Chaim Sheba Medical Center

Tel Aviv, Israel

Chaim Sheba Medical Center

Tel Aviv, Israel
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News Article | July 10, 2017
Site: www.biosciencetechnology.com

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings offer an example of how extreme population-level tragedies can have an impact on health. Holocaust survivors were exposed to a variety of factors that have been linked with cancer. Siegal Sadetzki, MD, MPH, of the Chaim Sheba Medical Center in Israel, and her colleagues wondered whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals. To investigate, the team studied 152,622 Holocaust survivors who were followed for more than 45 years. Two separate definitions of exposure were used. One definition was based on the individual's entitlement for compensation according to a set of laws. The other was based on the country of origin, using a classification of countries during the war into those that were directly governed by Nazi Germany and other non-occupied countries. Cancer was diagnosed in 22 percent of those who were granted compensation for suffering persecution during the war versus 16 percent of those who were denied compensation. Survivors who were granted compensation had a six percent higher risk of developing any type of cancer than those who were denied compensation, and they had a 12 percent increased risk for colorectal cancer and a 37 percent increased risk for lung cancer. Those born in occupied countries had an eight percent increased risk of developing any cancer than those born in non-occupied countries, as well as eight percent and 12 percent increased risks of colorectal cancer and lung cancer, respectively. The investigators observed no elevated risks for breast cancer and gynecologic cancers among female survivors. "The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II," said Prof. Sadetzki. "Such inspection cannot be conducted by experimental studies and could only be evaluated by using observational epidemiological surveys." An accompanying editorial notes that the associations reported by Prof. Sadetzki and colleagues between the extreme deprivation experienced by Holocaust survivors and cancer may also have parallels with other extreme population-level events, including in racial/ethnic minority groups who experience severe social deprivation over time.


News Article | July 10, 2017
Site: www.reuters.com

(Reuters Health) - Torn from their homes and families, Jewish holocaust survivors endured starvation, enslavement and staggering physical and emotional abuse at the hands of the Nazis during World War II. Now, a study released on Monday shows that survivors suffer an elevated risk of cancer, especially lung and colorectal malignancies. Israeli researchers examined the medical records of more than 152,000 holocaust survivors over more than 45 years and compared those who qualified for compensation as a result of their persecution during the war to those whose compensation bids were rejected. Survivors whose compensation bids were rejected were generally those who had been caught up in the war but who spent little or no time in a closed ghetto or a concentration camp and who survived with minimal disability. Cancer was diagnosed in 22 percent of those granted compensation and 16 percent of those denied it, according to the report in the journal Cancer. The differences were most striking for lung and colon cancers. Survivors granted compensation had a 37 percent higher risk of lung cancer and a 12 percent higher risk of colorectal cancer than those denied compensation, after adjustments for age, gender and country of origin. “This study brings to light again that outside forces can cause cancer,” said cancer epidemiologist Electra Paskett of The Ohio State University in Columbus. “Stress really does get under your skin to cause disease.” “Many have not given this hypothesis its due justice,” she said in an email. Paskett was not involved with the study but was one of the authors of an accompanying editorial. The study also found heightened cancer risk for survivors born in countries occupied by Nazi Germany compared to survivors born elsewhere. Survivors born in Nazi-occupied countries had an 8 percent higher risk of developing cancer than survivors born elsewhere, the study found. Those born in occupied countries also had a 12 percent higher risk of lung cancer and an 8 percent higher risk of colorectal cancer. Holocaust survivors experienced a myriad of potential risk factors for cancer, including infectious disease, severe and prolonged hunger, mental stress, physical abuse and overcrowding, lead author Dr. Siegal Sadetzki of the Chaim Sheba Medical Center in Tel Hashomer, Israel said in a phone interview. Although the study cannot explain the reasons for heightened risk, Sadetzki speculated about a possible explanation for the increase in lung cancer among compensated holocaust survivors. “I believe the risk for lung cancer is by a secondary, indirect mechanism,” she said. “Due to the stress, maybe the holocaust survivors smoked more and experienced lifestyle habits that are not so good for you.” Previous studies have found that starvation might protect against colon cancer. But prolonged starvation and deprivations from all vitamins and nutrients, such as what holocaust survivors experienced, might have had a different effect, Sadetzki said. An alternative theory for the rise in colon cancer rates could be that survivors compensated for their lack of food during the war by overeating afterward, she said. A previous study also found an overall increased risk of cancer, and in particular colorectal and lung cancer, among Jewish holocaust survivors. The prior study also reported an increased risk of breast cancer among women survivors. The new study, however, showed no increase in risk for breast or gynecologic cancer among female survivors. Nearly 95 percent of Hungarian Jewish women held in concentration camps during the war stopped menstruating, another previous study found. Not menstruating appears to protect against breast cancer. The longer women menstruate, the more likely they are to be diagnosed with hormone-related cancers, like breast cancer, the authors write. In their editorial, Paskett and her colleagues draw parallels between the privations experienced by holocaust survivors and those experienced by poor racial minority groups in the United States today. “Both groups had or have stressors of violence, lack of food, housing insecurity, discrimination and loss of power,” Paskett said. “Today we can think about those living in urban neighborhoods or rural areas with crumbling housing, drug use and unemployment, or low wages, contributing to increasing violence, lack of good food in area food markets, discrimination and even environmental pollution caused by large businesses.” “We need people who are willing to go into these communities and work with the people who live there to develop strategies and solutions to be able to help themselves,” she said.


