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Simple Summary: Talimogene laherparepvec (TVEC), a modified virus, is a local injected therapy that has been demonstrated to be an effective treatment in patients with advanced melanoma. Recent reports have suggested that radiation treatment (RT) may activate the immune system when combined with TVEC to further improve both local and systemic responses. However, studies on the combined effect of TVEC and RT remain limited. Here, we reviewed twenty melanoma patients who had received TVEC and RT (fourteen patients to the same region and six patients to different regions of the body) and found a benefit in progression-free survival (PFS) and time to distance metastasis (DM) with a combined regional approach of TVEC and RT. These results suggest that the regional approach of using these two treatment modalities may confer a therapeutic benefit. Talimogene laherparepvec (TVEC) is a genetically modified oncolytic herpes simplex virus (HSV-1) that is used for the intralesional treatment of advanced or metastatic melanoma. Given that TVEC produces the granulocyte–macrophage colony-stimulating factor (GM-CSF), recent reports have suggested that radiation treatment (RT) given in conjunction with TVEC may provide synergistic immune activation at the site, and possibly systemically. However, studies on combining RT with TVEC remain limited. We conducted a retrospective review of melanoma patients from a single cancer center who received TVEC and RT in the same region of the body and compared them to patients who received TVEC with RT at another site (other than the site of TVEC injection). Between January 2015 and September 2022, we identified twenty patients who were treated with TVEC and RT; fourteen patients received TVEC and RT in the same region, and six had treatments in separate regions. Regions were determined at the time of analysis and were based on anatomic sites (such as arm, leg, torso, etc.). Kaplan–Meier analysis of progression-free survival (PFS), analyses of time to distant metastasis (DM), overall survival (OS), and locoregional control (LRC), and the corresponding log-rank test were performed. With a median follow-up of 10.5 months [mos] (range 1.0–58.7 mos), we found an improvement in PFS with TVEC and RT in the same region compared to different regions, which were 6.4 mos (95% CI, 2.4–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively; p = 0.005. There was also a significant improvement in DM when TVEC and RT were used in the same region compared to different regions: 13.8 mos (95% CI, 4.6–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively (p = 0.001). However, we found no difference in overall survival (OS) between patients who had TVEC and RT in the same region (19.0 mos, 95% confidence interval [CI], 4.1–not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0–NR mos); p = 0.366. There was no statistically significant improvement in locoregional control (LRC) in patients who had TVEC and RT in the same region was 26.0 mos (95% CI, 6.4–26.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7–NR mos) (p = 0.115). No grade 3 or higher toxicities were documented in either group. Overall, there were improvements in PFS and DM when TVEC and RT were delivered to the same region of the body compared to when they were used in different regions. However, we did not find a significant difference in locoregional recurrence or OS. Future studies are needed to assess the sequence and timing of combining RT and TVEC to potentially enhance the immune response both locally and distantly. [ABSTRACT FROM AUTHOR]

Brachytherapy is a critical component of the standard-of-care curative radiotherapy regimen for women with locally advanced cervical cancer (LACC). However, existing literature suggests that many patients will not receive the brachytherapy boost. We used machine learning (ML) and explainable artificial intelligence to characterize this disparity. Patients with LACC diagnosed from 2004 to 2020 who received definitive radiation were identified in the National Cancer Database. Five ML models were trained to predict if a patient received a brachytherapy boost. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To identify trends that may be attributable to the coronavirus disease 2019 (COVID-19) pandemic, the previous analysis was repeated and limited to 2019 to 2020. A total of 37,564 patients with LACC were identified; 5799 were diagnosed from 2019 to 2020 (COVID cohort). Of these patients, 59.3% received a brachytherapy boost, with 76.4% of patients diagnosed in 2019 to 2020 receiving a boost. The random forest model achieved the best performance for both the overall and COVID cohorts. In the overall cohort, the most important predictive features were the year of diagnosis, stage, age, and insurance status. In the COVID cohort, the most important predictive features were FIGO stage, age, insurance status, and hospital type. Of the 26 patients who tested positive for COVID-19 during their course of radiotherapy, 19 (73.1%) received a brachytherapy boost. A gradual increase in brachytherapy boost utilization has been noted, which did not seem to be significantly impacted by the onset of the COVID-19 pandemic. ML could be considered to identify patient populations where brachytherapy is underutilized, which can provide actionable feedback for improving access. [ABSTRACT FROM AUTHOR]

