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Retsky, Michael

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Retsky

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Retsky, Michael
Author's Publications: search.filters.isAuthorOfPublication.442ae438-c726-4cf2-a3ae-a2a6933f22cc

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    Reduction of Breast Cancer Relapses with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review
    (Bentham Science Publishers Ltd., 2013) Retsky, Michael; Demicheli, Romano; Hrushesky, William; Forget, Patrice; Kock, Marc; Gukas, Isaac; Rogers, Rick; Baum, Michael; Sukhatme, Vikas; Vaidya, Jayant
    To explain a bimodal pattern of hazard of relapse among early stage breast cancer patients identified in multiple databases, we proposed that late relapses result from steady stochastic progressions from single dormant malignant cells to avascular micrometastases and then on to growing deposits. However in order to explain early relapses, we had to postulate that something happens at about the time of surgery to provoke sudden exits from dormant phases to active growth and then to detection. Most relapses in breast cancer are in the early category. Recent data from Forget et al. suggest an unexpected mechanism. They retrospectively studied results from 327 consecutive breast cancer patients comparing various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Relapse hazard updated Sept 2011 are presented. A common Non-Steroidal Anti-Inflammatory Drug (NSAID) analgesic used in surgery produced far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. Transient systemic inflammation accompanying surgery could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent.
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    Computer Model Challenges Breast Cancer Treatment Strategy
    (Informa UK Limited, 1994) Retsky, Michael; Swartzendruber, Douglas E.; Bame, Paul D.; Wardwell, Robert H.
    The breast cancer treatment failure rate remains unacceptably high. The current breast cancer treatment paradigm, based primarily on Gompertzian kinetics and animal models, advocates short-course, intensive chemotherapy subsequent to tumor debulking, citing drug resistance and host toxicity as the primary reasons for treatment failure. To better understand treatment failure, we have studied breast cancer from the perspective of computer modeling. Our results demonstrate breast cancers grow in an irregular fashion; this differs from the Gompertzian mode of animal models and thus challenges the validity of the current paradigm. Clinical and laboratory data support the concept of irregular growth rather than the common claim that human tumors grow in a Gompertzian fashion. Treatment failure mechanisms for breast cancer appear to differ from those for animal models, and thus treatments optimize on animal models may not be optimal for breast cancer. A failure mechanism consistent with our results involves temporarily dormant tumor cells in anatomical or pharmacological sanctuary, which eventually result in aggressive metastatic disease.
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    An argument for discovery-driven research: from physicist to cancer researcher
    (Cancer Intelligence, 2014) Retsky, Michael
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    Multimodal Hazard Rate for Relapse in Breast Cancer: Quality of Data and Calibration of Computer Simulation
    (MDPI AG, 2014) Retsky, Michael; Demicheli, Romano
    Much has occurred since our 2010 report in Cancers. In the past few years we published several extensive reviews of our research so a brief review is all that will be provided here. We proposed in the earlier reports that most relapses in breast cancer occur within 5 years of surgery and seem to be associated with some unspecified manner of surgery-induced metastatic initiation. These events can be identified in relapse data and are correlated with clinical data. In the last few years an unexpected mechanism has become apparent. Retrospective analysis of relapse events by a Brussels anesthesiology group reported that a perioperative NSAID analgesic seems to reduce early relapses five-fold. We then proposed that primary surgery produces a transient period of systemic inflammation. This has now been identified by inflammatory markers in serum post mastectomy. That could explain the early relapses. It is possible that an inexpensive and non-toxic NSAID can reduce breast cancer relapses significantly. We want to take this opportunity to discuss database quality issues and our relapse hazard data in some detail. We also present a demonstration that the computer simulation can be calibrated with Adjuvant-on-line, an often used clinical tool for prognosis in breast cancer.
