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1. Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial

Author: Christopher O’Callaghan, Scott Berry, Petr Kavan, Jonathan M Loree, Felix Couture, Dongsheng Tu, Sheryl Koski, Lucy X Ma, Emma Titmuss, Derek J Jonker, Hagen F Kennecke, Chaudhary E Ahmad, John R Goffin, Mohammed Harb, Bruce Colwell, Setareh Samimi, Benoit Samson, Tahir Abbas, Nathalie Aucoin, Francine Aubin, and Eric X Chen
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background Nutritional stress is a mechanism that allows tumor cells to evade the immune system. Arginine (ARG), an amino acid involved in immunomodulation, aids in regulating T-lymphocyte cell activity and the antitumor response. ARG deficiency in the tumor microenvironment can impair T-cell response while ARG supplementation may promote antitumor immune activity. In this exploratory post hoc analysis of the randomized phase II CO.26 trial, we investigated the role of plasma ARG in predicting response to immune checkpoint inhibitors (ICI) in patients with microsatellite stable refractory metastatic colorectal cancer (mCRC).Methods CO.26 randomized patients with refractory mCRC to durvalumab plus tremelimumab (D+T) versus best supportive care (BSC). Plasma ARG concentrations were determined from pretreatment blood samples using high-performance liquid chromatography-tandem mass spectrometry. The median plasma ARG value was used as a cut-off stratifying patients into ARG-high (≥10 700 ng/mL) versus ARG-low (
Published: 2024
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2. Feasibility and safety of endoscopic ultrasound-guided diffusing alpha emitter radiation therapy for advanced pancreatic cancer: Preliminary data

Author: Corey S Miller, Magali Lecavalier-Barsoum, Kim Ma, Miriam Santos Dutra, Youri Kaitoukov, Boris Bahoric, Nada Tomic, Francine Dinelle, Shirin Enger, Gerald Batist, Stephen Yang, Donald Laporta, Petr Kavan, Anand Sahai, David Roberge, and David Donath
Subjects: Endoscopic ultrasonography, Pancreas, Intervention EUS, Diseases of the digestive system. Gastroenterology, RC799-869
Published: 2024
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3. The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma

Author: Daniel J. Renouf, Jonathan M. Loree, Jennifer J. Knox, James T. Topham, Petr Kavan, Derek Jonker, Stephen Welch, Felix Couture, Frederic Lemay, Mustapha Tehfe, Mohammed Harb, Nathalie Aucoin, Yoo-Joung Ko, Patricia A. Tang, Ravi Ramjeesingh, Brandon M. Meyers, Christina A. Kim, Pan Du, Shidong Jia, David F. Schaeffer, Sharlene Gill, Dongsheng Tu, and Chris J O’Callaghan
Subjects: Science
Abstract: Metastatic pancreatic ductal adenocarcinoma (mPDAC) has limited therapeutic options and is associated with a poor prognosis. Here the authors report the results of a randomized phase II trial showing that combining checkpoint inhibitors (durvalumab and tremelimumab) with chemotherapy (gemcitabine and nab-paclitaxel) does not improve survival compared to chemotherapy alone in patients with mPDAC.
Published: 2022
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4. Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

Author: Marc Carrier, Normand Blais, Mark Crowther, Petr Kavan, Grégoire Le Gal, Otto Moodley, Sudeep Shivakumar, Deepa Suryanarayan, Vicky Tagalakis, Cynthia Wu, and Agnes Y. Y. Lee
Subjects: cancer-associated thrombosis, venous thromboembolism, pulmonary embolism, anticoagulation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications. Risks vary significantly between individuals based on cancer status, treatment, and other characteristics. To facilitate the evidence-based management of anticoagulant therapy in this patient population, a committee of 11 Canadian clinical experts updated a consensus-based algorithm for the acute and extended treatment of symptomatic and incidental CAT that was developed in 2018. Following a systematic review of the literature, updates to the algorithm were discussed during an online teleconference, and the algorithm was subsequently refined based on feedback from committee members. Clinicians using this treatment algorithm should consider bleeding risk, type of cancer, and drug–drug interactions, as well as patient and clinician preferences, in tailoring anticoagulation for patients with CAT. Anticoagulant therapy should be adapted as the patient’s cancer status and management change over time.
Published: 2021
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5. Copy number and transcriptome alterations associated with metastatic lesion response to treatment in colorectal cancer

Author: Karen Gambaro, Maud Marques, Suzan McNamara, Mathilde Couetoux du Tertre, Zuanel Diaz, Cyrla Hoffert, Archana Srivastava, Steven Hébert, Benoit Samson, Bernard Lespérance, Yoo‐Joung Ko, Richard Dalfen, Eve St‐Hilaire, Lucas Sideris, Felix Couture, Ronald Burkes, Mohammed Harb, Errol Camlioglu, Adrian Gologan, Vincent Pelsser, André Constantin, Celia M.T. Greenwood, Sabine Tejpar, Petr Kavan, Claudia L. Kleinman, and Gerald Batist
Subjects: colorectal cancer, copy number aberrations, metastasis, treatment response, Medicine (General), R5-920
Abstract: Abstract 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.
Published: 2021
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6. The Cost-Effectiveness of Lenvatinib in the Treatment of Advanced or Unresectable Hepatocellular Carcinoma from a Canadian Perspective

Author: Brandon M. Meyers, Arndt Vogel, Paul Marotta, Petr Kavan, Laveena Kamboj, Janice Pan, Marc Geadah, David Trueman, and Suthakar Sabapathy
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Lenvatinib is an oral multikinase inhibitor indicated for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). In the Phase III REFLECT trial, lenvatinib was noninferior in the primary endpoint of overall survival versus sorafenib, the only systemic therapy funded in Canada prior to the introduction of lenvatinib. Lenvatinib also demonstrated statistically significant improvement compared to sorafenib in secondary endpoint progression-free survival, time to progression, and objective response rate. The aim of this analysis was to estimate the cost-effectiveness of lenvatinib versus sorafenib for the first-line treatment of patients with uHCC from a Canadian perspective. A cost-utility analysis was conducted using partitioned survival modelling, with health states representing progression-free disease, progressed disease, and death. Health effects were measured using quality-adjusted life years (QALYs), and costs were represented in Canadian dollars. Clinical inputs were derived from the REFLECT trial, with outcomes extrapolated using parametric survival models. EQ-5D data collected in REFLECT were used to determine health state utility values, and estimates of resource use came from a survey of clinicians. The model predicted incremental costs of-$5,021 and incremental QALYs of 0.17, making lenvatinib dominant over sorafenib. The model demonstrates lenvatinib to be a cost-effective use of resources versus sorafenib in Canada for the treatment of uHCC. Overall costs are lower compared with sorafenib, while health benefits are greater, with modelled progression-free and overall survival extended by 4.1 and 2.6 months in the lenvatinib arm, respectively.
Published: 2021
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7. Reasons for delay in timely administration of adjuvant chemotherapy for patients with stage III colon cancer: a multicentre cohort study from the McGill University Department of Oncology

Author: Arielle Elkrief, Petr Kavan, Genevieve Redstone, Luca Petruccelli, Alla'a Ali, Doneal Thomas, Myriam Fernandez, Caroline Rousseau, Olga Aleynikova, Dawn Anderson, Gabriela Ghitulescu, Carol-Ann Vasilevsky, Richard Dalfen, Adrian Langleben, Sender Liberman, and Thierry Alcindor
Subjects: Medicine (General), R5-920
Abstract: Purpose Adjuvant chemotherapy within 56 or 84 days following curative resection is globally accepted as the standard of care for stage III colon cancer as it has been associated with improved overall survival. Initiation of adjuvant chemotherapy within this time frame is therefore recommended by clinical practice guidelines, including the European Society for Medical Oncology. The objective of this study was to evaluate adherence to these clinical practice guidelines for patients with stage III colon cancer across the Rossy Cancer Network (RCN); a partnership of McGill University’s Faculty of Medicine, McGill University Health Centre, Jewish General Hospital and St Mary’s Hospital Center.Patients and methods 187 patients who had been diagnosed with stage III colon cancer and received adjuvant chemotherapy within the RCN partner hospitals from 2012 to 2015 were included. Patient and treatment information was retrospectively determined by chart review. Χ2 and Wilcoxon rank-sum tests were used to measure associations and a multivariate Cox regression model was used to determine risk factors contributing to delays in administration of adjuvant chemotherapy.Results The median turnaround time between surgery and adjuvant chemotherapy was 69 days. Importantly, only 27% of patients met the 56-day target, and 71% met the 84-day target. Increasing age, having more than one surgical complication and being diagnosed between 2013–2014 and 2014–2015 reduced the likelihood that patients met these targets. Furthermore, delays were observed at most intervals from surgery to first adjuvant chemotherapy treatment.Conclusion Our study found that within these academic hospital settings, 27% of patients met the 56-day target, and 71% met the 84-day target. Delays were associated with hospital, surgeon and patient-related factors. Initiatives in quality improvement are needed in order to improve adherence to recommended treatment guidelines for prompt administration of adjuvant chemotherapy for stage III colon cancer.
Published: 2021
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8. Prevention of venous thromboembolism in ambulatory patients with cancer

Author: Marc Carrier, Alok A Khorana, Alexander T Cohen, Guy Meyer, Petr Kavan, and Philip S Wells
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Patients with cancer are at high risk of venous thromboembolic events, and this risk can be further increased in patients with certain cancer types and by cancer treatments. Guidelines on the prevention of cancer-associated thrombosis (CAT) recommend thromboprophylaxis for hospitalised patients; however, this is not routinely recommended for ambulatory patients receiving chemotherapy and is limited to specified high-risk patients. Identification of the ambulatory patients at risk of CAT who would most benefit from anticoagulant therapy is therefore critical to reduce the incidence of this complication. For patients receiving thromboprophylaxis for CAT, treatment options include low molecular weight heparin, acetylsalicylic acid, warfarin or direct oral anticoagulants (apixaban or rivaroxaban), dependent on the cancer type and cancer treatment regimen. This review discusses emerging clinical trial data and their potential clinical impact.
Published: 2020
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9. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Author: L John Hoffer, Line Robitaille, Robert Zakarian, David Melnychuk, Petr Kavan, Jason Agulnik, Victor Cohen, David Small, and Wilson H Miller
Subjects: Medicine, Science
Abstract: Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.ClinicalTrials.gov NCT01050621.
Published: 2015
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10. Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial

