Background: It is critical patients understand the terms used to describe oncology treatments; however, even basic chemotherapy terminology can be misunderstood. Rural communities tend to have especially low levels of health literacy compared with nonrural communities. To address low health literacy in rural communities, this study tested rural participants' understanding of previously developed educational chemotherapy videos that were designed for an underserved urban population. Participants were also asked for feedback to determine if the videos could be improved. Methods: Fifty English-speaking patients who reside in counties classified as rural according to the Rural-Urban Continuum Code designations (RUCC 4-9) participated in the study. Participants were asked to define 6 chemotherapy terms before and after viewing a short, animated video explaining the term in English. Rates of correct and incorrect definitions provided by participants were also compared with previously published results from an urban cohort. Results: All participants had statistically significantly higher rates of correct definitions for all 6 terms following the video intervention. Palliative chemotherapy understanding improved the most (10% correct prevideo and 76% postvideo intervention). For each video, the majority of participants (77%-92%) suggested no changes to the videos. Conclusion: Given the prevalence of low health literacy in rural communities, it is important to have effective educational interventions to improve the understanding of basic oncology-treatment terminology. This study found that short, educational videos, originally designed for an underserved urban population, can significantly improve understanding of commonly misunderstood chemotherapy terminology in a rural setting as well. Lay Summary: Chemotherapy terminology can be confusing to patients. Understanding can be especially difficult in areas with low health literacy, such as underserved urban and rural communities. To address this concern, previously developed short, animated videos describing basic chemotherapy terminology were found to improve patient understanding in an underserved urban setting. In this study, the videos were tested in a rural population and their effectiveness was established. Participants in the rural setting were significantly more likely to correctly define all 6 tested terms after watching the videos. Educational tools for high-need populations are essential to ensure patients can understand the treatment they receive.

Purpose: Early diagnosis is fundamental to reducing breast cancer (BC) mortality, and understanding potential barriers from initial screening to confirmed diagnosis is essential. The aim of this study was to evaluate patient characteristics that contribute to delay in diagnosis of screen-detected cancers and the contribution of delay to tumor characteristics and BC mortality. Methods: Three hundred sixty-two White and 368 Black women were identified who were screened and received subsequent BC diagnoses within Emory Healthcare, a part of Emory University health care system (2010-2014). Multivariable-adjusted logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) associating patient characteristics with delay to diagnostic evaluation (≥30 versus <30 days), delay to biopsy (≥15 versus <15 days), and total delay (≥45 versus <45 days). Additionally, the ORs and 95% CIs associating delay with tumor characteristics and BC mortality were computed. Results: Black women and women diagnosed at later stages, with larger tumor sizes, and with triple-negative tumors were more likely to experience ≥45 days to diagnosis. In multivariable-adjusted models, Black women had at least a two-fold increase in the odds of delay to diagnostic evaluation (OR, 1.98; 95% CI, 1.45-2.71), biopsy delays (OR, 2.41; 95% CI, 1.67-3.41), and total delays ≥45 days (OR, 2.22; 95% CI, 1.63-3.02) compared with White women. A 1.6-fold increased odds of BC mortality was observed among women who experienced total delays ≥45 days compared with women without delays in diagnosis (OR, 1.57, 95% CI, 0.96-2.58). Conclusions: The study demonstrated racial disparities in delays in the diagnostic process for screen-detected malignancies. Total delay in diagnosis was associated with an increase in BC mortality.

Objective. This study examined recurrence patterns in breast cancer patients younger than age of 40 and older than age of 75, two groups that are underrepresented in clinical trials and not routinely screened by mammography. Methods. The records of 230 breast cancer patients (n = 125 less than 40 and n = 105 greater than 75) who presented to the Emory University Department of Radiation Oncology for curative treatment between 1997 and 2010 were reviewed. Data recorded included disease presentation, treatment, and areas of locoregional recurrence. Results. Women less than 40 years of age had higher rates of locoregional recurrence (20% versus 7%, P = 0.004) and distant recurrence (18% versus 5%, P = 0.003) than patients above 75 years of age. On multivariate analysis, patient age less than 40 was the only significant predictor of locoregional recurrence (P = 0.018). In a univariate analysis of each age group, receptor status and postlumpectomy radiation were significant predictors of locoregional recurrence-free survival in younger women while mammography screening predicted for distant recurrence-free survival in older patients. Conclusion. The factors identified in our age-stratified analysis highlight patients who are at high risk of locoregional and distant recurrence. Future studies aimed at enhancing therapies in young patients are warranted.

