Publications by authors named "Jean-Michel Lavoie"

32 Publications

Development of secondary urothelial carcinoma following complete response to immune checkpoint inhibitors.

Urol Case Rep 2021 Nov 25;39:101762. Epub 2021 Jun 25.

Department of Medical Oncology, BC Cancer - Vancouver, Vancouver, Canada.

The management of metastatic urothelial cancer is rapidly evolving since immune checkpoint inhibitors were introduced. We present the case of a patient with metastatic upper tract urothelial cancer who had a complete response to durvalumab and tremelimumab. This patient then developed multiple non-invasive papillary bladder tumours. Next-generation sequencing revealed that the tumours shared ancestry with the upper tract cancer, although there were key differences, most notably the presence of a missense mutation in the upper tract disease that was absent in the bladder tumours. This illustrates an important practice point in the management of exceptional responders to checkpoint inhibitors.
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http://dx.doi.org/10.1016/j.eucr.2021.101762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254020PMC
November 2021

The Rapidly Evolving Landscape of First-Line Targeted Therapy in Metastatic Urothelial Cancer: A Systematic Review.

Oncologist 2021 Aug 11;26(8):e1381-e1394. Epub 2021 Jun 11.

Medical Oncology, BC Cancer - Vancouver, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Metastatic urothelial carcinoma (mUC) historically is treated with first-line platinum-based combination chemotherapy, preferably cisplatin plus gemcitabine whenever possible. In recent years, multiple classes of targeted therapy have demonstrated benefit, with some receiving approval in mUC. This review will summarize phase III efficacy and safety data for targeted agents, principally immune checkpoint inhibitors (ICIs), as either first-line or first-line switch-maintenance therapy for mUC and interpret these findings in the context of the current treatment landscape.

Materials And Methods: Published and presented phase III data on targeted therapy for the first-line or first-line switch-maintenance treatment of mUC were identified using the key search terms "targeted therapy" AND "urothelial carcinoma" AND "advanced" OR respective aliases according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results: Of the six eligible phase III targeted therapy trials, two assessing ICIs met their primary endpoints in platinum-eligible patients. First-line ICI plus chemotherapy combinations have not improved overall survival (OS), although final OS results of the IMVigor 130 trial are pending. Switch-maintenance using an ICI in patients achieving at least stable disease following platinum-based chemotherapy statistically significantly improved OS (21.4 vs. 14.3 months, hazard ratio, 0.69; 95% confidence interval, 0.56-0.86; p = .001). Current sequencing options for mUC include first-line platinum-based chemotherapy with a switch to ICI either immediately or upon disease progression.

Conclusion: Recent targeted therapy trials have expanded ICI sequencing options for mUC. The treatment landscape is likely to evolve rapidly, with results from multiple phase III trials expected in the next 5 years.

Implications For Practice: Multiple classes of targeted agents are approved for use in metastatic urothelial carcinoma (mUC). Six phase III trials have recently provided insight on the benefit of these agents in the first-line setting. In platinum-eligible patients, immune checkpoint inhibitors (ICIs) combined with first-line platinum-based chemotherapy failed to demonstrate improved survival, although ICI monotherapy as switch-maintenance significantly improved overall survival in patients with mUC who had achieved at least stable disease following first-line platinum-based chemotherapy. In patients ineligible for any chemotherapy, pembrolizumab, atezolizumab, or pembrolizumab in combination with enfortumab vedotin may be options.
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http://dx.doi.org/10.1002/onco.13827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342568PMC
August 2021

Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer.

Nat Commun 2021 01 8;12(1):184. Epub 2021 Jan 8.

Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.

Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
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http://dx.doi.org/10.1038/s41467-020-20493-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794518PMC
January 2021

Integrated Expression of Circulating miR375 and miR371 to Identify Teratoma and Active Germ Cell Malignancy Components in Malignant Germ Cell Tumors.

Eur Urol 2021 01 4;79(1):16-19. Epub 2020 Nov 4.

Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ cell tumor patients, divided into two cohorts, were enrolled in a prospective multi-institutional study. In the discovery cohort, patients with pure teratoma and with no/low risk of harboring teratoma were compared; the validation cohort included patients with confirmed teratoma, active germ cell malignancy, or complete response after chemotherapy. The area under the receiver operating characteristic curve values for miR375, miR371, and miR371-miR375 were, respectively, 0.93 (95% confidence interval [CI]: 0.87-0.99), 0.59 (95% CI: 0.44-0.73), and 0.95 (95% CI: 0.90-0.99) in the discovery cohort and 0.55 (95% CI: 0.36-0.74), 0.74 (95% CI: 0.58-0.91), and 0.77 (95% CI: 0.62-0.93) in the validation cohort. Our study demonstrated that the plasma miR371-miR375 integrated evaluation is highly accurate to detect teratoma. PATIENT SUMMARY: The evaluation of two micro-RNAs (miR375-miR371) in the blood of patients with germ cell tumors is promising to predict teratoma. This test could be particularly relevant to the identification of teratoma in patients with postchemotherapy residual disease.
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http://dx.doi.org/10.1016/j.eururo.2020.10.024DOI Listing
January 2021

Genome and Transcriptome Biomarkers of Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors.

