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Hodgkin Disease/Lymphoma Clinical Practice Guidelines

Memorial Sloan-Kettering Cancer Center

Cure rates for Hodgkin disease/lymphoma have increased to such an extent that the overriding treatment considerations often relate to long-term toxicity, especially for patients with early- or intermediate-stage disease. Current management programs are based on comprehensive clinical staging followed by combined modality therapy for patients with favorable and intermediate prognosis, or chemotherapy alone for patients with advanced disease. Relapse is uncommon, but secondary management with peripheral stem cell transplantation may be effective. The excellent prognosis for these patients mandates careful long-term follow-up to detect late treatment effects.

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Surgery for Early-Stage Small Cell Lung Cancer

Bryan J. Schneider, Ashish Saxena, and Robert J. Downey

Limited-stage small cell lung cancer remains one of the more frustrating malignancies to treat. Current standard of care typically includes platinum-based chemotherapy with thoracic radiation, and although response to therapy is high, most patients will ultimately experience relapse and die of recurrent disease. No high-level data exist supporting surgical resection of early-stage disease; however, several retrospective reviews and small single-arm studies suggest surgery may benefit patients with very limited extent of disease. This article reviews the available literature, and proposes guidelines for including potentially curative resection in the management of patients with limited-stage small cell lung cancer.

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Small Cell Lung Cancer

UCSF Helen Diller Family Comprehensive Cancer Center

Small cell lung cancer (SCLC) accounts for 15% of lung cancers. Nearly all cases of SCLC are attributable to cigarette smoking, and the remaining cases are presumably caused by environmental or genetic factors. Compared with non-small cell lung cancer, SCLC generally has a more rapid doubling time, a higher growth fraction, and earlier development of widespread metastases. SCLC is highly sensitive to initial chemotherapy and radiotherapy, but most patients eventually die from recurrent disease. These guidelines detail the management of SCLC from initial diagnosis and staging through treatment, and include information on supportive and palliative care. Important updates to the 2008 version include refined categories for performance status and the addition of topotecan as an option for patients who experience relapse.

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New First-Line Systemic Treatment Options for Metastatic Esophageal Squamous Cell Carcinoma

Presented by: Michael K. Gibson

Esophageal squamous cell carcinoma is an aggressive malignancy with histologic variability depending on where in the world it is diagnosed, with most of these cancers occurring in China and other parts of Asia. Previous studies with cytotoxic chemotherapy combinations led to a plateau median overall survival of approximately 10 to 12 months, as well as a need for more effective treatment options. Cytotoxic chemotherapy served as the control arm in 3 studies that evaluated the safety and efficacy of immunotherapy + chemotherapy versus chemotherapy alone; in all 3 prospective randomized trials, the addition of immunotherapy resulted in a survival benefit in the first-line relapsed/metastatic setting. Data support these immunotherapy regimens as new standard-of-care systemic therapy options for unresectable, locally advanced, recurrent or metastatic esophageal cancers, and these regimens have now been incorporated into the NCCN Guidelines.

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The Quickening Pace of Oncology Research

Rodger J. Winn

in relapsed, refractory myeloma . N Engl J Med 2003 ; 348 : 2609 - 2617 .

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The Aromatase Inhibitors as Adjuvant Therapy for Hormone Receptor-Positive Breast Cancer

Jennifer A. Ligibel and Eric P. Winer

Adjuvant hormonal therapy has been shown to decrease the risk of breast cancer recurrence and overall mortality in patients with hormone receptor-positive breast cancer. Tamoxifen has been used in this setting for many years, both in premenopausal and postmenopausal patients. Tamoxifen is not devoid of toxicity, and attempts have been made to develop newer hormonal agents with better efficacy and less toxicity. The aromatase inhibitors have shown equivalent or superior efficacy to tamoxifen in the treatment of metastatic breast cancer, and efforts are underway to determine the role of these agents in early breast cancer. The ATAC trial recently showed that use of the third-generation aromatase inhibitor anastrozole in the adjuvant setting led to a modest improvement in relapse-free survival as compared with tamoxifen. Patients treated with anastrozole were also less likely to develop uterine cancer or experience a thromboembolic event. However, patients treated with anastrozole were more likely than those treated with tamoxifen to suffer a fracture or other musculosketal problem. An ASCO technology assessment panel reviewed the relevant data and issued a consensus statement regarding the use of aromatase inhibitors in the adjuvant setting. In general, the panel favored the continued use of tamoxifen as adjuvant hormonal therapy for most postmenopausal women. Within the next few years, further data from the ATAC trial and from other trials of aromatase inhibitors in the adjuvant setting should be available to guide treatment recommendations for this patient population.

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Adjuvant Chemotherapy for Lung Cancer: Cisplatin Doublets Only?

Daniel Morgensztern and Ramaswamy Govindan

Lung cancer is the leading cause of cancer-related mortality world-wide. Despite adequate resection, more than half of patients die of recurrent disease, usually at distant sites. Adjuvant systemic chemotherapy is mainly used to eradicate micrometastatic disease. Since the seminal 1995 meta-analysis from earlier studies showed a trend toward improved survival with the use of cisplatin-based adjuvant chemotherapy, several randomized prospective adjuvant trials have addressed this question and eventually established the role for platinum-based adjuvant chemotherapy in patients with stage II or IIIA non–small cell lung cancer who have undergone complete resection. The role of adjuvant chemotherapy in patients with stage I disease remains controversial. Although no clinical or molecular predictors of recurrent disease after surgical resection are reliable, encouraging preliminary data on gene expression studies suggest that identifying, and perhaps treating, only patients at high risk for relapse might be possible in the near future. Furthermore, molecular predictors of resistance may guide the selection of chemotherapy in this setting.

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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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Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary

Jennifer Shih, Babar Bashir, Karen S. Gustafson, Mark Andrake, Roland L. Dunbrack, Lori J. Goldstein, and Yanis Boumber

Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.

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Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors

Andrea Maurichi, Rosalba Miceli, Roberto Patuzzo, Francesco Barretta, Gianfranco Gallino, Ilaria Mattavelli, Consuelo Barbieri, Andrea Leva, Umberto Cortinovis, Elena Tolomio, Milena Sant, Gianpiero Castelli, Leonardo Zichichi, Giovanni Pellacani, Ignazio Stanganelli, Marco Simonacci, Ausilia Manganoni, Corrado Del Forno, Gioachino Caresana, Catherine Harwood, Daniele Bergamaschi, Konstantinos Lasithiotakis, Dorothy Bennett, Vittoria Espeli, Cristina Mangas, Sandra Leoni Parvex, Barbara Valeri, Mara Cossa, Marta Barisella, Alessandro Pellegrinelli, Claudia Miranda, Andrea Anichini, Roberta Mortarini, Odysseas Zoras, and Mario Santinami

Background: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. Patients and Methods: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. Results: Median follow-up was 126 months (interquartile range, 104–157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node–negative and 3 patients who were sentinel node–positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%–99.2%) and 82.2% (95% CI, 77.3%–87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. Conclusions: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.