Author: Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni, Richard Epstein, Paul Vasey, Jeremy Shapiro, Matthew Burge, Yu Jo Chua, Marion Harris, Nick Pavlakis, Niall Tebbutt, Gerald Prager, Christian Dittrich, Friedrich Längle, Kathrin Philipp-Abbrederis, Richard Greil, Herbert Stöger, Michael Girschikofsky, Thomas Kuehr, Jean-Luc Van Laethem, Stéphanie Laurent, Neesha Dhani, Yoo Joung Ko, Scot Dowden, Petr Kavan, Mustapha Édouard Tehfe, Eugen Kubala, Milan Kohoutek, Per Pfeiffer, Mette Yilmaz, Vibeke Parner, Tapio Salminen, Leena-Maija Soveri, Eija Korkeila, Pia Osterlund, Julien Taieb, David Tougeron, Pascal Artru, François Xavier Caroli-Bosc, Rosine Guimbaud, Antony Turpin, Thomas Walter, Jean Baptiste Bachet, Volker Kunzmann, Florian Kreth, Andreas Block, Marino Venerito, Helmut Oettle, Meinolf Karthaus, Jörg Trojan, Gunnar Folprecht, Markus Lerch, Frank Kullmann, Marcel Reiser, Volker Heinemann, Marcus-Alexander Wörns, Holger Schulz, Benjamin Garlipp, Thomas Yau, Lam Stephen Chan, Balazs Juhasz, László Landherr, Tamas Pinter, György Bodoky, Zsuzsanna Kahán, Raymond McDermott, Derek Power, Luca Gianni, Salvatore Siena, Michele Milella, Alfredo Falcone, Rossana Berardi, Cinzia Bagalà, Francesco Di Costanzo, Fausto Roila, Andrea Ardizzoni, Evaristo Maiello, Silvia Fanello, Johanna Wilmink, Jan Willem de Groot, Geert Creemers, Eduardo Barroso, Tânia Rodrigues, Cristina Sarmento, Cheng Ean Chee, David Tai, Teresa Macarulla Mercade, Manuel Hidalgo Medina, Alfredo Carrato Mena, Joan Maurel Santasusana, Maria Jose Flor Oncala, Carlos Gomez Martin, Rafael Lopez, Andres Muñoz, Ruth Vera Garcia, Inmaculada Ales, Berta Laquente Sáez, Fernando Rivera, Javier Sastre, Cheng-Chung Wu, Yu-Wen Tien, De-Chuan Chan, Tsann-Long Hwang, Jeffry Evans, Jonathan Wadsley, Pippa Corrie, Andrew Biankin, Andrew Ko, Dana Cardin, Elena Chiorean, Johanna Bendell, Anne Noonan, Hedy Kindler, Nishan Fernando, Muhammad Beg, Thomas George, Marcus Noel, Noelle LoConte, Francis Arena, James Posey, Rajat Malhotra, Charles Lopez, Davendra Sohal, Robert McWilliams, Warren Brenner, Mark Womack, Rahul Seth, Renuka lyer, Nathan Bahary, Robert Marsh, Robert Ramirez, Cynthia Chua, James Reeves, Gulam Manji, Anthony El-Khoueiry, Robert Weaver, Vaibhav Sahai, Wells Messersmith, Robert Dreicer, Ahmed Zakari, Andrea Bullock, Benjamin Musher, Mitesh Borad, Edward Kim, David Bajor, Tim Huyck, Hassan Hatoum, Henry Xiong, Boris Pasche, Jill Lacy, Olugbenga Olowokure, Allen Cohn, Donald Richards, Robert Martin, Andrew Paulson, Paul Fanta, Smitha Krishnamurthi, Paul Oberstein, Jyotsna Fuloria, Institut Català de la Salut, [Tempero MA] University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. [Pelzer U] Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. [O'Reilly EM] Memorial Sloan Kettering Cancer Center, New York, NY. [Winter J] Thomas Jefferson University Hospital, Philadelphia, PA. [Oh DY] Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea. [Li CP] Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Adjuvants, Immunologic [CHEMICALS AND DRUGS], acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::adyuvantes inmunitarios [COMPUESTOS QUÍMICOS Y DROGAS], terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Quimioteràpia combinada, Oncology, Adjuvants immunològics - Ús terapèutic, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], neoplasias::neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas::neoplasias::neoplasias por localización::carcinoma ductal pancreático [ENFERMEDADES], Pàncrees - Càncer - Tractament, Neoplasms::Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms::Neoplasms::Neoplasms by Site::Carcinoma, Pancreatic Ductal [DISEASES], APACT Investigators
Abstract: PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
Published: 2023

11. Genomic Analysis of Tumors from Patients with Glioblastoma with Long-Term Response to Afatinib

Author: Scott Owen, Scheryll Alken, Jad Alshami, Marie-Christine Guiot, Petr Kavan, David A Reardon, Thierry Muanza, Neil Gibson, Karine Pemberton, Flavio Solca, Agnieszka Cseh, and Frank Saran
Subjects: Oncology, Pharmacology (medical), OncoTargets and Therapy
Abstract: Scott Owen,1 Scheryll Alken,2,3 Jad Alshami,1 Marie-Christine Guiot,1,4 Petr Kavan,1 David A Reardon,5 Thierry Muanza,1,4,6 Neil Gibson,7 Karine Pemberton,8 Flavio Solca,9 Agnieszka Cseh10 ,â Frank Saran2,11 1Clinical Research Unit, Montreal Neurological Institute and Hospital, McGill University Health Center, Montreal, Canada; 2Radiation Oncology Unit, Royal Marsden Hospital, London, UK; 3St Jamesâs Hospital, Dublin, Ireland; 4Neuropathology Division, Montreal Neurological Institute and Hospital, McGill University Health Center, Montreal, Canada; 5Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; 6Radiation Oncology, Jewish General Hospital, Montreal, Canada; 7Drug Metabolism & Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; 8Medical Department, Boehringer Ingelheim Ltd., Bracknell, UK; 9Department of Pharmacology, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 10Department of Medical Affairs, Boehringer Ingelheim International, Ingelheim am Rhein, Germany; 11Department of Blood and Cancer, Auckland City Hospital, Auckland, New Zealandâ Agnieszka Cseh passed away in May 2021Correspondence: Frank Saran, Auckland City Hospital, Cancer and Blood Service, Building 8, 99 Park Road, Grafton, Private Bag 92024, Auckland, 1142, New Zealand, Tel +64 09 623 6046, Email FSaran@adhb.govt.nzAbstract: Glioblastoma is an aggressive form of central nervous system tumor. Recurrence rates following primary therapy are high, and few second-line treatment options provide durable clinical benefit. Aberrations of the epidermal growth factor receptor (EGFR) gene are observed in up to 57% of glioblastoma cases and EGFR overexpression has been identified in approximately 60% of primary glioblastomas. In preclinical studies, afatinib, a second-generation ErbB blocker, inhibited cell proliferation in cells harboring mutations commonly found in glioblastoma. In two previous Phase I/II studies of afatinib plus temozolomide in patients with glioblastoma, limited efficacy was observed; however, there was notable benefit in patients with the EGFR variant III (EGFRvIII) mutation, EGFR amplification, and those with loss of phosphatase and tensin homolog (PTEN). This case series report details treatment histories of three long-term responders from these trials. Next-generation sequencing of tumor samples identified alterations in a number of cancer-related genes, including mutations in, and amplification of, EGFR. Tumor samples from all three patients shared favorable prognostic factors, eg O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter methylation; however, negative prognostic factors were also observed, suggesting that these shared genetic features did not completely account for the favorable responses. The genetic profile of the tumor from Patient 1 showed clear differences from the other two tumors: lack of involvement of EGFR aberrations but with a mutation occurring in PTPN11. Preclinical studies showed that single-agent afatinib and temozolomide both separately inhibit the growth of tumors with a C-terminal EGFR truncation, thus providing further rationale for combining these two agents in the treatment of glioblastomas harboring EGFR aberrations. These findings suggest that afatinib may provide treatment benefit in patients with glioblastomas that harbor ErbB family aberrations and, potentially, other genetic aberrations. Further studies are needed to establish which patients with newly diagnosed/recurrent glioblastomas may potentially benefit from treatment with afatinib.Keywords: next-generation sequencing, long-term response, EGFR, genetic aberrations
Published: 2022

12. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164

Author: Chloe E. Atreya, Tae Won Kim, Elena Elez, Ravit Geva, Hiroki Hara, Tong Dai, Hiroya Taniguchi, Luis A. Diaz, Dung T. Le, Patrick McKay Boland, Rosine Guimbaud, Salah-Eddin Al-Batran, Todd S. Crocenzi, Matthew Burge, Thierry André, Petr Kavan, Dirk Jäger, Eric Van Cutsem, Yi Cui, Takayuki Yoshino, Patricia Marinello, Bert H. O'Neil, Institut Català de la Salut, [Le DT] Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. [Kim TW] Asan Medical Center, Seoul, Republic of Korea. [Van Cutsem E] University Hospitals Gasthuisberg Leuven, KU Leuven, Leuven, Belgium. [Geva R] Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. [Jäger D] Nationales Centrum Tumorerkrankungen, Heidelberg, Germany. [Hara H] Saitama Cancer Center, Saitama, Japan. [Elez E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, 0301 basic medicine, Cancer Research, Colorectal cancer, Medicaments antineoplàstics - Ús terapèutic, Pembrolizumab, Other subheadings::Other subheadings::/drug therapy [Other subheadings], DNA Mismatch Repair, Cohort Studies, 0302 clinical medicine, Open label study, Còlon - Càncer, Neoplasms, Monoclonal, Gastrointestinal Cancer, 80 and over, Humanized, Antitumor activity, Treatment refractory, Neoplasms::Neoplastic Processes::Neoplasm Metastasis [DISEASES], Middle Aged, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Treatment Outcome, Immunological, Oncology, 030220 oncology & carcinogenesis, Recte - Càncer, Female, DNA mismatch repair, Microsatellite Instability, Colorectal Neoplasms, Intravenous, Adult, Infusions, Clinical Sciences, Oncology and Carcinogenesis, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Antineoplastic Agents, and over, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, Antibodies, Young Adult, 03 medical and health sciences, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], RAPID COMMUNICATIONS, medicine, Humans, Oncology & Carcinogenesis, Aged, business.industry, Microsatellite instability, medicine.disease, 030104 developmental biology, neoplasias::procesos neoplásicos::metástasis neoplásica [ENFERMEDADES], Cancer research, business, Biomarkers
Abstract: PURPOSE KEYNOTE-164 (NCT02460198) evaluated the antitumor activity of pembrolizumab in previously treated, metastatic, microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) colorectal cancer (CRC). METHODS This phase II open-label study involved 128 centers worldwide. Eligible patients were age ≥ 18 years and had metastatic MSI-H/dMMR CRC treated with ≥ 2 prior lines of standard therapy, including fluoropyrimidine, oxaliplatin, and irinotecan with or without anti–vascular endothelial growth factor/epidermal growth factor receptor monoclonal antibody (cohort A) or ≥ 1 prior line of therapy (cohort B). MSI-H/dMMR status was assessed locally. Patients received pembrolizumab 200 mg every 3 weeks for up to 2 years until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate by RECIST version 1.1 by independent central review. Secondary end points were duration of response, progression-free survival (PFS), overall survival, safety, and tolerability. RESULTS A total of 124 patients with MSI-H/dMMR CRC (61 in cohort A, 63 in cohort B) enrolled. At data cutoff, median follow-up was 31.3 months (range, 0.2-35.6 months) for cohort A and 24.2 months (range, 0.1-27.1 months) for cohort B. Objective response rate was 33% (95% CI, 21% to 46%) and 33% (95% CI, 22% to 46%), respectively, with median duration of response not reached in either cohort. Median PFS was 2.3 months (95% CI, 2.1 to 8.1 months) and 4.1 months (95% CI, 2.1 to 18.9 months). Median overall survival was 31.4 months (95% CI, 21.4 months to not reached) and not reached (95% CI, 19.2 months to not reached). Treatment-related grade 3-4 adverse events occurred in 10 patients (16%) in cohort A and 8 (13%) in cohort B, with the most common occurring in ≥ 2 patients being pancreatitis, fatigue, increased alanine aminotransferase, and increased lipase (2 patients each; 3%) in cohort A. CONCLUSION Pembrolizumab is effective with a manageable safety profile in patients with MSI-H/dMMR CRC.
Published: 2019