Clin Cancer Res 2021 01 5;27(1):202-212. Epub 2020 Oct 5.

Department of Medical Oncology, BC Cancer, Vancouver, British Columbia, Canada.

Purpose: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of solid tumors with dramatic and durable responses seen across multiple tumor types. However, identifying patients who will respond to these drugs remains challenging, particularly in the context of advanced and previously treated cancers.

Experimental Design: We characterized fresh tumor biopsies from a heterogeneous pan-cancer cohort of 98 patients with metastatic predominantly pretreated disease through the Personalized OncoGenomics program at BC Cancer (Vancouver, Canada) using whole genome and transcriptome analysis (WGTA). Baseline characteristics and follow-up data were collected retrospectively.

Results: We found that tumor mutation burden, independent of mismatch repair status, was the most predictive marker of time to progression ( = 0.007), but immune-related CD8 T-cell and M1-M2 macrophage ratio scores were more predictive for overall survival (OS; = 0.0014 and 0.0012, respectively). While [programmed death-ligand 1 (PD-L1)] gene expression is comparable with protein levels detected by IHC, we did not observe a clinical benefit for patients with this marker. We demonstrate that a combination of markers based on WGTA provides the best stratification of patients ( = 0.00071, OS), and also present a case study of possible acquired resistance to pembrolizumab in a patient with non-small cell lung cancer.

Conclusions: Interpreting the tumor-immune interface to predict ICI efficacy remains challenging. WGTA allows for identification of multiple biomarkers simultaneously that in combination may help to identify responders, particularly in the context of a heterogeneous population of advanced and previously treated cancers, thus precluding tumor type-specific testing.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1163DOI Listing
January 2021

Clinical characteristics and outcomes for young patients with advanced urothelial carcinoma.

Can Urol Assoc J 2021 Feb;15(2):E123-E126

Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada.

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http://dx.doi.org/10.5489/cuaj.6405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864708PMC
February 2021

Plasma Circulating Tumor DNA and Clonal Hematopoiesis in Metastatic Renal Cell Carcinoma.

Clin Genitourin Cancer 2020 08 8;18(4):322-331.e2. Epub 2020 Jan 8.

Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, British Columbia, Canada; Department of Medical Oncology, BC Cancer, British Columbia, Canada.

Background: There is a lack of molecularly-informed biomarkers for patients with metastatic renal cell carcinoma (RCC). Plasma cell-free DNA (cfDNA) sequencing is a minimally-invasive alternative to tissue for profiling the genome in other cancers but relevance in metastatic RCC remains unclear.

Materials And Methods: Whole blood was collected from 55 patients with metastatic RCC. Plasma cfDNA and leukocyte DNA were subjected to targeted sequencing across 981 cancer genes. Matched tumor tissue from 14 patients was analyzed.

Results: Thirty-three percent of patients had evidence for RCC-derived circulating tumor DNA (ctDNA), significantly lower than patients with metastatic prostate or bladder cancer analyzed using the same approach. Among ctDNA-positive patients, ctDNA fraction averaged only 3.9% and showed no strong association with clinical variables. In these patients, the most commonly mutated genes were VHL, BAP1, and PBRM1, and matched tissue concordance was 77%. Evidence of somatic expansions unrelated to RCC, such as clonal hematopoiesis of indeterminate potential, were detected in 43% of patients. Pathogenic germline mutations in DNA repair genes were detected in 11% of patients. CtDNA-positive patients had shorter overall survival and progression-free survival on first-line therapy. Patients with evidence of clonal hematopoiesis of indeterminate potential had an intermediate prognosis compared with ctDNA-positive and -negative patients.

Conclusions: CfDNA sequencing enables straightforward characterization of the somatic RCC genome in a minority of patients with metastatic RCC. Owing to low ctDNA abundance, and the presence of non-RCC derived somatic clones in circulation, cfDNA sequencing may not be a simple pan-patient alternative to tissue biopsy in metastatic RCC.
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http://dx.doi.org/10.1016/j.clgc.2019.12.018DOI Listing
August 2020

Patient selection for a developmental therapeutics program using whole genome and Transcriptome analysis.

Invest New Drugs 2020 10 6;38(5):1601-1604. Epub 2020 Jan 6.

Department of Medical Oncology, BC Cancer, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6, Canada.

