Kazzem Gheybi, Jue Jiang, Shingai B.A. Mutambirwa, Pamela X.Y. Soh, Zsofia Kote-Jarai, Weerachai Jaratlerdsiri, Rosalind A. Eeles, M.S. Riana Bornman, and Vanessa M. Hayes
Background: Germline testing for prostate cancer is on the increase, with clinical implications for risk assessment, treatment, and management. Regardless of family history, NCCN recommends germline testing for patients with metastatic, regional, very-high-risk localized, and high-risk localized prostate cancer. Although African ancestry is a significant risk factor for aggressive prostate cancer, due to a lack of available data no testing criteria have been established for ethnic minorities. Patients and Methods: Through deep sequencing, we interrogated the 20 most common germline testing panel genes in 113 Black South African males presenting with largely advanced prostate cancer. Bioinformatic tools were then used to identify the pathogenicity of the variants. Results: After we identified 39 predicted deleterious variants (16 genes), further computational annotation classified 17 variants as potentially oncogenic (12 genes; 17.7% of patients). Rare pathogenic variants included CHEK2 Arg95Ter, BRCA2 Trp31Arg, ATM Arg3047Ter (2 patients), and TP53 Arg282Trp. Notable oncogenic variants of unknown pathogenicity included novel BRCA2 Leu3038Ile in a patient with early-onset disease, whereas patients with FANCA Arg504Cys and RAD51C Arg260Gln reported a family history of prostate cancer. Overall, rare pathogenic and early-onset or familial-associated oncogenic variants were identified in 6.9% (5/72) and 9.2% (8/87) of patients presenting with a Gleason score ≥8 or ≥4 + 3 prostate cancer, respectively. Conclusions: In this first-of-its-kind study of southern African males, we provide support of African inclusion for advanced, early-onset, and familial prostate cancer genetic testing, indicating clinical value for 30% of current gene panels. Recognizing current panel limitations highlights an urgent need to establish testing guidelines for men of African ancestry. We provide a rationale for considering lowering the pathologic diagnostic inclusion criteria and call for further genome-wide interrogation to ensure the best possible African-relevant prostate cancer gene panel.
Mostafa R. Mohamed, Kah Poh Loh, Supriya G. Mohile, Michael Sohn, Tracy Webb, Megan Wells, Sule Yilmaz, Rachael Tylock, Eva Culakova, Allison Magnuson, Can-Lan Sun, James Bearden, Judith O. Hopkins, Bryan A. Faller, and Heidi D. Klepin
Background: Older adults (age ≥65 years) receiving chemotherapy are at risk for hospitalization. Predictors of unplanned hospitalization among older adults receiving chemotherapy for cancer were recently published using data from a study conducted by the Cancer and Aging Research Group (CARG). Our study aimed to externally validate these predictors in an independent cohort including older adults with advanced cancer receiving chemotherapy. Methods: This validation cohort included patients (n=369) from the GAP70+ trial usual care arm. Enrolled patients were aged ≥70 years with incurable cancer and were starting a new line of chemotherapy. Previously identified risk factors proposed by the CARG study were ≥3 comorbidities, albumin level <3.5 g/dL, creatinine clearance <60 mL/min, gastrointestinal cancer, ≥5 medications, requiring assistance with activities of daily activities (ADLs), and having someone available to take them to the doctor (ie, presence of social support). The primary outcome was unplanned hospitalization within 3 months of treatment initiation. Multivariable logistic regression was applied including the 7 identified risk factors. Discriminative ability of the fitted model was performed by calculating the area under the receiver operating characteristic (AUC) curve. Results: Mean age of the cohort was 77 years, 45% of patients were women, and 29% experienced unplanned hospitalization within the first 3 months of treatment. The proportions of hospitalized patients with 0–3, 4–5, and 6–7 identified risk factors were 24%, 28%, and 47%, respectively (P=.04). Impaired ADLs (odds ratio, 1.76; 95% CI, 1.04–2.99) and albumin level <3.5 g/dL (odds ratio, 2.23; 95% CI, 1.37–3.62) were significantly associated with increased odds of unplanned hospitalization. The AUC of the model, including the 7 identified risk factors, was 0.65 (95% CI, 0.59–0.71). Conclusions: The presence of a higher number of risk factors was associated with increased odds of unplanned hospitalization. This association was largely driven by impairment in ADLs and low albumin level. Validated predictors of unplanned hospitalization can help with counseling and shared decision-making with patients and their caregivers.
