Tolerance of radiotherapy with concomitant glofitamab in diffuse large B cell lymphoma: a case report.

Glofitamab, an anti-CD20 antibody, is approved as a third-line treatment for relapsed or refractory (r/r) diffuse large-cell B lymphoma (DLBCL), achieving a complete response in nearly 40% of patients. This humanized IgG1 bispecific monoclonal antibody binds to CD20 on malignant B lymphocytes and to CD3 on cytotoxic T cells. This dual binding forms an immunological synapse, activating T lymphocytes and leading to the lysis of tumor cells. Salvage radiotherapy is also effective for r/r DLBCL, but its combination with systemic treatments like glofitamab may increase radiation-induced toxicity. We report the first case of a patient with r/r DLBCL receiving concurrent salvage radiotherapy and glofitamab. A 68-year-old female diagnosed with stage IV DLBCL underwent initial treatment with R-CHOP, then Car-T cell therapy, followed by glofitamab for recurrence. Upon early metabolic progression detected by 18FDG-PET/CT, salvage radiotherapy was administered to the refractory site concurrently with glofitamab. The patient experienced mild para-spinal pain post-radiotherapy but no other significant toxicities. Three months post-treatment, she showed a complete metabolic response with no radiotherapy toxicity, as evidenced by PET-CT, and no signs of radiation pneumonitis. This case indicates that combining glofitamab with salvage radiotherapy is tolerable and suggests potential efficacy, warranting further investigation in prospective studies for r/r DLBCL.

APR-246 induces early cell death by ferroptosis in acute myeloid leukemia.

APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). APR-246 reactivates the transcriptional activity of p53 mutants by facilitating their binding to DNA target sites. Recent studies in solid cancers have found that APR-246 can also induce p53-independent cell death. In this study, we demonstrate that AML cell death occurring early after APR-246 exposure is suppressed by iron chelators, lipophilic antioxidants and inhibitors of lipid peroxidation, and correlates with the accumulation of markers of lipid peroxidation, thus fulfilling the definition of ferroptosis, a recently described cell death process. The capacity of AML cells to detoxify lipid peroxides by increasing their cystine uptake to maintain major antioxidant molecule glutathione biosynthesis after exposure to APR-246 may be a key determinant of sensitivity to this compound. The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo.

Proton Therapy Reduces the Effective Dose to Immune Cells in Mediastinal Hodgkin Lymphoma Patients.

Purpose: Effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction compared with volumetric modulated arc therapy (VMAT) in mediastinal Hodgkin lymphoma (mHL) patients. Materials and Methods: Ten consecutive mHL patients treated with involved-site IMPT after frontline chemotherapy were included. The mean dose to the heart, lung, and liver and the integral dose to the body were obtained, and we calculated EDIC based on these variables. The effective dose to circulating immune cells was compared between IMPT and VMAT schedules. Results: The median EDIC was reduced from 1.93 Gy (range: 1.31-3.87) with VMAT to 1.08 Gy (0.53-2.09) with IMPT (P < .01). Integral dose reduction was the main driver of EDIC reduction with IMPT, followed by lung sparing. Conclusion: Intensity-modulated proton therapy significantly reduced EDIC in mHL patients undergoing consolidation involved-site radiation therapy. Integral dose reduction combined with improved lung sparing was the main driver of EDIC reduction with IMPT.

Prognostic impact of early minimal residual disease combined with complete molecular evaluation in acute myeloid leukemia with mutated NPM1: a single center study.

We evaluated prognostic factors in 83 intensively treated adult patients with NPM1 mutated AML. Targeted next-generation sequencing revealed high frequency of co-mutations in epigenetic modifiers or proliferation pathways. NPM1 minimal residual disease (MRD), assessed in bone marrow by specific polymerase chain reaction after one chemotherapy course, was >0.01% in 50 patients considered poor responders (PR). On multivariate analysis, including all variables with a p value <.1 on univariate analysis, age >60, performance status (PS) ≥1, presence of FLT3 mutations, DNMT3A-R882, and PR status, were independently associated with lower leukemia-free survival. Age >60, a previous hematological disease and PR status were independent negative predictive factors for overall survival. In our study, early NPM1 MRD was confirmed as an important prognostic factor. All FLT3 and DNMT3A-R882 mutations have also an independent prognostic value. We support the rational for in-depth investigations for a better approach in patients who achieving a first complete remission.