News Article | July 10, 2017
Site: www.eurekalert.org

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings offer an example of how extreme population-level tragedies can have an impact on health. Holocaust survivors were exposed to a variety of factors that have been linked with cancer. Siegal Sadetzki, MD, MPH, of the Chaim Sheba Medical Center in Israel, and her colleagues wondered whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals. To investigate, the team studied 152,622 Holocaust survivors who were followed for more than 45 years. Two separate definitions of exposure were used. One definition was based on the individual's entitlement for compensation according to a set of laws. The other was based on the country of origin, using a classification of countries during the war into those that were directly governed by Nazi Germany and other non-occupied countries. Cancer was diagnosed in 22 percent of those who were granted compensation for suffering persecution during the war versus 16 percent of those who were denied compensation. Survivors who were granted compensation had a six percent higher risk of developing any type of cancer than those who were denied compensation, and they had a 12 percent increased risk for colorectal cancer and a 37 percent increased risk for lung cancer. Those born in occupied countries had an eight percent increased risk of developing any cancer than those born in non-occupied countries, as well as eight percent and 12 percent increased risks of colorectal cancer and lung cancer, respectively. The investigators observed no elevated risks for breast cancer and gynecologic cancers among female survivors. "The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II," said Prof. Sadetzki. "Such inspection cannot be conducted by experimental studies and could only be evaluated by using observational epidemiological surveys." An accompanying editorial notes that the associations reported by Prof. Sadetzki and colleagues between the extreme deprivation experienced by Holocaust survivors and cancer may also have parallels with other extreme population-level events, including in racial/ethnic minority groups who experience severe social deprivation over time. "Cancer Risk Among Holocaust Survivors in Israel--A Nationwide Study." Siegal Sadetzki, Angela Chetrit, Laurence S. Freedman, Nina Hakak, Micha Barchana, Raphael Catane, and Mordechai Shani. CANCER; Published Online: July 10, 2017 (DOI: 10.1002/cncr.30783). "Extreme Population-Level Events: Do They Have an Impact on Cancer?" Beti Thompson, Sarah Gehlert, and Electra D. Paskett. CANCER; Published Online: July 10, 2017 (DOI: 10.1002/cncr.30778). Author Contact: Lee Gat, of the Sheba Medical Center, at Lee.gat@sheba.health.gov.il or 03- 530 3296. CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology, course, and treatment of human cancer. CANCER is published on behalf of the American Cancer Society by Wiley and can be accessed online at http://wileyonlinelibrary. . Follow us on Twitter @JournalCancer and Facebook https:/ Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical, and scholarly journals, combined with our digital learning, assessment and certification solutions help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www. .


