four patients (1%) in the in-hospital thromboprophylaxis group (P=0.8). Major surgery related bleeding in the first postoperative week was reported in one person (<1%) in the extended duration and in six people (2%) in the in-hospital thromboprophylaxis group (P=0.1). No difference was noted for overall survival at five years in 272 (89%) patients in the extended duration group and 280 (91%) patients in the in-hospital thromboprophylaxis group (hazard ratio 1.12; 95% confidence interval 0.72 to 1.76; P=0.1).CONCLUSIONS:Extended duration to perioperative anticoagulation with tinzaparin did not improve disease-free survival or overall survival in patients with colorectal cancer undergoing surgical resection compared with in-patient postoperative thromboprophylaxis alone. The incidences of venous thromboembolism and postoperative major bleeding were low and similar between groups.TRIAL REGISTRATION:ClinicalTrials.gov NCT01455831.

AbstractObjectiveTo evaluate the effectiveness of remote proactive management of toxicities during chemotherapy for early stage breast cancer.DesignPragmatic, cluster randomised trial.Setting20 cancer centres in Ontario, Canada, allocated by covariate constrained randomisation to remote management of toxicities or routine care.ParticipantsAll patients starting adjuvant or neoadjuvant chemotherapy for early stage breast cancer at each centre. 25 patients from each centre completed patient reported outcome questionnaires.InterventionsProactive, standardised, nurse led telephone management of common toxicities at two time points after each chemotherapy cycle.Main outcome measuresThe primary outcome, cluster level mean number of visits to the emergency department or admissions to hospital per patient during the whole course of chemotherapy treatment, was evaluated with routinely available administrative healthcare data. Secondary patient reported outcomes included toxicity, self-efficacy, and quality of life.ResultsBaseline characteristics of participants were similar in the intervention (n=944) and control arms (n=1214); 22% were older than 65 years. Penetration (that is, the percentage of patients who received the intervention at each centre) was 50-86%. Mean number of visits to the emergency department or admissions to hospital per patient was 0.91 (standard deviation 0.28) in the intervention arm and 0.94 (0.40) in the control arm (P=0.94); 47% (1014 of 2158 patients) had at least one visit to the emergency department or a hospital admission during chemotherapy. Among 580 participants who completed the patient reported outcome questionnaires, at least one grade 3 toxicity was reported by 48% (134 of 278 patients) in the intervention arm and by 58% (163 of 283) in the control arm. No differences in self-efficacy, anxiety, or depression were found. Compared with baseline, the functional assessment of cancer therapy trial outcome index decreased by 6.1 and 9.0 points in the intervention and control participants, respectively.ConclusionsProactive, telephone based management of toxicities during chemotherapy did not result in fewer visits to the emergency department or hospital admissions. With the rapid rise in remote care because of the covid-19 pandemic, identifying scalable strategies for remote management of patients during cancer treatment is particularly relevant.Trial registrationClinicalTrials.govNCT02485678.