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

Author: Mathilde Couetoux du Tertre, Eve St-Hilaire, Archana Srivastava, Steven Hébert, Lucas Sideris, Sabine Tejpar, Bernard Lespérance, Petr Kavan, Claudia L. Kleinman, Yoo-Joung Ko, Richard Dalfen, Karen Gambaro, Adrian Gologan, Gerald Batist, Maud Marques, Celia M. T. Greenwood, André Constantin, Mohammed Harb, Ronald Burkes, Benoit Samson, Suzan McNamara, Vincent Pelsser, Errol Camlioglu, Cyrla Hoffert, Zuanel Diaz, and Félix Couture
Subjects: 0301 basic medicine, Oncology, Male, Candidate gene, Medicine (General), Colorectal cancer, Medicine (miscellaneous), Research & Experimental Medicine, Metastasis, Transcriptome, 0302 clinical medicine, Medicine, Exome sequencing, Research Articles, Cause of death, Aged, 80 and over, Liver Neoplasms, Middle Aged, Progression-Free Survival, Bevacizumab, Gene Expression Regulation, Neoplastic, Exact test, Medicine, Research & Experimental, 030220 oncology & carcinogenesis, Molecular Medicine, Female, medicine.symptom, Colorectal Neoplasms, Life Sciences & Biomedicine, Research Article, Adult, medicine.medical_specialty, DNA Copy Number Variations, Antineoplastic Agents, colorectal cancer, Lesion, 03 medical and health sciences, R5-920, Internal medicine, Exome Sequencing, Humans, metastasis, Aged, Science & Technology, business.industry, copy number aberrations, treatment response, medicine.disease, 030104 developmental biology, Drug Resistance, Neoplasm, business
Abstract: 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., Graphical Abstract and Graphical Headlights Liver metastatic lesions from colorectal cancer patients were collected before and after first‐line standard chemotherapy and comprehensively profiled with the objective to assess the genomic impact of systemic therapy and investigate association with response and survival. This study allowed identification of novel CNAs having an impact on the transcriptome with a potential prognostic value in patients with colorectal cancer.
Published: 2021

14. Rationale and Design of the IROCAS Study: Multicenter, International, Randomized Phase 3 Trial Comparing Adjuvant Modified (m) FOLFIRINOX to mFOLFOX6 in Patients With High-Risk Stage III (pT4 and/or N2) Colon Cancer—A UNICANCER GI-PRODIGE Trial

Author: Loïc Campion, Florence Borde, Sandrine Hiret, Claire Jouffroy, Laurent Mineur, Sharlene Gill, Petr Kavan, You-Heng Lam, Pascal Artru, Laurent Miglianico, Timothy R. Asmis, Olivier Bouché, Laetitia-Shana Rajpar, Yann Touchefeu, Julien Taieb, Jean-François Emile, Thierry André, Jaafar Bennouna, Sorbonne Université (SU), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut Sainte Catherine [Avignon], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Louis Pasteur [Chartres], UNICANCER, and University of British Columbia (UBC)
Subjects: medicine.medical_specialty, Randomization, Organoplatinum Compounds, Colorectal cancer, FOLFIRINOX, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Leucovorin, Adenocarcinoma, Irinotecan, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, Humans, 030212 general & internal medicine, Neoplasm Staging, business.industry, medicine.disease, 3. Good health, Oxaliplatin, Survival Rate, Regimen, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, Fluorouracil, business, Adjuvant, medicine.drug
Abstract: Background According to the IDEA trial, 6-month adjuvant chemotherapy should remain the treatment standard in stage III T4 or N2 colon cancer. The relatively poor survival in this high-risk subgroup—a 3-year disease-free survival (DFS) rate of 65%—and the potential synergistic efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan suggest that FOLFIRINOX may be a regimen of particular interest in this setting. Patients and Methods This multicenter international phase 3 trial (ClinicalTrials.gov NCT02967289 ) being conducted in 49 centers in France and Canada plans to randomize (1:1; minimization method) 640 patients aged 18 to 70 years with Eastern Cooperative Oncology Group performance status ≤ 1. Randomization occurs within 42 days (with treatment initiated within 56 days) after curative-intent R0 surgical resection of a pT4N1 or pT1-4N2 colon adenocarcinoma. Patients will be randomized to receive adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 180 mg/m2, and 5-FU 2.4 g/m2 over 46 hours) or modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU bolus 400 mg/m2, then 2.4 g/m2 over 46 hours) every 2 weeks for 24 weeks (12 cycles). Patients will be followed for 5 years after the end of adjuvant chemotherapy. A gain of 9% in 3-year DFS (primary end point) is expected (74% in the experimental arm vs. 65% in the control arm; α, 5% [2-sided log-rank test]; 1-β, 80%). Secondary end points of this study include 2-year DFS, overall survival, and toxicity.
Published: 2019
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15. Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus

Author: Mark Crowther, Sudeep Shivakumar, Normand Blais, G. Le Gal, O. Moodley, Petr Kavan, Vicky Tagalakis, Marc Carrier, Agnes Y.Y. Lee, Cynthia Wu, Thrombosis Program, University of Ottawa [Ottawa], Department of Medicine (DM - McMaster), McMaster University [Hamilton, Ontario], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), and Calvez, Ghislaine
Subjects: Change over time, Canada, Consensus, [SDV]Life Sciences [q-bio], Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, heparin, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Neoplasms, medicine, Humans, Cancer associated thrombosis, cardiovascular diseases, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Key Words Venous thromboembolism, business.industry, Anticoagulants, Expert consensus, Cancer, Thrombosis, equipment and supplies, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, [SDV] Life Sciences [q-bio], Venous thrombosis, Practice Guideline, low-molecular-weight, 030220 oncology & carcinogenesis, venous thrombosis, hemorrhage, business, Venous thromboembolism, Algorithm, Algorithms, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Management of anticoagulant therapy for the treatment of venous thromboembolism (VTE) in cancer patients is complex because of an increased risk of recurrent VTE and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent VTE and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental VTE, to prevent recurrent VTE, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug–drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient’s cancer status and management change over time.
Published: 2018

16. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial

Author: Michael Weller, Nicholas Butowski, David D Tran, Lawrence D Recht, Michael Lim, Hal Hirte, Lynn Ashby, Laszlo Mechtler, Samuel A Goldlust, Fabio Iwamoto, Jan Drappatz, Donald M O'Rourke, Mark Wong, Mark G Hamilton, Gaetano Finocchiaro, James Perry, Wolfgang Wick, Jennifer Green, Yi He, Christopher D Turner, Michael J Yellin, Tibor Keler, Thomas A Davis, Roger Stupp, John H Sampson, Jian Campian, Lawrence Recht, Samuel Goldlust, Kevin Becker, Gene Barnett, Garth Nicholas, Annick Desjardins, Tara Benkers, Naveed Wagle, Morris Groves, Santosh Kesari, Zsolt Horvath, Ryan Merrell, Richard Curry, James O'Rourke, David Schuster, Maciej Mrugala, Randy Jensen, John Trusheim, Glenn Lesser, Karl Belanger, Andrew Sloan, Benjamin Purow, Karen Fink, Jeffrey Raizer, Michael Schulder, Suresh Nair, Scott Peak, Alba Brandes, Nimish Mohile, Joseph Landolfi, Jon Olson, Ross Jennens, Paul DeSouza, Bridget Robinson, Marka Crittenden, Kent Shih, Alexandra Flowers, Shirley Ong, Jennifer Connelly, Costas Hadjipanayis, Pierre Giglio, Frank Mott, David Mathieu, Nathalie Lessard, Sanchez Juan Sepulveda, József Lövey, Helen Wheeler, Po-Ling Inglis, Claire Hardie, Daniela Bota, Maciej Lesniak, Jana Portnow, Bruce Frankel, Larry Junck, Reid Thompson, Lawrence Berk, John McGhie, David Macdonald, Frank Saran, Riccardo Soffietti, Deborah Blumenthal, Sá Barreto Costa Marcos André de, Anna Nowak, Nimit Singhal, Andreas Hottinger, Andrea Schmid, Gordan Srkalovic, David Baskin, Camilo Fadul, Louis Nabors, Renato LaRocca, John Villano, Nina Paleologos, Petr Kavan, Marshall Pitz, Brian Thiessen, Ahmed Idbaih, Jean Sébastien Frenel, Julien Domont, Oliver Grauer, Peter Hau, Christine Marosi, Jan Sroubek, Elizabeth Hovey, P.S. Sridhar, Lawrence Cher, Erin Dunbar, Thomas Coyle, Jane Raymond, Kevin Barton, Michael Guarino, Sumul Raval, Baldassarre Stea, Jorge Dietrich, Kirsten Hopkins, Sara Erridge, Joachim-Peter Steinbach, Losada Estela Pineda, Quintero Carmen Balana, Barco Berron Sonia del, Miklós Wenczl, Katalin Molnár, Katalin Hideghéty, Alexander Lossos, Linde Myra van, Ana Levy, Rosemary Harrup, William Patterson, Zarnie Lwin, Sith Sathornsumetee, E-Jian Lee, Jih-Tsun Ho, Steven Emmons, J. Paul Duic, Spencer Shao, Hani Ashamalla, Michael Weaver, Jose Lutzky, Nicholas Avgeropoulos, Wahid Hanna, Mukund Nadipuram, Gary Cecchi, Robert O'Donnell, Susan Pannullo, Jennifer Carney, Mark Hamilton, Mary MacNeil, Ronald Beaney, Michel Fabbro, Oliver Schnell, Rainer Fietkau, Guenther Stockhammer, Bela Malinova, Karel Odrazka, Martin Sames, Gil Miguel Gil, Evangelia Razis, Konstantin Lavrenkov, Guillermo Castro, Francisco Ramirez, Clarissa Baldotto, Fabiana Viola, Suzana Malheiros, Jason Lickliter, Stanislaw Gauden, Arunee Dechaphunkul, Iyavut Thaipisuttikul, Ziad Thotathil, Hsin-I Ma, Wen-Yu Cheng, Chin-Hong Chang, Fernando Salas, Pierre-Yves Dietrich, Christoph Mamot, Lakshmi Nayak, Shona Nag, University of Zurich, Weller, Michael, and Dietrich, Pierre-Yves
Subjects: Male, Internationality, Time Factors, ACT IV trial investigators, Kaplan-Meier Estimate, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Cancer, ddc:616, Vaccines, Brain Neoplasms, Middle Aged, Dacarbazine, ErbB Receptors, Gene Expression Regulation, Neoplastic, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, 6.1 Pharmaceuticals, Vaccines, Subunit, Female, 2730 Oncology, Drug, medicine.drug, Adult, medicine.medical_specialty, Subunit, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, 610 Medicine & health, Cancer Vaccines, Disease-Free Survival, Drug Administration Schedule, Dose-Response Relationship, 03 medical and health sciences, Young Adult, Rare Diseases, Double-Blind Method, Clinical Research, Internal medicine, medicine, Temozolomide, Humans, Oncology & Carcinogenesis, Adverse effect, Survival analysis, Aged, Proportional Hazards Models, Neoplastic, Intention-to-treat analysis, Dose-Response Relationship, Drug, business.industry, Patient Selection, Neurosciences, Evaluation of treatments and therapeutic interventions, Interim analysis, Minimal residual disease, Survival Analysis, Surgery, Brain Disorders, 10040 Clinic for Neurology, Clinical trial, Brain Cancer, Gene Expression Regulation, business, Glioblastoma, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Summary Background Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. Methods In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries. Eligible patients had newly diagnosed glioblastoma confirmed to express EGFRvIII by central analysis, and had undergone maximal surgical resection and completion of standard chemoradiation without progression. Patients were stratified by European Organisation for Research and Treatment of Cancer recursive partitioning analysis class, MGMT promoter methylation, and geographical region, and randomly assigned (1:1) with a prespecified randomisation sequence (block size of four) to receive rindopepimut (500 μg admixed with 150 μg GM-CSF) or control (100 μg keyhole limpet haemocyanin) via monthly intradermal injection until progression or intolerance, concurrent with standard oral temozolomide (150–200 mg/m 2 for 5 of 28 days) for 6–12 cycles or longer. Patients, investigators, and the trial funder were masked to treatment allocation. The primary endpoint was overall survival in patients with minimal residual disease (MRD; enhancing tumour 2 post-chemoradiation by central review), analysed by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01480479. Findings Between April 12, 2012, and Dec 15, 2014, 745 patients were enrolled (405 with MRD, 338 with significant residual disease [SRD], and two unevaluable) and randomly assigned to rindopepimut and temozolomide (n=371) or control and temozolomide (n=374). The study was terminated for futility after a preplanned interim analysis. At final analysis, there was no significant difference in overall survival for patients with MRD: median overall survival was 20·1 months (95% CI 18·5–22·1) in the rindopepimut group versus 20·0 months (18·1–21·9) in the control group (HR 1·01, 95% CI 0·79–1·30; p=0·93). The most common grade 3–4 adverse events for all 369 treated patients in the rindopepimut group versus 372 treated patients in the control group were: thrombocytopenia (32 [9%] vs 23 [6%]), fatigue (six [2%] vs 19 [5%]), brain oedema (eight [2%] vs 11 [3%]), seizure (nine [2%] vs eight [2%]), and headache (six [2%] vs ten [3%]). Serious adverse events included seizure (18 [5%] vs 22 [6%]) and brain oedema (seven [2%] vs 12 [3%]). 16 deaths in the study were caused by adverse events (nine [4%] in the rindopepimut group and seven [3%] in the control group), of which one—a pulmonary embolism in a 64-year-old male patient after 11 months of treatment—was assessed as potentially related to rindopepimut. Interpretation Rindopepimut did not increase survival in patients with newly diagnosed glioblastoma. Combination approaches potentially including rindopepimut might be required to show efficacy of immunotherapy in glioblastoma. Funding Celldex Therapeutics, Inc.
Published: 2017
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17. Progression pattern and adverse events with bevacizumab in glioblastoma

