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Grant A. McArthur

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignancy of the skin and subcutaneous tissues that only rarely forms distant metastases. More than 90% of cases are associated with a chromosomal translocation involving the COL1A1 gene on chromosome 17 and the platelet-derived growth factor B gene on chromosome 22. Management of this disease is primarily surgical with excellent rates of local control obtained using either wide local excision or Mohs micrographic surgery. Data have recently shown that inhibiting platelet-derived growth factor receptors (PDGFR) with imatinib can induce high rates of clinical response in patients with unresectable or metastatic DFSP. These data have led to approval of imatinib by the U.S. Food and Drug Administration for treating uresectable DFSP. Although wide surgical excision remains standard care, patients with locally advanced disease not suitable for surgical excision can be treated with the PDGFR-inhibitor imatinib, which sometimes allows residual DFSP to be surgically excised.

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The University of Michigan Comprehensive Cancer Center

The incidence of primary malignant brain tumors is increasing, especially in the elderly, and metastatic disease to the central nervous system (CNS) occurs even more frequently (an incidence about 10 times that of primary brain tumors). In fact, estimates are that 20% to 40% of patients with systemic cancer will develop brain metastases. Primary and metastatic brain tumors are heterogeneous, with varied outcomes and management strategies. This marked heterogeneity means that prognostic features and treatment options must be carefully reviewed for each patient. As these guidelines note, the involvement of an interdisciplinary team is key in the appropriate management of these patients. Important updates to the guidelines include the addition of systemic chemotherapy as a salvage therapy treatment option for local recurrence and limited metastatic lesions and its deletion as an option for multiple metastatic lesions.

For the most recent version of the guidelines, please visit NCCN.org

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Presenter: Maura L. Gillison

Cisplatin and 70 Gy of intensity-modulated radiotherapy remain the standard of care (SoC) in HPV-positive head and neck cancer, with no data to support de-escalation as a new SoC. Cetuximab compromises locoregional tumor control and overall survival without reduced toxicity, although with different toxicity. Eliminating cisplatin and reducing radiation by 10 Gy compromise progression-free survival but not overall survival, and replacement of SoC adjuvant chemoradiotherapy with low-dose radiotherapy plus docetaxel compromises progression-free survival for patients with extracapsular extension and/or multiple cervical metastases, without significantly reducing grade 3 toxicities. The current trend toward numerous, single-institution phase II trials should be minimized, because they can be difficult to interpret. Instead, to move the field forward with more definitive outcomes, focus should be placed on taking promising concepts to multicenter, randomized phase II/III studies with clear statistical endpoints.

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Christopher E. Desch

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Christopher E. Desch

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Katy K. Tsai, Neharika Khurana, Timothy McCalmont, Adil Daud, Boris Bastian, and Iwei Yeh

Abstract

Clear cell basal cell carcinoma (BCC) is an unusual variant of BCC. Its pathogenesis, prognosis, and optimal management remain poorly described due to its rarity. This report presents a 51-year-old man with a history of excised BCC and cutaneous squamous cell carcinomas of the face, with multiple recurrent poorly differentiated carcinomas with clear cell changes of the shoulder for which further classification using conventional histologic means was not possible. His tumor tissue was sent to Foundation Medicine for testing, which revealed a high number of pathogenic genomic alterations, including a mutation in PTCH1. He was diagnosed with dedifferentiated BCC and started on vismodegib. He developed lung metastases while receiving vismodegib, and his disease continued to progress while he was undergoing treatment in a phase I clinical trial. Given the high number of pathogenic alterations suggestive of high tumor mutational burden, immunotherapy was considered and off-label authorization was obtained for treatment with a PD-1 antibody (pembrolizumab). He had a dramatic disease response after 4 infusions of pembrolizumab. Molecular testing was instrumental in determining the correct diagnosis and formulating appropriate treatment options for this patient. Molecular profiling of metastatic BCCs and its subtypes is essential to the development of effective targeted therapies and combination approaches.