Introduction Given the high level of uncertainty surrounding the outcomes of early phase clinical trials, whole genome and transcriptome analysis (WGTA) can be used to optimize patient selection and study assignment. In this retrospective analysis, we reviewed the impact of this approach on one such program. Methods Patients with advanced malignancies underwent fresh tumor biopsies as part of our personalized medicine program (NCT02155621). Tumour molecular data were reviewed for potentially clinically actionable findings and patients were referred to the developmental therapeutics program. Outcomes were reviewed in all patients, including those where trial selection was driven by molecular data (matched) and those where there was no clear molecular rationale (unmatched). Results From January 2014 to January 2018, 28 patients underwent WGTA and enrolled in clinical trials, including 2 patients enrolled in two trials. Fifteen patients were matched to a treatment based on a molecular target. Five patients were matched to a trial based upon single-gene DNA changes, all supported by RNA data. Ten cases were matched on the basis of genome-wide data (n = 4) or RNA gene expression only (n = 6). With a median follow-up of 6.7 months, the median time on treatment was 8.2 weeks. Discussion When compared to single-gene DNA-based data alone, WGTA led to a 3-fold increase in treatment matching. In a setting where there is a high level of uncertainty around both the investigational agents and the biomarkers, more data are needed to fully evaluate the impact of routine use of WGTA.
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http://dx.doi.org/10.1007/s10637-020-00892-8DOI Listing
October 2020

Seminoma presenting as a solitary metastasis in gastric mucosa with regressed testicular mass.

Urol Case Rep 2020 Mar 3;29:101083. Epub 2019 Dec 3.

Department of Pathology, BC Cancer Vancouver Centre, Vancouver, BC, Canada.

Gastric involvement by seminoma is extremely rare and all the reported cases were associated with bulky retroperitoneal disease or occurred late as part of advanced disease. We report a unique case of seminoma presenting as gastric mucosal metastasis. The diagnosis of this case was complicated by no residual testicular tumor or pelvic/retroperitoneal lymph nodes metastasis and no available specific serum markers. The histological morphology and immunostains allowed the correct diagnosis to be made in this case. This case highlights the rare manifestation of seminoma, which appears to be a primary tumor of an unusual site of germ cell tumor metastasis.
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http://dx.doi.org/10.1016/j.eucr.2019.101083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911888PMC
March 2020

Developing a Highly Specific Biomarker for Germ Cell Malignancies: Plasma miR371 Expression Across the Germ Cell Malignancy Spectrum.

J Clin Oncol 2019 11 25;37(33):3090-3098. Epub 2019 Sep 25.

BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, British Columbia, Canada.

Purpose: Our objective was to evaluate operating characteristics, particularly specificity and positive predictive value (PPV), by mapping plasma miR371 expression to actual clinical events in patients with a history of germ cell tumor.

Patients And Methods: One hundred eleven male patients with a history of or newly diagnosed germ cell tumors were evaluable. Biospecimens obtained before confirmed clinical events were analyzed for miR371 expression with blinding of providers and laboratory personnel to analytic results or clinical status, respectively. Cases (patients with clinically confirmed active germ cell malignancy [aGCM]) and controls (patients with no clinically confirmed aGCM) were assigned over the course of the management. Patients were assigned risk status (high, low, or moderate) based on the composite clinical picture at time points in management.

Results: Considering all cases and controls and results of prospectively obtained biosamples analyzed for miR371 expression, 46 (35%) of 132 samples had clinically confirmed aGCM over the course of management; 44 (96%) of these 46 patients had plasma miR371 expression (true positives) with no false positives. Two (4%) of 46 patients had no miRNA expression despite pathologic confirmation of aGCM (false negatives). Plasma miR371 expression in confirmed aGCM had a specificity, sensitivity, positive predictive value, and negative predictive value of 100%, 96%, 100%, and 98%, respectively. Interpretation of sensitivity and negative predictive value is limited by modest follow-up. Specificity and sensitivity were 100% and 98%, 100% and 92%, and 100% and 97% in the low-, moderate-, and high-risk groups, respectively, with a median follow-up time of 15 months.

Conclusion: Plasma miR371 expression predicts aGCM with high specificity and positive predictive value. Although other operating characteristics of miR371 await longer follow-up for more complete definition, the findings of a highly specific liquid biopsy strongly support moving forward with large-scale, real-world clinical trials to further define full operating characteristics and to identify clinical utility and areas of patient benefit.
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http://dx.doi.org/10.1200/JCO.18.02057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351323PMC
November 2019

Ethanol production from residual lignocellulosic fibers generated through the steam treatment of whole sorghum biomass.

Bioresour Technol 2019 Nov 9;292:121975. Epub 2019 Aug 9.