Author: S. Owen, J. Alshami, Ayesha Baig, M. Azam, Thierry Muanza, Marie-Christine Guiot, Young Soo Rho, Kevin Petrecca, Petr Kavan, S. Sahebjam, R. Sharma, and Aline Mamo
Subjects: medicine.medical_specialty, Bevacizumab, genetic structures, Anemia, Deep vein, Neutropenia, bevacizumab, urologic and male genital diseases, Glioblastoma multiforme, Gastroenterology, survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Adverse effect, business.industry, urogenital system, patterns of progression, medicine.disease, Thrombosis, female genital diseases and pregnancy complications, adverse events, Surgery, nervous system diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cohort, Original Article, business, 030217 neurology & neurosurgery, medicine.drug, Glioblastoma
Abstract: The use of bevacizumab in the management of glioblastoma multiforme (gbm) remains controversial. In Canada, bevacizumab is approved for the treatment of recurrent gbm. We describe a pattern of progression across treatment lines in gbm. During 2008&ndash, 2014, 64 patients diagnosed with gbm were treated with bevacizumab at McGill University hospitals. Of those patients, 30 (46.9%) received bevacizumab in the first line (B1L), and 34 (53.1%) received it in the second line and beyond (B2L+). The average length of treatment with bevacizumab was 24.4 weeks (range: 0&ndash, 232.7 weeks). The patterns of progression were categorized as local, distant, diffuse, multifocal, or multi-pattern. Local progression was seen in 46.7% of B1L patients and 26.5% of B2L+ patients, distant in 3.3% and 2.9%, diffuse in 20% and 47%, multifocal in 10% and 8.8%, and multi-pattern in 3.3% and 11.8%. No differences between the groups were observed for the distant (p = 0.3) or diffuse (p = 0.4) patterns. Grades 3 and 4 adverse events in the B1L and B2L+ groups were fatigue (33.3% vs. 17.6% respectively), hypertension (26.7% vs. 5.9%), thrombocytopenia (26.7% vs. 11.8%), neutropenia (26.7% vs. 11.8%), anemia (23.3% vs. 11.8%), leucopenia (20% vs. 8.8%), deep vein thrombosis (23.3% vs. 5.9%), seizure (16.7% vs. 8.8%), brain hemorrhage (6.7% vs.
Published: 2016
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18. 338. Comparing characteristics and survival outcomes of adolescent and young adults to mature patients with colorectal cancer

Author: R. Mcdermott, Daniele Marrelli, V. Petrova, Laurent Azoulay, Megan Greally, K. Kubackova, Marine Gilabert, A. Aladashvili, Zhasmina Mihaylova, V. Megdanova, Franco Roviello, Karol Polom, Niamh Coleman, Young Soo Rho, Petr Kavan, Gerald Batist, J. Peausova, and B. Zbynek
Subjects: Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, Internal medicine, medicine, Surgery, General Medicine, Young adult, medicine.disease, business
Published: 2016

19. Complete Resolution of Metastatic Gallbladder Cancer after Standard Gemcitabine-Cisplatin Combination Therapy

Author: Young Soo Rho, Ivan Barrera, Petr Kavan, and Peter Metrakos
Subjects: Oncology, medicine.medical_specialty, Combination therapy, medicine.medical_treatment, cisplatin, Disease, complete response, gallbladder cancer, Internal medicine, biliary tract cancer, Carcinoma, Medicine, Gallbladder cancer, Chemotherapy, business.industry, Gallbladder, General Engineering, Gastroenterology, gemcitabine, Combination chemotherapy, gastrointestinal malignancy, medicine.disease, Gemcitabine, medicine.anatomical_structure, business, medicine.drug
Abstract: Gallbladder carcinoma (GBC) is a rare and deadly disease. The only curative option is a total surgical resection. If the disease is inoperable, palliative combination chemotherapy with gemcitabine-cisplatin remains the standard of care. We present here a case of a 47-year-old gentleman diagnosed with metastatic GBC who saw a complete resolution of his disease with seven cycles of standard gemcitabine-cisplatin chemotherapy. This case illustrates the importance of multidisciplinary care to explore all available options to provide optimal and tailored patient care.
Published: 2015

20. High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

Author: Wilson H. Miller, David Small, Line Robitaille, L. John Hoffer, Jason Agulnik, Petr Kavan, David Melnychuk, Robert Zakarian, and Victor Cohen
Subjects: Oncology, Male, medicine.medical_specialty, medicine.medical_treatment, lcsh:Medicine, Antineoplastic Agents, Ascorbic Acid, Antioxidants, Pharmacotherapy, Internal medicine, Neoplasms, Medicine, Humans, Tissue Distribution, lcsh:Science, Adverse effect, Aged, Chemotherapy, Multidisciplinary, business.industry, lcsh:R, Cancer, Middle Aged, Ascorbic acid, medicine.disease, Chemotherapy regimen, Surgery, Clinical trial, Tolerability, Injections, Intravenous, cardiovascular system, Quality of Life, lcsh:Q, Drug Therapy, Combination, Female, business, Research Article
Abstract: Background Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. Methods and Findings We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Conclusions Despite IVC’s biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC’s value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials. Trial Registration ClinicalTrials.gov NCT01050621
Published: 2015

21. AT-18SURVIVAL ANALYSIS OF PATIENTS WITH A PFS EVENT WHO DID NOT RECEIVE POST-PROGRESSION THERAPY IN AVAGLIO (BEVACIZUMAB [BEV] PLUS RADIOTHERAPY [RT] AND TEMOZOLOMIDE [TMZ] FOR NEWLY DIAGNOSED GLIOBLASTOMA [GBM])

Author: Lauren E. Abrey, Warren P. Mason, Ryo Nishikawa, Antoine F. Carpentier, Cedric Revil, Khê Hoang-Xuan, Olivier Chinot, Roger Henriksson, Dana Cernea, Petr Kavan, Wolfgang Wick, Frank Saran, Alba A. Brandes, and Timothy F. Cloughesy
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Temozolomide, Bevacizumab, Surrogate endpoint, business.industry, medicine.medical_treatment, O-6-methylguanine-DNA methyltransferase, Newly diagnosed, medicine.disease, nervous system diseases, Radiation therapy, Abstracts, Internal medicine, medicine, Neurology (clinical), business, neoplasms, Survival analysis, medicine.drug, Glioblastoma
Abstract: BACKGROUND: Many patients with GBM only receive one line of therapy. GBM patients who cannot receive post-PD therapy are not easily identifiable at diagnosis and may represent up to 50% of patients (Graus, Neuro Oncol 2013; Chen, Asia Pac J Clin Oncol 2013). Since post-study treatment may confound OS analyses in clinical trials, we evaluated outcomes for AVAglio patients who did not receive post-PD therapy. METHODS: In AVAglio patients (n = 921) received: BEV + RT/TMZ or placebo + RT/TMZ (6wks); 28-day break; BEV + TMZ or placebo + TMZ (x6); BEV or placebo until PD/unacceptable toxicity. Co-primary endpoints: investigator-assessed PFS and OS. Post-PD therapy was received by 321 placebo (69%) and 284 BEV (62%) patients (post-PD BEV: 144 placebo-treated patients, 62 BEV-treated patients). An exploratory analysis of PFS/OS in patients who did not receive post-PD therapy was performed. RESULTS: In the intent-to-treat population, first-line BEV + RT/TMZ extended investigator-assessed PFS versus placebo + RT/TMZ (median 10.6 vs 6.2 months; HR 0.64, 95% CI 0.55-0.74; p < 0.0001,) but not OS (median 16.8 vs 16.7 months; HR 0.88, 95% CI 0.76-1.02; p = 0.0987). For patients with PFS events who did not receive post-PD therapy, placebo (n = 105) versus BEV (n = 120), respectively: median OS 8.0 vs 11.6 months (HR 0.67, 95% CI 0.49-0.91); median PFS 4.8 vs 8.4 months (HR 0.62, 95% CI 0.46-0.84). Cox multiple regression for OS treatment effect (adjusted for prognostic factors): HR 0.61, 95% CI 0.42-0.87. Baseline characteristics of patients with PFS events who did not receive post-PD therapy were balanced for standard prognostic factors (age, gender, WHO PS, recursive partitioning analysis class, MGMT status, Mini Mental State Examination score, corticosteroid use). CONCLUSION: In this post-hoc analysis of AVAglio patients in whom the potential confounding effect of subsequent therapies could not impact the effect of first-line therapy, the longer PFS observed with BEV + RT/TMZ (versus placebo + RT/TMZ) was associated with longer OS.
Published: 2014

