15 September 2017 (Friday) - Oncologist Newsletter

The regular email from “The Oncologist” arrived in my in-box this morning. Several snippets including:


Editorial

The Evolution of Clinical Trials in Oncology: Defining Who Benefits from New Drugs Using Innovative Study Designs

Richard M. Goldberg, Lai Wei, Soledad Fernandez
Historically, advocates of randomized drug treatment trials in oncology contributed to the changing paradigm for testing cancer treatments in the U.S., which led to global efforts to generate evidence of promise in preclinical model systems and translate those findings into improved patient outcomes. In the age of genomic medicine, the challenge to speed the evolution of how clinical trials are conducted in patients with cancer continues.

Commentaries

The Patients We Have to See

Kelly E. Irwin
A psychiatrist and health services researcher, specializing in serious mental illness and cancer, discusses the need for the integration of mental health care and cancer care to promote equity in patient care.

Commentary on “Weekly Low-Dose Versus Three-Weekly High-Dose Cisplatin for Concurrent Chemoradiation in Locoregionally Advanced Non-Nasopharyngeal Head and Neck Cancer: A Systematic Review and Meta-Analysis of Aggregate Data”

A. Dimitrios Colevas
Assessing a recent retrospective analysis, conclusions differ on whether a weekly regimen could be adopted as a reasonable standard of care option. This commentary questions how study results are interpreted, what considerations are most important for patient care, and where efforts should be focused for the next generation of trials.

Clinical Trial Results

A Phase Ib Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Cobimetinib and Duligotuzumab in Patients with Previously Treated Locally Advanced or Metastatic Cancers with Mutant KRAS

Christopher H. Lieu, Manuel Hidalgo, Jordan D. Berlin, Andrew H. Ko, Andres Cervantes, Patricia LoRusso, David E. Gerber, J. Paul Eder, S. Gail Eckhardt, Amy V. Kapp, Amy Tsuhako, Bruce McCall, Andrea Pirzkall, Anne Uyei, Josep Tabernero

Endogenous Heat-Shock Protein Induction with or Without Radiofrequency Ablation or Cryoablation in Patients with Stage IV Melanoma

Evidio Domingo-Musibay, James M. Heun, Wendy K. Nevala, Matthew Callstrom, Thomas Atwell, Evanthia Galanis, Lori A. Erickson, Svetomir N. Markovic

Breast Cancer

Targeting the Molecular Subtypes of Triple Negative Breast Cancer: Understanding the Diversity to Progress the Field

Clinton Yam, Sendurai A. Mani, Stacy L. Moulder
Recent advances in gene expression profiling have identified subgroups of triple-negative breast cancers with distinct molecular features that, if appropriately selected, may be more responsive to targeted therapy with existing FDA-approved drugs, leading to rapid improvement in outcomes in this high-risk breast cancer population. This article is a review of recent attempts to classify triple-negative breast cancers into various subtypes and the implications for the development of targeted therapies.

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results

Sibylle Loibl, Nicholas C. Turner, Jungsil Ro, Massimo Cristofanilli, Hiroji Iwata, Seock-Ah Im, Norikazu Masuda, Sherene Loi, Fabrice André, Nadia Harbeck, Sunil Verma, Elizabeth Folkerd, Kathy Puyana Theall, Justin Hoffman, Ke Zhang, Cynthia Huang Bartlett, Mitchell Dowsett
In the randomized, phase III PALOMA-3 trial, palbociclib plus fulvestrant (6 goserelin) prolonged investigator-assessed progression-free survival compared with placebo plus fulvestrant (6 goserelin) in women with HR1/HER2– advanced breast cancer after prior progression on endocrine therapy. PALOMA-3 was the first registrational study to include premenopausal women in this setting; in this article, results are described by menopausal status, with a focus on premenopausal women with prior endocrine-resistant HR1/HER2– advanced breast cancer.

