Gender and the Receipt of the Association of Residents in Radiation Oncology Educator of the Year Award.

Purpose: We hypothesized that there may be a gender disparity in the receipt of the Association of Residents in Radiation Oncology (ARRO) Educator of the Year Award and sought to elucidate factors that contribute to differences in award receipt. Methods and Materials: Using a database provided by the American Society for Radiation Oncology, award recipients were identified from 2010 to 2022. Publicly available websites were accessed to obtain data regarding gender, years since residency graduation, percentage of female faculty, size of residency program, and program director designation. A 1-sample Z-test was used to assess whether the proportion of female ARRO award winners, defined as the proportion of female radiation oncology faculty members in the nominating universities that year, was significantly less than the population average. Secondary analyses used univariable binary logistic regression to identify global associations between gender, year since gradation, or program size. Results: The lowest proportion of female awardees occurred in 2013 (14.3%) and the greatest proportion in 2022 (30.6%). Compared with the proportion of female faculty members in nominating programs for the respective year, there were significantly fewer female awardees in 2010 (18% female awardees vs 32% female faculty members; P = .02) and 2013 (14% female awardees vs 31% female faculty members; P = .01). There was a statistically significant increase in female awardees during the study period (P < .01). On logistic regression analysis, large program size (≥10 residents) (odds ratio [OR], 6.86; 95% CI, 2.71-23.1; P < .001) and medium program size (5-9 residents) (OR, 4.05; 95% CI, 1.60-13.7; P < .001) were associated with a greater proportion of female awardees compared with small program size (1-4 residents). There was no association between awardee gender and years since graduation. Conclusions: A gender disparity was present in the receipt of ARRO Educator Awards. Residency chiefs, program directors, and chairs should work to ensure that a diverse slate of faculty is considered annually for the ARRO Educator Award.

VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.

Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated hypoxia signaling and a tumor microenvironment (TME) highly enriched in myeloid and lymphoid cells. Loss of the von Hippel Lindau (VHL) gene is a critical early event in ccRCC pathogenesis and promotes stabilization of HIF. Whether VHL loss in cancer cells affects immune cells in the TME remains unclear. Using Vhl WT and Vhl-KO in vivo murine kidney cancer Renca models, we found that Vhl-KO tumors were more infiltrated by immune cells. Tumor-associated macrophages (TAMs) from Vhl-deficient tumors demonstrated enhanced in vivo glucose consumption, phagocytosis, and inflammatory transcriptional signatures, whereas lymphocytes from Vhl-KO tumors showed reduced activation and a lower response to anti-programmed cell death 1 (anti-PD-1) therapy in vivo. The chemokine CX3CL1 was highly expressed in human ccRCC tumors and was associated with Vhl deficiency. Deletion of Cx3cl1 in cancer cells decreased myeloid cell infiltration associated with Vhl loss to provide a mechanism by which Vhl loss may have contributed to the altered immune landscape. Here, we identify cancer cell-specific genetic features that drove environmental reprogramming and shaped the tumor immune landscape, with therapeutic implications for the treatment of ccRCC.

Tumor volume reduction evaluated by cone beam computed tomography during stereotactic body radiotherapy for early stage non-small cell lung cancer.

BACKGROUND: We hypothesized that significant tumor volume reduction (TVR) occurs over the course of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC), and that TVR correlates with clinical outcomes. METHODS: We conducted a retrospective review of patients treated with SBRT for early stage NSCLC across two academic centers. For each patient, we contoured the tumor volume (TV) on cone beam computed tomography (CBCT) images obtained before each treatment fraction. We then calculated TVR based on the TV from the first and last days of treatment. We used log-rank tests to quantify differences in overall survival (OS), progression-free survival (PFS) and recurrence based on TVR. RESULTS: Data from 69 patients and a total of 73 treated tumors were analyzed. The median follow-up for survivors was 51.8 months (range, 6.9 to 80.0 months). The median TVR for the cohort was 10.1% (range, -5.7% to 43.5%). There was no significant difference in either OS (median 33.4 vs. 29.1 months, P=0.79) or PFS (median 26.3 vs. 12.3 months, P=0.43) for those with high TVRs (≥10.1%) vs. low TVRs (<10.1%), respectively. There was a trend toward superior 2-year PFS in the high TVR group (52.2% vs. 36.7%, P=0.062), but this effect diminished on longer follow-up (4-year PFS 31.9% vs. 26.7%, P=0.15). No associations were observed between TVR and local, regional or distant recurrence. CONCLUSIONS: We were not able to demonstrate that TVR is a reliable predictive imaging marker for stage I/II NSCLC treated with SBRT. Future studies with larger sample sizes are needed to clarify a potential relationship between TVR and early outcomes.

