Publications by authors named "F Couture"

135 Publications

Intensive monitoring of minimal residual disease and chimerism after allogeneic hematopoietic stem cell transplantation for acute leukemia in children.

Bone Marrow Transplant 2021 Sep 2. Epub 2021 Sep 2.

Service d'Hématologie-Oncologie Pédiatrique, Centre de Cancérologie Charles-Bruneau, CHU Sainte-Justine, Montréal, QC, Canada.

Posttransplant leukemia detection before overt relapse is key to the success of immunotherapeutic interventions, as they are more efficient when leukemia burden is low. However, optimal schedule and monitoring methods are not well defined. We report the intensive bone marrow monitoring of minimal residual disease (MRD) using flow cytometry (FC) and nested reverse transcription polymerase chain reaction (RT-PCR) whenever a fusion transcript allowed it and chimerism by PCR at 11 timepoints in the first 2 years after transplant. Seventy-one transplants were performed in 59 consecutive children, for acute myeloid (n = 38), lymphoid (n = 31), or mixed-phenotype (n = 2) leukemia. MRD was monitored in 62 cases using FC (n = 58) and/or RT-PCR (n = 35). Sixty-seven percent of leukemia recurrences were detected before overt relapse, with a detection rate of 89% by RT-PCR and 40% by FC alone. Increased mixed chimerism was never the first evidence of recurrence. Two patients monitored by RT-PCR relapsed without previous MRD detection, one after missed scheduled evaluation and the other 4.7 years post transplant. Among the 22 cases with MRD detection without overt relapse, 19 received therapeutic interventions. Eight (42%) never relapsed. In conclusion, intensive marrow monitoring by RT-PCR effectively allows for early detection of posttransplant leukemia recurrence.
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September 2021

Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance).

Ann Oncol 2021 Oct 20;32(10):1267-1275. Epub 2021 Jul 20.

Department of Medical Oncology, Dana-Farber/Partners Cancer Care, Boston, USA.

Background: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer.

Patients And Methods: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.

Results: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895).

Conclusion: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
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October 2021

Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules.

Clin Cancer Res 2021 Jul 1. Epub 2021 Jul 1.

Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Standard-dose pembrolizumab plus alternative-dose ipilimumab (1 mg/kg Q3W for 4 doses) were tolerable and had robust antitumor activity in advanced melanoma in cohort B of the phase 1 KEYNOTE-029 study. Cohort C evaluated standard-dose pembrolizumab with two other alternative ipilimumab regimens.

Patients And Methods: Patients with treatment-naive unresectable stage III/IV melanoma were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for ≤24 months plus ipilimumab 50 mg Q6W for 4 doses (PEM200+IPI50), or the same pembrolizumab regimen plus ipilimumab 100 mg Q12W for 4 doses (PEM200+IPI100). Primary end points were incidence of grade 3-5 treatment-related adverse events (TRAE) and objective response rate (ORR) per RECIST v1.1 by independent central review. Per protocol-defined thresholds, grade 3-5 TRAE incidence ≤26% indicated meaningful toxicity reduction and ORR ≥48% indicated no decrease in efficacy versus data reported for other PD-1 inhibitor/ipilimumab combinations.

Results: Median follow-up on February 18, 2019, was 16.3 months in PEM200+IPI50 ( = 51) and 16.4 months in PEM200+IPI100 ( = 51). Grade 3-5 TRAEs occurred in 12 (24%) patients in PEM200+IPI50 and 20 (39%) in PEM200+IPI100. One patient in PEM200+IPI50 died from treatment-related autoimmune myocarditis. Immune-mediated AEs or infusion reactions occurred in 21 (42%) patients in PEM200+IPI50 and 28 (55%) in PEM200+IPI100. ORR was 55% in PEM200+IPI50; 61% in PEM200+IPI100.

Conclusions: Pembrolizumab 200 mg Q3W plus ipilimumab 50 mg Q6W or 100 mg Q12W demonstrated antitumor activity above the predefined threshold; pembrolizumab plus ipilimumab 50 mg Q6W had lower incidence of grade 3-5 TRAEs than the predefined threshold, suggesting a reduction in toxicity..
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July 2021

The increasing use of renal tumor biopsy amongst Canadian urologists: When is biopsy most utilized?