Clinical Management of Potential Toxicities and Drug Interactions Related to Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer: Practical Considerations and Recommendations

Laura M. Spring, Mark L. Zangardi, Beverly Moy, Aditya Bardia
This review article reports the clinical management of potential toxicities and drug interactions seen with the use of CDK4/6 inhibitors in breast cancer, with a focus on palbociclib and ribociclib, and summarizes practical management strategies for the oncologist.

Community Outreach

Perceptions of Cancer Care and Clinical Trials in the Black Community: Implications for Care Coordination Between Oncology and Primary Care Teams

Linda Sprague Martinez, Elmer R. Freeman, Karen M. Winkfield
To explore barriers to clinical trial participation experienced by the black community in Boston, MA, the Lazarex-MGH Cancer Care Equity Program at Massachusetts General Hospital partnered with the Center for Community Health Education Research and Service to implement a multiphase community-engaged assessment. This assessment set out to identify black Bostonians’ perceptions of cancer care and cancer clinical trials, drawing on qualitative research methods to inform programmatic and outreach activities. This article reports the implications of the findings in the context of care coordination and follow-up between oncologists and primary care providers.

Endocrinology

Complete Responses to Mitotane in Metastatic Adrenocortical Carcinoma—A New Look at an Old Drug

Diane L. Reidy-Lagunes, Betty Lung, Brian R. Untch, Nitya Raj, Anastasia Hrabovsky, Ciara Kelly, Scott Gerst, Seth Katz, Lewis Kampel, Joanne Chou, Anu Gopalan, Leonard B. Saltz
The management of adrenocortical cancer is challenging because of limited therapies, heterogeneous clinical presentations, and varying degree of aggressiveness at diagnosis. This article evaluates the use of mitotane for palliation in patients with advanced adrenocortical carcinomas, assessing response to treatment and treatment-related side effects.

Gastrointestinal Cancer

Appendiceal Mucinous Neoplasms: Diagnosis and Management

Walid L. Shaib, Rita Assi, Ali Shamseddine, Olatunji B. Alese, Charles Staley III, Bahar Memis, Volkan Adsay, Tonios Bekaii-Saab, Bassel F. El-Rayes
Appendiceal mucinous neoplasms are rare and challenging to manage. This review summarizes the current literature and controversies in classification, clinical presentation, molecular alterations, and treatment outcomes in this heterogeneous group of tumors and provides guidelines for treatment.

Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Karen-Lise G. Spindler, Anders K. Boysen, Niels Pallisgård, Julia S. Johansen, Josep Tabernero, Morten M. Sørensen, Benny V. Jensen, Torben F. Hansen, David Sefrioui, Rikke F. Andersen, Ivan Brandslund, Anders Jakobsen
Recently refined methods for cfDNA quantification and detection of mutations have been developed. Results of clinical investigations of the predictive and prognostic value of total cfDNA and plasma mutations in mCRC suggest a strong prognostic value of baseline plasma levels of cfDNA in this setting. This article presents a systematic review and meta-analysis of the prognostic value of total plasma cfDNA in patients with mCRC treated with chemotherapy and/or targeted agents.

Gynecologic Oncology

Reducing Uncertainty: Predictors of Stopping Chemotherapy Early and Shortened Survival Time in Platinum Resistant/Refractory Ovarian Cancer—The GCIG Symptom Benefit Study

Felicia T. Roncolato, Florence Joly, Rachel O'Connell, Anne Lanceley, Felix Hilpert, Luke Buizen, Aikou Okamoto, Eriko Aotani, Sandro Pignata, Paul Donnellan, Amit Oza, Elisabeth Avall-Lundqvist, Jonathan S. Berek, Florian Heitz, Amanda Feeney, Dominique Berton-Rigaud, Martin R. Stockler, Madeleine King, Michael Friedlander, for the GCIG Symptom Benefit Group
The aim of this study was to determine aspects of health-related quality of life and clinicopathological characteristics before starting chemotherapy for platinum-resistant/refractory ovarian cancer that were associated with early cessation of chemotherapy, survival time, and death within 30 days of chemotherapy.