Biomass Technology Laboratory (BTL), Department of Chemical Engineering and Biotechnological Engineering, University of Sherbrooke, QC, Canada. Electronic address:

Cellulosic ethanol could play a major role in the upcoming circular-economy once the process complexity, low carbohydrate extraction yields and high costs are resolved. To this purpose, different steam-treatment severity factors were employed on whole sweet sorghum biomass, followed by the delignification and hydrolysis of resulted lignocellulose fibers. A modified ASTM International (American Society for Testing and Material) standard cellulose hydrolysis approach as well as a newly developed SACH (Sulfuric Acid Cellulose Hydrolysis) process were used, recovering up to 24.3 wt% of cellulosic carbohydrates. This amounted to a total extractable and constitutive carbohydrate recovery of 51.7 wt% (dry basis) when a mild steam-treatment of whole sorghum biomass and the SACH cellulose hydrolysis were employed. An ethanol potential of 6378 L/ha/year was determined, comparable to values obtained from biomass such as sugarcane in warmer climates, supporting thus the opportunity of implementing this novel approach on a wider scale.
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http://dx.doi.org/10.1016/j.biortech.2019.121975DOI Listing
November 2019

Current Management of Disseminated Germ Cell Tumors.

Urol Clin North Am 2019 Aug 21;46(3):377-388. Epub 2019 May 21.

Division of Medical Oncology, Department of Medicine, BC Cancer--Vancouver Cancer Center, University of British Columbia, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. Electronic address:

The modern treatment of disseminated germ cell tumors (GCT) relies largely on cisplatin-based regimens, particularly combination chemotherapy with bleomycin, etoposide, and cisplatin. This article reviews the evidence supporting its use as well as common alterations based on prognostic grouping or contraindications to bleomycin. Special topics around the management of intermediate/poor prognosis choriocarcinoma and brain metastases are included. The management of residual masses for both seminoma and nonseminoma is discussed as well as long-term follow-up care of patients. Finally, the management of relapsed disseminated GCT is addressed.
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http://dx.doi.org/10.1016/j.ucl.2019.04.003DOI Listing
August 2019

Recent Advances in Power-to-X Technology for the Production of Fuels and Chemicals.

Front Chem 2019 5;7:392. Epub 2019 Jun 5.

Biomass Technology Laboratory (BTL), Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, QC, Canada.

Environmental issues related to greenhouse gas emissions are progressively pushing the transition toward fossil-free energy scenario, in which renewable energies such as solar and wind power will unavoidably play a key role. However, for this transition to succeed, significant issues related to renewable energy storage have to be addressed. Power-to-X (PtX) technologies have gained increased attention since they actually convert renewable electricity to chemicals and fuels that can be more easily stored and transported. H production through water electrolysis is a promising approach since it leads to the production of a sustainable fuel that can be used directly in hydrogen fuel cells or to reduce carbon dioxide (CO) in chemicals and fuels compatible with the existing infrastructure for production and transportation. CO electrochemical reduction is also an interesting approach, allowing the direct conversion of CO into value-added products using renewable electricity. In this review, attention will be given to technologies for sustainable H production, focusing on water electrolysis using renewable energy as well as on its remaining challenges for large scale production and integration with other technologies. Furthermore, recent advances on PtX technologies for the production of key chemicals (formic acid, formaldehyde, methanol and methane) and fuels (gasoline, diesel and jet fuel) will also be discussed with focus on two main pathways: CO hydrogenation and CO electrochemical reduction.
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http://dx.doi.org/10.3389/fchem.2019.00392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560054PMC
June 2019

Predictive Biomarkers for Checkpoint Blockade in Urothelial Cancer: A Systematic Review.

J Urol 2019 07 7;202(1):49-56. Epub 2019 Jun 7.

Department of Medical Oncology, British Columbia Cancer Agency , Vancouver , British Columbia , Canada.

Purpose: Immune checkpoint inhibitors have had a major impact on the management of advanced urothelial cancer. Despite the impact only a minority of patients derive benefit. In this context predictive biomarkers which can assist in patient selection are needed. In this systematic review we surveyed the current biomarkers which have been investigated in clinical studies and their potential for patient selection.

Materials And Methods: We searched MEDLINE® and EMBASE®, and manually reviewed major meeting abstracts to find studies in humans of immune checkpoint inhibitors given for urothelial cancer that included biomarkers and clinical outcomes. Studies had to provide the correlation between biomarkers and outcomes to be included in analysis. Results published only in abstract form were included since several important biomarker studies have yet to be published.

Results: We retrieved 1,236 studies, of which 921 were unique and screened, including 144 which met criteria for full review and 25 were included in the analysis. The manual search yielded 1 additional entry not included in our systematic review for a total of 26 entries. The checkpoint inhibitors used in these studies included atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab. The biomarkers tested included PD-L1 immunohistochemistry, molecular subtyping and immune gene expression analysis by RNA sequencing, targeted gene panels for mutations in DNA damage repair genes and estimation of the tumor mutational burden, genomic alterations and the total mutational burden by exome sequencing, analysis of tumor immune infiltrate by immunohistochemistry and T-cell receptor sequencing, and analysis of circulating immune cells and cytokines.