Dosimetric predictors of toxicity in patients treated with definitive chemoradiation for locally advanced non-small cell lung cancer are often identified through trial and error. This study used machine learning (ML) and explainable artificial intelligence to empirically characterize dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. A secondary analysis of the Radiation Therapy Oncology Group (RTOG) 0617 trial was performed. Multiple ML models were trained to predict grade ≥3 pulmonary, cardiac, and esophageal toxicities using clinical and dosimetric features. Model performance was evaluated using the area under the curve (AUC). The best performing model for each toxicity was explained using the Shapley Additive Explanation (SHAP) framework; SHAP values were used to identify relevant dosimetric thresholds and were converted to odds ratios (ORs) with confidence intervals (CIs) generated using bootstrapping to obtain quantitative measures of risk. Thresholds were validated using logistic regression. The best-performing models for pulmonary, cardiac, and esophageal toxicities, outperforming logistic regression, were extreme gradient boosting (AUC, 0.739), random forest (AUC, 0.706), and naive Bayes (AUC, 0.721), respectively. For pulmonary toxicity, thresholds of a mean dose >18 Gy (OR, 2.467; 95% CI, 1.049-5.800; P =.038) and lung volume receiving ≥20 Gy (V20) > 37% (OR, 2.722; 95% CI, 1.034-7.163; P =.043) were identified. For esophageal toxicity, thresholds of a mean dose >34 Gy (OR, 4.006; 95% CI, 2.183-7.354; P <.001) and V20 > 37% (OR, 3.725; 95% CI, 1.308-10.603; P =.014) were identified. No significant thresholds were identified for cardiac toxicity. In this data set, ML approaches validated known dosimetric thresholds and outperformed logistic regression at predicting toxicity. Furthermore, using explainable artificial intelligence, clinically useful dosimetric thresholds might be identified and subsequently externally validated. [ABSTRACT FROM AUTHOR]

In select cases of locally advanced cervical cancer, a hybrid brachytherapy (HBT) approach consisting of a combined intracavitary (IC)/insterstitial (IS) implant can yield improved target coverage and/or decreased organ at risk dose compared to IC techniques while limiting invasiveness compared to IS techniques. The technique involves placement of transvaginal and/or perineal needles in addition to the tandem and ring/ovoids using either a specialized applicator or free-hand placement. Following applicator and needle placement, brachytherapy may then be planned using principles similar to IC or IS techniques. During treatment planning, it can be helpful to obtain both MRI and CT imaging, as plastic MRI-compatible needles do not show up well on MRI. In patients where acceptable target coverage cannot be achieved using IC alone or doses to nearby OAR are too high, HBT should be evaluated. HBT can improve both dose to target and OAR while sparing patients the morbidity of perineal template-based interstitial brachytherapy. Specific scenarios where HBT may be preferred include bulky residual primary tumor especially with poor response to EBRT, extension into the lateral parametrium, vaginal extension of tumor, and an asymmetric target. Use of HBT can typically permit extension of dose coverage by an additional 1–2 cm beyond what can be achieved with an IC alone technique. HBT allows for improved therapeutic ratio by improving target volume coverage and/or lowering doses to OARs. Brachytherapists should be trained on the practical aspects of administering HBT to be able to offer a less invasive and impactful treatment option when appropriate. [ABSTRACT FROM AUTHOR]

