Correction: Hamilton et al. Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer. Int. J. Mol. Sci. 2017, 18, 2305.

In the original publication [...].

Association of Parental Status and Gender With Burden of Multidisciplinary Tumor Boards Among Oncology Physicians.

Importance: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited. Objective: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians. Design, Setting, and Participants: Tumor board burden was assessed by a cross-sectional convenience survey posted on social media and by email to Cedars-Sinai Medical Center cancer physicians between March 3 and April 3, 2022. Tumor board start times were independently collected by email from 22 top cancer centers. Main Outcomes and Measures: Tumor board burden was measured on a 4-point scale (1, not at all burdensome; 2, slightly burdensome; 3, moderately burdensome; and 4, very burdensome). Univariable and multivariable probabilistic index (PI) models were performed. Results: Surveys were completed by 111 physicians (median age, 42 years [IQR, 36-50 years]; 58 women [52.3%]; 60 non-Hispanic White [54.1%]). On multivariable analysis, factors associated with higher probability of tumor board burden included radiology or pathology specialty (PI, 0.68; 95% CI, 0.54-0.79; P = .02), attending 3 or more hours per week of tumor boards (PI, 0.68; 95% CI, 0.58-0.76; P < .001), and having 2 or more children (PI, 0.65; 95% CI, 0.52-0.77; P = .03). Early or late tumor boards (before 8 am or at 5 pm or after) were considered very burdensome by 33 respondents (29.7%). Parents frequently reported a negative burden on childcare (43 of 77 [55.8%]) and family dynamics (49 of 77 [63.6%]). On multivariable analysis, a higher level of burden from early or late tumor boards was independently associated with identifying as a woman (PI, 0.69; 95% CI, 0.57-0.78; P = .003) and having children (PI, 0.75; 95% CI, 0.62-0.84; P < .001). Independent assessment of 358 tumor boards from 22 institutions revealed the most common start time was before 8 am (88 [24.6%]). Conclusions and Relevance: This survey study of tumor board burden suggests that identifying as a woman or parent was independently associated with a higher level of burden from early or late tumor boards. The burden of early or late tumor boards on childcare and family dynamics was commonly reported by parents. Having 2 or more children, attending 3 or more hours per week of tumor boards, and radiology or pathology specialty were associated with a significantly higher tumor board burden overall. Future strategies should aim to decrease the disparate burden on parents and women.

Diazaborine-Mediated Bicyclization of Native Peptides with Inducible Reversibility.

Multicyclic peptides are appealing candidates for peptide-based drug discovery. While various methods are developed for peptide cyclization, few allow multicyclization of native peptides. Herein we report a novel cross-linker DCA-RMR1, which elicits facile bicyclization of native peptides via N-terminus Cys-Cys cross-linking. The bicyclization is fast, affords quantitative conversion, and tolerates various side chain functionalities. Importantly, the resulting diazaborine linkage, while stable at a neutral pH, can readily reverse upon mild acidification to give pH-responsive peptides.

Ablative Radiotherapy as a Strategy to Overcome TKI Resistance in EGFR-Mutated NSCLC.

Tyrosine kinase inhibitor (TKI) therapy is the recommended first-line treatment for metastatic non-small-cell lung cancer (NSCLC) positive for epidermal growth factor receptor (EGFR) gene mutation. However, most individuals treated with TKI therapy for EGFR-mutant NSCLC will develop tumor resistance to TKI therapy. Therapeutic strategies to overcome TKI resistance are the topic of several ongoing clinical trials. One potential strategy, which has been explored in numerous trials, is the treatment of progressive sites of disease with stereotactic body radiation treatment (SBRT) or stereotactic radiosurgery (SRS). We sought to review the literature pertaining to the use of local ablative radiation therapy in the setting of acquired resistance to TKI therapy and to discuss stereotactic radiation therapy as a strategy to overcome TKI resistance.

Overcoming Resistance to Immunotherapy in Head and Neck Cancer Using Radiation: A Review.

Radiation therapy remains at the center of head and neck cancer treatment. With improvements in treatment delivery, radiation therapy has become an affective ablative modality for head and neck cancers. Immune checkpoint inhibitors are now also playing a more active role both in the locally advanced and metastatic setting. With improved systemic options, local noninvasive modalities including radiation therapy are playing a critical role in overcoming resistance in head and neck cancer. The aim of this review is to describe the role of radiation therapy in modulating the tumor microenvironment and how radiation dose, fractionation and treatment field can impact the immune system and potentially effect outcomes when combined with immunotherapy. The review will encompass several common scenarios where radiation is used to improve outcomes and overcome potential resistance that may develop with immunotherapy in head and neck squamous cell carcinoma (HNSCC), including upfront locally advanced disease receiving definitive radiation and recurrent disease undergoing re-irradiation. Lastly, we will review the potential toxicities of combined therapy and future directions of their role in the management of HNSCC.

