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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.

In the past 2 years, several significant changes have been made to the NCCN Guidelines for Colorectal Cancer (CRC) Screening. The age for initiation of screening average-risk adults has been lowered from age 50 to 45 years—without differentiation by age and race—and from age50 to 45 years for those with second- and third-degree relatives with CRC. For several groups, surveillance intervals have been changed. Patients with 1 or 2 low-risk adenomas at index colonoscopy, on the other hand, can now wait 10 years rather than 5 to 7 years between surveillance examinations. The first surveillance examination following resection of large adenomas or sessile serrated polyps (SSPs) with unfavorable-risk characteristics or that were removed piecemeal should now occur at 6 months. For patients with ≥10 adenomas and SSPs on a single colonoscopy, time to first surveillance was lowered to 1 year.

For patients with newly diagnosed multiple myeloma (MM), treatment with 4-drug regimens produce deep responses and should be considered for those with high-risk features. Daratumumab + lenalidomide and dexamethasone is standard treatment for newly diagnosed patients not eligible for autologous stem cell transplantation (ASCT). Although lenalidomide remains standard maintenance therapy, in some instances more intensive regimens can be considered. ASCT is more effective when given up-front rather than delayed, but delaying transplantation until disease progression is acceptable. CAR T-cell therapy can provide durable responses, and 2 agents are now FDA-approved for use in multiple myeloma. Bispecific T-cell engagers are also effective for relapsed myeloma, as is the BCL2 inhibitor venetoclax, especially for patients with t(11;14) disease. An emerging novel class of drugs, the CELMoDs (cereblon E3 ligase modulator), target cereblon.

Abstract

A number of assays are now available to estimate the prognosis of early-stage colorectal cancer, including multigene assays, the Immunoscore, and circulating tumor DNA (ctDNA). Although the results of these assays may provide prognostic information regarding the risk for recurrence, their use as a predictive assay has not yet been validated. Therefore, although these assays may be useful for prognostication, further validation would be required to include in the NCCN Guidelines. For the treatment of metastatic colorectal cancer, major advances have included the use of checkpoint inhibition in metastatic disease. Studies are currently underway to further define their optimal use.

Although follicular lymphoma (FL) and marginal zone lymphoma (MZL) share similarities, the 2 diseases have distinct biologic differences that affect their presentation and treatment. Stage I disease is more common in MZL than in FL due to marginal zone biology, for example, and stage I MZL is curable by surgery or radiation therapy. Newer therapies for both FL and MZL provide chemotherapy-free options, but they are not identical. Brüton’s tyrosine kinase inhibitors are active in relapsed or refractory MZL but not in FL, for example. CAR T-cell therapy has just been approved for treatment of FL and is an ongoing area of investigation for both diseases.

Patients with cancer and cancer survivors are vulnerable to infection, rendering vaccination a necessary intervention. The vaccination process represents a unique challenge in these populations—it is often impossible or impractical to delay the start of cancer treatment for immunizations, and vaccines may fail to trigger an appropriate protective immune response in immunocompromised patients and cancer survivors, with residual immune deficits. Additionally, live attenuated vaccines are contraindicated due to an increased risk of prolonged shedding and disease presence. The current NCCN Guidelines for Survivorship, which reflect the most up-to-date, evidence-based data relating to survivorship, detail the appropriate immunization practices in these highly susceptible populations.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

The role of neoadjuvant therapy (NAT) for localized breast cancer has evolved tremendously over the past several years. Currently, NAT is the preferred option for high-risk early triple-negative (TN) and HER2-positive (HER2+) breast cancers and is indicated for some estrogen receptor–positive (ER+) breast cancers. In addition to traditional absolute indications for NAT, relative indications such as the assessment of outcomes at the time of surgery and guidance of treatment escalation and de-escalation have greatly evolved in recent years. Pathologic complete response (pCR) and the Residual Cancer Burden (RCB) index are highly prognostic for disease recurrence and survival, mainly in patients with TN or HER2+ disease. Furthermore, post-NAT escalation strategies have been shown to improve long-term outcomes of patients who do not achieve pCR. Additionally, by allowing the direct assessment of drug effect on the tumor, the neoadjuvant setting has become an attractive setting for the exploration of novel agents and the identification of predictive biomarkers. Neoadjuvant trial design has also evolved, using adaptive treatment approaches that enable treatment de-escalation or escalation based on response. However, despite multiple practice-changing neoadjuvant trials and the addition of various new agents to the neoadjuvant setting for early breast cancer, many key questions remain. For example, patient selection for neoadjuvant immunotherapy in TN breast cancer, de-escalation methods in HER2+ breast cancer, and the use of gene expression profiles to guide NAT recommendations in ER+ breast cancer. This article reviews the current approach for NAT in localized breast cancer as well as evolving NAT strategies, the key remaining challenges, and the ongoing work in the field.