ClinicalTrials.gov identifier: NCT02054741
Doris Howell, Gregory R. Pond, Denise Bryant-Lukosius, Melanie Powis, Patrick T. McGowan, Tutsirai Makuwaza, Vishal Kukreti, Sara Rask, Saidah Hack, and Monika K. Krzyzanowska
Background: Poorly managed cancer treatment toxicities negatively impact quality of life, but little research has examined patient activation in self-management (SM) early in cancer treatment. Methods: We undertook a pilot randomized trial to evaluate the feasibility, acceptability, and preliminary effectiveness of the SMARTCare (Self-Management and Activation to Reduce Treatment Toxicities) intervention. This intervention included an online SM education program (I-Can Manage) plus 5 sessions of telephone cancer coaching in patients initiating systemic therapy for lymphoma or colorectal or lung cancer at 3 centers in Ontario, Canada, relative to a usual care control group. Patient-reported outcomes included patient activation (Patient Activation Measure [PAM]), symptom or emotional distress, self-efficacy, and quality of life. Descriptive statistics and Wilcoxon rank-sum tests were used to examine changes over time (baseline and at 2, 4, and 6 months) within and between groups. We used general estimating equations to compare outcomes between groups over time. The intervention group completed an acceptability survey and qualitative interviews. Results: Of 90 patients approached, 62 (68.9%) were enrolled. Mean age of the sample was 60.5 years. Most patients were married (77.1%), were university educated (71%), had colorectal cancer (41.9%) or lymphoma (42.0%), and had stage III or IV disease (75.8%). Attrition was higher in the intervention group than among control subjects (36.7% vs 25%, respectively). Adherence to I-Can Manage was low; 30% of intervention patients completed all 5 coaching calls, but 87% completed ≥1. Both the continuous PAM total score (P<.001) and categorical PAM levels (3/4 vs 1/2) (P=.002) were significantly improved in the intervention group. Conclusions: SM education and coaching early during cancer treatment may improve patient activation, but a larger trial is needed.
ClinicalTrials.gov Identifier: NCT03849950
NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023
Featured Updates to the NCCN Guidelines
Kelvin A. Moses, Preston C. Sprenkle, Clinton Bahler, Geoffrey Box, Sigrid V. Carlsson, William J. Catalona, Douglas M. Dahl, Marc Dall’Era, John W. Davis, Bettina F. Drake, Jonathan I. Epstein, Ruth B. Etzioni, Thomas A. Farrington, Isla P. Garraway, David Jarrard, Eric Kauffman, Deborah Kaye, Adam S. Kibel, Chad A. LaGrange, Paul Maroni, Lee Ponsky, Brian Reys, Simpa S. Salami, Alejandro Sanchez, Tyler M. Seibert, Terrence M. Shaneyfelt, Marc C. Smaldone, Geoffrey Sonn, Mark D. Tyson, Neha Vapiwala, Robert Wake, Samuel Washington, Alice Yu, Bertram Yuh, Ryan A. Berardi, and Deborah A. Freedman-Cass
The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.
Christopher J. Forlenza, Amy Chadburn, and Lisa Giulino-Roth
Primary mediastinal B-cell lymphoma (PMBCL) is a rare but aggressive mature B-cell lymphoma that arises from thymic B cells and most commonly affects adolescents and young adults. PMBCL is now recognized by the WHO as a distinct entity from diffuse large B-cell lymphoma (DLBCL), not otherwise specified, with a unique clinical presentation and distinct morphologic features and molecular alterations. Similar to classic Hodgkin lymphoma, PMBCL tumors are characterized by alterations in the nuclear factor-κB and JAK/STAT pathways. These tumors also exhibit an immune evasion phenotype marked by upregulation of PD-L1 and loss of B2M. Historic data indicates that outcomes for pediatric patients with PMBCL are inferior compared with pediatric patients with DLBCL treated on the same protocols, and there is no current standard approach to initial treatment. Common regimens used for children with PMBCL include multiagent chemotherapy regimens designed for Burkitt lymphoma, such as Lymphomes Malins B (LMB)-based or Berlin-Frankfurt-Münster (BFM)-based chemotherapy ± rituximab. Based on initial data in adults showing excellent outcomes with the use of DA-EPOCH-R regimens, these regimens have also been adopted in pediatrics, although with mixed results. Novel agents are currently being studied in PMBCL with the goal of improving outcomes and reducing reliance on radiation and/or high-dose chemotherapy. Immune checkpoint blockade with PD-1 inhibition is of particular interest given the upregulation of PD-L1 in PMBCL and the known efficacy of these agents in the relapsed setting. Future efforts in PMBCL will also seek to determine the role of FDG-PET in evaluating response to therapy and the role of biomarkers in risk stratification.