Simple Summary: Magnetic resonance-guided radiotherapy (MRgRT) is an emerging radiotherapy technology combining real-time magnetic resonance imaging and radiation delivery. By administering radiation with a linear accelerator with built in low-field or high-field MRI, practitioners have a greater ability to align to the target for daily set-up, precisely track the motion of and thereby target or avoid tissues and adapt to inter-treatment daily changes. This decreased uncertainty has implications for facilitating smaller, less-toxic treatment margins, potentially allowing delivery of higher dose radiotherapy that will lead to better control of tumors. The technology has already found success in treating breast, prostate, pancreatic, liver, lung, and limited metastatic cancers, in addition to non-oncologic indications such as cardiac ablation. The present narrative review aims to describe the current and future state of MRgRT technology and research. Magnetic resonance-guided radiotherapy (MRgRT) represents a promising new image guidance technology for radiation treatment delivery combining an onboard MRI scanner with radiation delivery technology. By enabling real-time low-field or high-field MRI acquisition, it facilitates improved soft tissue delineation, adaptive treatment, and motion management. Now that MRgRT has been available for nearly a decade, research has shown the technology can be used to effectively shrink treatment margins to either decrease toxicity (in breast, prostate cancer, and pancreatic cancer) or facilitate dose-escalation and improved oncologic outcomes (in pancreatic and liver cancer), as well as enabling indications that require clear soft tissue delineation and gating (lung and cardiac ablation). In doing so, the use of MRgRT has the potential to significantly improve the outcomes and quality of life of the patients it treats. The present narrative review aims to describe the rationale for MRgRT, the current and forthcoming state of technology, existing studies, and future directions for the advancement of MRgRT, including associated challenges. [ABSTRACT FROM AUTHOR]

Simple Summary: Bridging therapy (BT) in the form of systemic therapy (ST), radiation therapy (RT), or combined-modality therapy (CMT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). Prior institutional experiences with BT, and RT in particular, suggest it does not lead to increased toxicity or compromise outcomes. Further investigation of the optimal use of BT is warranted. In this research, we sought to evaluate the impact of BT in a large institutional cohort of patients who received commercial CAR T-cell therapy for LBCL, specifically examining the effect of BT modality and disease burden on outcomes. Here, we report the long-term outcomes of our CAR T cohort. The patients with limited disease treated with RT had favorable outcomes. Prospective studies are warranted to better characterize the optimal management of patients with relapsed/refractory LBCL who are planning to undergo CAR T-cell therapy to optimize treatment. Background: Bridging therapy (BT) with systemic therapy (ST), radiation therapy (RT), or combined-modality therapy (CMT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). We report the long-term outcomes of the patients who received commercial CAR T-cell therapy with or without BT. Methods: The patients with LBCL who underwent infusion of a commercial CD19 CAR T product were eligible. The radiation was stratified as comprehensive or focal. The efficacy outcomes and toxicity were analyzed. Results: In total, 156 patients were included and, of them, 52.5% of the patients received BT. The median progression-free survival (PFS) was 0.65 years in the BT cohort compared to 1.45 years in the non-BT cohort. The median overall survival (OS) was 3.16 years in the BT cohort and was not reached in the non-BT cohort. The patients who received comprehensive radiation (versus focal) had significantly improved PFS and OS, achieving a 1-year PFS of 100% vs. 9.1% and 1-year OS of 100% vs. 45.5%. There was no difference in the severe toxicity between any of the nonbridging or BT cohorts. Conclusions: BT did not appear to compromise outcomes with respect to response rates, disease control, survival, and toxicity. The patients with limited disease treated with RT had favorable outcomes. [ABSTRACT FROM AUTHOR]

Purpose: External beam radiation therapy (EBRT) to oligometastases may improve outcomes in patients with oligometastatic hormone-sensitive prostate cancer (oHSPC). Follow-up on this cohort has been limited to <5 years and prospective data on de novo patients with oHSPC are lacking. We reviewed the long-term outcomes of patients with oHSPC treated with EBRT and androgen deprivation therapy on a prospective trial.Methods and Materials: From 2006 to 2011, patients with oHSPC with 1 to 5 metastases received 36 weeks of androgen deprivation therapy (luteinizing hormone-releasing hormone agonist + bicalutamide) and up to 53 Gy to all visible metastases. When indicated, the primary tumor or prostate bed was treated with EBRT up to 78 or 66 Gy, respectively.Results: Twenty-nine patients were treated: 15 de novo, 14 oligorecurrent, and 21 patients (72.4%) had bone metastases. Median number of metastases per patient was 1 (range, 1-5). EBRT was administered to 52 lesions (38 bone, 12 pelvic lymph nodes [LNs], 2 nonpelvic LNs) up to 53 Gy (range, 47-66). Median follow-up was 9.9 years (years; range, 0.2-14.4). Median overall survival was 9.7 years (95% confidence