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Diane L. Reidy-Lagunes

with progressing and advanced or symptomatic disease. This article discusses these recent trials and provides an update of systemic treatment options in patients with well-differentiated pancNETs. Well-differentiated NETs are rare neoplasms arising

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Matthias Holdhoff, Maciej M. Mrugala, Christian Grommes, Thomas J. Kaley, Lode J. Swinnen, Carlos Perez-Heydrich and Lakshmi Nayak

are well enough to tolerate HDC and/or ASCT. For patients with R/R PCNSL, HD-MTX–based therapies are often the most reasonable first option to try to reachieve a complete response. If systemic treatment options are available, WBRT should be avoided due

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Peter H. Carroll and James L. Mohler

Peter H. Carroll, MD, MPH, and James L. Mohler, MD, updated attendees on what is new in the 2018 NCCN Guidelines for Prostate Cancer Early Detection and for Prostate Cancer, respectively. Their presentations touched on new screening recommendations, shared decision-making, risk stratification, the role of genomic and molecular testing, active surveillance, and newer systemic treatments.

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Omar Abdel-Rahman, Hatim Karachiwala and Jacob C. Easaw

during first-line systemic treatment without providing detailed information about subsequent opioid use. Fourth, although the included clinical trials reported data regarding opioid use among patients with advanced gastrointestinal cancer, they did not

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Henry G. Kaplan

No effective systemic treatment exists for malignant peripheral nerve sheath tumors (MPNSTs). These tumors have been reported to show increased activity in the mitogen-activated protein kinase pathway from the loss of neurofibromatosis-1 regulation and occasionally from BRAF V600E mutation. A patient with sporadic metastatic MPNST and the BRAF V600E mutation was treated with standard doses of sorafenib and later vemurafenib and followed for response. The patient showed a rapid but modest and transient response to sorafenib and a very dramatic response to vemurafenib. This case represents the first report of successful systemic treatment of MPNST with an inhibitor of the BRAF V600E mutation. It will be important to define the general utility of this approach and related therapies in this disease.

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Matthew Zibelman and Elizabeth R. Plimack

Before 2005, systemic treatment of metastatic renal cell carcinoma (RCC) was limited to a few minimally effective options. Since then, new agents have emerged targeting the vascular endothelial growth factor and mTOR pathways, which has improved outcomes for patients. Options increased even further beginning in 2015 with 3 new agents, including the addition of nivolumab, the first immune checkpoint inhibitor to demonstrate improved survival in RCC. RCC has long been considered a malignancy with immunogenic potential, and nivolumab offers the potential for durable responses in some patients with a generally tolerable toxicity profile. With so many drugs available to clinicians and patients, properly integrating immune checkpoint blockade (ICB) into the treatment paradigm is challenging. Additionally, emerging research with other ICB agents, as well as ongoing trials of combination strategies, is likely to further impact clinical decision-making. This article attempts to provide some context to inform systemic treatment decisions in the current landscape, with a particular emphasis on the role of immunotherapy, outlines the ongoing immunotherapy research in RCC, and discusses how treatment may evolve.

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Xiuning Le, Renata Ferrarotto, Trisha Wise-Draper and Maura Gillison

Immunotherapy has revolutionized cancer treatment in the past 2 decades, mostly with immune checkpoint blockade approaches. In squamous cell carcinoma of the head and neck (SCCHN), the initial efficacy of immunotherapy was observed in patients with recurrent or metastatic (R/M) disease who received other prior systemic treatment. As monotherapy, anti–PD-1 therapies induce responses in 13% to 18% of patients. More recently, immunotherapy in combination with cytotoxic chemotherapy demonstrated greater safety and efficacy as first-line systemic treatment compared with chemotherapy alone. In R/M SCCHN, the most important benefit of immunotherapy is the significantly improved overall survival, especially in patients with PD-L1–positive tumors. As of 2019, immunotherapy can be used as first-line or subsequent treatment of R/M SCCHN. Many ongoing trials are evaluating immunotherapy combinations or novel immunotherapy strategies, aiming to improve response rate and overall survival. As new targets are identified and new approaches are leveraged, the role of immunotherapy in R/M SCCHN continues to evolve.

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Wells A. Messersmith

Advances have been made in the systemic treatment of colorectal cancer, with approximately 12 chemotherapy or biologic agents approved for use as a single agent or in a combination. However, numerous gaps in our understanding of the disease remain, such as the lack of benefit with biologics in the adjuvant setting, the absence of biomarkers for most systemic therapies, and the reason why left-sided and right-sided tumors behave differently. At the 22nd NCCN Annual Conference, Dr. Wells A. Messersmith presented several impactful updates to the 2017 NCCN Clinical Practice Guidelines in Oncology for Colon Cancer and reviewed the outcomes with a host of therapies used for both early-stage and metastatic disease.

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Shailender Bhatia and John A. Thompson

The 10-year survival rate for patients with metastatic melanoma is less than 10%. Although surgery and radiation therapy have a role in the treatment of metastatic disease, systemic therapy is the mainstay of treatment for these patients. After decades of failed attempts to improve treatment outcomes, recent successes with ipilimumab and vemurafenib have ushered in a new era in systemic therapy. Both ipilimumab and vemurafenib are associated with significant improvements in overall survival of patients in randomized phase III trials, an end point that had proven elusive so far. These breakthroughs not only provide more treatment options for patients with melanoma but also spur the investigation of a new generation of drugs for cancer therapy in general. This article reviews both the current systemic treatment options for metastatic melanoma and promising investigational approaches.

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Patricia Thompson and Mayer Fishman

The purpose of this article is to review the systemic management options for patients with metastatic renal cancer. We reviewed the literature regarding systemic management of metastatic renal cancer. Treatment options of chemotherapy agents, immunotherapy, molecularly targeted agents, allogeneic stem cell transplantation, vaccines, and other manipulations of the immune system are discussed. No chemotherapy agent used alone or in combination has consistently produced responses to substantiate its routine use. Interleukin-2 (IL-2) and interferon-α (IFN-α) have shown response rates ranging from 10% to 20%. Some studies have shown that retinoids may enhance the antitumor activity of IFN-α. Molecularly targeted agents and angiogenic agents are being actively pursued and several studies are showing response rates above 30%. Although nonmyeloablative allogeneic stem cell transplantation shows some promising results, they also have limitations to its use. Therapy strategies that incorporate vaccines as part of comprehensive immune manipulations are also being studied. The systemic treatment of patients with advanced renal cell cancer continues to be a significant challenge. Immunotherapy treatment has shown response in up to 20% of patients. Unfortunately, most do not respond. The current technologies are promising and may be the key step for introduction of better treatments for renal cancer care.