Clinical significance of pretreatment tumor growth rate for locally advanced non-small cell lung cancer.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) may exhibit significant tumor growth before the initiation of definitive chemoradiation therapy (CRT). We thus investigated the prognostic value of pretreatment tumor growth rate as measured by specific growth rate (SGR). METHODS: We conducted a retrospective review of 42 patients with locally advanced NSCLC treated with definitive concurrent CRT. For each patient, we contoured the primary gross tumor volume (GTV) on the pretreatment diagnostic chest computed tomography (CT) scan and the radiation therapy (RT) planning CT scan. We then calculated SGR based on the primary GTV from each scan and the time interval between scans. We used log-rank tests and univariate Cox regression models to quantify differences in progression-free survival (PFS), overall survival (OS) and recurrence based on SGR. RESULTS: We divided patients into two groups for analysis: those with an SGR greater than or equal to the upper tercile value of 0.94%/day (high SGR) and those with SGR less than 0.94%/day (low SGR). Patients with high SGRs versus low SGRs experienced inferior PFS (median, 5.6 vs. 13.6 months, P=0.016), without a significant difference in OS. The inferior PFS in the high SGR group persisted on multivariate analysis [adjusted hazard ratio (HR) 2.37, 95% confidence interval (CI): 1.07-5.25, P=0.034]. The risk of distant recurrence was higher in the high SGR group (HR 2.62, 95% CI: 1.08-6.38, P=0.033), but there was no difference in the risk of locoregional recurrence between groups. CONCLUSIONS: Pretreatment SGR was associated with inferior PFS and distant control among patients with locally advanced NSCLC treated with concurrent CRT. Further studies in larger populations may aid in elucidating optimal SGR cut-off points for risk stratification.

BCCIP suppresses tumor initiation but is required for tumor progression.

Dysfunctions of genome caretaker genes contribute to genomic instability and tumor initiation. Because many of the caretaker genes are also essential for cell viability, permanent loss of function of these genes would prohibit further tumor progression. How essential caretaker genes contribute to tumorigenesis is not fully understood. Here, we report a "hit-and-run" mode of action for an essential caretaker gene in tumorigenesis. Using a BRCA2-interacting protein BCCIP as the platform, we found that a conditional BCCIP knockdown and concomitant p53 deletion caused rapid development of medulloblastomas, which bear a wide spectrum of alterations involving the Sonic Hedgehog (Shh) pathway, consistent with a caretaker responsibility of BCCIP on genomic integrity. Surprisingly, the progressed tumors have spontaneously lost the transgenic BCCIP knockdown cassette and restored BCCIP expression. Thus, a transient downregulation of BCCIP, but not necessarily a permanent mutation, is sufficient to initiate tumorigenesis. After the malignant transformation has been accomplished and autonomous cancer growth has been established, BCCIP reverses its role from a tumor-initiation suppressor to become a requisite for progression. This exemplifies a new type of tumor suppressor, which is distinct from the classical tumor suppressors that are often permanently abrogated during tumorigenesis. It has major implications on how a nonmutagenic or transient regulation of essential caretaker gene contributes to tumorigenesis. We further suggest that BCCIP represents a paradoxical class of modulators for tumorigenesis as a suppressor for initiation but a requisite for progression (SIRP).