VILLEJUIF, Frankreich--(BUSINESS WIRE)--Das WIN Consortium (WIN) hat von der US-amerikanischen Gesundheitsbehörde FDA (US Food and Drug Administration) die Genehmigung zur Einleitung der klinischen Untersuchung eines neuartigen therapeutischen Ansatzes erhalten, der auf einer Kombination von drei zielgerichteten Therapien zur Erstlinienbehandlung von Patienten mit fortgeschrittenem nicht-kleinzelligem Lungenkrebs (NSCLC) beruht. Die Survival Prolongation by Rationale Innovative Genomics (SPRING)-Studie zielt darauf ab, Patienten zu rekrutieren, die üblicherweise mit einer platinbasierten Erstlinien-Chemotherapie behandelt werden. Patienten mit nachgewiesenen, als Target verwendbaren Treiber-Mutationen (Mutationen des EGF-Rezeptors, ALK-Rearrangements, ROS1 und MET Exon 14 Skipping-Mutationen) sind von dieser Behandlung ausgeschlossen. Die Population der NSCLC-Patienten ohne verfolgbare onkogene Treibermutationen, die für die Aufnahme in die SPRING-Studie vorgesehen sind, repräsentiert die große Mehrheit der Patienten mit metastasierendem NSCLC (rund 80 Prozent der weißen Bevölkerung). Da über 60 Prozent der Patienten mit NSCLC in einem fortgeschrittenen oder metastasierendem Stadium diagnostiziert werden und weniger als 5 Prozent der Patienten nach 5 Jahren noch leben, ist ein Paradigmenwechsel in der Strategie zur Behandlung der tödlichsten Form von Krebs dringend erforderlich. Der neuartige Ansatz von WIN basiert auf der kombinierten Anwendung zielgerichteter Medikamente im Rahmen einer Triple-Therapie, die aus dem historischen Erfolg dieser Methode bei AIDS und Tuberkulose abgeleitet wurde. In ähnlicher Weise beruht unser Konzept auf der Verbindung von drei zielgerichteten Medikamenten, die im Rahmen ihrer kombinierten Anwendung äußerst viel versprechend sind, während sie bei ihrer Anwendung als Monotherapie lediglich bescheidene klinische Ergebnisse nach sich ziehen. Die von Prüfern initiierte SPRING-Studie steht unter der gemeinsamen Leitung von Dr. Razelle Kurzrock (University of California San Diego, Moores Cancer Center) und Dr. Enriqueta Felip (Vall d'Hebron Institute of Oncology). Sie wird voraussichtlich in 5 Ländern und an 8 klinischen Zentren von WIN-Mitgliedern stattfinden: University of California San Diego Moores Cancer Center und Avera Cancer Institute (Dr. Benjamin Solomon), USA; Institut Curie (Dr. Nicolas Girard), Centre Léon Bérard (Dr. Pierre Saintigny) und Hôpital Paris Saint-Joseph (Dr. Eric Raymond), Frankreich; Vall d'Hebron Institute of Oncology, Spanien; Centre Hospitalier de Luxembourg (Dr. Guy Berchem) sowie Chaim Sheba Medical Center (Dr. Jair Bar), Israel. Die SPRING-Studie wird durch einen Phase-I-Abschnitt zur Untersuchung der Sicherheit der Kombination und Bestimmung der optimalen Dosierungen für die Phase II eingeleitet. Im Rahmen des Phase-II-Abschnitts wird die Wirksamkeit dieses Triple-Therapie-Schemas als Erstlinienbehandlung bei metastasierendem NSCLC untersucht. Die Studie wird darüber hinaus die Validierung eines neuartigen SIMS-Algorithmus (Simplified Interventional Mapping System) anstreben, der von WIN entwickelt wurde, um der Tumorbiologie jedes einzelnen Patienten für eine spezifische Medikamentenkombination gerecht zu werden. Zu diesem Zweck werden im Rahmen der SPRING-Studie Biopsien von Tumor- und normalem Lungengewebe entnommen und untersucht. Die DNA- und RNA-Untersuchungen werden von Dr. Brandon Young am Avera WIN Precision Oncology Laboratory in San Marcos (Kalifornien) an den Biopsien durchgeführt, wobei Illumina NGS (Next Generation Sequencing) und die Expression (mRNA und MicroRNA) EdgeSeq-Technologie von HTG Molecular zusammen mit Illumina (NGS) zum Einsatz kommen. Die Datenintegration für den SIMS-Algorithmus wird in Israel an der Ben-Gurion University of the Negev unter der Leitung von Dr. Eitan Rubin durchgeführt. „Hierbei handelt es sich um eine beispiellose Kooperation zwischen unseren WIN-Mitgliedern aus wissenschaftlichen Kreisen, aus der Industrie und aus Forschungsorganisationen.“, so Dr. Vladimir Lazar, Chief Scientific und Operating Officer von WIN. „Die Studie wird an acht klinischen Zentren durchgeführt. Die Medikamente werden von der Pfizer Inc., die DNA- und RNA-Analyse-Technologien von Illumina und HTG Molecular und die Pharmakovigilanz von Covance bereitgestellt. Wir sind der Foundation ARC im Rahmen der Krebsforschung in Frankreich für ihre finanzielle Unterstützung bei der Einleitung der SPRING-Studie zu besonderem Dank verpflichtet. Wir begrüßen darüber hinaus die Unterstützung aller Organisationen und privaten Spender, die einen Beitrag zum Erfolg dieses beispiellosen Projekts zur Bekämpfung von Lungenkrebs leisten möchten", ergänzte Dr. Lazar. „Wir sind hocherfreut zu sehen, dass diese Vision immer konkreter wird und sich diese beispiellose Kooperation verwirklichen lässt. Wir freuen uns nun auf die Durchführung in unseren klinischen Zentren. Wir werden darüber hinaus die rasche Einführung zusätzlicher Kombinationen und die Beteiligung weiterer Pharmaunternehmen bei der Umsetzung unserer Ziele benötigen", so Dr. Razelle Kurzrock, Trial Global Coordinator und Head of WIN Clinical Trials Committee. „WIN besitzt das Potenzial und die Expertise, andere Kombinationen testen zu können, und verfügt zudem über die erforderlichen Technologien, um der Tumorbiologie jedes einzelnen Patienten mit einer maßgeschneiderten Kombination gerecht zu werden.” Über das WIN Consortium Das WIN Consortium ist ein in Frankreich ansässiges gemeinnütziges Netzwerk von 41 weltweit führenden akademischen Gesundheitszentren und von Unternehmen aus den Bereichen Pharmazeutik und Diagnostik, Kostenträgern im Gesundheitswesen, Forschungsorganisationen und Stiftungen sowie Patientenvertretern aus 17 Ländern und 4 Kontinenten, die an der Entwicklung und Anwendung der vielversprechendsten Fortschritte in der Krebsforschung arbeiten, die von einer großen Zahl von Patienten und Familien so dringend benötigt werden.