Disparate outcomes in nonsmall cell lung cancer by immigration status.

OBJECTIVE: The purpose of this study was to evaluate overall survival (OS) outcomes by race, stratified by country of origin in patients diagnosed with NSCLC in California. METHODS: We performed a retrospective analysis of nonsmall cell lung cancer (NSCLC) patients diagnosed between 2000 and 2012. Race/ethnicity was defined as White (W), Black (B), Hispanic (H), and Asian (A) and stratified by country of origin (US vs. non-US [NUS]) creating the following patient cohorts: W-US, W-NUS, B-US, B-NUS, H-US, H-NUS, A-US, and A-NUS. Three multivariate models were created: model 1 adjusted for age, gender, stage, year of diagnosis and histology; model 2 included model 1 plus treatment modalities; and model 3 included model 2 with the addition of socioeconomic status, marital status, and insurance. RESULTS: A total of 68,232 patients were included. Median OS from highest to lowest were: A-NUS (15 months), W-NUS (14 months), A-US (13 months), B-NUS (13 months), H-US (11 months), W-US (11 months), H-NUS (10 months), and B-US (10 months) (p < 0.001). In model 1, B-US had worse OS, whereas A-US, W-NUS, B-NUS, H-NUS, and A-NUS had better OS when compared to W-US. In model 2 after adjusting for receipt of treatment, there was no difference in OS for B-US when compared to W-US. After adjusting for all variables (model 3), all race/ethnicity profiles had better OS when compared to W-US; B-NUS patients had similar OS to W-US. CONCLUSION: Foreign-born patients with NSCLC have decreased risk of mortality when compared to native-born patients in California after accounting for treatments received and socioeconomic differences.

Narrative review of immunotherapy and radiation therapy in elderly patients.

Cancer is primarily a disease of the elderly, but there is a disproportionate lack of data from clinical trials in this population. Oncologists tend to underdiagnose and undertreat geriatric patients with cancer, leading to poor survival outcomes. New therapies or therapeutic combinations such as immunotherapy and stereotactic body radiation therapy (SBRT) can be used in the elderly for better tumor control and survival, with fewer toxicities. The aim of this review is to describe the synergistic effects of immunotherapy and radiation therapy (RT) and to discuss the use of these therapies concurrently and/or sequentially in the elderly. To gain a fuller picture of their elderly patient's health, physicians may also consider incorporating a comprehensive geriatric assessment (CGA) to evaluate their functional capacity, cognition, physical and mental health, and social supports which we will discuss in this review. It is recommended that oncologists use geriatric assessments in their everyday practice to have better insight on their complex elderly patients, therefore providing them a higher quality of care. They should also be incorporated in clinical trials as a way to assess and include more elderly patients in the study. Ultimately, the elderly deserve to be treated with more than their chronological age in mind, and new combination therapies and use of a geriatric assessment can help achieve that.

Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) occurs in 10-15% of all breast cancer patients, yet it accounts for about half of all breast cancer deaths. There is an urgent need to identify new antitumor targets to provide additional treatment options for patients afflicted with this aggressive disease. Preclinical evidence suggests a critical role for insulin-like growth factor-2 (IGF2) and androgen receptor (AR) in regulating TNBC progression. To advance this work, a panel of TNBC cell lines was investigated with all cell lines showing significant expression of IGF2. Treatment with IGF2 stimulated cell proliferation in vitro (p < 0.05). Importantly, combination treatments with IGF1R inhibitors BMS-754807 and NVP-AEW541 elicited significant inhibition of TNBC cell proliferation (p < 0.001). Based on Annexin-V binding assays, BMS-754807, NVP-AEW541 and enzalutamide induced TNBC cell death (p < 0.005). Additionally, combination of enzalutamide with BMS-754807 or NVP-AEW541 exerted significant reductions in TNBC proliferation even in cells with low AR expression (p < 0.001). Notably, NVP-AEW541 and BMS-754807 reduced AR levels in BT549 TNBC cells. These results provide evidence that IGF2 promotes TNBC cell viability and proliferation, while inhibition of IGF1R/IR and AR pathways contribute to blockade of TNBC proliferation and promotion of apoptosis in vitro.