Small Cell Lung Cancer: Emerging Targets and Strategies for Precision Therapy.

Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody-drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody-drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients.

Race/Ethnicity and Gender Representation in Hematology and Oncology Editorial Boards: What is the State of Diversity?

INTRODUCTION: Women and underrepresented groups in medicine hold few academic leadership positions in the field of hematology/oncology. In this study, we assessed gender and race/ethnicity representation in editorial board positions in hematology/oncology journals. MATERIALS AND METHODS: Editorial leadership board members from 60 major journals in hematology and oncology were reviewed; 54 journals were included in the final analysis. Gender and race/ethnicity were determined based on publicly available data for Editor-in-Chief (EiC) and Second-in-Command (SiC) (including deputy, senior, or associate editors). Descriptive statistics and chi-squared were estimated. In the second phase of the study, editors were emailed a 4-item survey to self-identify their demographics. RESULTS: Out of 793 editorial board members, 72.6% were men and 27.4% were women. Editorial leadership were non-Hispanic white (71.1%) with Asian editorial board members representing the second largest majority at 22.5%. Women comprised only 15.9% of the EiC positions (90% White and 10% Asian). Women were about half as likely to be in the EiC position compared with men [pOR 0.47 (95% CI, 0.23-0.95, P = .03)]. Women represented 28.3% of SiC editorial positions. Surgical oncology had the lowest female representation at 2.3%. CONCLUSION: Women and minorities are significantly underrepresented in leadership roles on Editorial Boards in hematology/oncology journals. Importantly, the representation of minority women physicians in EiC positions is at an inexorable zero.

Association of vitamin D receptor gene polymorphisms with breast cancer risk.

BACKGROUND: Recent literature suggests that vitamin D signaling has a protective effect against breast cancer risk. Thus, the aim of the present study was to find the association of vitamin D receptor (VDR) gene polymorphisms with breast cancer risk. MATERIALS AND METHODS: Fok1, Bsm1, Apa1, and Taq1 polymorphisms were performed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method, and Poly A polymorphism was carried out using PCR-SSCP in 140 breast cancer patients and 155 controls. RESULTS: Odds ratio was significantly higher in both homozygous variant genotypes (LL) of Poly A polymorphism of VDR (odds ratio [OR] = 5.42, 95% confidence interval [CI] = 1.19-23.31, P = 0.02) and heterozygous variant genotypes (SL) of Poly A polymorphism of VDR (OR = 3.89, 95% CI = 1.10-13.7, P = 0.03). Fok1, Bsm1, Apa1, and Taq1 polymorphisms of VDR gene were not significantly associated with breast cancer risk. CONCLUSION: Poly A polymorphism at the 3' untranslated region (UTR) of VDR gene was significantly associated with breast cancer risk in West Indian population.

Evidence to Date: Evaluating Pembrolizumab in the Treatment of Extensive-Stage Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) is an aggressive subtype of lung cancer characterized by a rapid initial response and early development of resistance to systemic therapy and radiation. The management of SCLC significantly changed for the first time in decades with the introduction of immune checkpoint inhibitors. Pembrolizumab, a humanized IgG4 isotype antibody, targets the programmed cell death protein 1 (PD-1) pathway to restore anti-tumor immunity. Prospective trials of pembrolizumab in patients with previously treated SCLC showed significant durability of responses. These results led to the U.S. Food and Drug Administration (FDA) granting pembrolizumab accelerated approval as second- or third-line monotherapy for patients with extensive-stage (ES) SCLC. In a recent clinical trial that included patients with previously untreated ES-SCLC, pembrolizumab in combination with platinum/etoposide met its progression-free survival endpoint, but overall survival (OS) did not cross the threshold for superiority. With the therapeutic landscape for SCLC rapidly evolving, we review prior experience and future directions of pembrolizumab in ES-SCLC.

The Matilda Effect: Underrecognition of Women in Hematology and Oncology Awards.