Conclusions: No single biomarker has been able to accurately predict the response to immune checkpoint inhibitors. Most studies included only a treatment arm and without a comparator arm it is not possible to ascertain whether biomarkers are predictive or merely prognostic. While PD-L1 immunohistochemistry has been largely unsuccessful, other biomarkers reflecting the immunogenicity of the underlying tumor, the characteristics of the immune infiltrate and the properties of the patient immune system have shown promising data. However, all are in need of validation.
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http://dx.doi.org/10.1097/JU.0000000000000136DOI Listing
July 2019

Whole-genome and transcriptome profiling of a metastatic thyroid-like follicular renal cell carcinoma.

Cold Spring Harb Mol Case Stud 2018 12 17;4(6). Epub 2018 Dec 17.

Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 4S6, Canada.

Thyroid-like follicular renal cell carcinoma (TLFRCC) is a rare cancer with few reports of metastatic disease. Little is known regarding genomic characteristics and therapeutic targets. We present the clinical, pathologic, genomic, and transcriptomic analyses of a case of a 27-yr-old male with TLFRCC who presented initially with bone metastases of unknown primary. Genomic DNA from peripheral blood and metastatic tumor samples were sequenced. A transcriptome of 280 million sequence reads was generated from the same tumor sample. Tumor somatic expression profiles were analyzed to detect aberrant expression. Genomic and transcriptomic data sets were integrated to reveal dysregulation in pathways and identify potential therapeutic targets. Integrative genomic analysis with The Cancer Genome Atlas (TCGA) data set revealed the following outliers in gene expression profiles: (81st percentile), (99th percentile), (100th percentile), and (99th and 100th percentiles, respectively), and (86th percentile). The patient received first-line sunitinib to target PDGFRA and PDGFRB and had stable disease for >6 mo, followed by nivolumab upon progression. To the authors' knowledge, this is the first reported case of comprehensive somatic genomic analyses in a patient with metastatic TLFRCC. Somatic analyses provided molecular confirmation of the primary site of cancer and potential therapeutic strategies in a rare disease with little evidence of efficacy on systemic therapy.
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http://dx.doi.org/10.1101/mcs.a003137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318773PMC
December 2018

Clinical effectiveness of docetaxel for castration-sensitive prostate cancer in a real-world population-based analysis.

Prostate 2019 02 28;79(3):281-287. Epub 2018 Oct 28.

Division of Medical Oncology, University of British Columbia, BC Cancer, Vancouver, British Columbia.

Background: Adding docetaxel to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) has known efficacy, with an overall survival benefit in Phase III clinical trials. The effectiveness of docetaxel with ADT in the general patient population remains undefined.

Patients And Methods: We conducted a population-based retrospective review using the British Columbia Provincial Pharmacy Database. To be included, patients had to have castration-sensitive prostate cancer not previously treated (except in the adjuvant setting) and have received at least one cycle of docetaxel, with complete records available for review. Safety and clinical effectiveness were evaluated.

Results: From April 2015 to February 2017, we identified 183 cases; 156 met inclusion criteria. Most patients had high-volume disease (80%). All 6 planned docetaxel cycles were delivered in 126 cases (81%). Dose reductions and delays were required in 39% and 16% of cases. Grade 3-4 adverse events were noted in 40%, with no treatment-related deaths. The rate of febrile neutropenia was 18% and was significantly associated with the presence of high-volume disease (P = 0.038). PSA ≤ 0.2 ng/L was achieved in 27% of patients after 6 months of ADT and maintained in 16% after 12 months. Patients with over 20 bone metastases had worse time to castration resistant prostate cancer (CRPC) and time to treatment for CRPC, and a trend toward worse overall survival. CRPC developed in 41% within 1 year, with a median time to CRPC of 14.4 months. Treatment for CRPC was given in 84 cases, with 90% receiving either abiraterone or enzalutamide in the first-line, with a PSA decline ≥50% occurring in 47%.

Conclusions: The effectiveness of docetaxel with ADT in a general population of patients with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the published studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to reported outcomes.
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http://dx.doi.org/10.1002/pros.23733DOI Listing
February 2019

High-efficiency second generation ethanol from the hemicellulosic fraction of softwood chips mixed with construction and demolition residues.

Bioresour Technol 2018 Oct 20;266:421-430. Epub 2018 Jun 20.

Departement of Chemical Engineering and Biotechnological Engineering, University of Sherbrooke, Sherbrooke, Québec, Canada. Electronic address:

Using lignocellulosic residues for bioethanol production could provide an alternative solution to current approaches at competitive costs once challenges related to substrate recalcitrance, process complexity and limited knowledge are overcome. Thus, the impact of different process variables on the ethanol production by Saccharomyces cerevisiae using the hemicellulosic fraction extracted through the steam-treatment of softwood chips mixed with construction and demolition residues was assessed. A statistical design of experiments approach was developed and implemented in order to identify the influencing factors (various nutrient addition sources as well as yeast inoculum growth conditions and inoculation strategies) relevant for enhancing the ethanol production potential and substrate uptake. Ethanol yields of 74.12% and monomeric sugar uptakes of 82.12 g/L were predicted and experimentally confirmed in bench and bioreactor systems. This innovative approach revealed the factors impacting the ethanol yields and carbohydrate consumption allowing powerful behavioral predictions spanning different process inputs and outputs.
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http://dx.doi.org/10.1016/j.biortech.2018.06.056DOI Listing
October 2018

Two-Step Thermochemical Cellulose Hydrolysis With Partial Neutralization for Glucose Production.

