Intersectional Analysis of U.S. Medical Faculty Diversity over Four Decades.

The 2020 U.S. Census data show a rapidly diversifying U.S. population. We sought to evaluate whether clinical faculty and leadership representation at academic medical schools reflects the diversifying population over time. Using data from the Association of American Medical Colleges for the period of 1977 through 2019, we found notable progress in female representation among clinical faculty, with smaller gains among department chairs and medical school deans. Racial and ethnic groups that are underrepresented in medicine are designated as such because their presence within the medical profession is disproportionate to the U.S. Census data. Even with accounting for this underrepresentation, clinical faculty and leadership positions show even starker disparities. Thoughtful policy implementation could help address this persistent underrepresentation among medical school faculty and leadership positions.

Disrupting prostate cancer research: Challenge accepted; report from the 2023 Coffey-Holden Prostate Cancer Academy Meeting.

INTRODUCTION: The 2023 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, themed "Disrupting Prostate Cancer Research: Challenge Accepted," was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023. METHODS: The 2023 marked the 10th Annual CHPCA Meeting, a discussion-oriented scientific think-tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care. The 2023 CHPCA Meeting was attended by 81 academic investigators and included 40 talks across 8 sessions. RESULTS: The central topic areas covered at the meeting included: targeting transcription factor neo-enhancesomes in cancer, AR as a pro-differentiation and oncogenic transcription factor, why few are cured with androgen deprivation therapy and how to change dogma to cure metastatic prostate cancer without castration, reducing prostate cancer morbidity and mortality with genetics, opportunities for radiation to enhance therapeutic benefit in oligometastatic prostate cancer, novel immunotherapeutic approaches, and the new era of artificial intelligence-driven precision medicine. DISCUSSION: This article provides an overview of the scientific presentations delivered at the 2023 CHPCA Meeting, such that this knowledge can help in facilitating the advancement of prostate cancer research worldwide.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part III of a three-part series focusing on evaluation and management of suspected non-metastatic recurrence after radiotherapy (RT) and focal therapy, evaluation and management of regional recurrence, management for molecular imaging metastatic recurrence, and future directions. Please refer to Part I for discussion of treatment decision-making and Part II for discussion of treatment delivery for non-metastatic biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Guideline Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Continuous and deliberate efforts for multidisciplinary care in prostate cancer will be required to optimize and improve the oncologic and functional outcomes of patients treated with salvage therapies in the future.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part II: Treatment Delivery for Non-metastatic Biochemical Recurrence After Primary Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part II of a three-part series focusing on treatment delivery for non-metastatic biochemical recurrence (BCR) after primary radical prostatectomy (RP). Please refer to Part I for discussion of treatment decision-making and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Optimizing and personalizing the approach to salvage therapy remains an ongoing area of work in the field of genitourinary oncology and represents an area of research and clinical care that requires well-coordinated, multi-disciplinary efforts.

Approach to Patients with High-Risk Localized Prostate Cancer: Radiation Oncology Perspective.

OPINION STATEMENT: High-risk localized prostate cancer is a challenging clinical entity to treat, with heterogeneous responses to an evolving array of multidisciplinary treatment approaches. In addition, this disease state is growing in incidence due to a variety of factors, including shifting recommendations that discouraged routine prostate cancer screening. Current guidelines now incorporate an informed decision-making process for prostate cancer screening and evaluation. More work is underway to improve targeted screening for certain at-risk populations and to implement greater personalization in the use of diagnostic tools. Once diagnosed with high-risk localized disease, a multimodality treatment paradigm is warranted. Radiation-in its various forms and combinations-plays a large and continually evolving role in the management of high-risk prostate cancer, yet treatment outcomes are still suboptimal. There is a growing need to improve upon current treatment approaches, and better personalize a particular treatment recommendation based on both tumor and patient characteristics, as well as patient preference and goals of therapy. Given that treatment generally requires more than one therapy, there are notable implications on long-term quality of life, especially with respect to overlapping and cumulative side effects of local and systemic therapies, respectively. The desire for aggressive therapy to optimize cancer control outcomes must be weighed against the risk of morbidities and overtreatment and discussed with each patient so that an informed decision about treatment and care can be determined. High-level evidence to support treatment recommendations, where available, is critical for a data-driven and tailored approach to address all goals of care.

Advances in radiation therapy for testicular seminoma.

