6534 Background: Social determinants of health (SDOH) can predispose underserved communities to poor cancer outcomes. The CDC has created a Social Vulnerability Index (SVI) score for US counties that integrates four SDOH: socioeconomic status, household composition & disability, minority status & language, and housing type & transportation. Scores range from 0 to 1, with higher values signifying more vulnerability. SVI is a significant determinant of overall mortality, but its association with cancer mortality is unclear. This study aimed to investigate if there is a relationship between SVI and cancer mortality. Methods: CDC WONDER (Wide-Ranging Online Data for Epidemiological Research) was used to estimate age-adjusted mortality rates per 100,000 person-years with 95% CIs for adults > 18 years of age from 3,030 (96%) US counties between 2014-2018 for a composite of three cancers (lung, breast, and colon cancer), individual cancer subtypes, and demographic groups (sex, ethnicity/race, urban/rural classification). Age-adjusted mortality rates were compared across SVI quartiles: 1st (least vulnerable) to 4th (most vulnerable). Linear regression was used to identify the association between the 4th vs. 1st SVI quartile and the odds of being above the median mortality rate for composite cancers, individual cancer subtypes, and demographic groups. Results: Overall, age-adjusted composite cancer mortality rate per 100,000 person-years was 122.9 (lung cancer 82.8, breast cancer 38.1, colon cancer 21.9). The largest concentration of most vulnerable US counties and composite cancer mortality was in the southeastern US. Age-adjusted composite cancer mortality rates increased from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile vs. 1st SVI quartile were significantly more likely to be above the median mortality rate for composite cancer (OR 6.46 [95% CI, 5.16 - 8.08]), lung cancer (6.88 [5.46 - 8.66]), breast cancer (2.77 [2.17 - 3.54]), and colon cancer (6.20 [4.82 - 7.97]). Among all races, non-Hispanic Black adults in the 4th SVI quartile vs. 1st SVI quartile were significantly more likely to be above the median mortality rate for composite cancer (OR 9.46 [95% CI, 6.19 - 14.4]), lung cancer (13.8 [7.87 - 24.1]), breast cancer (5.53 [3.16 - 9.68]), and colon cancer (6.34 [3.69 - 10.9]). Moreover, rural counties in the 4th SVI quartile vs. 1st SVI quartile were between 2- to 8-times more likely to be above the median mortality rate for composite cancer and individual cancer subtypes. Conclusions: This study highlights the most socially vulnerable US counties have higher cancer mortality rates than the least vulnerable US counties. Furthermore, non-Hispanic Black adults and rural counties in the most socially vulnerable category have higher cancer mortality rates than those in the least socially vulnerable category. Additional work is needed to understand how SVI can be used for better resource allocation to help mitigate cancer mortality.
Undifferentiated pleomorphic sarcoma (UPS), a subtype of soft tissue sarcoma (STS), is an uncommon malignancy associated with a poor prognosis. As with other forms of sarcoma, surgical resection remains the only form of treatment with curative potential. The role of perioperative systemic therapy has not been definitively elucidated. Due to high recurrence rates and metastatic potential, management of UPS can pose a difficult task for clinicians. In cases of unresectable UPS due to anatomic limitations and in patients with comorbidities and poor performance status (PS), management options are limited. We describe a patient with UPS involving the chest wall with poor PS who achieved complete response (CR) following neoadjuvant chemotherapy and radiation in the setting of prior immune-checkpoint inhibitor (ICI) therapy.
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to differentiate MCL from other NHL types; however, recently, there has been an increase in the number of reported cases of CD10-positive MCL. This warrants further investigation into this rarer immunophenotype and its clinical significance. BCL6, which is a master transcription factor for the regulation of cell proliferation and key oncogene in B cell lymphomagenesis, has been reported to have co-expression with CD10 in MCL. The clinical significance of this aberrant antigen expression remains unknown. We conducted a systematic review by searching four databases and selected five retrospective analyses and five case series. Two survival analyses were conducted to determine if BCL6 positivity conferred a survival difference: 1. BCL6+ vs. BCL6− MCL. 2. BCL6+/CD10+ vs. BCL6−/CD10+ MCL. Correlation analysis was conducted to determine if BCL6 positivity correlated with the Ki67 proliferation index (PI). Overall survival (OS) rates were performed by the Kaplan–Meier method and log-rank test. Our analyses revealed that BCL6+ MCL had significantly shorter overall survival (median OS: 14 months vs. 43 months; p = 0.01), BCL6+/CD10+ MCL had an inferior outcome vs. BCL6+/CD10− MCL (median OS: 20 months vs. 55 months p = 0.1828), BCL6+ MCL had significantly higher percentages of Ki67% (Ki67% difference: 24.29; p = 0.0094), and BCL6 positivity had a positive correlation with CD10+ status with an odds ratio 5.11 (2.49, 10.46; p = 0.0000286). Our analysis showed that BCL6 expression is correlated with CD10 positivity in MCL, and BCL6 expression demonstrated an inferior overall survival. The higher Ki67 PI in BCL6+ MCL compared to BCL6− MCL further supports the idea that the BCL6+ immunophenotype may have prognostic value in MCL. MCL management should consider incorporating prognostic scoring systems adjusted for BCL6 expression. Targeted therapies against BCL6 may offer potential therapeutic options for managing MCL with aberrant immunophenotypes.
The treatment of urothelial carcinoma (UC) is challenging given its molecular heterogeneity and variable response to current therapies. To address this, many tools, including tumor biomarker assessment and liquid biopsies, have been developed to predict prognosis and treatment response. Approved therapeutic modalities for UC currently include chemotherapy, immune checkpoint inhibitors, receptor tyrosine kinase inhibitors, and antibody drug conjugates. Ongoing investigations to improve the treatment of UC include the search for actionable alterations and the testing of novel therapies. An important objective in recent studies has been to increase efficacy while decreasing toxicity by taking into account unique patient and tumor-related factors—an endeavor called precision medicine. The aim of this review is to highlight advancements in the treatment of UC, describe ongoing clinical trials, and identify areas for future study in the context of precision medicine.
Introduction Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%–5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP). Case report We report an unusual case of pneumonitis with atypical imaging in a patient who received pembrolizumab for metastatic p16-positive squamous cell carcinoma of the base of the tongue. We discuss the approach to the recognition and management of atypical CIP in patients on pembrolizumab with the intent to standardize workup and increase awareness among healthcare providers in the new era of immunotherapy. Management and Outcome Serologic workup including laboratory studies for complete blood count (CBC), lactate, procalcitonin, SARS-CoV-2 (COVID-19), Legionella, Cytomegalovirus (CMV), Coccidioides, Coxiella, and viral respiratory panel were negative for infectious processes. Since CIP was suspected, the patient was started on steroid therapy. Interval computed tomography (CT) of the chest without contrast showed a resolution of pneumonitis. Discussion In this case report, we discuss our workup of CIP and initial testing to rule out other possible causes of the patient's symptoms and radiographic findings, and management of the patient's diagnosis of atypical CIP which led to complete clinical recovery from CIP.
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