Urol Oncol 2021 08 27;39(8):499.e15-499.e22. Epub 2021 Jun 27.

Department of Urology, Centre Hospitalier Universitaire de Sherbrooke and Centre de Recherche du CHUS, Sherbrooke, QC, Canada. Electronic address:

Introduction: The role of renal tumor biopsy (RTB) in the management of small renal masses (SRMs) is progressively being recognized as a tool to decrease overtreatment. While an increasing number of studies assessing its role in diagnostics are becoming available, RTB remains variably used amongst urologists. Many patient-, tumor-, and institution-related factors may influence urologists on whether to perform a RTB to help guide management.

Objective: We aimed at identifying factors associated with the use of RTB for localized SRMs within a number of centers contributing data to the Canadian Kidney Cancer information system.

Material And Methods: We identified 3,838 patients diagnosed with a localized SRM (≤4 cm) between January 2011 and December 2018. Patients were stratified based on whether a RTB was performed prior to the primary therapeutic intervention. Factors associated with use of RTB were assessed using univariable and multivariable logistic regression models.

Results: A total of 993 patients (25.9%) underwent an RTB. There was an overall increase in RTB use over time (P < 0.001), with patients diagnosed between 2015 and 2018 undergoing more RTB than patients diagnosed between 2011 and 2014 (29.8% vs. 22.2%, respectively; P < 0.001). Patients managed in centers with the highest patient-volume had RTB more frequently than patients managed in low-volume centers. On multivariable analysis, increasing year of diagnosis was significantly associated with more RTB use. Patients treated with surgery underwent RTB statistically less often than patients undergoing thermal ablation (P < 0.001) or managed with active surveillance (P < 0.001). Larger SRMs were associated with more RTB use in patients on active surveillance (P = 0.009), but with less RTB in patients undergoing surgery (P = 0.045).

Conclusion: This large multicenter cohort study reveals an increasing adoption and overall use of RTB amongst Canadian urologists. Patients managed in high-volume centers and those undergoing non-surgical management were associated with greater use of RTB. Tumor size was also associated with RTB use. This study highlights the influence that physician perceptions and clinical factors may have in the decision to use RTB prior to initiating a therapeutic approach.
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August 2021

Copy number and transcriptome alterations associated with metastatic lesion response to treatment in colorectal cancer.

Clin Transl Med 2021 04;11(4):e401

McGill University-Segal Cancer Centre, Jewish General Hospital, 3755 Côte Ste-Catherine, Montreal, Quebec, H3T 1E2, Canada.

Background: Therapeutic resistance is the main cause of death in metastatic colorectal cancer. To investigate genomic plasticity, most specifically of metastatic lesions, associated with response to first-line systemic therapy, we collected longitudinal liver metastatic samples and characterized the copy number aberration (CNA) landscape and its effect on the transcriptome.

Methods: Liver metastatic biopsies were collected prior to treatment (pre, n = 97) and when clinical imaging demonstrated therapeutic resistance (post, n = 43). CNAs were inferred from whole exome sequencing and were correlated with both the status of the lesion and overall patient progression-free survival (PFS). We used RNA sequencing data from the same sample set to validate aberrations as well as independent datasets to prioritize candidate genes.

Results: We identified a significantly increased frequency gain of a unique CN, in liver metastatic lesions after first-line treatment, on chr18p11.32 harboring 10 genes, including TYMS, which has not been reported in primary tumors (GISTIC method and test of equal proportions, FDR-adjusted p = 0.0023). CNA lesion profiles exhibiting different treatment responses were compared and we detected focal genomic divergences in post-treatment resistant lesions but not in responder lesions (two-tailed Fisher's Exact test, unadjusted p ≤ 0.005). The importance of examining metastatic lesions is highlighted by the fact that 15 out of 18 independently validated CNA regions found to be associated with PFS in this study were only identified in the metastatic lesions and not in the primary tumors.

Conclusion: This investigation of genomic-phenotype associations in a large colorectal cancer liver metastases cohort identified novel molecular features associated with treatment response, supporting the clinical importance of collecting metastatic samples in a defined clinical setting.
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April 2021