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Hematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections. Primary series or monovalent booster vaccines reduce disease severity, hospitalization, and death among multiple myeloma patients. We characterized virus-neutralizing and spike-binding antibody profiles following monovalent (WA1) or bivalent (WA1/BA.5) SARS-CoV-2 booster vaccination in MM patients. Bivalent vaccination improved the breadth of binding antibodies but not neutralization activity against contemporary variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity., (© 2024. The Author(s).)

Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses., (© 2024. The Author(s).)

Purpose: Doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy is the current standard treatment for early-stage Hodgkins lymphoma (HL). The use of consolidative radiation therapy (RT) in addition to chemotherapy may lead to better survival rates but is controversial because of concerns about long-term toxicity. The aim of this study is to compare outcomes of patients receiving ABVD chemotherapy alone (CTX alone) versus ABVD with consolidative RT (CMT)., Methods and Materials: A single-institution, retrospective review of patients with HL diagnosed from 2000 to 2014 was conducted. Patients were identified from the National Cancer Database. Inclusion criteria included patients aged ≥18 years, with stage I or II HL, who received ABVD with a complete response with/without CMT. Consolidative RT must have been started within 90 days of completing chemotherapy. Institutional review board approval was obtained. Follow-up details and treatment responses were collected from medical record reviews. Standard statistical analysis and Kaplan-Meier curves were used to estimate relapse-free survival (RFS)., Results: One hundred and 8 patients with early-stage HL were identified. The median age at diagnosis was 31 years (range, 19-72). Most patients were female (63%) and Caucasian (65%). stage II HL was present in 89%of patients, 89% had an Eastern Cooperative Oncology Group score of 0 or 1, 35% had B symptoms, and 9% had extranodal involvement. A total of 52.8% received CMT ( n = 57) and 47.2% received CTX alone ( n = 51). The CMT group had fewer cycles of chemotherapy compared to the CTX-alone group (mean cycles, 5.2 vs 5.7, P = 0.045). Twenty-four relapse events occurred in the CTX-alone group, while no relapse events occurred in the CMT group. RFS at 10 years was significantly improved in the CMT group (100%) compared to CTX alone (47.4%, P < .0001; HR = .03, P < .001)., Conclusions: ABVD with consolidative RT was associated with improved RFS. Further studies of toxicity comparisons, advanced stages, and nonfavorable HL are warranted., Competing Interests: PBA reports the participation on a Data Safety Monitoring Board or Advisory Board: Seattle Genetics and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: American Society of Hematology Education Committee. No other conflicts of interest were reported from the other authors of the manuscript., (© 2024 The Author(s).)

Background: The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma., Methods: This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan-Meier method., Results: A total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%-84.0%) in younger patients versus 67.5% (95% CI: 66.7%-68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2-NA) versus 129.8 (95% CI: 125.4-138.7, p-value <0.0001) in males., Conclusions: Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma., (© 2024 Wiley Periodicals LLC.)

Background: Intraoperative radiotherapy (IORT) offers more convenience compared to external beam radiotherapy (EBRT) following breast-conserving surgery for early-stage breast cancer. This study describes the implementation of IORT at a metropolitan academic cancer center., Methods: Demographics, tumor characteristics, margin status, adjunct EBRT, and cosmetic results were retrospectively analyzed in patients undergoing BCS with IORT. IORT consists of 20 gray delivered to the partial mastectomy cavity., Results: From 2015 to 2020, 171 patients (65.5% African American) were included. Histologically, 104 (60.8%) patients had invasive ductal carcinoma (IDC), while 67 (39%) patients had DCIS only. Seventeen (15.9%) patients with IDC and 12 (8.6%) patients with DCIS had positive margins. There were 15 ipsilateral breast recurrences (8.8%) and three patients (20%) developed systemic disease. Twenty-five patients (14.6%) underwent adjuvant EBRT. The local recurrence-free survival at 60 months from date of IORT was 89.4% (95% CI 82.7%-93.6%). For overall survival (OS), 168 (98.2%) patients were alive at a median follow-up of 51.4 months, and three total deaths were recorded., Conclusions: IORT is a highly desirable and convenient alternative to EBRT for early-stage breast cancer especially for patients with poor compliance. IORT has an acceptable ipsilateral recurrence while not precluding adjunct EBRT based upon the final pathologic report., (© 2024 Wiley Periodicals LLC.)

Background: To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status., Methods: In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed., Results: We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677)., Conclusion: Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease., (© 2024 Wiley Periodicals LLC.)

Resistance to radiotherapy is a major barrier during cancer treatment. Here using genome-scale CRISPR/Cas9 screening, we identify CD274 gene, which encodes PD-L1, to confer lung cancer cell resistance to ionizing radiation (IR). Depletion of endogenous PD-L1 delays the repair of IR-induced DNA double-strand breaks (DSBs) and PD-L1 loss downregulates non-homologous end joining (NHEJ) while overexpression of PD-L1 upregulates NHEJ. IR induces translocation of PD-L1 from the membrane into nucleus dependent on deglycosylation of PD-L1 at N219 and CMTM6 and leads to PD-L1 recruitment to DSBs foci. PD-L1 interacts with Ku in the nucleus and enhances Ku binding to DSB DNA. The interaction between the IgC domain of PD-L1 and the core domain of Ku is required for PD-L1 to accelerate NHEJ-mediated DSB repair and produce radioresistance. Thus, PD-L1, in addition to its immune inhibitory activity, acts as mechanistic driver for NHEJ-mediated DSB repair in cancer., (© 2024. The Author(s).)