PURPOSE: Novel techniques and advances in radiation therapy (RT) have been explored to treat testicular seminoma, a highly radiosensitive and curable histology. We evaluated the historical and current indications for radiation therapy (RT) in testicular seminoma. METHODS: A narrative literature review was performed. Studies of RT for testicular seminoma were included. Additionally, recent trials testing the use of combination or surgical therapies for clinical stage (CS) II were included. Search parameters included radiation therapy, testicular seminoma, surgery, and chemoradiation. Parameters and outcomes assessed were progression-free survival (PFS), overall survival (OS), acute toxicities, long-term sequelae, and rates of secondary malignancies. RESULTS: Practice defining and changing studies in the use or omission of radiation therapy for testicular seminoma were identified along with resultant changes in National Comprehensive Cancer Network (NCCN) and European guidelines. Recent trials in combined chemoradiation and upfront surgical approaches to CS II disease were reviewed. CONCLUSION: RT has historically been used as adjuvant treatment for CS I disease and is highly effective at treating CS II (A/B) testicular seminoma. The drive to maintain therapeutic efficacy and reduce acute and long-term side effects, namely secondary malignancies, is being tested using new radiation technologies, combined modality therapy in the form of chemoradiation and with upfront surgical approaches. Also, as guidelines now "strongly prefer" surveillance instead of adjuvant RT for CS I disease, the current CS II population comprises patients presenting with CS II disease ("de novo") and those who present with CSII after relapsing post orchiectomy for CS I ("relapsed"). Emerging evidence suggests that these two groups have different outcomes with respect to RT and chemoradiation. Consequently, future trials may need to sub-stratify according to these groups.

Response prediction of neoadjuvant chemoradiation therapy in locally advanced rectal cancer using CT-based fractal dimension analysis.

OBJECTIVES: There are individual variations in neo-adjuvant chemoradiation therapy (nCRT) in patients with locally advanced rectal cancer (LARC). No reliable modality currently exists that can predict the efficacy of nCRT. The purpose of this study is to assess if CT-based fractal dimension and filtration-histogram texture analysis can predict therapeutic response to nCRT in patients with LARC. METHODS: In this retrospective study, 215 patients (average age: 57 years (18-87 years)) who received nCRT for LARC between June 2005 and December 2016 and underwent a staging diagnostic portal venous phase CT were identified. The patients were randomly divided into two datasets: a training set (n = 170), and a validation set (n = 45). Tumor heterogeneity was assessed on the CT images using fractal dimension (FD) and filtration-histogram texture analysis. In the training set, the patients with pCR and non-pCR were compared in univariate analysis. Logistic regression analysis was applied to identify the predictive value of efficacy of nCRT and receiver operating characteristic analysis determined optimal cutoff value. Subsequently, the most significant parameter was assessed in the validation set. RESULTS: Out of the 215 patients evaluated, pCR was reached in 20.9% (n = 45/215) patients. In the training set, 7 out of 37 texture parameters showed significant difference comparing between the pCR and non-pCR groups and logistic multivariable regression analysis incorporating clinical and 7 texture parameters showed that only FD was associated with pCR (p = 0.001). The area under the curve of FD was 0.76. In the validation set, we applied FD for predicting pCR and sensitivity, specificity, and accuracy were 60%, 89%, and 82%, respectively. CONCLUSION: FD on pretreatment CT is a promising parameter for predicting pCR to nCRT in patients with LARC and could be used to help make treatment decisions. KEY POINTS: • Fractal dimension analysis on pretreatment CT was associated with response to neo-adjuvant chemoradiation in patients with locally advanced rectal cancer. • Fractal dimension is a promising biomarker for predicting pCR to nCRT and may potentially select patients for individualized therapy.

Radiation treatment in prostate cancer: covering the waterfront.

OBJECTIVES: To present an overview of radiation therapy (RT) for prostate cancer over the past decade. METHODS: The literature on prostate cancer radiation therapy was reviewed and summarised. Radiation therapy (RT) for prostate cancer has dramatically evolved in the past decade, with superior techniques and exciting advances, pushing the role of the radiation oncologist to new frontiers. RESULTS: Innovations in imaging, treatment delivery, and a deeper understanding of biology has resulted in more tailored RT for individuals. In the present review, we summarise the changing landscape and broadly discuss new developments in prostate RT. CONCLUSIONS: Questions and challenges remain in the field, however there are multiple opportunities to further improve upon RT for our patients with prostate cancer.