A community approach to addressing excess breast and cervical cancer mortality among women of African descent in Boston.

In 2000, the REACH Boston 2010 Breast and Cervical Cancer Coalition conducted a community needs assessment and found several factors that may have contributed to disproportionately high breast and cervical cancer mortality among black women: (a) Focus group participants reported that many women in their communities had limited awareness about risk factors for cancer as well as about screening. (b) Black women experienced barriers to care related to the cultural competence of providers and of institutions. (c) Black women were not receiving adequate follow-up for abnormal mammograms and Pap smears. The Coalition's Community Action Plan to address disparities includes a model primary care service for black women; scholarships to increase the number of black mammogram technologists; primary care provider and radiology technologist training about disparities and cultural competence; and education to increase awareness among black women and to increase leadership and advocacy skills.

Trust yet verify: physicians as trusted sources of health information on HPV for black women in socioeconomically marginalized populations.

BACKGROUND: Human papilloma virus (HPV) infection is highest among Black women and women of low socio economic position (SEP). These groups face inequities in access to health information on HPV. OBJECTIVES: Our study sought to understand key information channels for delivering health information regarding HPV and the HPV vaccine to Black women of low SEP in Boston, Massachusetts. We anticipated that, owing to a legacy of experiences of discrimination, Black women of low SEP would prefer information from trusted and accessible sources, including friends, family, and community agencies, rather than clinical providers. METHODS: We conducted a qualitative analysis using focus groups. We conducted five focus groups among 25 women in Boston, Massachusetts. RESULTS: Contrary to what we anticipated, we found that women in all of the focus groups preferred to receive information from a physician or health center. Participants preferred to receive print materials they could triangulate with other sources. Notably, study participants had high access to care. CONCLUSIONS: Our study suggests that physicians are trusted and preferred sources of information on HPV for Black women of low SEP in Boston. Our data underscore an important avenue for intervention: to improve dissemination of HPV-related information through physicians, including outreach in community settings.

Case management intervention in cervical cancer prevention: the Boston REACH coalition women's health demonstration project.

BACKGROUND: The Boston REACH Coalition developed a case management intervention for Black women in primary care settings to identify and reduce medical and social obstacles to cervical cancer screening and following up abnormal results. METHODS: The 5-year intervention was evaluated among 732 Black women aged 18 to 75 who were at high risk for inadequate Pap smear screening and follow-up. Case managers provided social services referrals to address patient-identified social concerns (e.g., transportation, housing), as well as navigation to prompt screening and follow-up of abnormal tests. The three study aims were to (1) identify the social factors associated with Pap smear screening at baseline before intervention, (2) evaluate the correlation between exposure to case management intervention and achieving recommended Pap screening intervals, and (3) evaluate the correlation between exposure to case management intervention and having timely follow-up of abnormal Pap smear tests. RESULTS: We found that a lack of a regular clinical provider, concerns communicating with providers, poor self-rated health, and having less than a high school education were important correlates of recent Pap smear screening before the case management intervention. During the case management intervention, we found a significant increase in achieving recommended Pap smear screening intervals among women with a recent Pap smear at study entry (increasing from 52% in the first year to 80% after 4 or more years; p < .01), but not among women who entered the study without a recent Pap smear (increasing from 31% in the first year to 44% after 4 or more years; p = .39). During case management intervention, having social support for childcare was associated with regular screening among women without a recent Pap smear (odds ratio [OR], 3.52; 95% confidence interval [CI], 1.28-9.69). Insurance status was the key factor in timely clinically indicated follow-up of abnormal results (uninsured OR, 0.27; 95% CI, 0.08-0.86), rather than case management intervention. CONCLUSIONS: Exposure to case management was associated with regular Pap smear screening among women who recently engaged in screening. Future research should focus on systems changes to address social determinants of health, including strategies to facilitate screening for Black women without social support for childcare. To improve follow-up of abnormal results, financial access to care should be addressed.