Background: Currently, the use of radiotherapy alone for people with multiple myeloma is limited to palliation of pain, pending fracture, and control of spinal-cord compression. Single immune-checkpoint inhibitors, such as anti-programmed death-1 (anti-PD1), have not been successful. We aimed to evaluate the activity and safety of the combination of pembrolizumab and low-dose, single-fraction, hypofractionated radiotherapy to treat patients with relapsed or refractory multiple myeloma., Methods: For this prospective, single-centre, single-group, open-label, phase 2 trial, we recruited patients with relapsed or refractory multiple myeloma from the Winship Cancer Institute (Emory University, Atlanta, GA, USA). Key inclusion criteria were aged 18 years or older, Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, relapsed or refractory multiple myeloma as indicated by progression under International Myeloma Working Group (IMWG) criteria, and adequate candidacy for both pembrolizumab and radiotherapy. Baseline and post-treatment assessments were serial bone-marrow biopsy, peripheral blood collections, staging, serial serum and urine paraprotein analysis, serial PET-CT imaging, and a physical examination. On day 1, patients received hypofractionated 8 gray in 1 fraction (8 Gy/1 fx) radiotherapy to either symptomatic or progressing extra-osseous or osseous myeloma sites. Patients also received pembrolizumab (200 mg/kg intravenously) on day 2 or 3, then once every 3 weeks (±7 days) for 2 years or until progressive disease, unacceptable toxicity, withdrawal of consent, loss to follow-up, or death. Dose reduction and interruptions were not allowed. The primary outcome was acute toxicity defined as grade 3 or worse toxicity at 3 months within the radiated site when used in combination with pembrolizumab. All patients were analysed per protocol and included in safety analyses. This trial is registered on ClinicalTrials.gov (NCT03267888); it is completed and closed to accrual., Findings: 32 patients were screened between June 1, 2018, and Sept 2, 2022, and 25 were enrolled in the trial and treated on protocol. Of the 25 treated patients, 11 (44%) were female and 14 (56%) were male. 19 (76%) patients were White and six (24%) were Black or African American. Toxicity, as the primary outcome, was deemed to be acceptable as no grade 4 or 5 adverse events were observed. At 3-month follow-up, eight (32%) of 25 patients had treatment benefit (one had stable disease, three had partial response, two had very good partial response, and two had complete response). There was no grade 3 or worse radiation-related toxicity within irradiated volumes. One (4%) patient of the 25 who received combination treatment had a grade 3 pembrolizumab-related adverse event. There were no treatment-related deaths., Interpretation: Combination treatment of low-dose, single-fraction radiotherapy with pembrolizumab was safe, with early promise of response activity. Our approach could be an option for patients with relapsed or refractory multiple myeloma who have not responded to previous treatment. Larger trials to substantiate our findings are needed., Funding: Merck Sharp & Dohme., Competing Interests: Declaration of interests MKK received funding for this research, paid to their institution, from Merck Pharmaceutical. JMS received a grant for this research from the US National Institutes of Health. JLK has received contracts from Janssen, AbbVie, Genentech, Bristol Myers Squibb, Fortis, Takeda, and Amgen; has received consulting fees from AbbVie, Bristol Myers Squibb, Sebia, and Sanofi; has received support for attending meetings from Bristol Myers Squibb and Sanofi; and has participated on a data safety monitoring board and an advisory board for Incyte. AJN has been on advisory boards for and received honorarium from Adaptive Biotechnologies, Amgen, AstraZeneca, Bristol Myers Squibb, Cellectar Biosciences, GlaxoSmithKline, Janssen, K36 Therapeutics, ONK Therapeutics, Pfizer, Sanofi, Sebia, and Takeda; has received research support, paid to their institution, from Aduro Biotech, Amgen, Arch Oncology, Bristol Myers Squibb, Cellectis, Genentech, GlaxoSmithKline, Janssen, Karyopharm, Kite Pharma, Merck, Pfizer, and Takeda; and has received research support for investigator-initiated studies from Amgen, GlaxoSmithKline, Janssen, Merck, and Takeda. SL has received contracts from Merck, Novartis, Bristol Myers Squibb, and Janssen; has received consulting fees from Janssen, Bristol Myers Squibb, GlaxoSmithKline, Regeneron, Novartis, AbbVie, Genentech, Pfizer, Takeda, and Celsene; has been on the board of directors for TG Therapeutics; and holds stock in TG therapeutics. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Importance: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who experience different neighborhood contexts. Accounting for interactions among neighborhood deprivation, race, and other neighborhood characteristics may enhance understanding of the association., Objective: To investigate whether neighborhood deprivation is associated with breast cancer mortality among Black and White women and whether interactions with rurality, residential mobility, and racial composition, which are markers of access, social cohesion, and segregation, respectively, modify the association., Design, Setting, and Participants: This population-based cohort study used Georgia Cancer Registry (GCR) data on women with breast cancer diagnosed in 2010 to 2017 and followed-up until December 31, 2022. Data were analyzed between January 2023 and October 2023. The study included non-Hispanic Black and White women with invasive early-stage (I-IIIA) breast cancer diagnosed between 2010 and 2017 and identified through the GCR., Exposures: The Neighborhood Deprivation Index (NDI), assessed in quintiles, was derived through principal component analysis of 2011 to 2015 block group-level American Community Survey (ACS) data. Rurality, neighborhood residential mobility, and racial composition were measured using Georgia Public Health Department or ACS data., Main Outcomes and Measures: The primary outcome was breast cancer-specific mortality identified by the GCR through linkage to the Georgia vital statistics registry and National Death Index. Cox proportional hazards regression was used to estimate age-adjusted and multivariable-adjusted hazard ratios (HRs) and 95% CIs for the association between neighborhood deprivation and breast cancer mortality., Results: Among the 36 795 patients with breast cancer (mean [SD] age at diagnosis, 60.3 [13.1] years), 11 044 (30.0%) were non-Hispanic Black, and 25 751 (70.0%) were non-Hispanic White. During follow-up, 2942 breast cancer deaths occurred (1214 [41.3%] non-Hispanic Black women; 1728 [58.7%] non-Hispanic White women). NDI was associated with an increase in breast cancer mortality (quintile 5 vs 1, HR, 1.36; 95% CI, 1.19-1.55) in Cox proportional hazards models. The association was present only among non-Hispanic White women (quintile 5 vs 1, HR, 1.47; 95% CI, 1.21-1.79). Similar race-specific patterns were observed in jointly stratified analyses, such that NDI was associated with increased breast cancer mortality among non-Hispanic White women, but not non-Hispanic Black women, irrespective of the additional neighborhood characteristics considered., Conclusions and Relevance: In this cohort study, neighborhood deprivation was associated with increased breast cancer mortality among non-Hispanic White women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women, suggesting that factors beyond those explored here may contribute to breast cancer mortality in this racial group.

Purpose: The majority of breast cancer patients are diagnosed with early-stage estrogen receptor (ER) positive disease. Despite effective treatments for these cancers, Black women have higher mortality than White women. We investigated demographic and clinical factors associated with receipt of chemotherapy among those with a discretionary indication who are at risk for overtreatment., Methods: Using Georgia Cancer Registry data, we identified females diagnosed with ER positive breast cancer who had a discretionary indication for chemotherapy (2010-2017). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associating patient demographic and clinical characteristics with chemotherapy initiation overall, and comparing non-Hispanic Black (NHB) with non-Hispanic White (NHW) women within strata of patient factors., Results: We identified 11,993 ER positive breast cancer patients with a discretionary indication for chemotherapy. NHB patients were more likely to initiate chemotherapy compared with NHW women (OR = 1.41, 95% CI: 1.28, 1.56). Race differences in chemotherapy initiation were pronounced among those who did not receive Oncotype DX testing (OR = 1.47, 95% CI: 1.31, 1.65) and among those residing in high socioeconomic status neighborhoods (OR = 2.48, 95% CI: 1.70, 3.61). However, we observed equitable chemotherapy receipt among patients who received Oncotype DX testing (OR = 0.90, 95% CI: 0.71, 1.14), were diagnosed with grade 1 disease (OR = 1.00, 95% CI: 0.74, 1.37), and those resided in rural areas (OR = 1.01, 95% CI: 0.76, 1.36)., Conclusion: We observed racial disparities in the initiation of chemotherapy overall and by sociodemographic and clinical factors, and more equitable outcomes when clinical guidelines were followed., (© 2024. The Author(s).)

Diffuse large B-cell lymphoma (DLBCL) is a commonly diagnosed, aggressive non-Hodgkin's lymphoma. While R-CHOP chemoimmunotherapy is potentially curative, about 40% of DLBCL patients will fail, highlighting the need to identify biomarkers to optimize management. SAMHD1 has a dNTPase-independent role in promoting resection to facilitate DNA double-strand break (DSB) repair by homologous recombination. We evaluated the relationship of SAMHD1 levels with sensitivity to DSB-sensitizing agents in DLBCL cells and the association of SAMHD1 expression with clinical outcomes in 79 DLBCL patients treated with definitive therapy and an independent cohort dataset of 234 DLBCL patients. Low SAMHD1 expression, Vpx-mediated, or siRNA-mediated degradation/depletion in DLBCL cells was associated with greater sensitivity to doxorubicin and PARP inhibitors. On Kaplan-Meier log-rank survival analysis, low SAMHD1 expression was associated with improved overall survival (OS), which on subset analysis remained significant only in patients with advanced stage (III-IV) and moderate to high risk (2-5 International Prognostic Index (IPI)). The association of low SAMHD1 expression with improved OS remained significant on multivariate analysis independent of other adverse factors, including IPI, and was validated in an independent cohort. Our findings suggest that SAMHD1 expression mediates doxorubicin resistance and may be an important prognostic biomarker in advanced, higher-risk DLBCL patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Cancer.)

Importance: Inequities created by historical and contemporary mortgage discriminatory policies have implications for health disparities. The role of persistent mortgage discrimination (PMD) in breast cancer (BC) outcomes has not been studied., Objective: To estimate the race-specific association of historical redlining (HRL) with the development of BC subtypes and late-stage disease and a novel measure of PMD in BC mortality., Design, Setting, and Participants: This population-based cohort study used Georgia Cancer Registry data. A total of 1764 non-Hispanic Black and White women with a BC diagnosis and residing in an area graded by the Home Owners' Loan Corporation (HOLC) in Georgia were included. Patients were excluded if they did not have a known subtype or a derived American Joint Committee on Cancer stage or if diagnosed solely by death certificate or autopsy. Participants were diagnosed with a first primary BC between January 1, 2010, to December 31, 2017, and were followed through December 31, 2019. Data were analyzed between May 1, 2022, and August 31, 2023., Exposures: Scores for HRL were examined dichotomously as less than 2.5 (ie, nonredlined) vs 2.5 or greater (ie, redlined). Contemporary mortgage discrimination (CMD) scores were calculated, and PMD index was created using the combination of HRL and CMD scores., Main Outcomes and Measures: Estrogen receptor (ER) status, late stage at diagnosis, and BC-specific death., Results: This study included 1764 women diagnosed with BC within census tracts that were HOLC graded in Georgia. Of these, 856 women (48.5%) were non-Hispanic Black and 908 (51.5%) were non-Hispanic White; 1148 (65.1%) were diagnosed at 55 years or older; 538 (30.5%) resided in tracts with HRL scores less than 2.5; and 1226 (69.5%) resided in tracts with HRL scores 2.5 or greater. Living in HRL areas with HRL scores 2.5 or greater was associated with a 62% increased odds of ER-negative BC among non-Hispanic Black women (odds ratio [OR], 1.62 [95% CI, 1.01-2.60]), a 97% increased odds of late-stage diagnosis among non-Hispanic White women (OR, 1.97 [95% CI, 1.15-3.36]), and a 60% increase in BC mortality overall (hazard ratio, 1.60 [95% CI, 1.17-2.18]). Similarly, PMD was associated with BC mortality among non-Hispanic White women but not among non-Hispanic Black women., Conclusions and Relevance: The findings of this cohort study suggest that historical racist policies and persistent discrimination have modern-day implications for BC outcomes that differ by race. These findings emphasize the need for a more nuanced investigation of the social and structural drivers of disparate BC outcomes.