Quantitative tumor heterogeneity MRI profiling improves machine learning-based prognostication in patients with metastatic colon cancer.

OBJECTIVES: Intra-tumor heterogeneity has been previously shown to be an independent predictor of patient survival. The goal of this study is to assess the role of quantitative MRI-based measures of intra-tumor heterogeneity as predictors of survival in patients with metastatic colorectal cancer. METHODS: In this IRB-approved retrospective study, we identified 55 patients with stage 4 colon cancer with known hepatic metastasis on MRI. Ninety-four metastatic hepatic lesions were identified on post-contrast images and manually volumetrically segmented. A heterogeneity phenotype vector was extracted from each lesion. Univariate regression analysis was used to assess the contribution of 110 extracted features to survival prediction. A random forest-based machine learning technique was applied to the feature vector and to the standard prognostic clinical and pathologic variables. The dataset was divided into a training and test set at a ratio of 4:1. ROC analysis and confusion matrix analysis were used to assess classification performance. RESULTS: Mean survival time was 39 ± 3.9 months for the study population. A total of 22 texture features were associated with patient survival (p < 0.05). The trained random forest machine learning model that included standard clinical and pathological prognostic variables resulted in an area under the ROC curve of 0.83. A model that adds imaging-based heterogeneity features to the clinical and pathological variables resulted in improved model performance for survival prediction with an AUC of 0.94. CONCLUSIONS: MRI-based texture features are associated with patient outcomes and improve the performance of standard clinical and pathological variables for predicting patient survival in metastatic colorectal cancer. KEY POINTS: • MRI-based tumor heterogeneity texture features are associated with patient survival outcomes. • MRI-based tumor texture features complement standard clinical and pathological variables for prognosis prediction in metastatic colorectal cancer. • Agglomerative hierarchical clustering shows that patient survival outcomes are associated with different MRI tumor profiles.

The trajectory of racial/ethnic disparities in the use of cancer screening before and during the COVID-19 pandemic: A large U.S. academic center analysis.

Cancer screening rates declined sharply early in the COVID-19 pandemic. The impact of the pandemic may have exacerbated existing disparities in cancer screening due to the disproportionate burden of illness and job loss among racial/ ethnic minorities, and potentially, uneven resumption of care between different racial/ ethnic groups. Using electronic health record data from Mass General Brigham (MGB), we assessed changes in rates of breast, cervical, colorectal and lung cancer screening before and during the pandemic. Among patients who received primary care in an MGB-affiliated primary care practice, cancer screening rates were calculated as the number of individuals who received a screening test for each cancer type over the number of individuals due for each test, during each month between April 2019-November 2020. We conducted an interrupted time-series analysis to test for changes in screening rates by race/ethnicity before and during the pandemic. Prior to the pandemic, relative to White individuals, Asian women were less likely to receive breast cancer screening (p < 0.001), and Latinx and Black individuals were less likely to screen for lung cancer (p < 0.001 and p = 0.02). Our results did not show significant improvement or worsening of racial/ethnic disparities for any cancer screening type as screening resumed. However, as of November 2020 rates of screening for breast cancer were lower than pre-pandemic levels for Latinx individuals, and lung cancer screening rates were higher than baseline for Latinx, Black or White individuals. Further monitoring of disparities in cancer screening is warranted as the pandemic evolves.

Increase of pseudoprogression and other treatment related effects in low-grade glioma patients treated with proton radiation and temozolomide.

