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Risk Reduction Strategies for Ductal Carcinoma In Situ

Adam L. Cohen and John H. Ward

Ductal carcinoma in situ (DCIS) is a premalignant condition that, if left untreated, may progress to invasive breast cancer. After lumpectomy, DCIS can recur, and about half of recurrences are invasive. In 4 randomized trials, radiation has been shown to decrease the local recurrence rate by about half, though it does not change survival. Based on the results of 3 randomized trials, tamoxifen probably decreases cancer recurrence by about 30%, particularly in young women. Low fat diets, weight loss, and physical activity decrease invasive breast cancer recurrence and may be recommended to certain women with DCIS. Prognostic factors include age, extent of DCIS, margin status, grade, and presence of necrosis, although how these affect adjuvant therapy is unclear. Research evaluating other drugs to reduce recurrence risk and on different ways of delivering radiation continues.

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Using Imatinib as Neoadjuvant Therapy in Dermatofibrosarcoma Protuberans: Potential Pluses and Minuses

Hillary Johnson-Jahangir, William Sherman, and Désirée Ratner

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low grade soft-tissue malignancy associated with a high risk for local recurrence and widespread subclinical extension. Imatinib, a selective tyrosine kinase inhibitor, has been a beneficial adjuvant therapy in patients with unresectable, recurrent, or metastatic DFSP. Because of its characteristic infiltrative growth, effective surgical excision of DFSP may be limited by the risk for disfigurement or functional impairment. In recent cases, neoadjuvant imatinib mesylate therapy has been shown to reduce preoperative tumor size and lessen surgical morbidity associated with the removal of residual DFSP. Use of neoadjuvant imatinib before surgery, however, requires appropriate patient selection and careful weighing of the potential risks and benefits of this treatment.

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Role of Dermatologists in Treating Melanoma

Allan C. Halpern and Sanjay K. Mandal

Melanoma is a major focus of dermatology training and practice, with dermatologists playing a central role in managing melanoma through primary prevention, secondary prevention, diagnosis, and treatment of thinner tumors. Dermatologists have led public health efforts to raise melanoma awareness, promulgate the early warning signs of melanoma, and promote melanoma prevention through sun protection. Dermatologists have unique expertise in melanoma risk assessment and the clinical diagnosis of melanoma through visual inspection and the use of diagnostic aids, including dermoscopy and photographically assisted follow-up. Increasing incidence of melanoma, earlier melanoma detection, narrower excision margins, and improved surgical training in dermatology have recently combined to enhance the role of dermatologists in melanoma care. For patients with thin primary melanomas, dermatologists are increasingly assuming complete care, including wide local excision and long-term surveillance for both disease recurrence and detection of new primary melanoma. Conversely, the advent of sentinel lymph node biopsy and adjuvant therapy has made melanoma management more complex and has intensified the need for a multidisciplinary approach to the disease. In this context, dermatologists contribute significantly to the formation, administration, and implementation of multidisciplinary melanoma programs.

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Expanding the Use of Nephron-Sparing Surgery for Wilms Tumor

Christopher J. Long, Sameer Mittal, and Thomas F. Kolon

Radical nephrectomy combined with contemporary chemotherapeutic and radiation therapy protocols has drastically improved outcomes for children with Wilms tumor. Patients with bilateral disease and a syndrome predisposing to tumor development have necessitated the use of nephron-sparing surgery in select cases. Success in managing these patients has increased the indication for partial nephrectomy, although current guidelines for unilateral Wilms tumor are limited. Given that children are being cured with increasing success, recent focus has shifted to long-term health outcomes in addition to tumor treatment. Specifically, renal function has an impact on long-term cardiovascular health and events. Adult outcomes with partial nephrectomy provide a guideline for a paradigm shift in the management of children with Wilms tumor, particularly with advances in imaging and adjuvant therapy. The data are limited for children undergoing partial nephrectomy for unilateral Wilms tumor and outcomes for larger tumors will need to be studied closely in future trials. Increased utilization of neoadjuvant chemotherapy could further expand the number of patients eligible for partial nephrectomy.

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Larotrectinib in a Patient With Advanced Pleomorphic Liposarcoma of the Uterus

Anisley Valenciaga, O. Hans Iwenofu, and Gabriel Tinoco

Pleomorphic liposarcoma of the uterus (PLU) is an extremely rare disease with poor prognosis. Limited treatment options exist for these patients, and disease recurrence usually occurs rapidly within months of initial diagnosis. Few case reports of metastatic PLU are available in the literature. We describe a 70-year-old woman who presented with a large uterus and ovarian mass on imaging and negative serum tumor markers and endometrial biopsy. Staging revealed localized disease. Surgical resection revealed PLU on pathology. Immunohistochemistry was negative for smooth muscle actin (SMA), S100, and MDM2, and positive for CD10 and cyclin-D1. She was treated with adjuvant therapy and experienced disease recurrence in the liver at 15 months from surgery. Genetic testing of the metastasis showed IQGAP-NTRK3 gene fusion. She was given entrectinib but continued to show progression in the liver. Right partial hepatectomy was performed, showing positivity for CD10, BCL-1, MDM2, and SMA on tumor staining. Treatment was switched to pazopanib with disease progression in the neck. She was treated with larotrectinib last, showing no disease progression and adequate tolerance of therapy after 18 months of this treatment. This is the first case in the literature of metastatic PLU with NRTK3 fusion treated with sequential first-generation NRTK inhibitors. More case reports are needed to identify commonalities and therapeutic options. Genetic testing in all PLU cases is needed for targeted therapy approaches.