22. NEURO/MEDICAL ONCOLOGY

Author: Irene Helenowski, Naoya Hashimoto, Jan J. Heimans, Toshiki Yoshimine, Johan A F Koekkoek, Evelyne Emery, José L. Asencio, Andrea Chamczuck, Carly Bridge, Gilbert Faure, Barbara-Ann Millar, Arthur Rosiello, Michela Casanova, John Freymann, Giulio Bertani, Jun-ich Adachi, Christian LaFougere, Julianne Bloom, Paul Vincent Opinaldo, Tobey J. McDonald, Alexander Khandji, Maciej M. Mrugala, Agnieszka Kowalska, Clifford G. Robinson, Josef Pichler, Jayesh Mehta, Lisa M. DeAngelis, Katie Slusarz, Rachel Grossman, Juan Armando Mejía, Sadhana Kannan, In Ah Kim, Pierre Soubeyran, Nabil Ahmed, Matthew J. Matasar, David A. Reardon, Marie-Laure Tanguy, Andrea Pace, Vani Santosh, Tackeun Kim, Adrienne C. Lahti, John E. Donahue, Pavlina Poloskova, Marc H. A. Jansen, Nilanjana Banerji, Margaret Schwartz, Matthias Kirsch, Robert Jeraj, Guus A.M.S. van Dongen, Samuel Singer, Tom J. Snijders, Santosh Kesari, Riccardo Soffetti, Takashi Sasayama, Diana Ly, Kaoru Kurisu, Carsten Friedrich, Shinji Kawabata, Cedric Revil, Michael A. Jacobs, Ryuichi Hirayama, Wan-Soo Yoon, Kathleen Lupica, Christopher Reilly, Takuichiro Hideo, Miguel Gil, Josep Garcia, Ming Zheng, Edward K. Avila, Mairéad G McNamara, Hartmut Uschmann, Jeffrey S. Weinberg, Craig H. Moskowitz, Jörg Hense, Manmeet Ahluwalia, Georg Bjarnason, David Corwin, Shakti Ramkissoon, Jad Alshami, Eric C. Leuthardt, Paul Dilfer, Margaret Patton, Lindsey Heathcock, Cees van Montfort, Rakesh Kumar Gupta, Akihiko Yoshida, Carmine Maria Carapella, Guy K. Mckhann, Marian Hajduch, Meinhard Nevinny-Stickel, Patricia Bruns, Ashish Suri, Hernán Carranza, David A. Gutman, Carlos Yepes, Patrick Y. Wen, T. Cloughesy, Anna Kaltenboeck, Carlos Bartels, Paul D. Brown, Lisa Fichtel, Lorenzo Giammattei, Steven Hamilton, Nobuyuki Takayama, Nan Lin, Jan Drappatz, Roland Eils, Akihiro Tsuboi, Patrick Urban, Minesh P. Mehta, Remy Gressin, Zarnie Lwin, Clarence Eng, Ian F. Dunn, Sin-Soo Jeun, Alva B. Weir, Elisa Trevisan, silviya Meletath, Fumiyuki Yamasaki, Scott N. Hwang, Navya Nambudiri, Timothy F. Cloughesy, Paolo Rampini, Kathryn J. Ruddy, Justin Kirby, Marc C. Huisman, Normand Laperriere, Abajo Guijarro, Alberto González-Aguilar, David M. Peereboom, Antoine F. Carpentier, Steven M. Greenberg, Chikashi Ishioka, Sarah C. Gaffey, Sneha Arya, Guy M. McKhann, Richard Curry, Takashi Watanabe, Keishi Makino, Radek Trojanec, Hideo Takeshima, Joseph F. Megyesi, Jasmina I. Ivanova, Victor Rodriguez Berrocal, Marcel Kool, Eric Burton, Sandra K. Johnston, Hideyuki Arita, Konstantina Karabatsou, Robert C. Rostomily, Sean Grimm, Ralph G. Dacey, Karl Olson, Sonia Gómez, Harry C. Schouten, Christof M. Kramm, Fred H. Hochberg, Darren Hargrave, Kazuhiko Sugiyama, Wilhelm Boogerd, Stefano Tiziani, Christine McCluskey, Albert H. Kim, Tejpal Gupta, Ida Martinelli, Friedrich-Wilhelm Kreth, Lennea Coombs, Keith L. Ligon, J. Manuel Sarmiento, David R. Macdonald, Holly Dickinson, Cristian Massacesi, Basile Wittwer, Jung-Il Lee, Volker Hovestadt, Mark Smolkin, Sampath Somanna, Ingo K. Mellinghoff, Nancy Ann Oberheim Bush, Sanjeev Francis, Roland Goldbrunner, Jai Ho Choi, John Sampson, Roy Allan Dominique Torcuator, Kathleen R. Lamborn, Simon V. Liubinas, Daniel J. Sargent, Christina K. Cramer, Francine Armentano, Heather Leeper, Stefan Rutkowski, Prakash Shetty, Arivazhagan Arimappamagan, Alicia Ortega, Enrique Jiménez, Kazuhiro Tanaka, Kolette D. Fly, Seunggu Han, Nicolas U. Gerber, David Schiff, Antonella Castellano, Isabel Arrillaga-Romany, Robert J. Wechsler-Reya, Sophie Taillibert, Macarena de la Fuente, Wolfgang Wick, Monica Bennett, Francesco Cognetti, John de Groot, Michael Gonzales, Leon D. Ortiz, Yoshiaki Shiokawa, George Sachs, Ivo Tremont, Charles A. Conrad, Michael D. Taylor, Igor J. Barani, Shannon Langmead, Lisa Sturla, Doosik Kong, Rebecca D. Folkerth, Garrett Riggs, Yoon-La Choi, Carole Soussain, Calvin Soh, Peter Canoll, Mariza Daras, Melissa Hoag, James Rigas, Dana Cernea, Liu Diane, Kenji Wakiya, Sandra Silberman, Ivan A. Reveles, Jeffrey S. Wefel, Wenting Wu, Marie Blonski, MA Majaid, Vanessa A. Nestor, Maurits W.C.B. Sanders, Cynthia Harrison, Ruxandra Costa, Andrea Hawkins-Daarud, Mark R. Gilbert, Ruth Katz, Masayuki Kanamori, Tomek Janicki, Aaron C. Spalding, Dong-Sup Chung, Lauren Foresman, Fateme Salehi, Allan H. Friedman, Eric P. Winer, Robert Kwiecien, Joachim Kuehl, Motoo Nagane, Stanislaw Burzynski, Tomokazu Aoki, Gregory N. Fuller, Nina Paleologos, Darell D. Bigner, Max Wintermark, Adam E. Flanders, Eiichi Ishikawa, Subramanian Hariharan, Doreen Pachow, Glen Stevens, Ulrich Schüller, Jennifer Lycette, Jennifer Garst, Jeffery T. Williams, Gordana Vlahovic, Tjeerd J. Postma, Tribhwan Vats, Isabel Arrilaga, Krista Follmer, Henry S. Friedman, Kenneth Schwartz, James Perry, Jonas M. Sheehan, Christian Grommes, Annette M. Molinaro, Seung-Ho Yang, Peter Lichter, Naoki Kagawa, Trish Whitcomb, Monica Loghin, Amanda L. Bergner, Miroslav Vaverka, Jayashree Kalpathy-Cramer, Chitra Sarkar, Thomas Davidson, Nithya Ramnath, Leland Rogers, Roberta Rudà, Steven A. Toms, Martin Gore, Khê Hoang-Xuan, Emmanuel Gyan, Hani Malone, Jun-ichi Adachi, Jennifer Rifenburg, Stefan M. Pfister, Luis Carlos Mayor, Vanja Vaccaro, Hannah E. Goldstein, Karen Fink, Eva Dombi, Timothy Cloughsey, Sabina Eigenbrod, Jiri Ehrmann, Li Li, Pamela R. Jackson, Makoto Ohno, Craig Nolan, Gerald P. Linette, Tatjana Seute, Eric Bouffet, Patricia M. M. B. Soetekouw, David J. Pisapia, Marc Remke, Susan Snodgras, David Tran, Keiichi Kobayashi, Warren P. Mason, Setsu Sakamoto, Chiara Bosa, Gabriele Schackert, Alfred Yung, David Cachia, Toshihiko Kuroiwa, María Ángeles Vaz Salgado, F. Lonnqvist, Francesca Piludu, Alvina Acquaye, Keisuke Ueki, Jung Ho Han, Kathy Newell, Mythili Shastry, Yoon Jae Cho, Marco Riva, Laura M. Fayad, Kristin Diefes, André O. von Bueren, Ina Ly, Beatrix Lutiger, Hiroyoshi Suzuki, Jeanette K. Doorduijn, Eiji Kohmura, Olivier Chinot, Ichiyo Shibahara, Nathalie Jansen, Marta Del Álamo de Pedro, Scott L. Pomeroy, Andreas Zwergal, Terri S. Armstrong, Elmar Kirches, Daniel P. Cahill, Howard A. Fine, Cezary Szczylik, Stéphane Oudard, Gregg C. Shepard, Mark G. Kris, Andrea Milbourne, Dominique Jennings, Marco Locatelli, Dereck Amakye, Takumi Kudo, Simon Bailey, Alessandra Fabi, Taketoshi Maehara, Soumen Khatua, Caroline Houllier, Klaus J. Müller, Jaishri O. Blakeley, Karen Kelly, Jonathon Yun, Thomas Gergel, Diane Liu, Eric T. Wong, Alin Borha, Brian J. Williams, Rakesh Jalali, Birgit Geoerger, Naosuke Nonoguchi, Julie Walker, Jasmin Jo, Manmohan Singh, Mary Noel, Denise Lally-Goss, Tracy T. Batchelor, Andrea Falini, Maximilian Niyazi, Jeffrey Raizer, Martin J. van den Bent, Aleksandra Gruslova, Phioanh L. Nghiemphu, Kristin R. Swanson, Maaike J. Vos, Jethro Hu, Rebeca Alcalce Pampliega, Craig S. Sauter, Leena Ketonen, Michael A. Vogelbaum, Donald Picker, Robert Hawkins, Chris Halpin, Otto S. Hoekstra, Elizabeth Vera-Bolanos, Ahmad Awada, Sawan Kumar, Alexandra Benouaich-Amiel, Joseph Pernicone, Noriyuki Kawabata, Andrew H. Kaye, David Brachman, Kurt A. Jaeckle, Cameron J. Nowell, Maria Carlo, Tom Mikkelsen, Jorg Dietrich, Tomonari Suzuki, Kohei Fukuoka, Philippe Aftimos, Christine Schmid-Tannwald, Vera Wenter, Valeria Conte, Scott Turner, Brian J A Gill, John D. Cullen, Jiayi Huang, Saurabh Dahiya, Vincent Delwail, Lien Bekaert, Priya Kumthekar, Roberta Seidman, Scott R. Plotkin, Priya Deshpande, Christopher Zalewski, Vaibhav Patel, Peter Kurniali, Martha Nowosielski, Zvi Ram, Susan M. Chang, Dannis G. van Vuurden, Stuart A. Grossman, Vaishali Suri, Rajan Jain, Christine Carico, Ying Yuan, Yoji Yamashita, Bojana Milojkovic-Kerklaan, Yannick Kerloeguen, Michael B. Sisti, Rameen Beroukhim, Andrea Artoni, Frances McSherry, John J. Evans, Mark E. Shaffrey, Lauren E. Abrey, Akshal S. Patel, Laura Bernal-Vaca, Rolf-Dieter Kortmann, Robert Grubb, Mimi Lee, Jörg-Christian Tonn, Shinobu Yamada, Andrés Quintero, Kazuhiko Mishima, Ania Marszalek, Stephen Gancher, Amal Melhem-Bertrandt, Takamitsu Fujimaki, Monika Warmuth-Metz, George Avgeropoulos, Rifaquat Rahman, Franck Bourdeaut, Frank Feleppa, Jennifer Clarke, Meredith A. Reid, Maria Werner-Wasik, Andrew D. Norden, Kenneth D. Swanson, Jeffrey N. Bruce, Chae-Yong Kim, Steven S. Rosenfeld, Haiyan Jiang, Oliver Schnell, Toshihiro Kumabe, Michael J. Sullivan, W. Gladdines, Glenn J. Lesser, Chang-Ho Yun, Epari Sridhar, Sophie Lebouvier-Sadot, Andrea Baldwin, Chirag G. Patil, Thomas Smith, Shin-Ichi Miyatake, Renato LaRocca, Kent C. Shih, Russell C. Rockne, Katsu Mizukawa, Antonio Omuro, Ryuta Saito, Mohamed H. Hamza, Eunju Hurh, Silke Soucek, Michel Lacroix, Brian J. Scott, Thomas Kaley, Tetsuya Yamamoto, Gregory J. Zipfel, Andrew Lin, Elena Pentsova, Carlos Emilio Restrepo, Utkarsh Bhagat, Masao Matsutani, Andrew B. Lassman, Stephanie L. Pugh, Yasuji Miyakita, Manabu Kinoshita, Christian Hagel, D. Brandsma, Jorge M. Otero, Marco Timmer, Ke Zhang, S. Altintas, Thierry Lamy, Hirofumi Hirano, Mehar Chand Sharma, Wafik S. El-Deiry, Peter A. Sims, Evanthia Galanis, Yong-Kil Hong, Terence J. O'Brien, Haruo Sugiyama, Dieta Brandsma, Loretta Barron, Joshua J. Jacobs, Roger Henriksson, Albert Lai, David White, Xiao-Tang Kong, John D. Hainsworth, Petronella J Lugtenburg, Paul A. Northcott, Maryline Barrie, Kenneth J. Cohen, Tanuj Saaraswat, Xiaobu Ye, Sandra Ruland, Diana M. Haninger, Surasak Phuphanich, Marc C. Chamberlain, Kenneth Aldape, Ewa Matczak, Phyo Kim, Peter Bartenstein, Lumir Hrabalek, Howard Y. Chang, Donatella Tampieri, Fumi Higuchi, Katherine S. Panageas, Allicia C. Girvan, Majid Khan, Stevie Threatt, Tareq Juratli, Mitchel S. Berger, Linda Dirven, Michele Nikolai, Emmanuelle DiTomaso, Sarah Leary, Jan H.M. Schellens, Chuanlu Jiang, Michael Glantz, Harald Sontheimer, Michael D. Prados, Mauricio Lema, Marie-Christine Guiot, Shesh N. Rai, Minhee Won, Carlos Vargas, Eva Galanis, Kazunori Arita, David I. Sandberg, Gianluca Ardolino, Sylvain Choquet, Ondrej Kalita, Michael Rytting, Lorenzo Bello, Luis Ley Urzaiz, Martin J.B. Taphoorn, Kourosh Jafari-Khouzani, Alfred Rademaker, Juan Martinez San Millan, Isabelle Aerts, Sergio Bracarda, John Norton, Mark D. Anderson, Barbara Zarino, Jun Ichi Kuratsu, Nicholas Butowski, Derek R. Johnson, James E. Herndon, Diana Giannarelli, Debra LaFrankie, Filippo Cogiamanian, Yasuyoshi Chiba, Hideo Nakamura, Agnes Jager, Caroline Chung, Paula Warren, Frans S. S. Leijten, Peter Hau, Yusuke Oji, Yuichi Hirose, Kathryn Gilliland, Sadao Kaneko, W. K. Alfred Yung, Roger Stupp, Amy Chung, Yutaka Hata, Mary Frances McAleer, Hee-Won Jung, Miloslava Zlevorová, Brendan Killory, Raymond Sawaya, Anita Chawla, John Trusheim, H. Ian Robins, Judy Lima, Prakash Ambady, Barbara O'Brien, Sonia Bermúdez, Howard Colman, Matthias Gromeier, Jean-Sébastien Guillamo, Maria C. Pietanza, Antonello Vidiri, Laura Guyman, Kristin Swanson, Paul Rosenblatt, Joshua L. Dowling, Lakshmi Nayak, Ashlee Drawz, Yu Jung Kim, Mikael L. Rinne, Shlomit Yust-Katz, Jessi Stevens, Katharine J. Drummond, Patricia Wing, Sarah Taylor, Joshua E. Allen, Ron Schaafsma, John DeGroot, Shigetoshi Yano, Paula Rauschkolb, Anupam Kumar, Soichiro Shibui, M. E. van Linde, Shirish M. Gadgeel, Yoshitaka Narita, Nicholas G. Avgeropoulos, Luca Bertero, Hongjun Wang, Jason K. Rockhill, Suriya Jeyapalan, Yukihiko Sonoda, Hikaru Sasaki, Shirley L. Markant, Masamitsu Nishihara, Daniel J. Brat, Alexandra Flowers, Monica Sierra del Rio, Morgan Prust, Adam M. Sonabend, Pierre A. Robe, James J. Dignam, Julia C. Chisholm, Gregory J. Riely, Mary Gerard, Sajeel Chowdhary, Natalie Jäger, Giovanna M. D'Abaco, James J. Culhane, Tatsunori Okamura, Erik P. Sulman, L. Adriana Esparza, Ivo W. Tremont-Lukats, Emily Porensky, Yoshihiro Oka, Marcelo De Carvalho, Brigitte C. Widemann, Stacey Kalambakas, Rolf D. Kortmann, Stewart Goldman, Jaap C. Reijneveld, Andrew Brenner, Jacob Mandel, Riccardo Draghi, Yunus Arik, Shinji Yamashita, Torsten Pietsch, Tanweer Zaidi, Dawid Schellingerhout, Marta Penas-Prado, Veronica Villani, Adriana Olar, Vanessa L. Merker, Matthias Holdhoff, Joke W. Baars, Katrina H. Smith, Arnab Chakravarti, Giorgio Carrabba, Gertjan J.L. Kaspers, Susan Boulton, Peter A. Forsyth, David T.W. Jones, Anne Baldock, Meier Hsu, Soham Dasgupta, Jeremy Rudnick, Arun Rai, Jessica Sun, Naoki Shinojima, Christian Mawrin, Eita Uchida, Jaswinder Jutla, Koichi Ichimura, Alona Muzikansky, Jean Philippe Maire, Louis B. Nabors, Yuko Matsushita, Emilie Le Rhun, Annick Desjardins, Magali Lecavalier-Barsoum, Laurie Rice, Bradford A. Moffat, Kelly Hempfling, Andrew A. Kanner, Mark W. Kieran, Stephanie M. Robert, Hervé Ghesquières, Alba A. Brandes, E. Sander Connolly, Jingxia Liu, David T. Dicker, Katherine B. Peters, Gregory S. Burzynski, Charles Sweeley, Deborah T. Blumenthal, Nicolás Useche, Tulika Ranjan, Thierry Muanza, Mercedes Garcia Villanueva, Fernando Hakim, Yana Krutoshinskaya, Shintaro Fukushima, Ryo Nishikawa, Damien C. Weber, Michael R. Chicoine, Motomasa Furuse, André Busson, Joseph R. Simpson, Gabriele Röhn, Susanne Koeppen, Arjun Sahgal, Fabio M. Iwamoto, Leland Graves, Sarah Iglseder, Taro Yanagawa, Michael Lahn, Ramaswamy Govindan, Eduardo Roberts Cervantes, Eric S. Wong, Nadine Kliese, Feng Tai, Katja von Hoff, Vincenzo Anelli, Trevor J. Pugh, Andrés F. Cardona, Gebra Cuyun Carter, Yuko Watanabe, Bogdana Suchorska, Manuela Caroli, José Luis Asencio, Eudocia Q. Lee, John Floyd, Lucas Moreno, Samantha J Mills, Jun-ichiro Kuroda, Susan Chi, David N. Louis, Aanchal Kakkar, Elizabeth R. Gerstner, Annika Schlamann, Robert Cavaliere, John L. Villano, Asha Das, Petr Kavan, Takaaki Yanagisawa, Luc Taillandier, Jonathan Fratkin, Günther Stockhammer, Tomasz Janicki, Sherese Fralin, Wafik Zaky, Lisa Scarpace, Kazunari Yoshida, Magalie Hilton, Andrey Korshunov, Aliasgar Moiyadi, Alexandra Gorelick, Alfredo Carrato Mena, Yuya Nishiyama, Riccardo Soffietti, Marina Donativi, Andrew S. Chi, Lauren Schaff, Andrew P. Morokoff, Sophie E. M. Veldhuijzen van Zanten, Hans-Joachim Reimers, John G. Stewart, Clare Ferrigno, Jackson Hamilton, Do-Hyun Nam, Samantha Hammond, Regina Krel, Mika Watanabe, Anna K. Nowak, Elina Tsyvkin, Michael W. McDermott, Jacoline E C Bromberg, Teiji Tominaga, Laila M. Poisson, Lisa Doherty, Alessia Lodi, Vino Apok, Magdalena Kneblova, Michelle Bell, Carl Jaffe, Sunita Dahr, Maria Koh, Pedro Garciarena, J. Gregory Cairncross, Ana Gómez Rueda, Augustus Perez, Ho Jun Seol, Frank Saran, Camillo Porta, Grace Elzinga, Michael Cloney, and Charles P. Hart
Subjects: Cancer Research, medicine.medical_specialty, business.industry, 010403 inorganic & nuclear chemistry, 01 natural sciences, 0104 chemical sciences, 03 medical and health sciences, Abstracts, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Medical physics, Neurology (clinical), business
Published: 2013