INTRODUCTION: Concurrent radiotherapy and temozolomide (TMZ) is associated with radiographic pseudoprogression (PsP) in glioblastoma. The occurrence of PsP and other treatment effects is less well understood in low-grade gliomas (LGG). The purpose of this study is to evaluate whether the addition of TMZ to radiotherapy increases the incidence of PsP in adults with LGG treated with proton radiotherapy (PRT). METHODS: Chart review and volumetric MRI-analysis was performed on radiotherapy-naive adults with WHO grade II or IDH mutant WHO grade III gliomas treated with PRT between 2005 and 2015. Progression was defined by histology, new chemotherapy initiation, or progressive increase in lesion volume beyond 40% from baseline. Post treatment related effects (PTRE) were defined as new/increased T2/FLAIR or abnormal enhancement which eventually resolved or stabilized without evidence of progression for a period of 6-12 months. PsP was defined as the subset of PRTE suspicious for progression or volumetrically increased at least 40% from baseline. Pearson's chi-squared test and Cox-proportional hazards models were used for statistical analysis. RESULTS: There were 119 patients meeting inclusion criteria. There was an increased risk of PsP following PRT + TMZ versus PRT-alone (HR = 2.2, p = 0.006, on Cox univariate analysis). Presence of PsP was associated with improved OS (p = 0.02 with PsP as time-varying covariate). CONCLUSIONS: TMZ use, when added to PRT, was associated with increased PsP in patients with LGG; however, patients with PsP tended to achieve longer survival.

Quality of life in patients with proton-treated pediatric medulloblastoma: Results of a prospective assessment with 5-year follow-up.

BACKGROUND: To the authors' knowledge, health-related quality of life (HRQOL) outcomes are not well described in patients with medulloblastoma. The use of proton radiotherapy (RT) may translate into an improved HRQOL. In the current study, the authors report long-term HRQOL in patients with proton-treated pediatric medulloblastoma. METHODS: The current study was a prospective cohort HRQOL study of patients with medulloblastoma who were treated with proton RT and enrolled between August 5, 2002, and October 8, 2015. Both child report and parent-proxy report Pediatric Quality of Life Inventory (PedsQL) surveys were collected at baseline during RT and annually thereafter (score range on surveys of 0-100, with higher scores indicating better HRQOL). Patients were dichotomized by clinical/treatment variables and subgroups were compared. Mixed-model analysis was performed to determine the longitudinal trajectory of PedsQL scores. The Student t test was used to compare long-term HRQOL measures with published means from a healthy child population. RESULTS: Survey data were evaluable for 116 patients with a median follow-up of 5 years (range, 1-10.6 years); the median age at the time of diagnosis was 7.6 years (range, 2.1-18.1 years). At baseline, children reported a total core score (TCS) of 65.9, which increased by 1.8 points annually (P<.001); parents reported a TCS of 59.1, which increased by 2.0 points annually. Posterior fossa syndrome adversely affected baseline scores, but these scores significantly improved with time. At the time of last follow-up, children reported a TCS of 76.3, which was 3.3 points lower than that of healthy children (P = .09); parents reported a TCS of 69, which was 11.9 points lower than that of parents of healthy children (P<.001). Increased follow-up time from diagnosis correlated with improved HRQOL scores. CONCLUSIONS: HRQOL scores appear to increase over time after treatment in children treated with proton RT for medulloblastoma but remain lower compared with those of parent-proxy reports as well as published means from a healthy normative sample of children. Additional follow-up may translate into continued improvements in HRQOL. Cancer 2018. © 2018 American Cancer Society.

Comparison of outcomes for MR-guided versus CT-guided high-dose-rate interstitial brachytherapy in women with locally advanced carcinoma of the cervix.

OBJECTIVE: The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT). METHODS: 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005-2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®. RESULTS: Median follow-up time was 19.7months (MR group) and 18.4months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07-0.72) in a model with MR BT (HR 0.35, 95% CI 0.08-1.18). There was no difference in toxicities between CT and MR BT. CONCLUSION: In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent survival and toxicity rates.

Therapeutic radiation and the potential risk of second malignancies.

Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society.

Advances in the Management of Gastric and Gastroesophageal Cancers.

Management of gastric and gastroesophageal cancers is a complex, evolving paradigm. Involvement of multimodality specialties is the key. In gastric cancer, data are conflicting with regard to the specific roles of surgery, chemotherapy, and radiation, particularly between Asian and Western studies. However, current ongoing phase III trials will further elucidate the optimal treatment for this heterogeneous disease. For resectable gastroesophageal junction (GEJ) tumors, the publication of a landmark study in 2012 out of the Netherlands revealed a clear benefit in the utilization of trimodality therapy. This changed practice almost immediately around the world. In unresectable gastroesophageal disease, chemoradiation has been firmly established as a paradigm for treatment. The optimal chemotherapy regimen is still in flux. However, for both gastric and GEJ tumors, technological breakthroughs in genomics and pharmacologic targeting will soon provide physicians more options in the armamentarium to fight these diseases and, one day, individually personalize treatment.

miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction.

