Citations

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.

Background: The extent of cardiac involvement has a major impact on clinical outcomes in patients with newly diagnosed light chain (AL) amyloidosis. Here, we present the hematologic responses, major organ deterioration progression-free survival (MOD-PFS) and event-free survival (MOD-EFS), and organ responses by cardiac stage in patients with newly diagnosed AL amyloidosis treated with cyclophosphamide, bortezomib, and dexamethasone (VCd) with or without daratumumab subcutaneous (DARA SC) in the ANDROMEDA trial (NCT03201965). Methods: Key eligibility criteria included newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage I-IIIA (based on the European Modification of the Mayo staging system), eGFR ≥20 mL/min, and absence of symptomatic multiple myeloma. Patients were randomized (1:1) to receive DARA-VCd or VCd alone. All patients received bortezomib (1.3 mg/m2 SC weekly), cyclophosphamide (300 mg/m2 oral [PO] or intravenous [IV] weekly [500 mg maximum]), and dexamethasone (20-40 mg PO or IV weekly) for six 28-day cycles. DARA SC (1800 mg, co-formulated with recombinant human hyaluronidase PH20 in 15 mL) was administered by injection weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks thereafter for up to 24 cycles. Disease evaluations occurred every 4 weeks (Cycles 1-6) and every 8 weeks (after Cycle 7) until major organ deterioration, hematologic progression, death, end of study, or withdrawal. The primary endpoint was overall (ie, at any time) hematologic complete response (CR) rate. Secondary endpoints included MOD-PFS, MOD-EFS, organ response rate, time to hematologic response, survival, and safety. Analyses of hematologic CR and MOD-PFS were performed on the intent-to-treat analysis set; cardiac response analyses were based on patients who were evaluable for cardiac response, defined as patients with baseline NT-ProNBP value ≥650 ng/L or baseline NYHA class 3 or 4 and received at least 1 administration of study treatment. Patients without a baseline assessment or post-baseline assessment were censored at randomization for the MOD-PFS analysis. Descriptive statistics were used to summarize overall CR rate and organ response rate. Hazard ratios and corresponding 95% confidence intervals were estimated based on Cox proportional hazard model. Results: A total of 388 patients were randomized to receive DARA-VCd (n=195) or VCd alone (n=193). Baseline characteristics were well balanced between treatment groups. The median age was 64 years and the proportions of patients with cardiac stage I, II, and III were 23%, 40%, and 37%, respectively. The median duration of treatment was 9.6 months for DARA-VCd and 5.3 months for VCd. Median follow-up was 11.4 months (range, 0.03-21.3+). Baseline characteristics were generally balanced across cardiac stages, except increasing cardiac stage was associated with older age (≥65 years), worse Eastern Cooperative Oncology Group performance status, more advanced renal failure (CrCl ≤30), and functionally worse heart failure (NYHA IIIA). Hematologic CR rates were higher in the DARA-VCd group than in the VCd group in patients with cardiac stages I, II, and III at baseline (Table). Cardiac and renal response rates at 6 months were also higher in the DARA-VCd group regardless of cardiac stage at baseline (Table). The hazard ratios (HRs) for MOD-PFS were 0.33, 0.55 and 0.66 for cardiac stages I, II and III, respectively, favoring DARA-VCd. Corresponding HRs for MOD-EFS were 0.24, 0.39, and 0.48, respectively. Rates of any grade adverse events (AEs) were similar in patients with and without cardiac involvement at baseline. Across both treatment arms, rates of serious treatment-emergent AEs were higher in patients with cardiac involvement at baseline than in those without. Conclusions: The benefit of DARA-VCd was retained over VCd alone across cardiac stages for hematologic CR, MOD-PFS, MOD-EFS, and organ responses. Disclosures Minnema: Kite, a Gilead Company: Speakers Bureau; Celgene: Other: travel support, Research Funding; Amgen: Consultancy; Servier: Consultancy. Dispenzieri:Alnylam: Research Funding; Intellia: Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Comenzo:Unum: Consultancy; Prothena: Consultancy, Research Funding; Amgen: Consultancy; Sanofi: Consultancy; Caleum: Consultancy; Janssen: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Kastritis:Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Wechalekar:Takeda: Honoraria, Other: Travel; Celgene: Honoraria; Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory. Witteles:Pfizer: Membership on an entity's Board of Directors or advisory committees; Alnylam Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Maurer:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alnylam: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ionis: Research Funding; Eidos: Research Funding; Akcea: Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Qin:Janssen: Current Employment. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Jaccard:Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding; Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding.

PURPOSE There is increasing interest in implementing digital systems for remote monitoring of patients’ symptoms during routine oncology practice. Information is limited about the clinical utility and user perceptions of these systems. METHODS PRO-TECT is a multicenter trial evaluating implementation of electronic patient-reported outcomes (ePROs) among adults with advanced and metastatic cancers receiving treatment at US community oncology practices (ClinicalTrials.gov identifier: NCT03249090 ). Questions derived from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) are administered weekly by web or automated telephone system, with alerts to nurses for severe or worsening symptoms. To elicit user feedback, surveys were administered to participating patients and clinicians. RESULTS Among 496 patients across 26 practices, the majority found the system and questions easy to understand (95%), easy to use (93%), and relevant to their care (91%). Most patients reported that PRO information was used by their clinicians for care (70%), improved discussions with clinicians (73%), made them feel more in control of their own care (77%), and would recommend the system to other patients (89%). Scores for most patient feedback questions were significantly positively correlated with weekly PRO completion rates in both univariate and multivariable analyses. Among 57 nurses, most reported that PRO information was helpful for clinical documentation (79%), increased efficiency of patient discussions (84%), and was useful for patient care (75%). Among 39 oncologists, most found PRO information useful (91%), with 65% using PROs to guide patient discussions sometimes or often and 65% using PROs to make treatment decisions sometimes or often. CONCLUSION These findings support the clinical utility and value of implementing digital systems for monitoring PROs, including the PRO-CTCAE, in routine cancer care.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel’s recommendations regarding the age to initiate screening in average risk individuals and follow-up for low-risk adenomas.

Emerging data supports a potential role of neurotensin (NT) in the development of obesity, obesity-associated comorbidities, and certain cancers. The association of NT with colon cancer risk has not been explicitly explored. We determined plasma levels of pro-NT, a stable NT precursor fragment, in 223 incident colon cancer patients and 223 age-, gender-, BMI-matched population controls participating in a population-based case–control study of colon cancer. On average, the cases have significantly higher levels of pro-NT than the controls (median = 205.6 pmol/L vs 183.1 pmol/L, respectively; P = 0.02). Multivariate logistic regression models, adjusted for age, gender, BMI, family history of colorectal cancer, smoking, diabetes mellitus, alcohol, and non-steroidal anti-inflammatory drugs use, show statistically significant risk associations: for continuous measure of pro-NT, the OR estimate was 1.30 (95% CI =1.03–1.64; P = 0.026) for each increment of 175 pmol/L; for dichotomized measure of pro-NT, the OR estimate was 1.75 (95% CI = 1.12–2.74; P = 0.025) for those in the top quartile comparing to the other participants. Our results support circulating levels of pro-NT as a novel risk biomarker for colon cancer.