23. Bevacizumab-based therapy for colorectal cancer: experience from a large Canadian cohort at the Jewish General Hospital between 2004 and 2009

Author: Gerald Batist, P. Metrakos, D. W. Wasserman, Aline Mamo, P. Chaudhury, Petr Kavan, Mazen Hassanain, and N. Bouganim
Subjects: safety, medicine.medical_specialty, Bevacizumab, genetic structures, Colorectal cancer, efficacy, colorectal cancer, Internal medicine, medicine, Medical history, Adverse effect, business.industry, medicine.disease, digestive system diseases, humanities, eye diseases, Surgery, Pulmonary embolism, Clinical trial, Expanded access, Cohort, Original Article, sense organs, business, medicine.drug
Abstract: Before its regulatory approval in Canada, bevacizumab to treat patients with colorectal cancer (crc) was accessed through the Bevacizumab Expanded Access Trial and a special-access program at the Jewish General Hospital. We retrospectively evaluated patient outcomes in that large cohort. All patients (n = 196) had metastatic crc, were bevacizumab-na&iuml, ve, and received bevacizumab in combination with chemotherapy at the Jewish General Hospital between 2004 and 2009. We collected patient demographics and clinical characteristics, relevant medical history, disease stage and tumour pathology at diagnosis, type, duration, and line of therapy, grades 3 and 4 adverse events (aes), time to disease progression (ttp), and overall survival (os) from diagnosis. Median follow-up was 36.0 months. Median ttp was 8.0 months [95% confidence interval (ci): 7.0 to 9.0 months). Median os was 41.0 months (95% ci: 36.0 to 47.0 months). Of the 40 grades 3 and 4 bevacizumab-related aes experienced by 38 patients (19.4%), the most common were thrombocytopenia (n = 17), deep-vein thrombosis (n = 6), pulmonary embolism (n = 4), and hypertension (n = 3). In an expanded access setting, our data reflect the efficacy and safety of bevacizumab-based therapy in the controlled post-registration clinical trial setting.
Published: 2013

24. Systemic cancer therapy: achievements and challenges that lie ahead

Author: Michael Ostario Palumbo, R. Thomas Jagoe, Francois Patenaude, Victor Cohen, Lawrence Panasci, Nathalie A. Johnson, Michael Pollak, Gerald Batist, Sarit Assouline, Petr Kavan, and Wilson H. Miller
Subjects: medicine.medical_specialty, medicine.medical_treatment, Population, Review Article, Pharmacology, chemotherapy, Systemic therapy, Targeted therapy, systemic therapy, medicine, Pharmacology (medical), Intensive care medicine, education, Chemotherapy, education.field_of_study, hormonal therapy, business.industry, Cancer, toxicity, Immunotherapy, medicine.disease, targeted therapy, Hormonal therapy, immunotherapy, business, Developed country
Abstract: In the last half of the century, advances in the systemic therapy of cancer, including chemotherapy, hormonal therapy, targeted therapy, and immunotherapy have been responsible for improvements in cancer related mortality in developed countries even as the population continues to age. Although such advancements have yet to benefit all cancer types, systemic therapies have led to an improvement in overall survival in both the adjuvant and metastatic setting for many cancers. With the pressure to make therapies available as soon as possible, the side-effects of systemic therapies, in particular long-term side-effects are not very well characterized and understood. Increasingly, a number of cancer types are requiring long-term and even lifelong systemic therapy. This is true for both younger and older patients with cancer and has important implications for each subset. Younger patients have an overall greater expected life-span, and as a result may suffer a greater variety of treatment related complications in the long-term, whereas older patients may develop earlier side-effects as a result of their frailty. Because the incidence of cancer in the world will increase over the next several decades and there will be more people living with cancer, it is important to have an understanding of the potential side-effects of new systemic therapies. As an introductory article, in this review series, we begin by describing some of the major advances made in systemic cancer therapy along with some of their known side-effects and we also make an attempt to describe the future of systemic cancer therapy.
Published: 2013

