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Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology

Jaffer A. Ajani, Thomas A. D’Amico, David J. Bentrem, David Cooke, Carlos Corvera, Prajnan Das, Peter C. Enzinger, Thomas Enzler, Farhood Farjah, Hans Gerdes, Michael Gibson, Patrick Grierson, Wayne L. Hofstetter, David H. Ilson, Shadia Jalal, Rajesh N. Keswani, Sunnie Kim, Lawrence R. Kleinberg, Samuel Klempner, Jill Lacy, Frank Licciardi, Quan P. Ly, Kristina A. Matkowskyj, Michael McNamara, Aaron Miller, Sarbajit Mukherjee, Mary F. Mulcahy, Darryl Outlaw, Kyle A. Perry, Jose Pimiento, George A. Poultsides, Scott Reznik, Robert E. Roses, Vivian E. Strong, Stacey Su, Hanlin L. Wang, Georgia Wiesner, Christopher G. Willett, Danny Yakoub, Harry Yoon, Nicole R. McMillian, and Lenora A. Pluchino

years and the 5-year survival rate remains low. 8 Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. 9 In

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Role of Immune Therapies for Myeloma

Jacalyn Rosenblatt and David Avigan

Immune therapy has emerged as a promising area of cancer therapeutics based on its potential for tumor selectivity and targeting of chemotherapy-resistant clones. Allogeneic transplantation produces durable remissions in a subset of patients, albeit at the cost of graft- versus-host disease. Recent years have witnessed efforts to induce more selective immune responses via dendritic cell vaccines, autologous and engineered T-cell therapy, and immune checkpoint blockade. Optimizing these immunotherapeutic approaches, understanding how to best use them in combination, and determining how to integrate them with standard anti-myeloma therapy could provide the potential to alter the natural history of this disease.

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The Changing Treatment Landscape for Metastatic Urothelial Carcinoma

Thomas W. Flaig

Urothelial carcinoma is the predominant histologic type of bladder cancer. After 30 years of minimal progress in the treatment of advanced-stage disease, recent advances in the genomic characterization of urothelial cancer and breakthroughs in bladder cancer therapeutics have rejuvenated the field. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma. Yet the challenge for clinicians is to determine the optimal choice of agents as first-line or second-line therapy and which offers the best chance for overall survival for the individual patient in this rapidly changing field.

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New Treatment Options for Patients With Bladder Cancer

Presented by: Thomas W. Flaig

Bladder cancer is not rare—in men, it is the fourth most common cancer and the eighth leading cause of cancer-related death. The emergence of new systemic therapies, approval of PD-1 and PD-L1 inhibitors, and progress in the development of biomarkers have revolutionized the treatment of this urologic malignancy. The current NCCN Guidelines, which reflect the most up-to-date, evidence-based data relating to the evaluation and management of bladder cancer, support the incorporation of some of these novel therapeutics into clinical practice.

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Management of Metastatic Castration-Resistant Prostate Cancer

Presented by: Sandy Srinivas

Notable developments in the management of metastatic castration-resistant prostate cancer (mCRPC) include newer, more sophisticated imaging methods based on prostate-specific membrane antigen (PSMA) PET and development of radionuclide ligands for use with this modality. In the therapeutic area, PSMA PET–guided therapeutics are under study, and PARP inhibitors are being used to treat patients with gene alterations directly or indirectly involved with the homologous recombination repair pathway. Cabazitaxel has emerged as an effective third-line option for patients treated with prior novel hormonal agents and/or prior docetaxel. As investigators learn more about sequencing therapies for mCRPC, previous exposure is an important consideration for choice of treatment at disease progression.

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Infectious Complications Associated With Immunomodulating Monoclonal Antibodies Used in the Treatment of Hematologic Malignancy

Sophia Koo and Lindsey R. Baden

Immunomodulating monoclonal antibodies are a relatively new addition to the armamentarium of cancer therapeutics and have been shown to improve clinical outcomes in patients with various hematologic malignancies. Because of their targeted nature, these agents are often believed to be less immunosuppressive than standard cytotoxic chemotherapeutic agents. A clear causal association between an immunomodulating therapy and its infectious sequelae is often difficult to discern because of the burden of comorbid illness, intrinsic immunosuppression from the underlying malignancy, use in the salvage setting, and prior and concomitant use of immunosuppressive agents in this patient population. This article evaluates better-established and anecdotal infectious complications associated with major immunomodulating therapies used in hematologic malignancy and hematopoietic stem cell transplantation, including rituximab, alemtuzumab, gemtuzumab ozogamicin, infliximab, dacluzimab, and basiliximab.

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Optimizing Systemic Therapy for Bladder Cancer

Sumanta K. Pal, Matthew I. Milowsky, and Elizabeth R. Plimack

Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

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Optimizing Endocrine Therapy for Breast Cancer

Amelia B. Zelnak and Ruth M. O'Regan

Endocrine therapy has significantly improved outcomes for patients with early- and advanced-stage hormone-receptor (HR)–positive breast cancer. Despite the success of adjuvant endocrine therapy, some patients with early-stage disease will experience relapse. Additionally, all patients with advanced disease will eventually experience disease progression on endocrine therapy due to resistance. Improved understanding of the mechanisms associated with resistance to endocrine agents has recently led to the approval of new therapeutics. Multiple questions remain unanswered, including the optimal duration of adjuvant therapy, the role of ovarian ablation in early-stage breast cancer in premenopausal women, and how to best incorporate targeted agents with endocrine therapy in the metastatic setting. This article reviews the optimization of endocrine therapy in patients with HR-positive breast cancer, focusing on these controversial areas.

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Biologic Agents in the Management of Hodgkin Lymphoma

Armin Rashidi and Nancy L. Bartlett

The advent of biologic approaches for the treatment of solid tumors and hematologic malignancies has been a major accomplishment in oncology and a rapidly growing field of clinical and translational research in cancer therapeutics. Classical Hodgkin lymphoma (HL) is no exception. Although the investigation of biologic therapies in HL started decades ago, it has only recently flourished, largely because of the development of new monoclonal antibody drug conjugates and checkpoint inhibitors. Biologic therapies represent a potent treatment option that have produced durable remissions even in patients who have had multiple relapses or with refractory disease. This article reviews 8 major classes of biologic approaches that have been investigated in HL: monoclonal antibodies, immunotoxins, antibody-drug conjugates, radioimmunotherapy, adoptive immunotherapy, immunomodulators, chimeric antigen receptor T cells, and checkpoint inhibitors. An armamentarium of biologic therapies for HL that are well tolerated and potentially more effective is expected to be available in the near future.

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Novel Targets for Therapeutic Agents in Small Cell Lung Cancer

Patrick C. Ma and Ravi Salgia

Small cell lung cancer (SCLC) is known to have an aggressive phenotype and often presents with distant metastasis. Despite frequent initial response to chemotherapy, it inevitably relapses within 2 years in the majority of patients. Because of the poor overall prognosis of the disease and its unique tumor biology, the opportunity for improving clinical outcome of patients with development of novel therapeutics is great. This review provides current insights into the novel molecular targets in SCLC. Cellular signal transduction pathways and their relationship to cellular functions also are discussed. Discussion of the role receptor tyrosine kinases (RTKs) have in SCLC therapeutic inhibition is emphasized. In particular, the recent development of small molecule inhibitors of RTKs such as c-Kit, c-Met, and VEGF-R and the potential for clinical trials are highlighted.