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening malignancy that arises in the setting of immunosuppression (IS) after solid organ transplant. IS regimens containing belatacept have been associated with an increased risk of PTLD in Epstein-Barr virus (EBV)-seronegative renal transplant recipients, and the use of belatacept is contraindicated in this population. However, the impact of belatacept-based regimens on PTLD risk and outcomes in EBV-seropositive renal transplant recipients is less well characterized., Methods: A case-control study was conducted to investigate how combinatorial IS regimens impact the risk of PTLD and survival outcomes in renal transplant recipients at a large transplant center between 2010 and 2019. In total, 17 cases of PTLD were identified and matched 1:2 to controls without PTLD by age, sex, and transplanted organ(s). We compared baseline clinical characteristics, examined changes in IS regimen, viral loads, and renal function over time, and evaluated time-to-event analyses, including graft rejection and survival., Results: Cases of PTLD largely resembled matched controls in terms of baseline characteristics, although expected differences in EBV serostatus trended toward significance (42.9% of PTLD cases were donor-positive/recipient-negative vs. 8.3% controls, p  = 0.063). PTLD cases were not more likely to have received belatacept than controls. Belatacept was not associated with graft rejection or failure, re-transplant, hospitalization, or decreased survival., Conclusions: Belatacept was not associated with an increased risk of PTLD, and was not associated with decreased survival in either PTLD cases or in the entire cohort. Our case-control study supports the concept that belatacept remains a safe and effective option for IS in EBV-seropositive renal transplant patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author JK declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer-review process and the final decision., (© 2024 Koff, Karadkhele, Switchenko, Rupji, Little and Larsen.)

Purpose: To review our initial experience with proton-based SBRT to evaluate the planning outcomes and initial patient tolerance of treatment., Patients and Methods: From Sep. 2019 to Dec. 2020, 52 patients were treated with proton SBRT to 62 lesions. Fractionation varied by indication and site with a median of 5 fractions and median fractional dose of 8 Gy. Planning outcomes, including plan heterogeneity, conformity, and PTV volume receiving 100% of the prescription dose (PTV V100%) were evaluated. Acute toxicities were prospectively recorded, and patient reported outcomes were assessed prior to and at completion of treatment using the MD Anderson Symptom Inventory (MDASI) and EQ-5D5L visual analogue score (VAS)., Results: All treated patients completed their course of proton-based SBRT. The mean conformity index was 1.05 (range 0.51-1.48). R50% values were comparable to ideal photon parameters. PTV V100% was 89.9% on average (40.44% - 99.76%). 5 patients (10%) required plan modification due to setup or tumor changes. No patients developed a new grade 3 or greater toxicity during treatment. Comparing pretreatment to end of treatment timepoints, there was a significant improvement in the mean VAS (65 to 75, p = 0.014), with no significant change in the mean MDASI symptom (1.7, 1.8; p = 0.79) or interference (2.3, 2.4; p = 0.452) scores., Conclusion: Proton-based SBRT can achieve dosimetric goals required by major clinical photon trials. It was well-tolerated with no decrement in patient reported outcomes and a mean 10-point improvement in VAS at the conclusion of SBRT. Further follow-up is necessary for tumor control and late effects analysis., Competing Interests: Additional Information and Declarations The authors would like to thank the Winship Cancer Institute at Emory University and the Emory Proton Therapy Center. Research reported in this publication was supported in part by the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Authors’ disclosure of potential conflicts of interest Jeffrey Bradley reports Varian, Inc research grant and participation on Genentech, Inc, AstraZeneca, Inc, and Mevion Medical Systems Scientific Advisory Board. Other authors have nothing to disclose., (© 2024 Old City Publishing, Inc.)

Background: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined., Method: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed., Results: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418)., Conclusion: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Racial and ethnic minority populations are consistently under-represented in oncology clinical trials despite comprising a disproportionate share of a cancer burden. Phase I oncology clinical trials pose a unique challenge and opportunity for minority inclusion. Here we compared the sociodemographic characteristics of patients participating in phase 1 clinical trials a National Cancer Institute ( NCI)-designated comprehensive center to all patients at the center, patients with new cancer diagnosis in metropolitan Atlanta and patients with new cancer diagnoses in the state of Georgia. From 2015 to 2020, 2325 patients (43.4% female, 56.6% male) consented to participate in a phase I trial. Grouped self-reported race distribution was 70.3% White, 26.2% Black, and 3.5% other. Of new patient registrations at Winship Cancer Institute (N = 107 497) (50% F, 50% M), grouped race distribution was 63.3% White, 32.0% Black, and 4.7% other. Patients with new cancer diagnoses in metro Atlanta from 2015 to 2016 (N = 31101) were 58.4% White, 37.2% Black, and 4.3% other. Race and sex distribution of phase I patients was significantly different than Winship patients (P < .001). Over time, percent of White patients decreased in both phase I and Winship groups (P = .009 and P < .001, respectively); percentage of females did not change in either group (P = .54 phase I, P = .063 Winship). Although phase I patients were more likely to be White, male, and privately ensured than the Winship cohort, from 2015 to 2020 the percentage of White patients in phase I trials and among all new patients treated at Winship decreased. The intent of characterizing existing disparities is to improve the representation of patients from racial and ethnic minority backgrounds in phase I clinical trials., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Most patients with intrahepatic cholangiocarcinoma (IHCC) develop recurrence after resection. Adjuvant capecitabine remains the standard of care for resected IHCC. A combination of gemcitabine, cisplatin, and nab-paclitaxel (GAP) was associated with a 45% response rate and 20% conversion rate among patients with unresectable biliary tract cancers. The aim of this study was to evaluate the feasibility of delivering GAP in the neoadjuvant setting for resectable, high-risk IHCC., Methods: A multi-institutional, single-arm, phase II trial was conducted for patients with resectable, high-risk IHCC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Patients received preoperative GAP (gemcitabine 800 mg/m 2 , cisplatin 25 mg/m 2 , and nab-paclitaxel 100 mg/m 2 on days 1 and 8 of a 21-day cycle) for a total of 4 cycles prior to an attempt at curative-intent surgical resection. The primary endpoint was completion of both preoperative chemotherapy and surgical resection. Secondary endpoints were adverse events, radiologic response, recurrence-free survival (RFS), and overall survival (OS)., Results: Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection., Conclusion: Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes., (© 2023. Society of Surgical Oncology.)