25. Staged hepatectomy for bilobar colorectal hepatic metastases

Author: Stephanie M. Wong, Yasmine Yousef, Goffredo Orazio Arena, Mazen Hassanain, Eve Simoneau, Saleh Al-Abbad, Tung T. Tran, Yelda Jozaghi, Murad Aljiffry, Prosanto Chaudhury, Ayat Salman, Mohammad H. Jamal, Samir Jabbour, Petr Kavan, and Peter Metrakos
Subjects: Male, medicine.medical_specialty, Disease free survival, Time Factors, genetic structures, medicine.medical_treatment, Treatment outcome, Kaplan-Meier Estimate, Gastroenterology, Risk Assessment, Disease-Free Survival, X ray computed, Risk Factors, Internal medicine, medicine, Odds Ratio, Hepatectomy, Humans, Aged, Retrospective Studies, Chi-Square Distribution, Hepatology, business.industry, Liver Neoplasms, Quebec, Original Articles, Middle Aged, Surgery, Tomography x ray computed, Logistic Models, Treatment Outcome, Multivariate Analysis, Female, business, Colorectal Neoplasms, Tomography, X-Ray Computed
Abstract: ObjectivesThis study describes the management of patients with bilobar colorectal liver metastases (CRLM).MethodsA retrospective collection of data on all patients with CRLM who were considered for staged resection (n= 85) from January 2003 to January 2011 was performed. Patients who underwent one hepatic resection were considered to have had a failed staged resection (FSR), whereas those who underwent a second or third hepatic resection to produce a cure were considered to have had a successful staged resection (SSR). Survival was calculated from the date of diagnosis of liver metastases. Complete follow-up and dates of death were obtained from the Government of Quebec population database.ResultsMedian survival was 46months (range: 30–62months) in the SSR group and 22months (range: 19–29months) in the FSR group. Rates of 5-year survival were 42% and 4% in the SSR and FSR groups, respectively. Fifteen of the 19 patients who remained alive at the last follow-up date belonged to the SSR group.ConclusionsIn patients in whom staged resection for bilobar CRLM is feasible, surgery would appear to offer benefit.
Published: 2012

26. CLIN-NEURO/MEDICAL ONCOLOGY

Author: F. Girardi, C. Braun, Dennis C. Shrieve, Wei Chen, D. Kita, M. F. Fanelli, David Schiff, Sunyoung Ahn, Elizabeth Vera-Bolanos, J. Carrasquillo, S. Singer, James G. Herman, C. Bosa, Julia Selfridge, V. Tohidi, B.-A. Millar, M. Benavides, M. I. D. L. Fuente, Phioanh L. Nghiemphu, Kristin R. Swanson, John P. Kirkpatrick, Jonathan P.S. Knisely, Jörg C. Tonn, Kenneth Aldape, J. C. Streeter, R. Ruda, Seung Hong Choi, R. Curry, J. Yu, Ryo Nishikawa, E. Garoufalis, A. H. Friedman, Kurt A. Jaeckle, W. Zhang, Maryam Fouladi, Y. Odia, Arthur P. Chou, S. Sahebjam, E. Pentsova, Luis Souhami, Y. Yuan, F. N. Santos, C. Mesia, H. Friedman, Jennifer Linn, J. E. Adair, Yong Hwy Kim, Athanasios P. Kyritsis, Zvi Ram, M. G. Muhonen, Tracy T. Batchelor, Alissa A. Thomas, Stuart A. Grossman, M. Nasseri, Pedro Pérez Segura, S. Lacey, S. D. Bell, Helen A. Shih, E. Bit-Ivan, Timothy A. Chan, H. Pentsova, H. Wilson, Fumiko Shimizu, M. Forbes, L. Randolph, S. Kim, Amit Bhatt, Sabina Eigenbrod, T. Seigal, P. Dall'Occa, F. McSherry, R. M. Green, Michael D. Prados, Camilo E. Fadul, A. Guevarra, J.-Y. Han, Guido Reifenberger, E. Franceschi, D. Sageser, Jennie Taylor, Kevin Petrecca, M. K. Nicholas, Teresa Ribalta, Morris D. Groves, J.-Y. Blay, B. C. Beard, C. F. La, A. A. da Costa, K. Murillo-Medina, W. Pfisterer, R. Chu, Nan Lin, M. Ermani, A. J. Neuwelt, Samuel T. Chao, T. Ranjan, W. Taki, Hendrik Janssen, R. Agati, A. Mahta, T. N. Kreisl, E. Perez, J. Fuster, B. D. Fu, David M. Peereboom, N. Gresa-Arribas, Georg Widhalm, M. D'Apuzzo, J. Steinbach, Tom Mikkelsen, Michael Platten, R. Poggi, Sandra Ictech, I. Craven, A. Raghunathan, John B. Fiveash, N. L. Jansen, Rupert Egensperger, B. Badie, S. Medrano, Chul-Kee Park, K. Wong, Tae Min Kim, M. Bartolotti, M. Alejandro, T. Rosser, H.-P. Kiem, Marie-Christine Guiot, S. Gonzalez, J. Ljubimova, T. Furuta, J. Herndon, J. Finlay, Vivian Tabar, M. Hadjivassiliou, Christine Marosi, D. Hammoud, K. Black, S. K. Anderson, F. Bach, Gregory N. Fuller, N. Kased, S. Shpigel, Gianluca Marucci, Michael A. Vogelbaum, S. Bluml, J. Joo, M. D. Groves, X. Ye, Adam L. Cohen, J. A. Butman, M. D. Prados, X. Perez-Martin, R. Sharma, G. Colon-Otero, Richard M. Green, Paul D. Brown, Cornelia Sax, Robert J. Weil, J. Connelly, S. Burri, M. R. Welch, Marc K. Rosenblum, Minesh P. Mehta, Shlomit Yust-Katz, J. Canellas, Ulrich Bogdahn, S. Liker, P. U. Kumthekar, F. Gilles, M. Brock, Aaron T. Wild, A. Guerrero-Maldonado, Janet M. Bruner, A. Balmanoukian, E. Kitzweger, B. Schuknecht, Ayman I. Omar, J. Sampson, R. F. Del Maestro, W. Hruby, Niklas Thon, S. Zhao, F. Aboul-Enein, L. M. Alderson, J. McClain, J. Rudnick, J. Dorr, Vinay K. Puduvalli, Sonia Partap, Y. Hayashi, A. Kessinger, N. A. Shonka, T. Minamoto, D. Z. Lee, L. G. Berriel, T. Xie, J. Shih, J. S. Bubalo, Oscar Lin, J. E. Herndon, Michael Glantz, A. Gupta, H. Sabit, H. Heinrichs, Hans A. Kretzschmar, A. Asher, T. M. Bhavsar, A. Coan, V. A. Levin, M. Landeros, A. K. Choucair, D. Garbossa, G. Stockhammer, Jian Campian, C. J. Vecht, C. Ausch, Linda M. Liau, H. I. Farhat, M. Richards, H. I. Robins, R. Chaudhary, Agnieszka Korfel, Marta Penas-Prado, A. Jensen, I. Lolli, Amar J. Gajjar, K. Papsdorf, L. DeAngelis, Kathryn Beal, L. Phishniak, J. Joyce, Arnab Chakravarti, J. J. Vredenburgh, C. Dealis, A. F. Campos-Gines, Peter Hau, J.-I. Hamada, R. A. Gilbert, T. J. Kaley, Eric T. Wong, Ian F. Pollack, T. Gajewski, A. C. Levy, L. R. Bressler, X. Chen, C. Bernadette, O. Etxaniz, N. Antony, Birgit Flechl, D. Levacic, Byung Se Choi, J. I. Stenner, F. Pinto, Sandra K. Johnston, M. M. Mrugala, David Roberge, M. Wang, P. J. Anderson, H. A. Fine, M. J. Glantz, Alfred Yung, L. Alderson, M. Chamberlain, R. Naor, Jaume Capellades, Se-Hoon Lee, D. G. Brackman, Nathalie Jansen, T. Synold, Terri S. Armstrong, J. Pichler, X.-T. Kong, T. Cloughesy, P. Frankel, R. Valdez-Vazquez, Mathias Kunz, J. Dalmau, A. Baldock, Stewart Goldman, K. Rizzo, M. Nakada, Christoph Meisner, Ryan Merrell, C. Bomprezzi, Tomokazu Aoki, M. R. Gilbert, Jason K. Rockhill, Benjamin Ellezam, C. Sebastian, O. Arrieta, N. Wu, M. Magistrello, T. Patel, Adelheid Wöhrer, M. Sabel, F. Bokstein, V. Gomez-Molinar, S. Yovino, A. Kheder, Gaspar Reynes, R. Packer, M. Ronellenfitsch, Sasan Karimi, David Piccioni, J. M. Stachnik, C. Sebesta, Ryan Shanley, L. T. Chinen, H.-S. Gwak, E. A. Woyshner, D. Reuter, S. Bekker, K. Hunter, B. Haghighi, G. Poepperl, M. C. Chamberlain, W. Massey, M. A. Hamza, R. Cavaliere, Sichen Li, Daniela A. Bota, S. Spiegl-Kreinecker, G. Tatzreiter, Sigmund Hsu, M. Westphal, T. Pietsch, P. D. Barnes, C. Arango, G. Cervantes-Sanchez, C. Grommes, W. Brick, Vera Graute, M. P. Gabay, L. Bertero, Friedrich W. Kreth, F. M. Iwamoto, D. T. Blumenthal, M. Matsutani, K. B. Peters, S. F. Shakur, E. Flanagan, H. T. Kim, M. Simon, Michael Ackerl, Nadia N. Laack, J. Portnow, R. Ruckser, T. F. Cloughesy, H. Wayne Slone, A. A. Erazo-Valle-Solis, Karin Dieckmann, J. Baerhing, R. Soffietti, N. Laperriere, M. J. Gil, R. Fisher, Thierry Muanza, Reema R. Mody, W. Kim, L. Droms, Fabio M. Iwamoto, J. Grimm, Robert B. Jenkins, M. R. Aizenberg, E. Lipp, M. J. Taphoorn, V. Garcia-Navarro, J. H. Suh, Peter Bartenstein, E. Bourekas, Brett Theeler, W. G. Watkin, R. M. Tyson, Mira Zurayk, D. Alexandru, N. Uchiyam, J. Gilreath, A. J. Ramiro, R. Rockne, R. Naruse, M. Krieger, A. Kloet, Petr Kavan, E. Jaffe, D. A. Reardon, Jochen Herms, A. Willson, H. Zwinkels, M. Faedi, A. Moreno-Aspitia, J. Vredenburgh, Herbert H. Engelhard, C. Bridge, Paul W. Sperduto, H. Yoo, P. Friedman, N. Letarte, Tetsuya Ueba, Lisa M. DeAngelis, C. Nolan, Michael Weller, H. Colman, Jürgen Lutz, H. Ian Robins, J. McGregor, Pankaj Jalan, Joseph Landolfi, M. Di Battista, Bogdana Suchorska, Manuela Caroli, G. Nikkhah, A. Leibetseder, K. Aboody, V. Liu, Albert Lai, Yoshiki Arakawa, Kazuhiko Nozaki, G. Dhall, Kenneth R. Hess, Oscar Gallego, A. Naomi, A. Pace, T. M. Nguyen, K. Kawakami, K. DeBraganca, A. A. Brandes, V. K. Puduvalli, Lakshmi Nayak, Charles A. Conrad, Laurie E. Gaspar, P. J. Flynn, S. Ruiz-Gonzalez, Carmen Balana, J. Lange, T. Kaley, Vijay Pandav, J. Herrada, Eugenia Verger, S. Honigschnabel, M. Chen, C. A. Bridge, Yu Jung Kim, Mary Jo T. Necesito-Reyes, Bettina Hentschel, Victor A. Levin, J. Hu, K. Hoang-Xuan, Chae-Yong Kim, W. Sherman, L. Armbruster, T. Yun, C. Carapella, E. L. Diamond, A. Mahapatra, Warren P. Mason, X. Luo, R. C. Rockne, S. G. Crasto, L. Bailey, K. Sanghee, Matthias Preusser, R. Mathew, Jaclyn Wu, D. White, Susumu Miyamoto, A. Omuro, A. Desjardins, P.H. Gutin, J. S. Lee, Andrew D. Trister, Maxwell Lewis Neal, W. Zaky, A. L. Sumrall, C. M. Sperduto, A. L. Baldock, S. Phuphanich, J. Sul, S. H. Shin, E. A. Neuwelt, Heinrich Elinzano, C. Huang, H. S. Friedman, Laura Guyman, Sean Grimm, C. Sanchez, H. Newton, G. Oberhauser, Chunyue Yin, Wolfgang Wick, Caterina Giannini, Veronica Chiang, C. LaFougere, P. Metellus, A. Krauthammer, M. Kinoshita, J. Sheehan, Miguel J. Gil, E. Trevisan, J. Raizer, Shin-Ichi Miyatake, A. Olch, Jin Wook Kim, John L. Villano, Patricia Sneed, Brian P. O'Neill, A. Sahgal, Il Han Kim, A. Brickhouse, K. Herath, C. Zoccoli, M. J. van den Bent, T. Tsukahara, M. Heaney, B. Hassanzadeh, J. Quan, David R. Macdonald, Percy Ivy, D. Liue, John H. Suh, K. Miyashita, T. J. Fraum, W. A. Yung, I. Melguizo-Gavilanes, Maciej M. Mrugala, Matthew J. Matasar, and P. Garciarena
Subjects: Cancer Research, medicine.medical_specialty, Abstracts, Oncology, business.industry, medicine, Medical physics, Neurology (clinical), business
Published: 2012