Purpose: Novel techniques to deliver intensity modulated radiation therapy (IMRT) have resulted in improved treatment efficiency and dosimetric endpoints. We aimed to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated for adenocarcinoma of the prostate (ACP) using volumetric modulated arc therapy (VMAT). Methods and Materials: A total of 122 (71 IMRT and 51 VMAT) ACP patients treated from 2004 to 2011 with definitive external beam radiation therapy were analyzed. Dose-volume histogram endpoints (V40, V65, V70, and V75 of the bladder and rectum) were collected for each patient. Median follow-up for patients treated with VMAT was 269 days versus IMRT was 1121 days. Acute Common Toxicity Criteria for Adverse Events (CTCAE) GI and GU toxicity scores, obtained during each weekly treatment check, were compared across cohorts. The univariate (UV) association between the covariates and outcomes was assessed and multivariable (MV) cumulative logit models were fit for each outcome. Results: Median patient age was 68 years and median prostate-specific antigen was 8.3. Both bladder and rectal V40, V65, V70, and V75 were all higher in the IMRT group versus the VMAT group (P < .05), which was likely influenced by larger planning target volumes in the IMRT group. The VMAT group had significantly lower rates of acute GU and acute GI CTCAE toxicity on UV association analysis. On MV analysis, VMAT remained independently associated with acute GU (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.07-0.44; P < .001) and GI (OR, 0.16; 95% CI, 0.07-0.41; P < .001) toxicity. Conclusions: VMAT appears to be independently associated with lower rates of acute GI and GU toxicity when compared with traditional IMRT. Further exploration of toxicity improvements associated with VMAT use in the definitive treatment of ACP is needed. © 2013 American Society for Radiation Oncology.

Entry of antigen-specific T cells into human tumors is critical for immunotherapy, but the underlying mechanisms are poorly understood. Here, we combined high-dimensional spatial analyses with in vitro and in vivo modeling to study the mechanisms underlying immune infiltration in human multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS). Clustered tumor growth was a feature of MM but not MGUS biopsies, and this growth pattern was reproduced in humanized mouse models. MM biopsies exhibited intralesional as well as spatial heterogeneity, with coexistence of T cell–rich and T cell–sparse regions and the presence of areas of T cell exclusion. In vitro studies demonstrated that T cell entry into MM clusters was regulated by agonistic signals and CD2-CD58 interactions. Upon adoptive transfer, antigen-specific T cells localized to the tumor site but required in situ DC–mediated antigen presentation for tumor entry. C-type lectin domain family 9 member A–positive (CLEC9A+) DCs appeared to mark portals of entry for gradients of T cell infiltration in MM biopsies, and their proximity to T cell factor 1–positive (TCF1+) T cells correlated with disease state and risk status. These data illustrate a role for tumor-associated DCs and in situ activation in promoting the infiltration of antigen-specific T cells in MM and provide insights into spatial alterations in tumor/immune cells with malignant evolution.

PURPOSEVaccine-induced neutralizing antibodies (nAbs) play a critical role in protection from SARS CoV-2. Patients with B-cell malignancies including myeloma are at increased risk of COVID-19-related mortality and exhibit variable serologic response to the vaccine. The capacity of vaccine-induced antibodies in these patients to neutralize SARS CoV-2 or its variants is not known.METHODSSera from 238 patients with multiple myeloma (MM) undergoing SARS CoV-2 vaccination were analyzed. Antibodies against the SARS CoV-2 spike receptor-binding domain (RBD) and viral nucleocapsid were measured to detect serologic response to vaccine and environmental exposure to the virus. The capacity of antibodies to neutralize virus was quantified using pseudovirus neutralization assay and live virus neutralization against the initial SARS CoV-2 strain and the B1.617.2 (Delta) variant.RESULTSVaccine-induced nAbs are detectable at much lower rates (54%) than estimated in previous seroconversion studies in MM, which did not monitor viral neutralization. In 33% of patients, vaccine-induced antispike RBD antibodies lack detectable neutralizing capacity, including against the B1.617.2 variant. Induction of nAbs is affected by race, disease, and treatment-related factors. Patients receiving mRNA1273 vaccine (Moderna) achieved significantly greater induction of nAbs compared with those receiving BNT162b2 (Pfizer; 67% v 48%, P =.006).CONCLUSIONThese data show that vaccine-induced antibodies in several patients with MM lack detectable virus-neutralizing activity. Vaccine-mediated induction of nAbs is affected by race, disease, vaccine, and treatment characteristics. These data have several implications for the emerging application of booster vaccines in immunocompromised hosts.

