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Joshua B. Brown, Reetesh K. Pai, Melissa A. Burgess, Jennifer Chennat and Amer H. Zureikat
Gastrointestinal stromal tumors (GISTs) represent 1% of alimentary tract neoplasms. Up to 90% of GISTs are driven by activating mutations in tyrosine kinase KIT or PDGFRα genes. Imatinib mesylate is a tyrosine kinase inhibitor that has recently been used in a neoadjuvant role for locally advanced GIST. Pathologic complete response (pCR) to imatinib, however, is rare and may be limited to patients with certain mutations. We report on a 71-year-old woman with a large advanced gastric GIST near the gastroesophageal junction initially involving the pancreas, spleen, adrenal, and aortic wall. The tumor harbored a KIT exon 11 deletion mutation in codon 558, which predicts a favorable response to imatinib. After 6 months of neoadjuvant imatinib therapy, the tumor was downstaged to allow partial gastric resection without the need for total gastrectomy reconstruction. The patient underwent partial gastrectomy, distal pancreatectomy, and splenectomy, and histologic examination showed a margin-negative resection with a near-pCR, with <5% viable tumor. Prolonged neoadjuvant therapy was undertaken based on the prognostic significance of a KIT exon 11 deletion mutation in codon 558, which facilitated an R0 resection while minimizing the surgical extent of the resection. A near-pCR of a large gastric GIST after neoadjuvant imatinib therapy remains a rare occurrence. Molecular testing should be undertaken before neoadjuvant therapy, because specific mutations can identify patients who will respond to imatinib and those likely to achieve significant downstaging and pCR.
Jason Gotlib, Aaron T. Gerds, Prithviraj Bose, Mariana C. Castells, Michael W. Deininger, Ivana Gojo, Krishna Gundabolu, Gabriela Hobbs, Catriona Jamieson, Brandon McMahon, Sanjay R. Mohan, Vivian Oehler, Stephen Oh, Eric Padron, Philip Pancari, Nikolaos Papadantonakis, Animesh Pardanani, Nikolai Podoltsev, Raajit Rampal, Erik Ranheim, Lindsay Rein, David S. Snyder, Brady L. Stein, Moshe Talpaz, Swapna Thota, Martha Wadleigh, Katherine Walsh, Mary Anne Bergman and Hema Sundar
Mastocytosis is a group of heterogeneous disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin and/or in various extracutaneous organs. Systemic mastocytosis is the most common form of mastocytosis diagnosed in adults, characterized by mast cell infiltration of one or more extracutaneous organs (with or without skin involvement). The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of systemic mastocytosis. However, certain aspects of clinical care, particularly the diagnosis, assessment, and management of mediator-related symptoms continue to present challenges. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with systemic mastocytosis.
Endocrine therapy remains the backbone for treatment of hormone receptor-positive breast cancer in the metastatic setting. Despite the effectiveness of endocrine therapy, primary and acquired endocrine resistance continue to be important clinical challenges. The landscape of metastatic breast cancer treatment has changed considerably with the incorporation of novel agents, including cyclin-dependent kinase 4/6 and mammalian target of rapamycin inhibitors. This article reviews current endocrine treatment strategies and recent and ongoing studies of combination therapies in metastatic hormone receptor-positive, HER2-negative breast cancer.