BEDFORD, Mass.--(BUSINESS WIRE)--Augmenix, Inc., a medical technology company that develops, manufactures, and sells proprietary absorbable hydrogels that separate and protect organs at risk during radiotherapy, today announced that the first patients have been treated with SpaceOAR® hydrogel at the Chaim Sheba Medical Center in Tel Hashomer, Israel. SpaceOAR hydrogel is an absorbable prostate-rectum spacer that reduces rectal injury during prostate radiotherapy. “We are excited to offer our patients this new, innovative technology to significantly reduce risks of prostate cancer radiotherapy,” said Zvi Symon, M.D. from the Chaim Sheba Medical Center. “SpaceOAR hydrogel will provide meaningful long-term benefits, improving overall quality of life for our patients." “We are extremely pleased to bring our innovative SpaceOAR hydrogel to physicians and patients in Israel," commented John Pedersen, CEO of Augmenix. "Our growing body of clinical evidence demonstrates that SpaceOAR hydrogel significantly reduces the risk of rectal and urinary toxicities and loss of sexual function associated with prostate cancer radiotherapy. SpaceOAR hydrogel is making a significant difference in the lives of men around the world.” Radiation therapy in the treatment of prostate cancer can cause unintended injury to adjacent healthy tissue, which can lead to bowel, urinary and sexual symptoms that can affect patient health and quality of life. With SpaceOAR hydrogel, physicians can place a hydrogel barrier to separate the prostate from surrounding healthy tissue. In January 2017, Augmenix announced three-year post-treatment data from a prospective, randomized, multi-center, patient-blinded clinical trial showing that patients treated with SpaceOAR hydrogel technology prior to prostate cancer radiotherapy demonstrated significant rectal (bowel), urinary, and sexual benefit through three years of follow up. Overall patient wellness at three years was assessed by looking at the percent of patients with clinically significant declines in all three quality of life (QOL) domains (bowel, urinary and sexual). Fully 20% (1 in 5 patients) of men in the Control arm had clinically significant declines in all three QOL areas compared to only 2.5% (1 in 40 patients) of men in the SpaceOAR hydrogel arm (p=0.002).1 Among men who were potent at baseline, the analysis showed that SpaceOAR hydrogel treated men were better able to maintain erections sufficient for intercourse through 3 years of follow-up (p=0.03). Of the men treated with SpaceOAR hydrogel, 66.7% could achieve erections sufficient for intercourse at three years compared to 37.5% in the Control arm, a 77.8% improvement.2 Radiation therapy in the treatment of prostate cancer can cause unintended radiation injury to adjacent healthy tissue (organs at risk). This injury can lead to a range of bowel, urinary and sexual symptoms that can affect patient health and quality of life during radiotherapy, and for years afterward. In recent years, radiation oncologists have considered use of “spacing” techniques to reduce the risk of radiation injury to surrounding tissue during radiotherapy. SpaceOAR hydrogel is intended to temporarily position the anterior rectal wall away from the prostate during radiotherapy for prostate cancer and in creating this space it is the intent of SpaceOAR hydrogel to reduce the radiation dose delivered to the anterior rectum. The SpaceOAR hydrogel is injected as a liquid into the space between the prostate and rectum where it pushes the structures apart and then solidifies into a soft hydrogel. The hydrogel remains stable for three months during radiation therapy then liquefies and is completely absorbed by the body. See the Instructions for Use for complete information on potential risks, warnings and precautions. Augmenix, Inc. is a privately held U.S. company based in the Boston, Massachusetts area focused on the development and commercialization of radiation oncology products using its proprietary hydrogel technology. Focusing initially on protection during prostate radiation therapy, Augmenix next-generation products will address spacing and marking applications throughout the body to improve radiotherapy and interventional oncology procedure outcomes. The company’s lead product, SpaceOAR System, is FDA cleared and is currently being used in the majority of leading cancer centers in the United States. It is also CE marked, approved in Australia and licensed in Canada. SpaceOAR is a registered trademark of Augmenix, Inc. More information about Augmenix and the SpaceOAR hydrogel can be found at http://www.Augmenix.com. Chaim Sheba Medical Center is the largest medical center in Israel and the Middle-East and one of the most comprehensive and advanced hospitals in the world. Adjacent to Tel Aviv, it is renowned for its compassionate care and leading-edge medicine. It is also a major medical-scientific research center that collaborates internationally with the medtech and pharmaceutical industries to develop new treatments and technologies, and a foremost global center for medical education. Visit www.eng.sheba.co.il for more information. 1) Hamstra D, et al. Continued Benefit to Rectal Separation for Prostate RT: Final Results of a Phase III Trial. Int J Radiat Oncol Biol Phys; 2017 Volume 97, Issue 5, Pages 976–985. 2) Hamstra D, et al. Evaluation of sexual function on a randomized trial of a prostate rectal spacer. J Clin Oncol 35, 2017 (suppl 6S; abstract 69)