Background: Preclinical studies showed metformin reduces exhaustion of tumor-infiltrating lymphocytes and potentiates programmed cell death protein-1 (PD-1) blockade. We hypothesized that metformin with nivolumab would elicit potent antitumor and immune modulatory activity in metastatic microsatellite stable (MSS) colorectal cancer (CRC). We evaluated this hypothesis in a phase II study., Methods: Nivolumab (480 mg) was administered intravenously every 4 weeks while metformin (1000 mg) was given orally, two times per day following a 14-day metformin only lead-in phase. Patients ≥18 years of age, with previously treated, stage IV MSS CRC, and Eastern Cooperative Oncology Group 0-1, having received no prior anti-PD-1 agent were eligible. The primary endpoint was overall response rate with secondary endpoints of overall survival (OS) and progression-free survival (PFS). Correlative studies using paired pretreatment/on-treatment biopsies and peripheral blood evaluated a series of immune biomarkers in the tumor microenvironment and systemic circulation using ChipCytometry and flow cytometry., Results: A total of 24 patients were enrolled, 6 patients were replaced per protocol, 18 patients had evaluable disease. Of the 18 evaluable patients, 11/18 (61%) were women and the median age was 58 (IQR 50-67). Two patients had stable disease, but no patients had objective response, hence the study was stopped for futility. Median OS and PFS was 5.2 months (95% CI (3.2 to 11.7)) and 2.3 months (95% CI (1.7 to 2.3)). Most common grade 3/4 toxicities: Anemia (n=2), diarrhea (n=2), and fever (n=2). Metformin alone failed to increase the infiltration of T-cell subsets in the tumor, but combined metformin and nivolumab increased percentages of tumor-infiltrating leukocytes (p=0.031). Dual treatment also increased Tim3+ levels in patient tissues and decreased naïve CD8+T cells (p=0.0475)., Conclusions: Nivolumab and metformin were well tolerated in patients with MSS CRC but had no evidence of efficacy. Correlative studies did not reveal an appreciable degree of immune modulation from metformin alone, but showed trends in tumorous T-cell infiltration as a result of dual metformin and PD-1 blockade despite progression in a majority of patients., Competing Interests: Competing interests: MA has consulted for Eisai, Ipsen, Exelixis, GSK, QED, Isofol, Curio Science, AstraZeneca and Genentech and has received research funding from Tesaro (Inst), RedHill Biopharma Limited (Inst), Polaris (Inst), Bristol-Myers Squibb-Ono Pharmaceutical (Inst), Xencor (Inst), Merck Sharp & Dohme (Inst), Eisai (Inst), GSK (Inst). BER has consulted for AZ, Ipsen, Exelixis, Seagen and received research funding from BMS, Merck, AZ, Novartis, EUSA, adptamune, Bayer, Exelixis. GBL has consulted for ProDa Biotech, LLC and received compensation. GBL has received research funding through a sponsored research agreement between Emory University and Merck and Co., Bristol-Myers Squibb, Boerhinger-Ingelheim, and Vaccinex. CW has consulted for Array Biopharma, Natera, Seagen, Pfizer, Daiichi Sankyo/Lilly and has received research funding (trial funding to institution) through Pfizer, Hutchmed and Seagen. Employment/leadership/stock and other ownership—nothing to disclose. Honoraria: Cancer Treatment Centers of America, Medscape. WLS is on the advisory board of Mylan, BMS, Esai, Tesaro, Blueprints, Seagen and a member of the speaker’s bureau of Guardant health, Cumberland therapeutics, Seagen. His research has been funded by GSK, Eli Lilly, Tesaro. BO has received research funding through a sponsored research agreement between Emory University and Boehringer Ingelheim. OBA has consulted for Ipsen Pharmaceuticals, Aadi Bioscience, Taiho, Pfizer, Seagen Inc. Bristol-Myers Squibb and AstraZeneca. He has received research funding from Taiho Oncology, Ipsen Pharmaceuticals, GSK, Bristol-Myers Squibb, PCI Biotech AS, ASCO, Calithera Biosciences, Inc., SynCore Biotechnology Co. Ltd., Suzhou Transcenta Therapeutics Co., Ltd, Corcept Therapeutics Inc., Hutchison MediPharma, Boehringer Ingelheim, Xencor Inc., Cue Biopharma, Inc., Merck, Syros Pharmaceuticals Inc., Inhibitex Inc, Arcus Biosciences Inc. and ImmunoGen. MD has consulted for Novartis and Guardant Health. The rest of the authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Although high-dose, multiagent chemotherapy has improved leukemia survival rates, treatment outcomes remain poor in high-risk subsets, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in infants. The development of new, more effective therapies for these patients is therefore an urgent, unmet clinical need., Methods: The dual MERTK/FLT3 inhibitor MRX-2843 and BCL-2 family protein inhibitors were screened in high-throughput against a panel of AML and MLL-rearranged precursor B-cell ALL (infant ALL) cell lines. A neural network model was built to correlate ratiometric drug synergy and target gene expression. Drugs were loaded into liposomal nanocarriers to assess primary AML cell responses., Results: MRX-2843 synergized with venetoclax to reduce AML cell density in vitro. A neural network classifier based on drug exposure and target gene expression predicted drug synergy and growth inhibition in AML with high accuracy. Combination monovalent liposomal drug formulations delivered defined drug ratios intracellularly and recapitulated synergistic drug activity. The magnitude and frequency of synergistic responses were both maintained and improved following drug formulation in a genotypically diverse set of primary AML bone marrow specimens., Conclusions: We developed a nanoscale combination drug formulation that exploits ectopic expression of MERTK tyrosine kinase and dependency on BCL-2 family proteins for leukemia cell survival in pediatric AML and infant ALL cells. We demonstrate ratiometric drug delivery and synergistic cell killing in AML, a result achieved by a systematic, generalizable approach of combination drug screening and nanoscale formulation that may be extended to other drug pairs or diseases in the future., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Background: Patients with resectable noncardia gastric cancer may be subjected to perioperative chemotherapy (PEC), postoperative chemoradiation (POCR), or postoperative chemotherapy (POC). We analyzed these treatment strategies to determine optimal therapy based on nodal status., Method: The National Cancer Database was used to identify patients with resected noncardia gastric cancer (2004-2016). Patients were stratified based on clinical nodal status-negative (cLN-), positive (cLN+) and pathological nodal status (pLN-, pLN+). In cLN- patients who underwent upfront resection and were upstaged to pLN+, POC, and POCR were compared. Overall survival (OS) with PEC, POCR, and POC were compared in cLN- and cLN+., Results: We identified 6142 patients (cLN-: 3831; cLN+: 2311). In cLN- patients who underwent upfront resection (N = 3423), 69% were upstaged to pLN+ disease (N = 2499; POCR = 1796, POC = 703). On MVA, POCR was associated with significantly improved OS when compared to POC (hazard ratio [HR]: 0.75; p < 0.001). In patients with cLN- disease (PEC = 408; POCR = 2439; POC = 984), PEC(HR: 0.77; p = 0.01) and POCR(HR: 0.81; p < 0.001) were associated with improved OS compared with POC. In cLN+ group (PEC = 452; POCR = 1284; POC = 575), POCR was associated with improved OS compared with POC (HR: 0.81; p < 0.01), and trend towards improved OS was noted when PEC(HR: 0.83; p = 0.055) was compared with POC., Conclusion: Postoperative chemoradiation may be the preferred treatment strategy over postoperative chemotherapy in non-cardia gastric cancer patients who receive upfront resection and are upstaged from clinically node negative to pathologically node positive disease., (© 2023 Wiley Periodicals LLC.)

Background: Multimodal treatment strategies with surgery as its centerpiece have been accepted as the standard of care in nonmetastatic cardia gastric cancer (CGC). There remains a lack of consensus regarding the optimal multimodal treatment strategy., Method: We queried National Cancer Database from 2004 to 2016 to identify patients with resected nonmetastatic CGC who received perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), or postoperative chemotherapy (POC). A subgroup analysis was performed in optimally treated patients defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection, and standard radiation dose (45 Gy). Kaplan-Meier, Univariate analysis (UVA), and Multivariable analysis (MVA) were performed., Results: We identified 2387 patients. Median survival was 38.8 months in the PEC group, 36 months in the POCR group, and 32.3 months in the POC group (p = 0.1025). On UVA, patients treated with PEC had an association with improved survival (HR, 0.83; p = 0.037) when compared with POC. On MVA, no significant difference was noted in overall survival (OS) between PEC, POCR, and POC, similar to subgroup analysis of optimally treated cohort., Conclusion: OS rate in nonmetastatic CGC is not significantly different between patients receiving PEC, POCR, or POC., (© 2023 Wiley Periodicals LLC.)

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., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Childhood cancer incidence is known to vary by age, sex, and race/ethnicity, but evidence is limited regarding external risk factors. We aim to identify harmful combinations of air pollutants and other environmental and social risk factors in association with the incidence of childhood cancer based on 2003-2017 data from the Georgia Cancer Registry. We calculated the standardized incidence ratios (SIR) of Central Nervous System (CNS) tumors, leukemia and lymphomas based on age, gender and ethnic composition in each of the 159 counties in Georgia, USA. County-level information on air pollution, socioeconomic status (SES), tobacco smoking, alcohol drinking and obesity were derived from US EPA and other public data sources. We applied two unsupervised learning tools (self-organizing map [SOM] and exposure-continuum mapping [ECM]) to identify pertinent types of multi-exposure combinations. Spatial Bayesian Poisson models (Leroux-CAR) were fit with indicators for each multi-exposure category as exposure and SIR of childhood cancers as outcomes. We identified consistent associations of environmental (pesticide exposure) and social/behavioral stressors (low socioeconomic status, alcohol) with spatial clustering of pediatric cancer class II (lymphomas and reticuloendothelial neoplasms), but not for other cancer classes. More research is needed to identify the causal risk factors for these associations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Methods: This retrospective study of 86 413 patients (40-64 years old) undergoing surgical resection for a new diagnosis of invasive, nonmetastatic colon cancer included in the National Cancer Database (NCDB) from 2010 to 2015 compared overall survival (OS) in MES to NES. Cox proportional hazard models, fit for OS, and propensity score-matching (PSM) analysis were performed., Results: In this sample, 51 297 cases (59.2%) lived in MES and 35 116 (40.8%) in NES. Medicaid expansion states had earlier pathological stage compared to NES (stage I 25.38% vs 24.17%, stage II 32.93 vs 33.4%, and stage III 41.69 vs 42.43%; P < .001). 5-year OS in MES was higher than NES (79.1% vs 77.3%; P < .001); however, on both multivariable analysis (MVA) and PSM analysis, MES did not have significantly different OS from NES (hazard ratio (HR), .99, 95% confidence interval (CI), .95-1.03; P = .570; HR, .99, 95% CI, .95-1.03; P = .68)., Conclusion: Among NCDB patients with invasive, nonmetastatic colon cancer residing in MES at time of diagnosis was associated with earlier pathological stage. However, on both MVA and PSM analysis, OS was not significantly different in MES vs NES. Research on patient outcomes, such as receipt of guideline concordant care, can further inform the impact of insurance coverage expansion efforts on cancer outcomes.