Front Chem 2018 24;6:117. Epub 2018 Apr 24.

Industrial Research Chair on Cellulosic Ethanol and Biocommodities, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, QC, Canada.

Cellulose hydrolysis processes using concentrated acid usually involve two steps in order to obtain high glucose yields. The first step (pre-treatment) decrystallizes cellulose while the second step (post-hydrolysis) converts the amorphous cellulose to glucose. The two-step process developed by the Industrial Research Chair on Cellulosic Ethanol and Biocommodities and its industrial partner CRB Innovations Inc., includes an intermediate partial neutralization step, whose purpose is to decrease the amount of dilution water to be added for post-hydrolysis thus minimizing handling costs. In this work, the effect of several operating parameters on the glucose yield of this process was investigated using triticale cellulose and the best conditions yielding fermentable glucose (close to 100%) were determined. These conditions involve pre-treating cellulose at 30°C using 72 wt% HSO with a HSO/dry cellulose mass ratio of 36 over 2 h, followed by a partial neutralization using 20 wt% NaOH at an H/OH molar ratio of 2.3-2.5 and a post-hydrolysis at 121°C for 10 min. Influence of operating parameters on the glucose yield have been investigated.Conditions for producing cellulosic glucose with yields close to 100% have been identified.
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http://dx.doi.org/10.3389/fchem.2018.00117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928260PMC
April 2018

A novel hybrid first and second generation hemicellulosic bioethanol production process through steam treatment of dried sorghum biomass.

Bioresour Technol 2018 Sep 13;263:103-111. Epub 2018 Apr 13.

Industrial Research Chair on Cellulosic Ethanol and Biocommodities (CRIEC-B), Département de Génie Chimique et de Génie Biotechnologique, Université de Sherbrooke, Québec, Canada. Electronic address:

Sweet sorghum was subjected to an impregnation step, which recovered most of the 1st generation sugars, prior to a steam-treatment extraction of the 2nd generation sugars, at three different severity factors (SF). A medium severity (3.56 SF) treatment proved to be an optimal compromise between the amount of sugars extracted and the fermentation inhibitors generated following the subsequent depolymerization approaches applied on the broth. Next, a series of detoxification approaches (ozonation, overliming and a combination of both) were investigated following a concentration and depolymerization step. Results show that higher steam-treatment severity required more intense detoxification steps. However, when combining the 1st and 2nd generation streams at a 2:1 ratio, the inhibitors did not affect the fermentation process and ethanol yields above 90% of the theoretical maximum were achieved.
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http://dx.doi.org/10.1016/j.biortech.2018.04.045DOI Listing
September 2018

CFD Simulations of an Air-Water Bubble Column: Effect of Luo Coalescence Parameter and Breakup Kernels.

Front Chem 2017 21;5:68. Epub 2017 Sep 21.

Industrial Research Chair on Cellulosic Ethanol and Biocommodities, University of SherbrookeSherbrooke, QC, Canada.

In this work, CFD simulations of an air-water bubbling column were performed and validated with experimental data. The superficial gas velocities used for the experiments were 0.019 and 0.038 m/s and were considered as an homogeneous regime. The former involves simpler physics when compared to a heterogeneous regime where the superficial velocities are higher. In order to simulate the system, a population balance model (PBM) was solved numerically using a discrete method and a closure kernels involving the Luo coalescence model as well as two different breakup models: Luo's and Lehr's. For the multi-phase calculations, an eulerian framework was selected and the interphase momentum transfer included drag, lift, wall lubrication, and turbulent dispersion terms. A sensitivity analysis was performed on a Luo coalescence kernel by changing the coalescence parameter () from 1.1 to 0.1 and results showed that the radial profiles of gas holdup and axial liquid velocity were significantly affected by such parameter. From the simulation results, the main conclusions were: (a) A combination of the Luo coalescence and Luo breakup kernels (Luo-Luo) combined with a decreasing value of improves the gas holdup profiles as compared to empirical values. However, at the lowest value of investigated in this work, the axial liquid velocity deteriorates with regards to experimental data when using a superficial gas velocity of 0.019 m/s. (b) A combination of the Luo coalescence and Lehr breakup models (Luo-Lehr) was shown to improve the gas holdup values with experimental data when compared to the Luo-Luo kernels. However, as decreases, the Luo-Lehr models underestimate the axial liquid velocity profiles with regards to empirical values. (c) A first and second order numerical schemes allowed predicting similar radial profiles of gas holdup and axial liquid velocity. (d) The mesh sensitivity results show that a 3 mm mesh size can be considered as reasonable for simulating experimental data. (e) The inclusion of wall lubrication parameter was found to be significant, although only when using finer meshing. In addition, it allows an improvement of the axial liquid velocity at the core of the bubble column.
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http://dx.doi.org/10.3389/fchem.2017.00068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613131PMC
September 2017

A two-step optimization strategy for 2nd generation ethanol production using softwood hemicellulosic hydrolysate as fermentation substrate.