VILLEJUIF, France--(BUSINESS WIRE)--WIN Consortium (WIN) received the US Food and Drug Administration (FDA)’s approval to start the clinical investigation of a novel therapeutic approach using a combination of three targeted therapies for the first line treatment of patients with advanced Non Small Cell Lung Cancer (NSCLC). The Survival Prolongation by Rationale Innovative Genomics (SPRING) trial will aim to enroll patients who are usually offered first line platinum-based chemotherapy. Patients with documented targetable driver alterations (EGFR mutations, ALK rearrangements, ROS1 and MET exon 14 skipping mutations) will be excluded. The population of NSCLC patients without actionable oncogenic driver mutations, envisioned for the enrollment in SPRING trial, represents the vast majority of patients with metastatic NSCLC (~80% in the Caucasian population). With over 60% of NSCLC detected in an advanced or metastatic stage, and less than 5% of patients alive at 5 years, a paradigm changing strategy for treating the deadliest cancer is needed. WIN’s novel approach is based on the utilization of the tri-therapy combination of targeted drugs, following the historical success of this approach in AIDS and tuberculosis. Similarly, our concept relies on the association of three targeted drugs that used in combination are expected to be highly potent, whereas used alone in monotherapy they produce only modest clinical outcome. ‘’Nevertheless, it is important to acknowledge a significant difference between cancer and AIDS which lies in the higher biological complexity and heterogeneity of cancer compared to AIDS. In AIDS, one tri-therapy combination is effective for a majority of patients, whereas in cancer it is expected that many combinations will be needed to treat all patients effectively. WIN Consortium has developed new technologies for tailoring combinations for each individual patient.’’ said Dr. John Mendelsohn, Chairman of WIN. "WIN’s trial, entitled SPRING, is therefore a first proof of concept of this novel approach in the treatment of lung cancer, and will test as a first combination three drugs from WIN’s big pharma members, Merck’s Avelumab combined with Pfizer’s Palbociclib and Axitinib.’’ added Dr. Mendelsohn. SPRING’s investigator initiated research will be led by Dr. Razelle Kurzrock (University of California San Diego, Moores Cancer Center) and co-led by Dr. Enriqueta Felip (Vall d'Hebron Institute of Oncology) and is planned to be launched in 5 countries and 8 WIN member sites: University of California San Diego Moores Cancer Center and Avera Cancer Institute (Dr. Benjamin Solomon), USA; Institut Curie (Dr. Nicolas Girard), Centre Léon Bérard (Dr. Pierre Saintigny) and Hôpital Paris Saint-Joseph (Dr. Eric Raymond), France; Vall d'Hebron Institute of Oncology, Spain; Centre Hospitalier de Luxembourg (Dr. Guy Berchem); and Chaim Sheba Medical Center (Dr. Jair Bar), Israel. The SPRING trial will start with a Phase I portion to explore the safety of the combination and determine the optimal doses for the Phase II that will explore the efficacy of this tri-therapy regimen in first line treatment of metastatic NSCLC. The trial will also aim to validate a novel algorithm SIMS (Simplified Interventional Mapping System) developed by WIN and designed to match each patient’s tumor biology to a specific drug combination. For this purpose, both tumor and normal lung tissue biopsies will be obtained and explored in the SPRING trial. DNA and RNA analysis will be performed by Dr. Brandon Young at Avera WIN Precision Oncology Laboratory in San Marcos, California on biopsies using, respectively, Illumina NGS (next generation sequencing) and HTG Molecular’s expression (mRNA and microRNA) EdgeSeq technology used in conjuction with Illumina (NGS). Data integration for the SIMS algorithm will be performed by Ben-Gurion University of the Negev (Dr. Eitan Rubin), Israel. ‘’It is an unprecedented cooperation between our WIN members from academia, industry and research organizations.“ said Dr. Vladimir Lazar, WIN Chief Scientific and Operating Officer. ‘’Eight clinical sites will activate the study, drugs will be provided by Pfizer Inc., DNA and RNA analysis technologies by Illumina and HTG Molecular and pharmacovigilance by Covance. In particular, we are grateful to Foundation ARC on cancer research in France for financial support to initiate the SPRING trial. We are welcoming the support of any other organization or private donors, wishing to join this unique global effort dedicated to lung cancer patients.’’ added Dr. Lazar. ‘’It is very exciting to see this endeavor becoming more concrete and this unprecedented cooperation materializing. We are looking forward to the activation of our clinical sites. We will need more combinations to be launched rapidly and other pharma companies to join us in this effort.’’, said Dr. Razelle Kurzrock, trial global coordinator, and Head of WIN Clinical Trials Committee. ‘’WIN has the potential and expertise to test other combinations and has the technologies needed to match patients’ tumor biology profile with the appropriate combination”. About WIN Consortium WIN Consortium is a French based non-profit network of 41 world-class academic medical centers, industries (pharmaceutical and diagnostic companies), health payer, research organizations and foundation and patient advocates spanning 17 countries and 4 continents, aligned to deliver now the progress in cancer treatment that is awaited by so many patients and families around the world. For further information, please visit www.winconsortium.org.