Background and Objectives: The majority of patients undergoing mastectomy before the COVID-19 pandemic were admitted for 23-h observation to the hospital. Indications for observation included drain care education, pain control and observation for possible early surgical complications. This study compared the rates of outpatient mastectomy before, during, and after the COVID-19 pandemic and indirectly evaluated the safety of same-day discharge., Methods: We retrospectively analyzed patients undergoing mastectomy using Current Procedural Terminology code 19303., Results: A total of 357 patients were included: 113 were treated pre-COVID-19, 82 patients during COVID-19 and 162 post-COVID-19. The rate of outpatient mastectomies tripled during the pandemic from 17% to 51% (p < 0.001); after the pandemic remain high at 48%. The rate of bilateral mastectomies decreased during the pandemic to 30% from 48% prepandemic (p = 0.015). Pectoralis muscle block utilization increased during the COVID-19 period from 36% to 59% (p = 0.002). No difference in complication rates, including surgical site infections, hematomas, and readmissions, pre and during COVID., Conclusions: The rate of outpatient mastectomy increased during the COVID-19 pandemic. During this timeframe, perioperative complications did not increase, suggesting the safety of this practice. After the pandemic, the rate of outpatient mastectomy continued to be significantly higher than pre-COVID., (© 2023 Wiley Periodicals LLC.)

Patients with multiple myeloma (MM) mount suboptimal neutralizing antibodies (nAb) following 2 doses of SARS-CoV-2 mRNA vaccines. Currently, circulating SARS-CoV-2 variants of concern (VOC) carry the risk of breakthrough infections. We evaluated immune recognition of current VOC including BA.1, BA.2, and BA.5 in 331 racially representative patients with MM following 2 or 3 doses of mRNA vaccines. The third dose increased nAbs against WA1 in 82%, but against BA variants in only 33% to 44% of patients. Vaccine-induced nAbs correlated with receptor-binding domain (RBD)-specific class-switched memory B cells. Vaccine-induced spike-specific T cells were detected in patients without seroconversion and cross-recognized variant-specific peptides but were predominantly CD4+ T cells. Detailed clinical/immunophenotypic analysis identified features correlating with nAb/B/T-cell responses. Patients who developed breakthrough infections following 3 vaccine doses had lower live-virus nAbs, including against VOC. Patients with MM remain susceptible to SARS-CoV-2 variants following 3 vaccine doses and should be prioritized for emerging approaches to elicit variant-nAb and CD8+ T cells., Significance: Three doses of SARS-CoV-2 mRNA vaccines fail to yield detectable VOC nAbs in nearly 60% and spike-specific CD8+ T cells in >80% of myeloma patients. Patients who develop breakthrough infections following vaccination have low levels of live-virus nAb. This article is highlighted in the In This Issue feature, p. 101., (©2022 American Association for Cancer Research.)

Background: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown., Methods: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities., Results: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality., Conclusions: There is minimal difference between 90-day mortality in patients treated with TORS or radiotherapy for early-stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment., (© 2022 Wiley Periodicals LLC.)

Background: Risk factors for progression to advanced-stage mycosis fungoides (MF) are poorly defined., Methods: The authors performed a single-center, retrospective cohort study among patients with MF at an academic medical center from 1990 to 2020 to identify clinical variables associated with progression to advanced-stage MF (stage IIB-IVB), and 388 patients who had a clinicopathologic diagnosis of early stage (IA-IIA) MF were identified from their cutaneous lymphoma database. Baseline clinical characteristics, laboratory values, imaging, and blood flow cytometry or T-cell receptor gene rearrangement (TCR) data were collected. Logistic regression was used to assess risk factors associated with progression., Results: Overall, 93 of 388 patients (24.0%) progressed to advanced stage. Patients who progressed had an increased risk of death (hazard ratio, 4.50; 95% CI, 2.89-7.00; p < .001). Progression was associated with a higher overall stage at diagnosis, tumor stage, lymph node stage, low-level blood involvement, as measured with TCR data and/or flow cytometry, and elevated lactate dehydrogenase (LDH). Limitations included missing data for LDH, imaging, peripheral blood TCR data, or flow cytometry assessed at diagnosis., Conclusions: Staging and baseline laboratory assessments with imaging, peripheral blood flow cytometry, TCR data, and LDH in patients who have newly diagnosed MF may identify those who are at risk for progression to advanced stage., (© 2022 American Cancer Society.)

Purpose: Commonly used first-line (1L) treatments for mantle cell lymphoma include high-dose cytarabine-based induction followed by autologous stem-cell transplant (ASCT) for younger patients and several chemoimmunotherapy regimens for older patients. Continuous debates exist on the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus rituximab (BR)., Methods: Retrospective data from 4,216 patients with mantle cell lymphoma in the Flatiron Health electronic record-derived deidentified database diagnosed between 2011 and 2021, mostly in US community oncology settings, were evaluated for treatment patterns and outcomes. The efficacy findings with ASCT and MR were validated in an independent cohort of 1,168 patients from 12 academic centers., Results: Among 3,614 patients with documented 1L treatment, BR was the most used. Among 1,265 patients age < 65 years, 30.5% received cytarabine-based induction and 23.5% received ASCT. There was no significant association between ASCT and real-world time to next treatment (hazard ratio [HR], 0.84; 95% CI, 0.68 to 1.03; P = .10) or overall survival (HR, 0.86; 95% CI, 0.63 to 1.18; P = .4) among ASCT-eligible patients. Among MR-eligible patients, MR after BR versus BR alone was associated with a longer real-world time to next treatment (HR, 1.96; 95% CI, 1.61 to 2.38; P < .001) and overall survival (HR, 1.51; 95% CI, 1.19 to 1.92; P < .001). The efficacy findings were consistent in the validation cohort., Conclusion: In this large cohort of patients treated primarily in the US community setting, only one in four young patients received cytarabine or ASCT consolidation, suggesting the need to develop treatments that can be delivered effectively in routine clinical practice. Together with the validation cohort, data support future clinical trials exploring regimens without ASCT consolidation in young patients, whereas MR should be considered for patients after 1L BR and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Introduction: As immunotherapy has improved distant metastasis-free survival (DMFS) in Non-Small Cell Lung Cancer (NSCLC), isolated locoregional recurrences have increased. However, management of locoregional recurrences can be challenging. We report our institutional experience with definitive intent re-irradiation using Intensity Modulated Proton Therapy (IMPT)., Method: Retrospective cohort study of recurrent or second primary NSCLC or LS-SCLC treated with IMPT. Kaplan-Meier method and log-rank test were used for time-to-event analyses., Results: 22 patients were treated from 2019 to 2021. After first course of radiation (median 60 Gy, range 45-70 Gy), 45% received adjuvant immunotherapy. IMPT re-irradiation began a median of 28.2 months (8.8-172.9 months) after initial radiotherapy. The median IMPT dose was 60 GyE (44-60 GyE). 36% received concurrent chemotherapy with IMPT and 18% received immunotherapy after IMPT. The median patient's IMPT lung mean dose was 5.3 GyE (0.9-13.9 GyE) and 5 patients had cumulative esophagus max dose >100 GyE with 1-year overall survival (OS) 68%, 1-year local control 80%, 1-year progression free survival 45%, and 1-year DMFS 60%. Higher IMPT (HR 1.4; 95% CI 1.1-1.7, p=0.01) and initial radiotherapy mean lung doses (HR 1.3; 95% CI 1.0-1.6, p=0.04) were associated with worse OS. Two patients developed Grade 3 pneumonitis or dermatitis, one patient developed Grade 2 pneumonitis, and seven patients developed Grade 1 toxicity. There were no Grade 4 or 5 toxicities., Discussion: Definitive IMPT re-irradiation for lung cancer can prolong disease control with limited toxicity, particularly in the immunotherapy era., Competing Interests: KH and JB report as potential commercial or financial conflicts of interest the following relationships: AstraZeneca consultant/advisory board RefleXion Medical funded research, advisory board, Jazz pharmaceuticals funded research, Ultimate Opinions in medicine honorarium. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Janopaul-Naylor, Cao, McCall, Switchenko, Tian, Chen, Stokes, Kesarwala, McDonald, Shelton, Bradley and Higgins.)