BACKGROUND: The proportion of women in the field of hematology and oncology (H&O) has increased over recent decades, but the representation of women in leadership positions remains poor. In an effort to close the gender gap in academia, it is important to report on such inequities in hopes to close these gaps and improve career development. MATERIALS AND METHODS: We conducted a retrospective, observational study of published award recipients from 1994 to 2019 from the seven major H&O societies in the world. Gender was determined based on publicly available data. The χ2 and Cochran-Armitage tests were used for data analysis. RESULTS: Of the 1,642 awardees over the past 26 years, 915 met inclusion criteria. Award recipients were overwhelmingly men (77.9%) and non-Hispanic White (84.7%). Women awardees received 30.3% of the humanistic and education-related awards, whereas only receiving 16.0% of basic science awards (p < .01). Women represent 35.6% of all hematologists and oncologists but only received 24.0% of awards given to these physicians (p = .004). Black, Hispanic, and Asian awardees represented 3.7%, 3.3%, and 6.8% of the total awardees, respectively. CONCLUSION: From 1994 to 2019, women were less likely to receive recognition awards from the seven major H&O societies studied compared with men. We also observed a considerably low proportion of minority awardees across all oncology subspecialties. Further studies examining how selection criteria favor either gender would be warranted in order to achieve equal representation in academic awards. IMPLICATIONS FOR PRACTICE: In this study, women and minority groups were found to be underrepresented amongst award recipients. Significant disparities were seen in disciplines that have been historically male predominant, such as basic sciences. As awards on an international level enhance academic resumes and assist with career advancement, it is important that awards are being given in an equitable manner. First steps to promote diversity and inclusion in academic medicine is reporting of gender and racial disparities in various areas of academia.

Stress, Resilience, and Coping of Healthcare Workers during the COVID-19 Pandemic.

OBJECTIVE: To estimate the health care workers (HCWs) self-reported stress, resilience, and coping during the COVID-19 pandemic, and to determine inter-professional differences. PARTICIPANTS AND METHODS: An email survey was sent to 474 HCW at a Midwestern HealthCare facility between April 9, 2020 and April 30, 2020. A total of 311 (65.6%) responses were received by May 31, 2020. The survey utilized 3 validated instruments: Perceived Stress Scale (PSS), Brief Resilience Scale (BRS), Brief Resilience Coping Scale (BRCS). RESULTS: Of the 311 responses, 302 were evaluated: 97 from nonmedical staff with patient contact (NMPC); 86 from nonmedical staff with no patient contact (NMNPC); 62 from medical doctors (MD), physician assistants (PA) and nurse practitioners (NP); and 57 from nurses. Significant differences were noted across job categories for stress and resilience, with nurses reporting highest PSS scores (effect estimates: -2.72, P = .009 for NMNPC; -2.50, P = .015 for NMPC; -3.21, P = .006 for MD/NP/PA respectively), and MD/NP/PA group with highest BRS scores: nurses (-0.31, P = .02); NMPC (-0.3333, P = .01); and NMNPC (-0.2828, P = .02). Younger personnel had higher stress (-1.59 per decade of age, P < .01) and more resilience (0.11 per decade of age, P = .002). CONCLUSION: These self-reported data indicate that MD/NP/PA had the highest resilience scores and the nurses had highest stress levels. Efforts are warranted to include all HCWs in systematic stress mitigating interventions with particular attention to understand specific factors contributing to stress for the nursing team.

Real-World Experiences With Yoga on Cancer-Related Symptoms in Women With Breast Cancer.

PURPOSE: Integrative therapies such as yoga are potential treatments for many psychological and physical symptoms that occur during and/or after treatment for cancer. The purpose of the current study was to evaluate the patient-perceived benefit of yoga for symptoms commonly experienced by breast cancer survivors. METHODS: 1,049 breast cancer survivors who had self-reported use of yoga on a follow up survey, in an ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR), received an additional mailed yoga-focused survey asking about the impact of yoga on a variety of symptoms. Differences between pre- and post- scores were assessed using Wilcoxon Signed Rank Test. RESULTS: 802/1,049 (76%) of women who were approached to participate, consented and returned the survey. 507/802 (63%) reported use of yoga during and/or after their cancer diagnosis. The vast majority of respondents (89.4%) reported some symptomatic benefit from yoga. The most common symptoms that prompted the use of yoga were breast/chest wall pain, lymphedema, and anxiety. Only 9% of patients reported that they had been referred to yoga by a medical professional. While the greatest symptom improvement was reported with breast/chest wall pain and anxiety, significant improvement was also perceived in joint pain, muscle pain, fatigue, headache, quality of life, hot flashes, nausea/vomiting, depression, insomnia, lymphedema, and peripheral neuropathy, (all p-values <0.004). CONCLUSION: Data supporting the use of yoga for symptom management after cancer are limited and typically focus on mental health. In this study, users of yoga often reported physical benefits as well as mental health benefits. Further prospective studies investigating the efficacy of yoga in survivorship are warranted.