News Article | July 10, 2017
Site: www.chromatographytechniques.com

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings offer an example of how extreme population-level tragedies can have an impact on health. Holocaust survivors were exposed to a variety of factors that have been linked with cancer. Siegal Sadetzki, MD, MPH, of the Chaim Sheba Medical Center in Israel, and her colleagues wondered whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals. To investigate, the team studied 152,622 Holocaust survivors who were followed for more than 45 years. Two separate definitions of exposure were used. One definition was based on the individual's entitlement for compensation according to a set of laws. The other was based on the country of origin, using a classification of countries during the war into those that were directly governed by Nazi Germany and other non-occupied countries. Cancer was diagnosed in 22 percent of those who were granted compensation for suffering persecution during the war versus 16 percent of those who were denied compensation. Survivors who were granted compensation had a six percent higher risk of developing any type of cancer than those who were denied compensation, and they had a 12 percent increased risk for colorectal cancer and a 37 percent increased risk for lung cancer. Those born in occupied countries had an eight percent increased risk of developing any cancer than those born in non-occupied countries, as well as eight percent and 12 percent increased risks of colorectal cancer and lung cancer, respectively. The investigators observed no elevated risks for breast cancer and gynecologic cancers among female survivors. "The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II," said Sadetzki. "Such inspection cannot be conducted by experimental studies and could only be evaluated by using observational epidemiological surveys." An accompanying editorial notes that the associations reported by Sadetzki and colleagues between the extreme deprivation experienced by Holocaust survivors and cancer may also have parallels with other extreme population-level events, including in racial/ethnic minority groups who experience severe social deprivation over time.