For people living with HIV (PLWH) who are subsequently diagnosed with non-Hodgkin lymphoma (NHL), we investigate the impact of standard-of-care (SoC) cancer treatment on all-cause, NHL-specific, and HIV-specific survival outcomes. The focus is on a registry-derived, population-based sample of HIV + adults diagnosed with NHL within 2004-2012 in the state of Georgia. SoC treatment is defined as receipt of multi-agent systemic therapy (MAST). In multivariable survival analyses, SoC cancer treatment is significantly associated with better all-cause and NHL-specific survival, but not better HIV-specific survival across 2004-2017. Having a CD4 count <200 near the time of cancer diagnosis and Ann Arbor stage III/IV disease are associated with worse all-cause and HIV-specific survival; the effects on NHL survival trend negative but are not significant. Future work should expand the geographic base and cancers examined, deepen the level of clinical detail brought to bear, and incorporate the perspectives and recommendations of patients and providers.

Importance: Controversy exists regarding management of the clinically node-negative neck in patients with recurrent larynx or hypopharynx cancers who received total laryngectomy after definitive radiation with or without chemotherapy., Objective: To explore clinical and oncologic outcomes after elective neck dissection vs observation in patients who received clinically node-negative salvage total laryngectomy., Design, Setting, and Participants: This cohort study was performed from January 2009 to June 2021 at a single, high-volume tertiary care center. Follow-up was conducted through June 2021 for all patients. Survival outcomes were based on at least 2 years of follow-up. Patients aged 18 years or older with recurrent, clinically node-negative larynx or hypopharynx tumors after definitive nonsurgical treatment who were treated with a salvage total laryngectomy were included. Data were analyzed from October 2021 through September 2022., Exposures: Elective neck dissection., Main Outcomes and Measures: Presence and location of occult nodal metastasis in electively dissected necks, along with differences in fistula rates and overall and disease-free survival between patients receiving elective neck dissection vs observation., Results: Among 107 patients receiving clinically node-negative salvage total laryngectomy (median [IQR] age, 65.0 [57.8-71.3] years; 91 [85.0%] men), 81 patients underwent elective neck dissection (75.7%) and 26 patients underwent observation (24.3%). Among patients with elective neck dissection, 13 patients had occult nodal positivity (16.0%). Recurrent supraglottic (4 of 20 patients [20.0%]) or advanced T classification (ie, T3-T4; 12 of 61 patients [19.7%]) had an occult nodal positivity rate of 20% or more, and positive nodes were most likely to occur in levels II and III (II: 6 of 67 patients [9.0%]; III: 6 of 65 patients [9.2%]; VI: 3 of 44 patients [6.8%]; IV: 3 of 62 patients [4.8%]; V: 0 of 4 patients; I: 0 of 18 patients). There was a large difference in fistula rate between elective neck dissection (12 patients [14.8%]) and observed (8 patients [30.8%]) groups (difference, 16.0 percentage points; 95% CI, -3.4 to 35.3 percentage points), while the difference in fistula rate was negligible between 50 patients undergoing regional or free flap reconstruction (10 patients [20.0%]) vs 57 patients undergoing primary closure (10 patients [17.5%]) (difference, 2.5 percentage points; 95% CI, -12.4 to 17.3 percentage points). Undergoing elective neck dissection was not associated with a clinically meaningful improvement in overall or disease-free survival compared with observation. Recurrent hypopharynx subsite was associated with an increased risk of death (hazard ratio, 4.28; 95% CI, 1.81 to 10.09) and distant recurrence (hazard ratio, 7.94; 95% CI, 2.07 to 30.48) compared with glottic subsite., Conclusions and Relevance: In this cohort study, patients with recurrent supraglottic or advanced T classification tumors had an increased occult nodal positivity rate, elective neck dissection was not associated with survival, and patients with recurrent hypopharynx subsite were more likely to have a distant recurrence and die of their disease. These findings suggest that underlying disease pathology rather than surgical management may be associated with survival outcomes in this population.

Background: Black women are 40% more likely to die of breast cancer compared to White women. Inadequate representation of Black patients in clinical trials may contribute to health care inequity. We aimed to assess breast cancer clinical outcomes in Non-Hispanic Black (Black) versus Non-Hispanic White (White) women with metastatic breast cancer (MBC) enrolled on investigator-initiated clinical trials at Winship Cancer Institute at Emory University, given the significant number of patients from underrepresented minority groups seen at Winship., Materials and Methods: Black and White women with MBC on investigator-initiated trials at Emory between 2009 and 2019 were retrospectively evaluated. Univariate analyses and multiple logistic regression models were used to assess clinical response and treatment toxicities. Differences in overall survival between groups was assessed using quantile analysis., Results: Sixty-two women with MBC were included (66% White vs. 34% Black). Black patients had less clinical benefit from the trial therapy as only 57% had partial response or stable disease as best response compared to 78% of White women (P = .09). Quantile analysis showed significant difference in mean survival between Whites and Blacks by the end of follow up (64 vs. 38 months). There were no significant differences in toxicities between groups., Conclusion: Participation rates of Black women with MBC on investigator-initiated clinical trials at an urban cancer center were higher compared to key national trials. Black women had worse treatment response and survival. These results reinforce the need for assessment of tumor differences by ancestry and continued improvement in minority representation on clinical trials., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest related to this study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of unknown etiology and unpredictable natural history. To date, no large-scale studies have been published evaluating this disease due to its rare occurrence., Methods: The National Cancer Database was reviewed between 2004 and 2016 to identify patients with HEH. Univariate analysis with overall survival (OS) was performed by Cox proportional hazards model. Kaplan-Meier method was used to create OS curves and compared using the log-rank test., Results: We identified 229 patients with HEH. The majority of patients were female (61.1%), white (84.3%), and had a Charlson-Deyo score of 0 (75%). Chemotherapeutic intervention was seen in 26% of the patients while 33% received surgical intervention in the form of wedge/segmental liver resection (n = 27), hepatectomy lobectomy/extended lobectomy (n = 18), and liver transplant (n = 22). Five-year survival in surgical patients was 90.5%, 66.5% and 81%, respectively (p = 0.485). Age greater than 55 years (hazard ratio [HR], 2.78; p < 0.001), Asian ethnicity compared to white (HR, 2.84; p = 0.012), and a higher Charlson-Deyo score (score 1: HR, 2.28; p < 0.001 and score ≥2: HR, 2.76; p = 0.011) were associated with worse OS., Conclusion: Treatment for HEH remains variable with only a third of the patients undergoing surgery. International collaboration is necessary to determine the optimal treatment for this rare disease., (© 2022 Wiley Periodicals LLC.)

Purpose: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 ( 90 Y) (scout 90 Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic 90 Y (Rx 90 Y) dose for patients with hepatocellular carcinoma (HCC)., Materials and Methods: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout 90 Y. Rx 90 Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout 90 Y were compared with those by Rx 90 Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout 90 Y and MAA with that of Rx 90 Y. The safety of scout 90 Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout 90 Y., Results: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx 90 Y. Scout 90 Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx 90 Y. Furthermore, the TNR and LSF of scout 90 Y had a stronger agreement with those of Rx 90 Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx 90 Y, whereas scout 90 Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout 90 Y had a strong linear correlation with the TD and NTLD of Rx 90 Y., Conclusions: Compared with MAA, scout 90 Y is a more accurate surrogate for Rx 90 Y biodistribution for nonsegmental therapies., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Carbohydrate antigen (CA) 19-9 is a biomarker to monitor treatment effect. A threshold to predict prognostic significance remains undefined. We evaluated the impact of CA19-9 on overall survival (OS) in patients with early-stage pancreatic cancer (PC) utilizing the National Cancer Database (NCDB)., Methods: The NCDB was queried from 2010 to 2014 to identify patients with clinical stage I-II PC. Patients who had undocumented pretreatment CA19-9 were excluded. Patients were stratified into two cohorts: CA19-9 < 98 U/mL and CA19-9 ≥ 98 U/mL, and further categorized into surgery versus no surgery. Twelve- and 24-month OS rates are reported., Results: Overall, 32,382 patients (stage I: 12,173; stage II: 20,209) were included. The majority of stage I (52.1%) and II (60%) patients had CA19-9 ≥ 98 U/mL. Stage I-II patients with CA19-9 < 98 U/mL had improved OS rates (stage I: 67.5%, 42.6%; stage II: 59.8%, 32.8%) compared with stage I and II patients with CA19-9 ≥ 98 U/mL (stage I: 50.7%, 26.9%; stage II: 48.1%, 22%). Among resected stage I patients, CA19-9 <98 U/mL was associated with improved OS (< 98: 80.5%, 56%; ≥ 98: 70.2%, 42.8%), and a similar trend was seen in resected stage II patients (< 98: 77.6%, 49.9%; ≥ 98: 71%, 39.2%). Unresected stage I patients with lower CA19-9 had improved OS (< 98: 42.1%, 17.5; ≥ 98: 29.9%, 10%), with similar findings in unresected stage II patients (< 98: 41.1%, 15.3%; ≥ 98: 33.4%, 10.6%)., Conclusions: Our study demonstrated the prognostic value of CA19-9 in patients with clinical stage I-II PC, with a value < 98 U/mL demonstrating improved survival. Surgery significantly improved survival at 12 and 24 months irrespective of CA19-9., (© 2022. Society of Surgical Oncology.)