Bioresour Technol 2017 Nov 29;244(Pt 1):708-716. Epub 2017 Jul 29.

Department of Chemical Engineering and Biotechnology Engineering, Université de Sherbrooke, Sherbrooke, Québec, Canada. Electronic address:

Ethanol production using waste biomass represents a very attractive approach. However, there are considerable challenges preventing a wide distribution of these novel technologies. Thus, a fractional-factorial screening of process variables and Saccharomyces cerevisiae yeast inoculum conditions was performed using a synthetic fermentation media. Subsequently, a response-surface methodology was developed for maximizing ethanol yields using a hemicellulosic solution generated through the chemical hydrolysis of steam treatment broth obtained from residual softwood biomass. In addition, nutrient supplementation using starch-based ethanol production by-products was investigated. An ethanol yield of 74.27% of the theoretical maximum was observed for an initial concentration of 65.17g/L total monomeric sugars. The two-step experimental strategy used in this work represents the first successful attempt to developed and use a model to make predictions regarding the optimal ethanol production using both softwood feedstock residues as well as 1st generation ethanol production by-products.
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http://dx.doi.org/10.1016/j.biortech.2017.07.107DOI Listing
November 2017

Sensitivity Analysis and Accuracy of a CFD-TFM Approach to Bubbling Bed Using Pressure Drop Fluctuations.

Front Bioeng Biotechnol 2017 24;5:38. Epub 2017 Jun 24.

Department of Chemical Engineering and Biotechnology, University of Sherbrooke, Sherbrooke, QC, Canada.

Based upon the two fluid model (TFM) theory, a CFD model was implemented to investigate a cold multiphase-fluidized bubbling bed reactor. The key variable used to characterize the fluid dynamic of the experimental system, and compare it to model predictions, was the time-pressure drop induced by the bubble motion across the bed. This time signal was then processed to obtain the power spectral density (PSD) distribution of pressure fluctuations. As an important aspect of this work, the effect of the sampling time scale on the empirical power spectral density (PSD) was investigated. A time scale of 40 s was found to be a good compromise ensuring both simulation performance and numerical validation consistency. The CFD model was first numerically verified by mesh refinement process, after what it was used to investigate the sensitivity with regards to minimum fluidization velocity (as a calibration point for drag law), restitution coefficient, and solid pressure term while assessing his accuracy in matching the empirical PSD. The 2D model provided a fair match with the empirical time-averaged pressure drop, the relating fluctuations amplitude, and the signal's energy computed as integral of the PSD. A 3D version of the TFM was also used and it improved the match with the empirical PSD in the very first part of the frequency spectrum.
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http://dx.doi.org/10.3389/fbioe.2017.00038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483033PMC
June 2017

Getting under the skin.

Eur J Cancer 2017 09 4;82:228-229. Epub 2017 Jun 4.

BC Cancer Agency, Medical Oncology, 600 West 10th Avenue, Vancouver, BC, V5Z4E6, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2017.04.028DOI Listing
September 2017

Structural changes of Salix miyabeana cellulose fibres during dilute-acid steam explosion: impact of reaction temperature and retention time.

Carbohydr Polym 2015 Mar 20;119:8-17. Epub 2014 Nov 20.

Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, 2500 Boulevard de l'Université, J1K 2R1 Sherbrooke, Québec, Canada. Electronic address:

Dilute-acid steam explosion of Salix miyabeana has been carried out to understand the effect of processing conditions, expressed through a severity factors (SFT), on the changes in cellulose fibre structures in a perspective of using these in polymer composites. This thermo-chemico-mechanical extraction leads to the isolation of cellulose fibres as observed by SEM images. Fibre length as well as length to diameter aspect ratios decreased with the severity of the treatment. Likewise, fibre whiteness diminished with an increasing severity factor, which could be a tangible effect of physical degradation. Variations in crystallinity seemed to be dependent upon the reaction temperature, generally decreasing with regards to retention time. Above a severity threshold, a structural disorganization was observed. Overall, dilute-acid steam explosion was shown to be a valuable cellulose extraction process that can provide a variety of fibre structures.
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http://dx.doi.org/10.1016/j.carbpol.2014.11.031DOI Listing
March 2015

Review on dry reforming of methane, a potentially more environmentally-friendly approach to the increasing natural gas exploitation.

Front Chem 2014 11;2:81. Epub 2014 Nov 11.

Département de Génie Chimique et de Génie Biotechnologique, Faculté de Génie, Université de Sherbrooke Sherbrooke, QC, Canada.