VILLEJUIF, France--(BUSINESS WIRE)--Le Consortium WIN (WIN) a reçu l'approbation de la Food and Drug Administration (FDA) américaine pour le lancement de la recherche clinique en vue d'une nouvelle approche thérapeutique utilisant une combinaison de trois thérapies ciblées pour le traitement en première ligne des patients atteints du cancer du poumon non à petites cellules (CPNPC) au stade métastatique. L'essai Survival Prolongation by Rationale Innovative Genomics (SPRING) [prolongation de la survie par la génomique rationnelle innovante] visera à inclure des patients à qui l'on propose généralement en première ligne une chimiothérapie à base de platine. Les patients présentant des altérations génomiques avérées (mutations de l'EGFR, réarrangements de ALK, ROS1 et mutation de l'exon 14 de MET) seront exclus de l'étude. Les patients souffrant de CPNPC sans altération génomique qui soit une cible thérapeutique, qui sont envisagés pour le recrutement dans l'essai SPRING, représentent la vaste majorité de patients atteints de CPNPC métastatique (~80% chez la population caucasienne). Avec plus de 60% des CPNPC détectés au stade avancé ou métastatique, et moins de 5% des patients en vie après 5 ans, un changement de stratégie du traitement du cancer le plus mortel est nécessaire. L'approche novatrice de WIN est basée sur l'utilisation de la trithérapie de médicaments ciblés utilisés en combinaison, suite au succès historique de cette approche pour le SIDA et la tuberculose. De façon analogue, notre concept repose sur l'association de trois médicaments ciblés qui, utilisés en combinaison, devraient être efficaces, alors qu'ils ne parviennent qu’ à des résultats cliniques limités en monothérapie. "Cependant, il est nécessaire de souligner une différence importante entre le cancer et le SIDA, qui réside dans la plus grande complexité biologique et l'hétérogénéité du cancer par rapport au SIDA. Pour le SIDA, une seule trithérapie est efficace pour une majorité de patients, tandis que pour le cancer il faut s'attendre à ce que de nombreuses combinaisons soient requises pour traiter efficacement tous les patients. Le Consortium WIN a mis au point de nouvelles technologies afin d'adapter des combinaisons à chaque patient individuel", a déclaré le Dr John Mendelsohn, président de WIN. "L'étude de WIN, baptisée SPRING, constitue dès lors une première preuve de concept pour cette nouvelle approche dans le traitement du cancer du poumon, et testera pour commencer une combinaison de trois médicaments appartenant aux laboratoires pharmaceutiques membres de WIN, l'Avelumab de Merck en combinaison avec le Palbociclib et l'Axitinib de Pfizer", a ajouté le Dr Mendelsohn. L’essai SPRING, recherche d'initiative académique, sera menée par le Dr Razelle Kurzrock (Université de Californie à San Diego, Moores Cancer Center), codirigée par le Dr Enriqueta Felip (Vall d'Hebron Institute of Oncology). Son lancement est prévu dans cinq pays au sein de huit sites membres de WIN: le Moores Cancer Center de l'Université de Californie à San Diego, et l'Avera Cancer Institute (Dr Benjamin Solomon), États-Unis; l'Institut Curie (Dr Nicolas Girard), le Centre Léon Bérard (Dr Pierre Saintigny) et l'Hôpital Paris Saint-Joseph (Dr Eric Raymond), France; Vall d'Hebron Institute of Oncology, Espagne; le Centre Hospitalier de Luxembourg (Dr Guy Berchem); et le Chaim Sheba Medical Center (Dr Jair Bar), Israël. L'étude SPRING débutera avec une Phase I visant à étudier la tolérabilité de la combinaison et de déterminer les doses optimales pour la Phase II, qui explorera l'efficacité de cette trithérapie en première ligne thérapeutique du CPNPC métastatique. L'étude visera également à valider un nouvel algorithme SIMS (Simplified Interventional Mapping System) mis au point par WIN et conçu pour adapter la combinaison thérapeutique ciblée à la biologie de la tumeur de chaque patient. À cette fin, les biopsies du tissu tumoral et du tissu pulmonaire normal seront obtenues dans le cadre de l'étude SPRING. Les tests génomiques et transcriptomiques SIMS sur les biopsies seront effectués par le Dr Brandon Young à l'Avera WIN Precision Oncology Laboratory de San Marcos en Californie, utilisant respectivement le séquençage de nouvelle génération Illumina et l'expression de HTG Molecular (mRNA et microRNA) du panel de gènes SIMS. L'intégration des données pour l'algorithme SIMS sera effectuée par la Ben-Gurion University of the Negev (Dr Eitan Rubin), Israël. "Il s'agit ici d'une coopération sans précédent entre les membres académiques, industriels et les organismes de recherche de WIN.", a déclaré le Dr Vladimir Lazar, directeur scientifique et opérationnel de WIN. "Huit sites cliniques activeront l'étude, les médicaments seront fournis par Pfizer Inc., les tests génomiques et transcriptomiques respectivement par Illumina et HTG Molecular et la pharmacovigilance par Covance. Nous sommes particulièrement reconnaissants à la Fondation ARC pour la recherche sur le cancer en France pour son soutien financier permettant de démarrer l'étude SPRING. Nous accueillons d'ailleurs le soutien de toute autre organisation souhaitant se joindre à cette initiative mondiale unique dédiée aux patients atteints du cancer du poumon", a poursuivi le Dr Lazar. "Il est très réjouissant de voir cet effort se concrétiser et d'assister à la mise en forme de cette coopération unique. Nous avons hâte d'activer les sites cliniques. Nous devrons lancer d'autres essais de combinaisons thérapeutiques très rapidement et aurons besoin que d'autres laboratoires pharmaceutiques se joignent à notre effort", a déclaré le Dr Razelle Kurzrock, coordinatrice internationale de l’essai et chef du Comité d'essais cliniques de WIN. "WIN a le potentiel et l'expertise pour tester d'autres combinaisons ainsi que les technologies requises pour adapter la combinaison au profil biologique de la tumeur du patient." À propos du Consortium WIN Le Consortium WIN est un réseau français à but non-lucratif regroupant 41 membres : centres académiques de renommée internationale, acteurs de l'industrie (laboratoires pharmaceutiques et industriels du diagnostique), assureurs, organismes et fondations de recherche et défenseurs des patients répartis sur 17 pays et 4 continents, réunis pour faire avancer les progrès dans les traitements du cancer, tant attendus par de nombreux patients et leurs familles partout dans le monde.


