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Presenter: Smitha S. Krishnamurthi

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.

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Presenters: Ann S. LaCasce and Ariela Noy

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.

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Presenter: Maria Alma Rodriguez

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.

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William J. Gradishar, Meena S. Moran, Jame Abraham, Rebecca Aft, Doreen Agnese, Kimberly H. Allison, Bethany Anderson, Harold J. Burstein, Helen Chew, Chau Dang, Anthony D. Elias, Sharon H. Giordano, Matthew P. Goetz, Lori J. Goldstein, Sara A. Hurvitz, Steven J. Isakoff, Rachel C. Jankowitz, Sara H. Javid, Jairam Krishnamurthy, Marilyn Leitch, Janice Lyons, Joanne Mortimer, Sameer A. Patel, Lori J. Pierce, Laura H. Rosenberger, Hope S. Rugo, Amy Sitapati, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, Erica M. Stringer-Reasor, Melinda L. Telli, John H. Ward, Kari B. Wisinski, Jessica S. Young, Jennifer Burns, and Rashmi Kumar

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.

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Ryan M. Kahn, Sushmita Gordhandas, Emeline Aviki, and Kara Long Roche

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Laura M. Spring, Yael Bar, and Steven J. Isakoff

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.

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Abi Vijenthira, Lee Mozessohn, Chenthila Nagamuthu, Ning Liu, Danielle Blunt, Shabbir Alibhai, Anca Prica, and Matthew C. Cheung

Background: The objectives of this study were to determine whether frailty is associated with survival in a population-based sample of patients with diffuse large B-cell lymphoma (DLBCL) and to describe the healthcare utilization patterns of frail versus nonfrail patients during treatment. Methods: A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years diagnosed between 2006 and 2017 with DLBCL or transformed follicular lymphoma who received first-line curative-intent chemoimmunotherapy were included. Frailty was defined using a modified version of a generalizable frailty index developed for use with Ontario administrative data. Cox regression was performed to examine the association between frailty and 1-year mortality. Results: A total of 5,527 patients were included (median age, 75 years [interquartile range, 70–80 years]; 48% female), of whom 2,699 (49%) were classified as frail. Within 1 year of first-line treatment, 32% (n=868) of frail patients had died compared with 20% (n=553) of nonfrail patients (unadjusted hazard ratio, 1.8; 95% CI, 1.6–2.0; P<.0001). Frail patients had higher healthcare utilization during treatment, with most hospitalizations related to infection and/or lymphoma. In multivariable modeling controlling for age, inpatient diagnosis, number of chemoimmunotherapy cycles received, comorbidity burden, and healthcare utilization, frailty remained independently associated with 1-year mortality (adjusted hazard ratio, 1.5; 95% CI, 1.3–1.7; P<.0001). Conclusions: In a population-based sample of older adult patients with DLBCL receiving front-line curative-intent therapy, half were classified as frail, and their adjusted relative rate of death in the first year after starting treatment was 50% higher than that of nonfrail patients. Frailty seems to be associated with poor treatment tolerance and a higher likelihood of requiring acute hospital-based care.