RNA interference (RNAi) technology using short hairpin RNAs (shRNAs) expressed via RNA polymerase (pol) III promoters has been widely exploited to modulate gene expression in a variety of mammalian cell types. For certain applications, such as lineage-specific knockdown, embedding targeting sequences into pol II-driven microRNA (miRNA) architecture is required. Here, using the potential therapeutic target BCL11A, we demonstrate that pol III-driven shRNAs lead to significantly increased knockdown but also increased cytotoxcity in comparison to pol II-driven miRNA adapted shRNAs (shRNA(miR)) in multiple hematopoietic cell lines. We show that the two expression systems yield mature guide strand sequences that differ by a 4 bp shift. This results in alternate seed sequences and consequently influences the efficacy of target gene knockdown. Incorporating a corresponding 4 bp shift into the guide strand of shRNA(miR)s resulted in improved knockdown efficiency of BCL11A. This was associated with a significant de-repression of the hemoglobin target of BCL11A, human γ-globin or the murine homolog Hbb-y. Our results suggest the requirement for optimization of shRNA sequences upon incorporation into a miRNA backbone. These findings have important implications in future design of shRNA(miR)s for RNAi-based therapy in hemoglobinopathies and other diseases requiring lineage-specific expression of gene silencing sequences.

Reawakening fetal hemoglobin: prospects for new therapies for the ß-globin disorders.

The level of fetal hemoglobin (HbF) modifies the severity of the common ß-globin disorders. Knowledge of the normal mechanisms that repress HbF in the adult stage has remained limited until recently despite nearly 3 decades of molecular investigation, in part because of imperfect model systems. Recent studies have provided new insights into the developmental regulation of globin genes and identified specific transcription factors and epigenetic regulators responsible for physiologic silencing of HbF. Most prominent among these regulators is BCL11A, a transcriptional repressor that inhibits adult-stage HbF expression. KLF1 and c-Myb are additional critical HbF-regulating erythroid transcription factors more broadly involved in erythroid gene expression programs. Chromatin modifiers, including histone deacetylases and DNA methyltransferases, also play key roles in orchestrating appropriate globin gene expression. Taken together, these discoveries present novel therapeutic targets for further consideration. Although substantial hurdles remain, opportunities are now rich for the rational design of HbF inducers.

Disparities in Penile Cancer Incidence, Mortality, and Place of Death Trends From 1999 to 2020.

INTRODUCTION: Penile cancer is rare in the United States (US); however, disparities have been found in the incidence, treatment, and outcomes of penile cancer. There is a need for evaluation of recent trends in penile cancer mortality, incidence, and place of death across all demographics. MATERIALS AND METHODS: Using the CDC WONDER database, penile cancer-specific mortality (PNCSM) trends in the US were evaluated from 1999 to 2020 by race/ethnicity, age group, census region, and place of death. Penile cancer incidence trends for the US from 1995 to 2019 were gathered from the NAACCR database. Average annual percent changes for mortality and incidence rates were determined using Joinpoint regression modeling. Univariable and multivariable logistic regression were used to evaluate independent predictors associated with place of death. RESULTS: From 1999 to 2020, 5833 people died from penile cancer in the US. Overall PNCSM increased by 1.8% per year from 1999-2020 (95% CI, 1.3%, 2.2%). Non-Hispanic White patients and Hispanic patients had increasing PNCSM rates from 1999-2020 (2.1 [95% CI, 1.5%, 2.7%]; 1.9 [95% CI, 1.0%, 2.8%], respectively). From the place of death analysis, Hispanic patients were at higher odds of dying at home or hospice when compared to non-Hispanic White patients (adjusted odds ratio [aOR] = 1.19, P = .045). Age-adjusted incidence rates for all stages of penile cancer increased significantly from 1995-2016 (AAPC, 0.7% [95% CI, 0.4%, 1.0%]), driven by regional and distant penile cancer incidence rates (AAPC 1995-2019, regional: 2.0% [95% CI, 1.7%, 2.4%]; AAPC 1995-2019, distant: 2.5% [95% CI, 1.8%, 3.1%]). CONCLUSION: The increasing penile cancer-specific mortality and incidence rates indicate the need for further improvements in screening, diagnosis, and treatment. Widespread efforts across all demographics are needed to ensure early detection of the disease.