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    Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: learning from failures
    (Nature Publishing Group, 2007) Demicheli, Romano; Retsky, Michael; Hrushesky, William JM; Baum, Michael
    Primary tumor removal, usually considered intrinsically beneficial, can perturb metastatic homeostasis, and for some patients results in the acceleration of metastatic cancer. The continuous-growth model is required to yield to an interrupted-growth model, the implications of which are episodes of tumor dormancy. This Review analyzes the recent evolution of two paradigms related to the development of breast cancer metastases. The evolution of the paradigms described herein is supported by a growing body of findings from experimental models, and is required to explain breast cancer recurrence dynamics for patients undergoing surgery with or without adjuvant chemotherapy
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    Protocol For A Randomised, Multicentre, Double Blinded Phase III Study Of Perioperative Ketorolac In Women Of African Descent With Operable Breast Cancer.
    (Jacobs Publishers, 2016) Demicheli, Romano; Osaro, Erhabor; Retsky, Michael; Patrice, Forget; Jayant, Vaidya; SO., Bello
    Cancer remains one of the leading causes of morbidity and mortality worldwide. Breast cancer is the most common form of malignancy occurring in women around the world. The aim of this present protocol is to outline the procedure for a randomised, multicentre, double blinded phase III study of perioperative Ketorolac in Women of African Descent with Operable Breast Cancer. The typical type of breast cancer in sub Saharan Africa is triple negative breast cancer (TNBC) and is usually considered the worst early breast cancer diagnosis since there are no known targeted therapies and patients often relapse and die early. sub-Saharan Africa seems the perfect place to conduct a randomized controlled double blinded clinical trial of perioperative NSAID Romano Demicheli 1, Erhabor Osaro 2, Michael Retsky 3 Forget Patrice 4.Vaidya Jayant S 5. Scientific Directorate Fondazione IRCCS Istituto Nazionale Tumori di Milano Italy 1, Usmanu Danfodiyo University, Sokoto, Nigeria 2, Harvard TH Chan School of Public Health Boston MA USA 3, Department of Anesthesiology, Universite catholique de Louvain, St-Luc Hospital, Av. Hippocrate 10-1821, 1200 Brussels, Belgium 4, University College Hospital, London, UK 5.etorolac to potentially reduce early relapses in breast cancer. The primary and secondary objectives of this trial are to evaluate and compare the Disease Free Survival (DFS) and Overall Survival (OS) of operable breast cancer patients randomised to standard treatment versus standard treatment plus perioperative Ketorolac and to compare the safety and tolerability of the treatment as well as to identify pre- and post-operative factors with prognostic relevance and establish correlations with clinical outcomes. It is anticipated that trial will be successful and would turn TNBC from the worst prognosis to the best and potentially help improve the quality of life of African women suffering from breast cancer.
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    Dormancy and surgery-driven escape from dormancy help explain some clinical features of breast cancer
    (Wiley-Blackwell, 2008) Retsky, Michael; Demicheli, R.; Hrushesky, W. J. M.; Baum, M.; Gukas, I. D.
    To explain bimodal relapse patterns observed in breast cancer data, we have proposed that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell phase and the avascular micrometastasis phase. The half-lives of these states are 1 and 2 years respectively. We also suggested that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. These iatrogenic events are very common in that over half of all metastatic relapses progress in that manner. Assuming this is true, there should be ample and clear evidence in clinical data. We review here the breast cancer paradigm from early detection, through treatment and follow-up, and consider how dormancy and surgery-driven escape from dormancy would be observed. We examine mammography data, effectiveness of adjuvant chemotherapy, heterogeneity and aggressiveness, timing of surgery within the menstrual cycle and racial differences in outcome. Dormancy can be identified in these diverse data but most conspicuous is the sudden escape from dormancy following primary surgery. These quantitative findings provide linkage between experimental studies of tumor dormancy and clinical efforts to improve patient outcome.
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    Omics Conferences and Breast Cancer in Sub-Saharan Africa
    (OMICS Publishing Group, 2015) Retsky, Michael
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