Cardiovascular Health during and after Cancer Therapy.

Certain cancer treatments have been linked to specific cardiovascular toxicities, including (but not limited to) cardiomyopathy, atrial fibrillation, arterial hypertension, and myocarditis. Radiation, anthracyclines, human epidermal growth factor receptor 2 (Her2)-directed therapies, fluoropyrimidines, platinums, tyrosine kinase inhibitors and proteasome inhibitors, immune checkpoint inhibitors, and chimeric antigen-presenting (CAR)-T cell therapy can all cause cardiovascular side effects. Management of cardiovascular dysfunction that occurs during cancer therapy often requires temporary or permanent cessation of the risk-potentiating anti-neoplastic drug as well as optimization of medical management from a cardiovascular standpoint. Stem cell or bone marrow transplant recipients face unique cardiovascular challenges, as do patients at extremes of age.

Clinical significance of serum 25 hydroxyvitamin D in breast cancer: An Indian scenario.

Recent evidences suggest a protective mechanism of vitamin D signaling against breast cancer by the autocrine/paracrine manner and may modestly reduce the risk of breast cancer. Despite lots of sunshine, vitamin D deficiency is widespread in India. Moreover, there are limited studies from Indian population regarding circulatory 25(OH) D and breast cancer risk. Thus, the aim of the present study is to investigate circulatory 25(OH) D in relation to breast cancer risk and its association with various clinico-pathological parameters from Indian population. Total 297 subjects, comprising of 157 controls and 140 breast cancer patients were enrolled for the study. Circulatory 25(OH) D was analyzed by HPLC. Statistical analysis was carried out by SPSS software version 15. Further, subjects were categorized into severe, moderate, mild vitamin D deficiency and sufficiency. The prevalence of severe and moderate 25(OH) D deficiency was higher in breast cancer patients as compared to controls. Mean values of 25(OH) D were lower in breast cancer patients as compared to controls in mild, moderate and severe deficient groups (p = 0.07, p = 0.003 and p = 0.001). Moreover, 25(OH) D was significantly lower in postmenopausal breast cancer patients as compared to premenopausal breast cancer patients, particularly in severe deficient group. The levels of 25(OH) D were lower in ER and PR negative receptor status as compared to the positive receptor in severe deficient category (p = 0.06 and p = 0.09 respectively). Whereas, the mean values of 25(OH) D were lower in HER 2 negative receptor status as compared to positive receptor status in the moderate deficient category (p = 0.09). Further, severe deficient group showed significantly lower levels of 25(OH) Din TNBC as compared to luminal A subtype (p = 0.01). Thus, Results indicate that 25(OH) D deficiency might be associated with increased risk of breast cancer. Moreover, severe 25(OH) D deficiency is associated with aggressive behavior of breast cancer.

Osimertinib-Induced Cardiomyopathy.

Osimertinib is the preferred treatment in patients with metastatic non-small cell lung cancer with epidermal growth factor receptor mutations. We report a case series of acute cardiomyopathy with heart failure exacerbation during osimertinib treatment. We suggest that cardiotoxicity from osimertinib is reversible and occurs at a dose of 80 mg/day. (Level of Difficulty: Intermediate.).

Recent candidate molecular markers: vitamin D signaling and apoptosis specific regulator of p53 (ASPP) in breast cancer.

Regardless of advances in treatment modalities with the invention of newer therapies, breast cancer remains a major health problem with respect to its diagnosis, treatment and management. This female malignancy with its tremendous heterogeneous nature is linked to high incidence and mortality rates, especially in developing region of the world. It is the malignancy composed of distinct biological subtypes with diverse clinical, pathological, molecular and genetic features as well as different therapeutic responsiveness and outcomes. This inconsistency can be partially overcome by finding novel molecular markers with biological significance. In recent years, newer technologies help us to indentify distinct biomarkers and increase our understanding of the molecular basis of breast cancer. However, certain issues need to be resolved that limit the application of gene expression profiling to current clinical practice. Despite the complex nature of gene expression patterns of cDNAs in microarrays, there are some innovative regulatory molecules and functional pathways that allow us to predict breast cancer behavior in the clinic and provide new targets for breast cancer treatment. This review describes the landscape of different molecular markers with particular spotlight on vitamin D signaling pathway and apoptotic specific protein of p53 (ASPP) family members in breast cancer.