PARP inhibitors are known to be effective in patients with ovarian cancer (OC) and germline mutations in BRCA1 and BRCA2 genes (BRCA mutations). Little is known, however, about any correlation between the deletion size and location of the BRCA mutation and the response to PARP inhibitors. Women with OC commonly undergo genetic testing because the presence of a germline BRCA mutation impacts therapeutic decisions and is important for cancer surveillance in patients and their family members. This report presents a case of a rare entire germline BRCA1 gene deletion and an exceptional response to a PARP inhibitor, olaparib, in a heavily pretreated patient with OC. Her disease course was also remarkable for complete responses to platinum-based chemotherapy and long chemotherapy-free intervals. Interestingly, the deletion of the entire BRCA1 gene was found after previously negative BRCA test results and is associated with a deletion of 6 adjacent genes without known clinical significance. She has remained progression-free and asymptomatic for >3 years on olaparib, with an overall survival of >12 years. We postulate that this unusually favorable response and prolonged overall survival is related to the cancer cells’ inability to reverse the entire gene deletion to wild-type (a common mechanism of resistance to PARP inhibition). This case shows the value of genetic testing for patients with OC and highlights the utility of additional testing with previously negative results and limited genetic testing. It also provides insight into a potential mechanism of an exceptional response to PARP inhibition.
Megan Randall, Kelly Burgess, Lela Buckingham and Lydia Usha
June M. McKoy, Peggy S. Burhenn, Ilene S. Browner, Kari L. Loeser, Katrina M. Tulas, Megan R. Oden and Randall W. Rupper
The number of older individuals with cancer is increasing exponentially, mandating that oncologists contemplate more comprehensive and multidisciplinary approaches to treatment of this cohort. Recruitment of assessment instruments validated in older patients can be invaluable for guiding treatment and decision-making by both patients and providers, and can arguably contribute to improving outcomes and health-related quality of life. The Comprehensive Geriatric Assessment is one such validated instrument that can be used by oncologists to assess patient readiness and appropriateness for prescribed cancer therapy. As a multidisciplinary diagnostic and treatment process, it comprises functional status, cognitive status, social support, and advance care preferences, and is an ideal instrument for evaluating complex older individuals. It is well established that many older individuals with cancer travel with multiple comorbid illnesses, including cognitive impairment, and when presented with a cancer diagnosis struggle to choose from multiple treatment options. In addition to the complete medical history, the ability of patients to decide on a course of therapy in concert with their oncologist is critically important. Alternatively, many oncologists are conflicted as to whether true informed consent for treatment can be obtained from many older patients. Having a roadmap to decision-making capacity is therefore an inescapable imperative in geriatric oncology, because careful attention must be directed at identifying older patients with cancer who might benefit from these assessments and the individualized treatment plans that emerge.
Robert I. Haddad, William M. Lydiatt, Douglas W. Ball, Naifa Lamki Busaidy, David Byrd, Glenda Callender, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Megan Haymart, Carl Hoh, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M. Lamonica, Judith C. McCaffrey, Jeffrey F. Moley, Lee Parks, Christopher D. Raeburn, John A. Ridge, Matthew D. Ringel, Randall P. Scheri, Jatin P. Shah, Robert C. Smallridge, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Karin G. Hoffmann and Miranda Hughes
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.
R. Michael Tuttle, Robert I. Haddad, Douglas W. Ball, David Byrd, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Megan Haymart, Carl Hoh, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M. Lamonica, William M. Lydiatt, Judith McCaffrey, Jeffrey F. Moley, Lee Parks, Christopher D. Raeburn, John A. Ridge, Matthew D. Ringel, Randall P. Scheri, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang, Lori J. Wirth, Karin G. Hoffmann and Miranda Hughes
These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on “Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer” was added to the NCCN Guidelines to assist with using these novel targeted agents.
Robert I. Haddad, Christian Nasr, Lindsay Bischoff, Naifa Lamki Busaidy, David Byrd, Glenda Callender, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Whitney Goldner, Megan Haymart, Carl Hoh, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M. Lamonica, Bryan McIver, Christopher D. Raeburn, John A. Ridge, Matthew D. Ringel, Randall P. Scheri, Jatin P. Shah, Rebecca Sippel, Robert C. Smallridge, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Richard J. Wong, Alyse Johnson-Chilla, Karin G. Hoffmann and Lisa A. Gurski
The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, Hürthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E–mutated anaplastic thyroid carcinoma.
William G. Wierda, John C. Byrd, Jeremy S. Abramson, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Jennifer Brown, Asher A. Chanan-Khan, Julio C. Chavez, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Megan S. Lim, Shuo Ma, Sami Malek, Anthony Mato, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Suchitra Sundaram, Nina Wagner, Mary Dwyer and Hema Sundar
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are characterized by a progressive accumulation of leukemic cells in the peripheral blood, bone marrow, and lymphoid tissues. Treatment of CLL/SLL has evolved significantly in recent years because of the improved understanding of the disease biology and the development of novel targeted therapies. In patients with indications for initiating treatment, the selection of treatment should be based on the disease stage, patient’s age and overall fitness (performance status and comorbid conditions), and cytogenetic abnormalities. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.