To report the activity of venetoclax in patients with relapsed mantle cell lymphoma (MCL), we identified 81 patients treated with venetoclax monotherapy (n = 50, 62%) or in combination with a Bruton tyrosine kinase inhibitor (BTKi) (n = 16, 20%), an anti-CD20 monoclonal antibody (n = 11, 14%), or other active agents at 12 US academic medical centers. Patients had high-risk disease features including Ki67 >30% (61%), blastoid/ pleomorphic histology (29%), complex karyotype (34%), and TP53 alterations (49%), and received a median of 3 prior treatments including BTKis in 91%. Venetoclax alone or in combination resulted in an overall response rate (ORR) of 40% and median progression-free (PFS) and overall survival (OS) of 3.7 and 12.5 months, respectively. The receipt of ≤3 prior treatments was associated with higher odds of response to venetoclax in a univariable analysis. In a multivariable analysis, having a high-risk Mantle Cell Lymphoma International Prognostic Index score before receiving venetoclax and disease relapse or progression within 24 months of diagnosis were associated with inferior OS whereas the use of venetoclax in combination was associated with superior OS. Although most patients (61%) had low risk for tumor lysis syndrome (TLS), 12.3% of patients developed TLS despite the implementation of several mitigation strategies. In conclusion, venetoclax resulted in good ORR but short PFS in patients with MCL who are at high risk, and may have a better role in earlier lines of treatment and/or in conation with other active agents. TLS remains an important risk in patients with MCL who initiate treatment with venetoclax.

Recently, TROG 02.01 results showed that in stage III melanoma patients with nodal metastasis, adjuvant radiation to lymph node basin after nodal dissection improves lymph node field relapse without an overall survival (OS) benefit. However, this trial was neither designed nor powered to detect an OS difference. In the present study, we analyzed patients in the National Cancer Database (NCDB) with stage III melanoma with pathologically involved nodes and compared survival outcomes of adjuvant radiation and no-radiation cohorts. Inclusion criteria were as follows: age at least 18 years; diagnosed 2003-2011; surgery to regional lymph nodes; pathologically involved lymph nodes; and American Joint Committee on Cancer stage (IIIA-C). We used propensity score matching analysis to compare the OS of patients with similar baseline demographic, clinical, and pathologic characteristics who received adjuvant radiation and no adjuvant radiation. Overall, 912 patients were analyzed with an average age at diagnosis of 54.4 years and a median follow-up time of 5.5 years. In this cohort, the 5-year OS was 69.0, 51.1, and 30.6% for stage IIIA, IIIB, and IIIC, respectively. On propensity score-adjusted multivariate analysis, we found that adjuvant radiation had no statistically significant impact on OS (hazard ratio: 1.09, 95% confidence interval: 0.75-1.58, P=0.640). Furthermore, age older than 60 years, number of nodes, increasing pathologic stage, and absence of immunotherapy correlated with worse OS. In this NCDB analysis, we found that the adjuvant radiotherapy for node-positive, stage III melanoma patients did not improve OS. This is consistent with TROG 02.01; however, there may be patient selection bias not accounted for by the NCDB.

Objective: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT). Methods: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues. Results: The sibling issues identified included: (1) feeling negative effects of separation from the patient and caregiver(s); (2) experiencing difficult emotions; (3) being faced with additional responsibilities or burdens; (4) lacking information; and (5) feeling excluded. Families and health care providers reported the following strategies to support siblings: (1) sharing information; (2) using social support and help offered by family or friends; (3) taking siblings to the hospital; (4) communicating virtually; (5) providing special events or gifts or quality time for siblings; (6) offering siblings a defined role to help the family during the transplant process; (7) switching between parents at the hospital; (8) keeping the sibling's life constant; and, (9) arranging sibling meetings with a certified child life specialist or school counselor. Conclusions: Understanding the above strategies and sharing them with other families in similar situations can begin to address sibling issues during HSCT and can improve hospital-based, family-centered care efforts.

Background: When using area under the concentration-time curve-based strategies for dosing carboplatin, accurate estimation of glomerular filtration rate is required for determining dose. Commonly, the Cockcroft-Gault equation is used, which is dependent on measurement of serum creatinine (SCr). Because analysis of SCr changed to an isotope dilution mass spectrometry (IDMS) standard, we sought to determine the impact of this assay change on carboplatin dosing and related toxicity. Methods: This was a single-center, retrospective chart review of adults treated with carboplatin between April 2008 and April 2010 divided into cohorts that initiated carboplatin before or after IDMS standardization. End points included grade 3 thrombocytopenia, decrease in platelet count, and hospitalization and were evaluated in cohorts based on concomitant chemotherapy. Results: The chart review identified 158 patients, with 63 patients in the pre-IDMS group and 95 patients in the post-IDMS group. Average SCr (pre 1.01 mg/dl vs post 0.86 mg/dl, p<0.001) and average carboplatin dose (pre 580 mg vs post 703 mg, p<0.001) were significantly different between the groups. The frequency of grade 3 thrombocytopenia was not statistically significant across three partner chemotherapy cohorts before and after IDMS implementation. Conclusions: IDMS standardization led to an overall decrease in SCr with subsequent increase in carboplatin doses. However, no increase in recorded adverse events was observed, suggesting that the clinical relevance in toxicity from higher doses was minimal.