Lydia F.J. van Overveld, Robert P. Takes, Jozé C.C. Braspenning, Robert J. Baatenburg de Jong, Jan P. de Boer, John J.A. Brouns, Rolf J. Bun, Eric A. Dik, Boukje A.C. van Dijk, Robert J.J. van Es, Frank J.P. Hoebers, Barry Kolenaar, Arvid Kropveld, Ton P.M. Langeveld, Hendrik P. Verschuur, Jan G.A.M. de Visscher, Stijn van Weert, Max J.H. Witjes, Ludi E. Smeele, Matthias A.W. Merkx and Rosella P.M.G. Hermens
Background: Monitoring and effectively improving oncologic integrated care requires dashboard information based on quality registrations. The dashboard includes evidence-based quality indicators (QIs) that measure quality of care. This study aimed to assess the quality of current integrated head and neck cancer care with QIs, the variation between Dutch hospitals, and the influence of patient and hospital characteristics. Methods: Previously, 39 QIs were developed with input from medical specialists, allied health professionals, and patients' perspectives. QI scores were calculated with data from 1,667 curatively treated patients in 8 hospitals. QIs with a sample size of >400 patients were included to calculate reliable QI scores. We used multilevel analysis to explain the variation. Results: Current care varied from 29% for the QI about a case manager being present to discuss the treatment plan to 100% for the QI about the availability of a treatment plan. Variation between hospitals was small for the QI about patients discussed in multidisciplinary team meetings (adherence: 95%, range 88%–98%), but large for the QI about malnutrition screening (adherence: 50%, range 2%–100%). Higher QI scores were associated with lower performance status, advanced tumor stage, and tumor in the oral cavity or oropharynx at the patient level, and with more curatively treated patients (volume) at hospital level. Conclusions: Although the quality registration was only recently launched, it already visualizes hospital variation in current care. Four determinants were found to be influential: tumor stage, performance status, tumor site, and volume. More data are needed to assure stable results for use in quality improvement.
Michelle C. Nguyen, Manisha H. Shah, David A. Liebner, Floor J. Backes, John Phay and Lawrence A. Shirley
Therapeutic agents targeting the PD-1/PD-L1 axis have shown durable clinical responses in patients with various cancer types. Although objective responses are common, intrapatient heterogeneous responses have been described, and the mechanism for the different organ responses remains unknown. We present a series of patients in whom a lack of response was noted solely in the adrenal glands. This is the first case series describing 3 patients with heterogeneous patterns of response to pembrolizumab with progression of adrenal metastatic disease despite objective response (complete or partial response) in all other sites of metastatic disease. Two patients, one with melanoma and one with uterine carcinosarcoma, underwent robotic adrenalectomy for enlarging adrenal metastases. An additional patient with melanoma underwent laparotomy with attempted resection, but infiltration of the adrenal tumor into the inferior vena cava prohibited safe excision. This report provides additional insight into the heterogeneous patterns of disease response to anti–PD-1 therapy, highlighting the adrenal gland as a potential sanctuary site for this immunotherapy. These cases display the potential benefit of early surgical resection in this scenario and the pitfalls of delaying referral to a surgeon for assessment of operative intervention.
Therese B. Bevers, Mark Helvie, Ermelinda Bonaccio, Kristine E. Calhoun, Mary B. Daly, William B. Farrar, Judy E. Garber, Richard Gray, Caprice C. Greenberg, Rachel Greenup, Nora M. Hansen, Randall E. Harris, Alexandra S. Heerdt, Teresa Helsten, Linda Hodgkiss, Tamarya L. Hoyt, John G. Huff, Lisa Jacobs, Constance Dobbins Lehman, Barbara Monsees, Bethany L. Niell, Catherine C. Parker, Mark Pearlman, Liane Philpotts, Laura B. Shepardson, Mary Lou Smith, Matthew Stein, Lusine Tumyan, Cheryl Williams, Mary Anne Bergman and Rashmi Kumar
The NCCN Guidelines for Breast Cancer Screening and Diagnosis have been developed to facilitate clinical decision making. This manuscript discusses the diagnostic evaluation of individuals with suspected breast cancer due to either abnormal imaging and/or physical findings. For breast cancer screening recommendations, please see the full guidelines on NCCN.org.
Parijatham S. Thomas
Atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are nonmalignant breast lesions that confer a 4- to 10-fold increased risk for breast cancer in women. Often, AH and LCIS are diagnosed through breast biopsy due to a mammographic or palpable finding. Although AH and LCIS are benign breast disease, further management is necessary due to their high-risk nature and premalignant potential. Over the decades, management of AH and LCIS has changed as more is learned about these disease processes. This review explores the studies evaluating the risk for breast cancer in women with AH or LCIS and the clinical management of these lesions, which can include a combination of surgical excision, surveillance, and risk-reduction therapy.