27. Complete response of hepatocellular carcinoma with sorafenib and 90Y radioembolization

Author: J.M. Bouteaud, Mazen Hassanain, I. Feteih, Prosanto Chaudhury, C. Nudo, Petr Kavan, David Valenti, Thierry Alcindor, T. Cabrera, and Peter Metrakos
Subjects: Oncology, Sorafenib, medicine.medical_specialty, business.industry, Cancer, medicine.disease, gastrointestinal, digestive system diseases, surgery, Internal medicine, Hepatocellular carcinoma, oncology, Overall survival, Medicine, business, neoplasms, Complete response, medicine.drug
Abstract: Advanced hepatocellular carcinoma has a dismal prognosis, with a median overall survival of 7.9 months if untreated and of 10.7 months if treated with sorafenib. We present a case of advanced previously unresectable hepatocellular carcinoma in a 49-year-old man that achieved a pathologic complete response and was made amenable to surgery with sorafenib in combination with 90Y radioembolization. The patient&rsquo, s survival was more than double the median for patients treated with sorafenib alone.
Published: 2010
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28. P-0214 - Use of Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer (MCRC): A Post-Hoc Analysis of the Glutox Study

Author: Benoit, Samson, Pierre, Dube, Nathalie, Aucoin, Rafal, Wierzbicki, Jean, Maroun, Richard, Letourneau, Eric, Chen, Danielle, Charpentier, Felix, Couture, Mark, Vincent, Jean, Lepine, Pierre, Whitlock, Karine, Alloul, Francois, Leblond, Wei, Zhou, and Petr, Kavan
Published: 2014
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29. P-0215 - Efficacy, Safety and Patient-Reported Outcomes of Oxaliplatin-Based Chemotherapy in Elderly Patients with Colorectal Cancer (CRC): A Post-Hoc Analysis of the Glutox Study

Author: Benoit, Samson, Pierre, Dube, Nathalie, Aucoin, Rafal, Wierzbicki, Jean, Maroun, Richard, Letourneau, Eric, Chen, Danielle, Charpentier, Felix, Couture, Mark, Vincent, Jean, Lepine, Pierre, Whitlock, Helene, Grassin, Francois, Leblond, Wei, Zhou, and Petr, Kavan
Published: 2014
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30. Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy

Author: Mazen Hassanain, Prosanto Chaudhury, Dionisios Vrochides, Matthew Cesari, Peter Metrakos, Gabriel Chan, Amy Neville, Petr Kavan, and Victoria Marcus
Subjects: Male, Oncology, medicine.medical_specialty, Time Factors, recurrence, Colorectal cancer, medicine.medical_treatment, Pilot Projects, Kaplan-Meier Estimate, Risk Assessment, survival, Disease-Free Survival, Hospitals, University, neoplasm metastasis, hepatectomy, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Odds Ratio, medicine, Humans, Prospective Studies, Prospective cohort study, Neoadjuvant therapy, Proportional Hazards Models, Chemotherapy, Chi-Square Distribution, Hepatology, Proportional hazards model, business.industry, Liver Neoplasms, Quebec, Gastroenterology, Original Articles, Odds ratio, Middle Aged, medicine.disease, Chemotherapy regimen, Neoadjuvant Therapy, Treatment Outcome, Chemotherapy, Adjuvant, Female, Hepatectomy, Colorectal Neoplasms, business, Algorithms, neoadjuvant chemotherapy
Abstract: BackgroundThe complete resection of liver metastases from colorectal cancer is the major determinant of longterm survival. The effectiveness of current chemotherapy regimens has made treatment algorithms more flexible and resulted in many different options. Recently, the pathological response to chemotherapy has emerged as another important prognostic marker. Different systems have been used to grade the pathological response in these patients.MethodsThis study prospectively evaluates the prognostic value of the pathological response grade (PRG) in liver metastases treated with neoadjuvant chemotherapy.ResultsBetween 2002 and 2006, 50 patients were treated with a sandwich chemotherapy regimen and underwent liver resection. Complete resection was achieved in 45 patients (90%). A strong pathological response to chemotherapy (
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31. Portal vein embolization stimulates tumour growth in patients with colorectal cancer liver metastases

Author: Nasser Abualhassan, Peter Metrakos, Eve Simoneau, Arwa El Baage, Mazen Hassanain, Prosanto Chaudhury, Ayat Salman, Tatiana Cabrera, Murad Aljiffry, Petr Kavan, Saleh Al-Abbad, Mohammad H. Jamal, and David Valenti
Subjects: Male, Oncology, medicine.medical_specialty, Time Factors, genetic structures, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Angiogenesis Inhibitors, bevacizumab, Antibodies, Monoclonal, Humanized, Risk Assessment, colorectal cancer liver metastases, Muscle hypertrophy, degree of hypertrophy, Risk Factors, Internal medicine, medicine, Hepatectomy, Humans, liver regeneration, Neoadjuvant therapy, Retrospective Studies, portal vein embolization, Chi-Square Distribution, Hepatology, Portal Vein, business.industry, Liver Neoplasms, tumour growth, Quebec, Gastroenterology, Retrospective cohort study, Original Articles, medicine.disease, Embolization, Therapeutic, Neoadjuvant Therapy, Liver regeneration, Tumor Burden, Treatment Outcome, Chemotherapy, Adjuvant, Portal vein embolization, Female, Colorectal Neoplasms, Tomography, X-Ray Computed, business, medicine.drug
Abstract: ObjectivesPortal vein embolization (PVE) can facilitate the resection of previously unresectable colorectal cancer (CRC) liver metastases. Bevacizumab is being used increasingly in the treatment of metastatic CRC, although data regarding its effect on post-embolization liver regeneration and tumour growth are conflicting. The objective of this observational study was to assess the impact of pre-embolization bevacizumab on liver hypertrophy and tumour growth.MethodsComputed tomography scans before and 4weeks after PVE were evaluated in patients who received perioperative chemotherapy with or without bevacizumab. Scans were compared with scans obtained in a control group in which no PVE was administered. Future liver remnant (FLR), total liver volume (TLV) and total tumour volume (TTV) were measured. Bevacizumab was discontinued ≥4weeks before PVE.ResultsA total of 109 patients and 11 control patients were included. Portal vein embolization induced a significant increase in TTV: the right lobe increased by 33.4% in PVE subjects but decreased by 34.8% in control subjects (P < 0.001), and the left lobe increased by 49.9% in PVE subjects and decreased by 33.2% in controls (P= 0.022). A total of 52.8% of the study group received bevacizumab and 47.2% did not. There was no statistical difference between the two chemotherapy groups in terms of tumour growth. Median FLR after PVE was similar in both groups (28.8% vs. 28.7%; P= 0.825).ConclusionsAdequate liver regeneration was achieved in patients who underwent PVE. However, significant tumour progression was also observed post-embolization.
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32. A Study of Administering FOLFIRINOX Before Surgery For Potentially Curable Pancreatic Cancer (Folfirinox)

Author: Petr Kavan, Dr. Petr Kavan,Director,AYA Oncology,Associate Professor,Dept. of Oncology
Published: 2017

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32 results on '"Petr Kavan"'

1. Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial

2. Feasibility and safety of endoscopic ultrasound-guided diffusing alpha emitter radiation therapy for advanced pancreatic cancer: Preliminary data

3. The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma

4. Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

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

6. The Cost-Effectiveness of Lenvatinib in the Treatment of Advanced or Unresectable Hepatocellular Carcinoma from a Canadian Perspective

7. Reasons for delay in timely administration of adjuvant chemotherapy for patients with stage III colon cancer: a multicentre cohort study from the McGill University Department of Oncology

8. Prevention of venous thromboembolism in ambulatory patients with cancer

9. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

10. Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial

11. Genomic Analysis of Tumors from Patients with Glioblastoma with Long-Term Response to Afatinib

12. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164

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

14. Rationale and Design of the IROCAS Study: Multicenter, International, Randomized Phase 3 Trial Comparing Adjuvant Modified (m) FOLFIRINOX to mFOLFOX6 in Patients With High-Risk Stage III (pT4 and/or N2) Colon Cancer—A UNICANCER GI-PRODIGE Trial

15. Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus

16. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial

17. Progression pattern and adverse events with bevacizumab in glioblastoma

18. 338. Comparing characteristics and survival outcomes of adolescent and young adults to mature patients with colorectal cancer

19. Complete Resolution of Metastatic Gallbladder Cancer after Standard Gemcitabine-Cisplatin Combination Therapy

20. High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

21. AT-18SURVIVAL ANALYSIS OF PATIENTS WITH A PFS EVENT WHO DID NOT RECEIVE POST-PROGRESSION THERAPY IN AVAGLIO (BEVACIZUMAB [BEV] PLUS RADIOTHERAPY [RT] AND TEMOZOLOMIDE [TMZ] FOR NEWLY DIAGNOSED GLIOBLASTOMA [GBM])

22. NEURO/MEDICAL ONCOLOGY

23. Bevacizumab-based therapy for colorectal cancer: experience from a large Canadian cohort at the Jewish General Hospital between 2004 and 2009

24. Systemic cancer therapy: achievements and challenges that lie ahead

25. Staged hepatectomy for bilobar colorectal hepatic metastases

26. CLIN-NEURO/MEDICAL ONCOLOGY

27. Complete response of hepatocellular carcinoma with sorafenib and 90Y radioembolization

28. P-0214 - Use of Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer (MCRC): A Post-Hoc Analysis of the Glutox Study

29. P-0215 - Efficacy, Safety and Patient-Reported Outcomes of Oxaliplatin-Based Chemotherapy in Elderly Patients with Colorectal Cancer (CRC): A Post-Hoc Analysis of the Glutox Study

30. Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy

31. Portal vein embolization stimulates tumour growth in patients with colorectal cancer liver metastases

32. A Study of Administering FOLFIRINOX Before Surgery For Potentially Curable Pancreatic Cancer (Folfirinox)

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