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Meaghan Tenney and Joan L. Walker

Minimum surgical treatment for endometrial cancer is removal of the uterus. The operative approach to achieve that goal ranges from vaginal hysterectomy alone to laparotomy with radical hysterectomy, bilateral salpingoophorectomy, bilateral pelvic and para-aortic lymphadenectomy with possible omentectomy, and resection of all metastatic disease. Stratifying the risk factors for predicting presence of metastatic disease has error rates exceeding tolerance for many gynecologic oncologists. Most accept routine laparoscopic surgical staging with hysterectomy, pelvic and para-aortic lymphadenectomy, and removal of adnexa as standard care for patients with endometrial cancer. Modifying the extent of surgical staging for low-risk intrauterine findings or excessive risk for postoperative morbidity is also accepted. Laparoscopic surgery has become the ideal initial surgical approach for this disease, allowing for visual inspection of common metastatic sites, biopsy of abnormal areas, and cytology from peritoneal surfaces. The extent of staging can be altered depending on frozen section findings from the uterus, adnexa, and peritoneal surfaces. Intraoperative medical decision-making can be individualized, encompassing all known risk factors for metastases and balancing comorbidities and potential adverse outcomes. This article documents how laparoscopic surgery satisfies the needs of individual patients and surgeons treating this disease.

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Vanderbilt-Ingram Cancer Center

Occult primary tumors, or cancers of unknown primary, account for 5% to 10% of all diagnosed cancers, and are manifested by a wide variety of clinical presentations, while conferring a poor prognosis for most patients. Even after postmortem examination, the primary tumor is not identified in 20% to 50% of patients. Multiple sites of involvement are observed in more than 50% of patients. Although certain patterns of metastases suggest possible primaries, occult primaries can metastasize to any site. In most patients, occult primary tumors are refractory to systemic treatments, and chemotherapy is only palliative and does not significantly improve long-term survival. However, special pathologic studies can identify subsets of patients with tumor types that are more responsive. Treatment options should be individualized for this selected group to achieve improved response and survival rates. Important updates for the NCCN guidelines include the additions of tables on tumor-specific markers and their staining pattern as well as analysis of undifferentiated carcinoma.

For the most recent version of the guidelines, please visit NCCN.org

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Neelima Denduluri, Debra A. Patt, Yunfei Wang, Menaka Bhor, Xiaoyan Li, Anne M. Favret, Phuong Khanh Morrow, Richard L. Barron, Lina Asmar, Shanmugapriya Saravanan, Yanli Li, Jacob Garcia, and Gary H. Lyman

Background: A wide variety of myelosuppressive chemotherapy regimens are used for the treatment of cancer in clinical practice. Neutropenic complications, such as febrile neutropenia, are among the most common side effects of chemotherapy, and they often necessitate delays or reductions in doses of myelosuppressive agents. Reduced relative dose intensity (RDI) may lead to poorer disease-free and overall survival. Methods: Using the McKesson Specialty Health/US Oncology iKnowMed electronic health record database, we retrospectively identified the first course of adjuvant or neoadjuvant chemotherapy received by patients without metastases who initiated treatment between January 1, 2007, and March 31, 2011. For each regimen, we estimated the incidences of dose delays (≥7 days in any cycle of the course), dose reductions (≥ 15% in any cycle of the course), and reduced RDI (<85% over the course) relative to the corresponding standard tumor regimens described in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Results: This study included 16,233 patients with 6 different tumor types who received 1 of 20 chemotherapy regimens. Chemotherapy dose delays, dose reductions, and reduced RDI were common among patients treated in community oncology practices in the United States, but RDI was highly variable across patients, regimens, and tumor types (0.486–0.935 for standard tumor regimen cohorts). Reduced RDI was more common in older patients, obese patients, and patients whose daily activities were restricted. Conclusions: In this large evaluation of RDI in US clinical practice, physicians frequently administered myelosuppressive agents at dose intensities lower than those of standard regimens.

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Alan N. Houghton