Head and Neck Cancers

Weekly Low-Dose Versus Three-Weekly High-Dose Cisplatin for Concurrent Chemoradiation in Locoregionally Advanced Non-Nasopharyngeal Head and Neck Cancer: A Systematic Review and Meta-Analysis of Aggregate Data

Petr Szturz, Kristien Wouters, Naomi Kiyota, Makoto Tahara, Kumar Prabhash, Vanita Noronha, Ana Castro, Lisa Licitra, David Adelstein, Jan B. Vermorken
The level of evidence for the use of weekly cisplatin chemoradiation in locally advanced squamous cell carcinoma of the head and neck is limited. This systematic review of the literature compares the efficacy, toxicity, and compliance of low-dose cisplatin given once a week during external beam irradiation with the standard, three-weekly high-dose treatment schedule.

Hematologic Malignancies

Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!

Tamila L. Kindwall-Keller, Karen K. Ballen
Hematopoietic stem cell transplant is potentially curative for a wide variety of malignant diseases; however, choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic hematopoietic stem cell transplant has a potential donor in 2017.

Hepatobiliary

The Impact of a Hepatobiliary Multidisciplinary Team Assessment in Patients with Colorectal Cancer Liver Metastases: A Population-Based Study

Jennie Engstrand, Nikolaos Kartalis, Cecilia Strömberg, Mats Broberg, Anna Stillström, Tobias Lekberg, Eduard Jonas, Jacob Freedman, Henrik Nilsson
A retrospective analysis of patients with a diagnosis of colorectal cancer was conducted. Patients with liver metastases were re-evaluated by a liver-specific multidisciplinary team, and the resulting treatment decisions were compared with the original management. Improvement in resection rates were evaluated, and results are presented here.

Lung Cancer

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib

Zong-Han Yao, Wei-Yu Liao, Chao-Chi Ho, Kuan-Yu Chen, Jin-Yuan Shih, Jin-Shing Chen, Zhong-Zhe Lin, Chia-Chi Lin, James Chih-Hsin Yang, Chong-Jen Yu
The objective of this study was to identify independent prognostic factors for survival in a real-world population of patients with EGFR mutation-positive advanced non-small cell lung cancer undergoing treatment with gefitinib. The study also evaluates whether brain metastasis or intracranial progression is a poor prognostic predictor for gefitinib therapy.

Symptom Management and Supportive Care

Transitions in Prognostic Awareness Among Terminally Ill Cancer Patients in Their Last 6 Months of Life Examined by Multi-State Markov Modeling

Chen Hsiu Chen, Fur-Hsing Wen, Ming-Mo Hou, Chia-Hsun Hsieh, Wen-Chi Chou, Jen-Shi Chen, Wen-Cheng Chang, Siew Tzuh Tang
Accurate prognostic awareness is a cornerstone of preference-based end-of-life care decision-making for terminally ill cancer patients, promoting optimal quality of care at the end of life. This study explored the transition probabilities in distinct states of prognostic awareness in terminally ill cancer patients in the last 6 months of life.

Brief Communciations

Li-Fraumeni versus Pseudo-Li-Fraumeni Syndrome: Key Insights for Interpreting Next-Generation Sequencing Reports in Patients with Suspected Cancer Predisposition Syndromes

Steven Sorscher, Rodwige Desnoyers, Karen Ouyang, Shakti Ramkissoon
This brief communication describes the case of a patient with colorectal cancer with a TP53 germline mutation initially considered somatic because no TP53 germline mutation was noted in the liquid biopsy (cell-free DNA) next-generation sequencing assay.

Narratives in Oncology

On the Receiving End of Autonomy and Law

Hanneke W. M. van Laarhoven, Lisa J. Pijnenburg, Maarten C. C. M. Hulshof
It is well-recognized that mental illness is associated with a higher case fatality rate from cancer, although the incidence of cancer is no greater than in the general population. This narrative focuses on the efforts of a multidisciplinary team to guide a patient, who was experiencing psychotic episodes, through chemotherapy while staying within the limits of the law.

Chemo Heart

Ersilia M. DeFilippis
A physician recounts the story of a beloved patient who survived cancer but later developed heart disease.

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