interval [CI], 5.8-not reached). Median progression-free survival was 1.9 years (95% CI, 1.6-2.2). Patients who presented with prostate cancer-defined de novo metastases had significantly improved (P = .04) median progression-free survival (2.0 years; 95% CI, 1.3-6.0) compared with oligorecurrent patients (1.8 years; 95% CI, 1.0-2.0). Patients who presented with LN-only metastases had numerically improved (P = .13) median PFS (5.8 years; 95% CI, 1.2-not reached) compared with patients with bony metastases (1.8 years; 95% CI, 1.3-2.0). At last follow-up, 17 patients (58.6%) had local control of all EBRT-treated metastases. The metastases that locally progressed had previously been controlled for median 3.5 years (range, 1.7-10.5).Conclusions: Our results compare favorably with other reported studies of patients with oHSPC and provide new insights into their long-term outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Based on recent clinical trials, radiation is a standard treatment option for limited metastatic sites in metastatic breast cancer, with the potential to improve survival. This is typically given in the form of high-dose radiation called stereotactic body radiotherapy (SBRT). However, SBRT is a newer technology that is not on option for all patients and does not have long-term follow-up. Prior to the widespread implementation of SBRT, we performed a clinical trial utilizing high-dose chemotherapy and standard radiation for metastases in patients with limited metastatic breast cancer. In this research, we analyzed the long-term outcomes of these patients. We found that, despite not using SBRT, radiation provided promising long-term disease control and survival. Therefore, conventional radiation might still be considered if SBRT in not an option for a patient, and our results also help suggest what long-term outcomes of SBRT treatment might look like. Background: Patients with oligometastatic breast cancer (oMBC) may benefit from aggressive local therapy. We sought to assess the effects of consolidative radiation therapy (RT) on outcomes in oMBC patients treated on a prospective phase II trial of high-dose chemotherapy (HDCT). Methods: Between 2005 and 2009, 12 patients with oMBC (≤3 metastatic sites) cancer were treated on protocol. Patients were to receive tandem HDCT supported by hematopoietic cell rescue (HCR). All radiographically identifiable oligometastatic sites received targeted radiation. Results: HDCT was initiated at a median of 6.7 (3.5–12.7) months after diagnosis of oMBC. Hormone receptors (HR) were positive in 91.6% of patients, and HER2 was overexpressed in 25% of patients. Median radiation dose (EQD2) was 41.2 (37.9–48.7) Gy. Median follow-up was 13.1 (6.8–15.1) years for living patients. Ten-year PFS and OS were 33% (95%CI, 10–59%) and 55% (95%CI, 22–79%), respectively. Durable local control of treated lesions was 87.5%. At the last follow up, two patients remained progression free and two more were without evidence of disease following additional salvage treatment. Conclusions: Although modern systemic therapies have obviated the use of HDC, aggressive local therapy warrants further evaluation and fractionated radiotherapy is a viable alternative if SBRT is not available. [ABSTRACT FROM AUTHOR]

• There is interest in identifying patients who would benefit from PORT. • Using machine learning, nodal thresholds can be found to predict benefit from PORT. • A positive LNC of ≥3 and a LNR of ≥0.34 are prognostic and predictive. • In all-comers, on multivariable analysis, PORT does not confer an OS benefit. • When limited to patients who meet the nodal thresholds, PORT confers an OS benefit. The role of post-operative radiotherapy (PORT) for completely resected N2 non-small-cell lung cancer (NSCLC) is controversial in light of recent randomized data. We sought to utilize machine learning to identify a subset of patients who may still benefit from PORT based on extent of nodal involvement. Patients with completely resected N2 NSCLC were identified in the National Cancer Database. We trained a machine-learning based model of overall survival (OS). SHapley Additive exPlanation (SHAP) values were used to identify prognostic and predictive thresholds of number of positive lymph nodes (LNs) involved and lymph node ratio (LNR). Cox proportional hazards regression was used for confirmatory analysis. A total of 16,789 patients with completely resected N2 NSCLC were identified. Using the SHAP values, we identified thresholds of 3+ positive LNs and a LNR of 0.34+. On multivariate analysis, PORT was not significantly associated with OS (p = 0.111). However, on subset analysis of patients with 3+ positive LNs, PORT improved OS (HR: 0.91; 95% CI: 0.86–0.97; p = 0.002). On a separate subset analysis in patients with a LNR of 0.34+, PORT improved OS (HR: 0.90; 95% CI: 0.85–0.96; p = 0.001). Patients