Multiple Myeloma (MM) is a lymphatic neoplasm characterized by clonal proliferation of malignant plasma cell that eventually develops resistance to chemotherapy. Drug resistance, differentiation block and increased survival of the MM tumor cells result from high genomic instability. Chromosomal translocations, the most common genomic alterations in MM, lead to dysregulation of cyclin D, a regulatory protein that governs the activation of key cell cycle regulator--cyclin dependent kinase (CDK). Genomic instability was reported to be affected by over expression of another CDK regulator--cyclin E (CCNE). This occurs early in tumorigenesis in various lymphatic malignancies including CLL, NHL and HL. We therefore sought to investigate the role of cyclin E in MM. CCNE1 expression was found to be heterogeneous in various MM cell lines (hMMCLs). Incubation of hMMCLs with seliciclib, a selective CDK-inhibitor, results in apoptosis which is accompanied by down regulation of MCL1 and p27. Ectopic over expression of CCNE1 resulted in reduced sensitivity of the MM tumor cells in comparison to the paternal cell line, whereas CCNE1 silencing with siRNA increased the cell sensitivity to seliciclib. Adhesion to FN of hMMCLs was prevented by seliciclib, eliminating adhesion-mediated drug resistance of MM cells. Combination of seliciclib with flavopiridol effectively reduced CCNE1 and CCND1 protein levels, increased subG1 apoptotic fraction and promoted MM cell death in BMSCs co-culture conditions, therefore over-coming stroma-mediated protection. We suggest that seliciclib may be considered as essential component of modern anti MM drug combination therapy.


Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a safer toxicity profile than the oral formulation. Comparative studies of outcomes have been performed between oral Bu/Cy and Cy/TBI, but there have been no comparative trials in the era of IV Bu. We performed a retrospective registry-based study comparing outcomes of patients with AML in first or second remission after alloSCT from sibling donors who underwent IV Bu/Cy (n = 795) or Cy/TBI (n = 864) conditioning. Engraftment rate was 98% and 99% after IV Bu/Cy and Cy/TBI, respectively. Grade 2 to 4 acute graft-versus-host disease (GVHD) was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P < .001). Similarly, chronic GVHD was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P = .003). Cumulative incidence of 2-year nonrelapse mortality (NRM; ± standard deviation [SD]) was 12% ± 1% in the IV Bu/Cy group and 15% ± 2% in the Cy/TBI group (P = .14), and 2-year relapse incidence (RI; ± SD) was 26% ± 3% and 21% ± 1%, respectively (P = .012). Leukemia-free survival (LFS) rate (± SD) was 61% ± 2% after IV Bu/Cy and 64% ± 2% after Cy/TBI (P = .27). In multivariable analysis, adjusting for differences between both groups, patients who received IV Bu/Cy had lower acute and chronic GVHD, higher RI, and a trend toward lower NRM. LFS was not statistically different between the two conditioning regimens. This retrospective study shows that final outcomes after myeloablative conditioning using IV Bu/Cy were not statistically different from those after Cy/TBI.

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