Addressing social determinants of health to improve access to early breast cancer detection: results of the Boston REACH 2010 Breast and Cervical Cancer Coalition Women's Health Demonstration Project.

BACKGROUND: The Boston Racial and Ethnic Approaches to Community Health (REACH) 2010 Breast and Cervical Cancer Coalition developed a case management intervention for women of African descent to identify and reduce medical and social obstacles to breast cancer screening and following up abnormal results. METHODS: We targeted black women at high risk for inadequate cancer screening and follow-up as evidenced by a prior pattern of missed clinic appointments and frequent urgent care use. Case managers provided referrals to address patient-identified social concerns (e.g., transportation, housing, language barriers), as well as navigation to prompt screening and follow-up of abnormal tests. We recruited 437 black women aged 40-75, who received care at participating primary care sites. The study was conducted as a prospective cohort study rather than as a controlled trial and evaluated intervention effects on mammography uptake and longitudinal screening rates via logistic regression and timely follow-up of abnormal tests via Cox proportional hazards models. RESULTS: A significant increase in screening uptake was found (OR 1.53, 95% CI 1.13-2.08). Housing concerns (p < 0.05) and lacking a regular provider (p < 0.01) predicted poor mammography uptake. Years of participation in the intervention increased odds of obtaining recommended screening by 20% (OR 1.20, 95% CI 1.02-1.40), but this effect was attenuated by covariates (p = 0.53). Timely follow-up for abnormal results was achieved by most women (85%) but could not be attributed to the intervention (HR 0.95, 95% CI 0.50-1.80). CONCLUSIONS: Case management was successful at promoting mammography screening uptake, although no change in longitudinal patterns was found. Housing concerns and lacking a regular provider should be addressed to promote mammography uptake. Future research should provide social assessment and address social obstacles in a randomized controlled setting to confirm the efficacy of social determinant approaches to improve mammography use.

Mammography use among Black women: the role of electronic medical records.

BACKGROUND AND AIMS: Accurately documenting mammography use is essential to assess quality of care for early breast cancer detection in underserved populations. Self-reports and medical record reports frequently result in different accounts of whether a mammogram was performed. We hypothesize that electronic medical records (EMRs) provide more accurate documentation of mammography use than paper records, as evidenced by the level of agreement between women's self-reported mammography use and mammography use documented in medical records. METHODS: Black women aged 40-75 were surveyed in six primary care sites in Boston, Massachusetts (n = 411). Survey data assessed self-reported mammography prevalence within 2 years of study entry. Corresponding medical record data were collected at each site. Positive predictive value (PPV) of self-report and kappa statistics compared data agreement among sites with and without EMRs. Logistic regression estimated effects of site and patient characteristics on agreement between data sources. RESULTS: Medical records estimated a lower prevalence of mammography use (58%) than self-report (76%). However, self-report and medical record estimates were more similar in sites with EMRs. PPV of self-report was 88% in sites with continuous access to EMRs and 61% at sites without EMRs. Kappa statistics indicated greater data agreement at sites with EMRs (0.72, 95% CI 0.56-0.88) than without EMRs (0.46, 95% CI 0.29-0.64). Adjusted for covariates, odds of data agreement were greatest in sites where EMRs were available during the entire study period (OR 4.31, 95% CI 1.67-11.13). CONCLUSIONS: Primary care sites with EMRs better document mammography use than those with paper records. Patient self-report of mammography screening is more accurate at sites with EMRs. Broader access to EMRs should be implemented to improve quality of documenting mammography use. At a minimum, quality improvement efforts should confirm the accuracy of paper records with supplemental data.