Non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients elicit inadequate antibody responses after initial SARS-CoV-2 vaccination and remain at high risk of severe COVID-19 disease. We investigated IgG, IgA, and IgM responses after booster vaccination against recent SARS-CoV-2 variants including Omicron BA.5 in 67 patients. Patients had lower fold increase and total anti-spike binding titers after booster than healthy individuals. Antibody responses negatively correlated with recent anti-CD20 therapy and low B cell numbers. Antibodies generated after booster demonstrated similar binding properties against SARS-CoV-2 variants compared to those generated by healthy controls with lower binding against Omicron variants. Importantly, 43% of patients showed anti-Omicron BA.1 neutralizing antibodies after booster and all these patients also had anti-Omicron BA.5 neutralizing antibodies. NHL/CLL patients demonstrated inferior antibody responses after booster vaccination, particularly against Omicron variants. Prioritization of prophylactic and treatment agents and vaccination of patients and close contacts with updated vaccine formulations are essential., Competing Interests: Conflict of Interest Statement Victor M. Orellana-Noia Consulting or Advisory Role: ADC TherapeuticsUncompensated Relationships: Roche/Genentech Kristie A. Blum Honoraria: American Society of Hematology, Leidos Biomedical Research/NCIResearch Funding: Genentech/Roche (Inst), Seattle Genetics (Inst), BMSi (Inst)Travel, Accommodations, Expenses: American Society of Hematology Pamela B. Allen Consulting or Advisory Role: ADC therapeutics, Epizyme, Kyowa Kirin, Daichii Sankyo, Secura Bio. Mary Jo Lechowicz Consulting or Advisory Role: Kyowa Kirin, Secura Bio, EUSA Pharma Ajay K. Nooka Honoraria: Amgen, Janssen Oncology, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Takeda, Oncopeptides, Karyopharm Therapeutics, Adaptive Biotechnologies, Genzyme, BeyondSpring Pharmaceuticals, Secura BioConsulting or Advisory Role: Amgen, Janssen Oncology, Bristol Myers Squibb, GlaxoSmithKline, Takeda, Oncopeptides, Karyopharm Therapeutics, Adaptive Biotechnologies, Genzyme, BeyondSpring Pharmaceuticals, Secura BioResearch Funding: Amgen (Inst), Janssen Oncology (Inst), Takeda (Inst), Bristol Myers Squibb/Celgene (Inst), Arch Oncology (Inst), GlaxoSmithKline (Inst)Travel, Accommodations, Expenses: GlaxoSmithKline Jean L. Koff Consulting or Advisory Role: Janssen/Pharmacyclics, MorphoSys, TG Therapeutics, Gamida CellResearch Funding: Celgene, Janssen/Pharmacyclics, Oncternal Therapeutics, Viracta Therapeutics, Atara Biotherapeutics Madhav V. Dhodapkar Consulting or Advisory Role: Roche/Genentech, Amgen, Kite, a Gilead company, lava therapeutics, Janssen Oncology, Celgene Mehul S. Suthar Consulting or Advisory Role: Moderna Therapeutics, OcugenResearch Funding: Moderna Therapeutics (Inst), Ocugen (Inst) Jonathon B. Cohen Consulting or Advisory Role: AbbVie, Janssen, Loxo, Kite/Gilead, AstraZeneca, Aptitude Medical, Adicet Bio, Adaptive BiotechnologiesResearch Funding: Bristol Myers Squibb (Inst), Janssen (Inst), Novartis (Inst), Takeda (Inst), AI Therapeutics (Inst), Genentech (Inst), ASH (Inst), Lymphoma Research Foundation (Inst), Loxo (Inst), Bioinvent (Inst), AstraZeneca (Inst) Rafi Ahmed Research Funding: MerckPatents, Royalties, Other Intellectual Property: Patents on PD-1–directed immunotherapy; I am listed as a coinventor on an Emory University held patent for SARS-CoV-2 serology assays The remaining authors have no conflicts to declare.

Background: Gallbladder cancer (GBC) is the most common biliary malignancy frequently metastatic at diagnosis with poor prognosis. While surgery remains the standard for early-stage GBC, the role of surgery in patients with metastatic gastrointestinal cancers is expanding due to improvements in systemic therapies. We sought to evaluate the survival of patients with stage IV GBC undergoing surgery in an era of improved multi-agent systemic therapy., Methods: A retrospective review of the National Cancer Database was performed. Patients with stage IV GBC who underwent systemic therapy were included. Patients who received radiation therapy, palliative therapy or had missing survival data were excluded. Univariable and multivariable analysis was performed., Results: 4,145 patients were identified between 2004 and 2016. Mean age was 69. Surgery combined with systemic therapy predicted improved median survival compared with chemotherapy alone (11.1mo versus 6.8mo, HR 0.65, p < 0.001). Additionally, receipt of treatment after 2011 predicted improved survival (HR 0.86, p < 0.001). Patients treated with multi-agent chemotherapy in combination with surgery were associated with the greatest hazard ratio benefit (0.40, p < 0.001) versus single agent therapy alone., Conclusion: Patients with stage IV gallbladder cancer treated with a combination of surgery and chemotherapy are associated with an improved overall survival compared to chemotherapy alone. Patients receiving care during the more recent era demonstrated improved survival. These results support a role for surgery in selected patients with stage IV gallbladder cancer receiving chemotherapy., Competing Interests: Declaration of competing interest Research reported in this publication was supported in part by the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Context.—: The pathologic nodal staging of prostatic adenocarcinoma is binary for regional lymph nodes. Stages pN0 and pN1 indicate the absence or presence of regional nodal metastasis, respectively, whereas patients with metastasis to nonregional lymph nodes are staged as pM1a., Objective.—: To determine the risk of recurrence of pN1 prostatic adenocarcinoma patients based on the extent of nodal tumor burden., Design.—: We retrospectively reviewed pN1 patients with prostatic adenocarcinoma managed with radical prostatectomy seen between 2011 and 2019. Kaplan-Meier and Cox regression analyses were performed to compare disease-free survival., Results.—: Ninety-six patients were included (median [interquartile range] age, 62 years [57-67 years]; 70 of 96 [73%] White). On univariate analysis, age >65 years (P = .008), ≥2 positive regional lymph nodes (P < .001), and a maximum size of the tumor deposit ≥2 mm (P = .004) were significantly associated with an unfavorable outcome. Controlling for age, stage, metastatic deposit size, margin status, and the presence of extranodal extension, patients with ≥2 positive regional lymph nodes were 3.03 times more likely (95% confidence interval, 1.39-6.60; P = .005) to have an unfavorable outcome. Patients with pN1M1a stage showed a disease-free survival similar to that of pN1M0 patients, after controlling for the number of positive regional lymph nodes (P = .36)., Conclusions.—: Overall, pN1 patients with ≥2 positive regional lymph nodes are 3 times more likely to have an unfavorable outcome. The results suggest a benefit in further stratifying patients with metastatic prostatic adenocarcinoma to the lymph nodes into prognostically significant risk categories that could help the treating clinicians tailor subsequent patient follow-up and therapy., Competing Interests: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (© 2022 College of American Pathologists.)