With the actual growth of the natural gas industry in the US as well as the potential and availability of this non-renewable carbon source worldwide, reforming of methane gas is getting increasing attention. Methane can be used for the production of heat or electricity, as well, it can be converted to syngas, a building block that could lead to the production of liquid fuels and chemicals, a very promising pathway in light of the increasing price of oil. Amongst the different reforming techniques, dry reforming could represent a very interesting approach both to valorize a cheap source or carbon (CO2) as well as to reduce the overall carbon footprint of the increasing worldwide fossil-based methane consumption. In this short review, attention will be given to the thermodynamics of dry reforming followed by an investigation on dry reforming using heterogeneous catalyst by focusing on the most popular elements used in literature for dry reforming. Attention will as well be given to other emerging techniques that may allow countering at one point the high thermodynamic penalties that accompanies conversion of methane using carbon dioxide.
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http://dx.doi.org/10.3389/fchem.2014.00081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227528PMC
November 2014

Lignin extraction--reassessment of the severity factor with respect to hydroxide concentration.

Bioresour Technol 2014 Oct 17;169:707-712. Epub 2014 Jul 17.

Industrial Research Chair on Cellulosic Ethanol, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada. Electronic address:

Steam processes have often been associated with a severity factor, correlating the cooking temperature, time and catalyst used in the process. Although equations for treatments with and without acid catalyst have been suggested, there is so far no simple equation allowing a precise estimation of the amount of lignin extracted from lignocellulosic biomass. In this work, a new version of the severity factor equation is proposed. This has been shown to correlate effectively to the amount of lignin extracted from various types of lignocellulosic materials and different extraction methods. The resulting severity factor is robust with potential to be utilized both for acid and base-catalyzed extraction of lignin. Finally, the proposed correlation between the severity factor and extracted lignin under base conditions has been correlated with empirical data to validate the entire model and especially under mild condition where lesser information was available from open literature.
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http://dx.doi.org/10.1016/j.biortech.2014.07.038DOI Listing
October 2014

UV-Vis as quantification tool for solubilized lignin following a single-shot steam process.

Bioresour Technol 2013 Sep 20;144:658-63. Epub 2013 Jun 20.

Industrial Research Chair on Cellulosic Ethanol, Departement of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, Québec, Canada.

In this short communication, UV/Vis was used as an analytical tool for the quantification of lignin concentrations in aqueous mediums. A significant correlation was determined between absorbance and concentration of lignin in solution. For this study, lignin was produced from different types of biomasses (willow, aspen, softwood, canary grass and hemp) using steam processes. Quantification was performed at 212, 225, 237, 270, 280 and 287 nm. UV-Vis quantification of lignin was found suitable for different types of biomass making this a timesaving analytical system that could lead to uses as Process Analytical Tool (PAT) in biorefineries utilizing steam processes or comparable approaches.
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http://dx.doi.org/10.1016/j.biortech.2013.06.045DOI Listing
September 2013

Dry reforming of methane with CO2 on an electron-activated iron catalytic bed.

Bioresour Technol 2011 Dec 25;102(24):11244-8. Epub 2011 Sep 25.

Institut de Recherche d'Hydro-Québec, Laboratoire des technologies de l'énergie (LTE), 600 de la Montagne Avenue, Shawinigan, Quebec, Canada.

A preliminary experimental investigation of dry reforming of methane with carbon dioxide, that has been performed on an iron bed activated with an electric current is reported. Operating conditions for the reaction included temperature ranging from 700 to 800° C and pressure close to 1 atm. The reaction, involving an excess of pure methane and carbon dioxide, was performed with and without addition of water vapour, provided by hot water saturation of the gaseous feed. According to syngas compositions, the electron flow has a dramatic effect on the conversion of both methane and carbon dioxide. It was shown also that hot water saturation of the CO(2) and CH(4) mixture allowed very good conversion, giving a syngas with a composition very close to what was expected from equilibrium calculations.
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http://dx.doi.org/10.1016/j.biortech.2011.09.088DOI Listing
December 2011

Depolymerization of steam-treated lignin for the production of green chemicals.

Bioresour Technol 2011 Apr 13;102(7):4917-20. Epub 2011 Jan 13.

Departement of Chemical Engineering, Université de Sherbrooke, Sherbrooke, Québec, Canada J1K 2R1.

In this short communication, lignin produced by steam processing of agricultural (hemp) and forestry (softwood) was depolymerised via a base catalysis to produce a combination of monomers, dimers, trimers and residual char. The lignin broth produced directly after the base-catalysed steam treatment was treated under pressure (from 1300 to 1900 psi) at temperatures varying from 300 to 330 °C in a custom-made batch reactor. The lignin concentration in the aqueous base solution was 10 wt% whilst the NaOH concentration was 5 wt%. Identification of 26 compounds has been done: 17 compounds were common to the two feedstocks while the remaining 9 were specific to each feedstock used.
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http://dx.doi.org/10.1016/j.biortech.2011.01.010DOI Listing
April 2011
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