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BRAF/MEK Inhibition as a Bridge to Immunotherapy for Symptomatic BRAF V600 Melanoma Brain Metastases: A Case Series

Jacob Strelnikov, Alice Zhou, Omar Butt, Michael Ansstas, and George Ansstas

Targeted and immune therapies have changed the paradigm of treatment for patients with metastatic melanoma. Treatment of patients with symptomatic melanoma brain metastases, however, is complicated by the frequent use of immune suppression for the management of vasogenic edema and the urgency in addressing disease burden. Use of BRAF/MEK inhibitors in patients with a corresponding BRAF V600 mutation often results in rapid response but is hindered by high rates of disease relapse and progression. Immunotherapy has higher durability of response, but the rate of response is slower and responses can be significantly diminished for patients on concurrent steroid therapy. Considering this gap in evidence-based guidance for optimal adjuvant therapy sequence in immunosuppressed patients with BRAF V600–mutant melanoma brain metastases, we report on 4 cases utilizing BRAF/MEK inhibitors as a bridging therapy for brain metastases management before initiation of immune checkpoint inhibitor therapy. Future prospective studies will be required to determine the optimal treatment sequencing for patients in this population with high unmet medical need.

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Race of the Clock: Reducing Delay to Curative Breast Cancer Surgery

Loretta Loftus, Christine Laronga, Karen Coyne, and Lynne Hildreth

Analysis of Moffitt Cancer Center data on time from breast biopsy to first definitive surgery showed an average of 6.9 weeks, which concerned the breast program faculty members. Delays in curative surgery may impact mortality, quality of life, and time to adjuvant therapy. The purpose of this study was to analyze steps from breast biopsy to definitive breast cancer surgery and to develop proposals and strategies for improvement. Data were collected from various sources, including the tumor registry, patient appointment system, tumor board lists, and the NCCN Oncology Outcomes Database for Breast Cancer. Three phases of the surgical process were identified with regard to lead time: biopsy to first consult (BX-FC); first consult to tumor board (FC-TB); and tumor board to surgery (TB-SU). Other factors, including operating room capacity and schedules, were also evaluated. The greatest percentage of total lead time occurred in the TB-SU phase (52% vs 35% in BX-FC, and 13% in FC-TB phases). The longest average lead time, 3.6 weeks, was also in the TB-SU phase. The TB-SU time was greatest when surgery was scheduled after tumor board and if surgery required breast reconstruction. Limitation of physician capacity was a major factor in treatment delay. The Opportunity for Improvement project enabled institutional analysis of the need for quality improvement in time for curative surgery for breast cancer. A significant factor that created time delay was physician capacity. As a result, additional faculty and staff have been recruited. A new expanded facility is currently in progress that will provide more physical space and services.

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Integrating Perioperative Chemotherapy into the Treatment of Muscle-Invasive Bladder Cancer: Strategy Versus Reality

S. Machele Donat

Since the initial report in 2003 of the Intergroup-0080 trial confirming benefit of combined neoadjuvant M-VAC (methotrexate, vinblastine, adriablastine, and cisplatin) chemotherapy and cystectomy in the treatment of muscle-invasive bladder cancer, debate has continued in the literature as to the relative risk/benefits of integrating perioperative chemotherapy into the care of patients, especially in those with organ-confined, muscle-invasive, node-negative disease in whom the benefit may be less. Because of the inaccuracies of clinical staging, the potential morbidity related to M-VAC chemotherapy, a 70% cure rate in pT2No disease with surgery alone, and only a modest (5%) improvement in absolute overall survival with combined therapy, many favor limiting chemotherapy to patients with a pathologic stage of pT3 or greater or node-positive disease. This philosophy was also reflected in the 2008 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Bladder Cancer, in which neoadjuvant chemotherapy for clinical T2 disease versus adjuvant therapy based on pathologic risks is only “considered.” Additionally, a recent study looking at the perioperative integration of chemotherapy for stage III bladder cancer in the United States using the National Cancer Data Base showed that only 11.6% of patients underwent any perioperative chemotherapy, with most in the adjuvant setting. These findings indicate that despite randomized trial data showing survival benefit for perioperative chemotherapy, and the current guidelines for therapy supporting those findings, chemotherapy is not being integrated well into the care of patients with muscle-invasive bladder cancer, even in those who, experts agree, have the most potential for benefit.

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Outcomes in Nonmetastatic Hormone Receptor–Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study

Ryan Ying Cong Tan, Whee Sze Ong, Kyung-Hun Lee, Seri Park, Jabed Iqbal, Yeon Hee Park, Jeong Eon Lee, Jong Han Yu, Ching-Hung Lin, Yen-Shen Lu, Makiko Ono, Takayuki Ueno, Yoichi Naito, Tatsuya Onishi, Geok-Hoon Lim, Su-Ming Tan, Han-Byoel Lee, Jiwon Koh, Wonshik Han, Seock-Ah Im, Veronique Kiak Mien Tan, Nitar Phyu, Fuh-Yong Wong, Puay Hoon Tan, and Yoon-Sim Yap

Background: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. Methods: Individual patient-level data from 6 centers on stage I–III hormone receptor–positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. Results: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43–0.80), RFS (HR, 0.70; 95% CI, 0.56–0.89), and OS (HR, 0.71; 95% CI, 0.53–0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non–breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08–5.40), radiotherapy (HR, 0.44; 95% CI, 0.23–0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09–0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. Conclusions: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

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BPI21-009: Survival Benefit of Adjuvant Chemotherapy in Pulmonary Carcinoid: A Systematic Review

Philip Sobash and Nagla Abdel Karim

atypical disease and metastatic disease. Aim of the study is to explore the benefit of adjuvant therapy for thoracic carcinoid tumors. Methods: A literature review was conducted through PubMed in accordance with PRISMA guidelines to identify studies