Purpose/objective: Given the rarity of vulvar cancer, data on the incidence of acute and late severe toxicity and patients' symptom burden from radiotherapy (RT) are lacking., Materials/methods: This multi-center, single-institution study included patients with vulvar squamous cell carcinoma treated with curative intent RT between 2009 and 2020. Treatment-related acute and late grade ≥ 3 toxicities and late patient subjective symptoms (PSS) were recorded., Results: Forty-two patients with predominantly stage III/IV disease (n = 25, 59.5 %) were treated with either definitive (n = 25, 59.5 %) or adjuvant (n = 17, 40.5 %) external beam RT to a median dose of 64 Gy and 59.4 Gy, respectively. Five patients received a brachytherapy boost with a median total dose of 84.3 Gy in 2 Gy-equivalent dose (EQD2). Intensity-modulated RT was used in 37 (88.1 %) of patients, and 25 patients (59.5 %) received concurrent chemotherapy. Median follow-up was 27 months. Acute grade ≥ 3 toxicity occurred in 17 patients (40.5 %), including 13 (31.0 %) acute grade 3 skin events. No factors, including total RT dose (p = 0.951), were associated with acute skin toxicity. Eleven (27.5 %) patients developed late grade ≥ 3 toxicity events, including 10 (23.8 %) late grade ≥ 3 skin toxicity events. Patients with late grade ≥ 3 skin toxicity had a higher mean body-mass index (33.0 vs 28.2 kg/m 2 ; p = 0.009). Common late PSS included vaginal pain (n = 15, 35.7 %), skin fibrosis (n = 10, 23.8 %), and requirement of long-term opiates (n = 12, 28.6 %)., Conclusion: RT for vulvar cancer is associated with considerable rates of severe acute and late toxicity and PSS burden. Larger studies are needed to identify risk factors, explore toxicity mitigation strategies, and assess patient-reported outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: We conducted a pilot study assessing the feasibility of a personalized out-of-pocket cost communication, remote financial navigation, and counseling (CostCOM) intervention in cancer patients., Methods: Twenty-three adult, newly diagnosed cancer patients at a single community oncology practice were asked to complete a survey and participate in a CostCOM intervention, including patient-specific out-of-pocket cost communication, remote financial navigation, and counseling. Feasibility was defined as patient participation in CostCOM, and its impact on financial worry measured using the Comprehensive Score for Financial Toxicity (COST) (higher score = less worry) was assessed. Eight patients' and two providers' experience with CostCOM was evaluated using qualitative interviews., Results: Mean patient age was 61 (78.3% female; 100% white). Of 23 CostCOM patients, 86.9% completed CostCOM, 60% of them completed a financial assistance application, and 25% of those who applied were enrolled in a co-pay assistance program. Patients' financial worry significantly improved following CostCOM (COST score of 10.0 ± 9.6 at enrollment vs. 16.9 ± 8.1 at follow-up; p < 0.001). Mean general satisfaction (out of 5) with CostCOM was 4.1 ± 0.7. In qualitative interviews following OOPC communication, 75% felt a positive impact on their mental health, and all patients reported no change in their treatment plan; 83.3% found financial navigation beneficial. In providers' interviews, buy-in from relevant stakeholders, integration of the CostCOM with existing workflow, and larger studies to assess the effectiveness of CostCOM were identified as factors needed for CostCOM implementation in practice., Conclusion: CostCOM interventions are feasible and acceptable and decrease financial worry in patients with cancer., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The authors identified tumor, treatment, and patient characteristics that may contribute to differences in breast cancer (BC) mortality by race, rurality, and area-level socioeconomic status (SES) among women diagnosed with stage IIIB-IV BC in Georgia., Methods: Using the Georgia Cancer Registry, 3084 patients with stage IIIB-IV primary BC (2013-2017) were identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing mortality among non-Hispanic Black (NHB) versus non-Hispanic White (NHW), residents of rural versus urban neighborhoods, and residents of low- versus high-SES neighborhoods by tumor, treatment, and patient characteristics. The mediating effects of specific characteristics on the association between race and BC mortality were estimated., Results: Among the study population, 41% were NHB, 21% resided in rural counties, and 72% resided in low SES neighborhoods. The authors observed mortality disparities by race (HR, 1.27; 95% CI, 1.13, 1.41) and rurality (HR, 1.14; 95% CI, 1.00, 1.30), but not by SES (HR, 1.04; 95% CI, 0.91, 1.19). In the stratified analyses, racial disparities were the most pronounced among women with HER2 overexpressing tumors (HR, 2.30; 95% CI, 1.53, 3.45). Residing in a rural county was associated with increased mortality among uninsured women (HR, 2.25; 95% CI, 1.31, 3.86), and the most pronounced SES disparities were among younger women (<40 years: HR, 1.46; 95% CI, 0.88, 2.42)., Conclusions: There is considerable variation in racial, regional, and socioeconomic disparities in late-stage BC mortality by tumor, treatment, and patient characteristics., (© 2022 American Cancer Society.)

Purpose: Patients with non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) are at higher risk of severe SARS-CoV-2 infection. We investigated vaccine-induced antibody responses in patients with NHL/CLL against the original SARS-CoV-2 strain and variants of concern including B.1.167.2 (Delta) and B.1.1.529 (Omicron)., Materials and Methods: Blood from 121 patients with NHL/CLL receiving two doses of vaccine were collected longitudinally. Antibody binding against the full-length spike protein, the receptor-binding, and N-terminal domains of the original strain and of variants was measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the early WA1/2020 strains was measured using a focus reduction neutralization test. B cells were measured by flow cytometry. Correlation between vaccine response and clinical factors was determined., Results: Mean anti-SARS-CoV-2 spike immunoglobulin G-binding titers were 85-fold lower in patients with NHL/CLL compared with healthy controls, with seroconversion occurring in only 67% of patients. Neutralization titers were also lower and correlated with binding titers ( P < .0001). Treatment with anti-CD20-directed therapies within 1 year resulted in 136-fold lower binding titers. Peripheral blood B-cell count also correlated with vaccine response. At 3 months from last anti-CD20-directed therapy, B-cell count ≥ 4.31/μL blood around the time of vaccination predicted response (OR 7.46, P = .04). Antibody responses also correlated with age. Importantly, neutralization titers against Delta and Omicron were reduced six- and 42-fold, respectively, with 67% of patients seropositive for WA1/2020 exhibiting seronegativity for Omicron., Conclusion: Antibody binding and live-virus neutralization against SARS-CoV-2 and its variants of concern including Delta and Omicron were substantially lower in patients with NHL/CLL compared with healthy vaccinees. Anti-CD20-directed therapy < 1 year before vaccination and number of circulating B cells strongly predict vaccine response.

Purpose: Vaccine-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., Methods: Sera 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., Results: Vaccine-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)., Conclusion: These 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.

Background: The survival impact of multi-agent (MAC) compared with single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study was to compare survival outcomes of MAC and SAC in this population utilizing the National Cancer Database (NCDB)., Patients and Methods: Patients aged ≥70 years with pathological stage III CC diagnosed in 2004-2015 were identified in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify associations between MAC vs. SAC and overall survival (OS)., Results: Among 41 707 elderly patients (≥70 years old) with stage III CC, about half (n = 20 257; 48.5%) received AC; the majority (n = 12 923, 63.8%) received MAC. The median age was 79 (range 70-90). The majority were female (n = 11 201, 55.3%), Caucasians (88%) and had moderately differentiated tumor grade (n = 12 619, 62.3%), tumor size &gt;4 cm (11 785, 58.2%), and negative surgical margins (18 496, 91.3%). Low-risk stage III CC constituted 50.6% (n = 10 264) of the study population. High-risk stage III CC was associated with worse OS compared with low-risk disease (HR 0.35, 0.34-0.36, P &lt; .001). Multi-agent chemotherapy was associated with a better 5-year OS compared with SAC (P &lt; .001). High-risk stage III patients who received MAC vs. SAC had an OS of 4.2 vs. 3.4 years, respectively (P &lt; .001). Low-risk stage III patients who received MAC vs. SAC had a median OS of 8.5 vs. 7 years (P &lt; .001). In univariate and multivariable analyses, male sex, positive surgical margin, insurance and facility types, age, year of diagnosis, tumor size, and Charlson-Deyo score of &gt;2 were associated with worse OS (P &lt; .05)., Conclusions: Any adjuvant chemotherapy has a trend of survival benefits. Multi-agent chemotherapy seems to have an enhanced benefit in the 70-75 age group. Multi-agent chemotherapy seemed to have similar efficacy as SAC in those aged &gt;76 years., (© The Author(s) 2022. Published by Oxford University Press.)

Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma with poor survival. We performed a retrospective review of SS patients at Emory University from 1990 to 2020. We collected data on race, clinical characteristics, therapy, and social determinants of health. Clinical endpoints were overall survival (OS) and time to next treatment (TTNT). Univariate association and multivariable analyses were assessed by Cox proportional hazards models. Among 62 patients, 45.2% were AA. The median OS and TTNT were 3.1 years and 6.3 months, respectively, with no difference by race. AA patients had a higher median baseline LDH (360 vs. 232, p  = 0.002) and a longer delay in initiation of systemic therapy compared to CC patients (3.17 vs. 2.14 months, p  = 0.039), but a shorter commute (<10 miles) and no difference in insurance coverage ( p  = 0.260). AA patients at an academic center had unique clinical features and treatment patterns, but similar survival to CC SS patients.