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Novel targeted therapies (small molecule inhibitors, antibody–drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton’s tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

Background: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. Methods: We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. Results: A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51–2.96) and more recent year of diagnosis (2010–2013 vs 2017–2019; OR, 5.36; 95% CI, 3.59–8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86–0.92). Conclusions: Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.

Background: Growing concerns about opioid use disorder (OUD) and the resulting decrease in opioid availability for patients with cancer pain highlight the need for reliable screening tools to identify the subset of patients at increased risk for aberrant opioid use. Our study examines the utility of Current Opioid Misuse Measure (COMM) recommended by the NCCN Clinical Practice Guidelines in Oncology for Adult Cancer Pain. Patients and Methods: We analyzed prospectively collected patient-reported outcomes of 444 consecutive patients with cancer seen in pain clinics of a cancer center at 2 time points within 100 days. The relationship of COMM to other OUD screening tools, pain, opioid doses, patient demographics, and mortality was examined using univariate and multivariable logistic regression. We also examined individual items of COMM for face validity. Results: Among 444 patients who completed pain surveys at 2 time points, 157 (35.4%) did not complete COMM surveys. Using a COMM cutoff of ≥13, a total of 84 patients (29.3%; 84/287) scored positive for aberrant drug use. As patients remained on opioids for 49 to 100 days, the likelihood of improving COMM score (turning from positive to negative) was 6.1 times greater than the reverse. The number of patients with COMM ≥13 was 3.8 times higher than the number of patients with CPT diagnostic codes for OUD, 5.3 times higher than those with a positive urine drug screening, and 21 times higher than those with a positive CAGE (Cut Down, Annoyed, Guilty, Eye-Opener Questionnaire) score. COMM ≥13 was not associated with pain relief response (worst pain intensity score ≥2 points on the Brief Pain Inventory), opioid doses, gender, or age. Contrary to the intended use of COMM to identify aberrant opioid use, COMM ≥13 predicted mortality: patients with COMM ≥13 were 1.9 times more likely to die within 12 months. Conclusions: Our study found that using COMM in a cancer population may significantly overestimate the risk of opioid misuse. Using COMM without modifications can create an additional barrier to cancer pain management, such as limiting appropriate opioid use.

Background: Individuals with diabetes and prediabetes are at increased risk of pancreatic cancer. However, little is known about the effects of smoking or smoking cessation on pancreatic cancer risk in individuals with diabetes and prediabetes. We investigated the association between smoking status (particularly smoking cessation) and pancreatic cancer risk according to glycemic status. Patients and Methods: This nationwide cohort study included 9,520,629 adults without cancer who underwent the Korean National Health Screening in 2009 and were followed until 2018. Hazard ratios and 95% confidence intervals for pancreatic cancer were estimated after adjusting for potential confounders. Results: During the 78.4 million person-years of follow-up, 15,245 patients were newly diagnosed with pancreatic cancer. Among individuals with diabetes and prediabetes, current smoking synergistically increased pancreatic cancer risk (all P<.01). However, quitters with diabetes and prediabetes had a pancreatic cancer risk comparable to that of never-smokers (all P>.05). For pancreatic cancer in current smokers, quitters, and never-smokers, respectively, the hazard ratios were 1.48 (95% CI, 1.40–1.58), 1.11 (95% CI, 1.03–1.19), and 1.00 (reference) among individuals with normoglycemia; 1.83 (95% CI, 1.70–1.97), 1.28 (95% CI, 1.18–1.39), and 1.20 (95% CI, 1.14–1.26) among individuals with prediabetes; and 2.72 (95% CI, 2.52–2.94), 1.78 (95% CI, 1.63–1.95), and 1.63 (95% CI, 1.54–1.72) among individuals with diabetes. There were no differences in risk between quitters with a <20 pack-year smoking history and never-smokers in all glycemic status groups. Conclusions: Pancreatic cancer risk synergistically increased in current smokers with diabetes and prediabetes. However, smoking cessation reduced the synergistically increased risk of pancreatic cancer to the level of never-smokers, especially when smoking history was <20 pack-years. More individualized and intensive cancer prevention education should be underscored for individuals at an increased risk of pancreatic cancer beyond the one-size-fits-all approach.

Background: Prior work suggests that patients with vitamin D insufficiency may have a higher risk of chemotherapy-induced peripheral neuropathy (CIPN) from paclitaxel. The objective of this study was to validate vitamin D insufficiency as a CIPN risk factor. Methods: We used data and samples from the prospective phase III SWOG S0221 (ClinicalTrials.gov identifier: NCT00070564) trial that compared paclitaxel-containing chemotherapy regimens for early-stage breast cancer. We quantified pretreatment 25-hydroxy-vitamin D in banked serum samples using a liquid chromatography-tandem mass spectrometry targeted assay. We tested the association between vitamin D insufficiency (≤20 ng/mL) and grade ≥3 sensory CIPN via multiple logistic regression and then adjusted for self-reported race, age, body mass index, and paclitaxel schedule (randomization to weekly or every-2-week dosing). We also tested the direct effect of vitamin D deficiency on mechanical hypersensitivity in mice randomized to a regular or vitamin D–deficient diet. Results: Of the 1,191 female patients in the analysis, 397 (33.3%) had pretreatment vitamin D insufficiency, and 195 (16.4%) developed grade ≥3 CIPN. Patients with vitamin D insufficiency had a higher incidence of grade ≥3 CIPN than those who had sufficient vitamin D (20.7% vs 14.2%; odds ratio [OR], 1.57; 95% CI, 1.14–2.15; P=.005). The association retained significance after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; 95% CI, 1.18–2.30; P=.003) but not race (adjusted OR, 1.39; 95% CI, 0.98–1.97; P=.066). In the mouse experiments, the vitamin D–deficient diet caused mechanical hypersensitivity and sensitized mice to paclitaxel (both P<.05). Conclusions: Pretreatment vitamin D insufficiency is the first validated potentially modifiable predictive biomarker of CIPN from paclitaxel. Prospective trials are needed to determine whether vitamin D supplementation prevents CIPN and improves treatment outcomes in patients with breast and other cancer types.