with 3+ positive lymph nodes had a 5-year OS of 38% with PORT compared to 31% without PORT. Patient with positive lymph node ratio 0.34+ had a 5-year OS of 38% with PORT compared to 29% without PORT. Patients with a high lymph node burden or lymph node ratio may present a subpopulation of patients who could benefit from PORT. To our knowledge, this is the first study to use machine learning algorithms to address this question with a large national dataset. These findings address an important question in the field of thoracic oncology and warrant further investigation in prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: Approximately 50% of patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) will relapse post-autologous stem cell transplant (ASCT), and the role of salvage therapy is not well defined. We examined radiation therapy (RT) as salvage treatment in this patient population.Materials and Methods: A retrospective review of patients with DLBCL who had an ASCT during 2004 to 2016 and subsequently relapsed was performed. Clinical and pathologic characteristics were collected, including detailed information regarding post-ASCT treatment. Response rates were tabulated and survival analysis was performed, stratified by salvage modality.Results: A total of 165 patients with R/R DLBCL who relapsed after ASCT were identified; 91 of these patients received salvage chemotherapy as their first line of relapse therapy, and 14 received salvage radiation. Median salvage RT dose was 36 Gy (range, 24-50). The objective response rate with salvage chemotherapy and RT was 53.0% and 78.5%, respectively (P = 0.07), and the complete response rate was 31.3% and 57.1%, respectively (P = 0.06). Median follow-up among living patients was 48.9 months (range, 4.8-136.17). Among patients with one site of relapse post-ASCT, median overall survival in patients who received salvage RT was significantly improved (P = 0.008) relative to chemotherapy (not reached [95% confidence interval {CI}, 8.4-not reached] versus 10.0 months [95% CI, 5.3-17.8]). Median progression-free survival in patients who received salvage RT was not significantly different (P = 0.16) relative to chemotherapy (8.4 months [95% CI, 2.5-47.7] versus 3.9 months [95% CI, 2.4-8.5]).Conclusions: Patients who received RT as first salvage therapy post-ASCT, particularly with localized disease, had favorable oncologic outcomes. Future studies are needed to understand which patients with R/R DLBCL who relapse after ASCT may benefit from early salvage RT versus chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Report the outcomes of patients with non-small cell lung cancer (NSCLC) and peripheral tumors treated with simultaneous integrated biologically equivalent dose (BED)-escalation (SIBE) lung stereotactic body radiation therapy (SBRT) to achieve dose escalation. Materials/methods: Patients with NSCLC within 5 mm of the chest wall treated with a SIBE approach were eligible. Patients received 60 Gy in 5 fractions, with dose decreased to 50 Gy based on proximity to the chest wall. Dosimetry, oncologic outcomes, and toxicity were evaluated. Results: Twenty-four patients met inclusion criteria. Median BED to the PTV was 135.4 Gy. Median chest wall V30 was 18.7 cc. The 3-year LC, OS, and PFS of the non-metastatic cohort was 93%, 35%, and 39%, respectively. The crude rate of chest wall toxicity was 12.5%, with no rib fractures. Conclusions: SIBE lung SBRT appears to be well tolerated and achieves favorable local control rates and survival. [ABSTRACT FROM AUTHOR]

• APBI use is stable since 2008, but with a drop in brachytherapy and a rise in IORT. • There is a steady rise in patients considered "suitable" by ASTRO APBI guidelines. • Trends in APBI modality utilization appears to be influenced by available literature. To examine recent modality utilization trends in accelerated partial breast irradiation (APBI) in the National Cancer Database (NCDB) based on the American Society for Radiation Oncology (ASTRO) guidelines. A total of 58,194 patients treated with APBI were identified. Patients were segregated by APBI modality (brachytherapy, external beam radiotherapy [EBRT], and intraoperative radiotherapy ([IORT]). These patients were then further classified by suitability to receive APBI based on ASTRO guidelines. Temporal trends in utilization were evaluated using linear regression. Logistic regression was applied to study factors contributing to APBI modality choice and treatment within the ASTRO suitability groups. Patients treated with brachytherapy, EBRT, and IORT comprised 70.5%, 17.5%, and 12.0% of patients treated with APBI. From 2008 to 2017, total APBI cases remained relatively stable (−54.1 cases/year, p = 0.161) while brachytherapy cases decreased by 258.7 cases/year (p < 0.001). EBRT and IORT increased by 51.5 cases/year (p = 0.019) and 153.1 cases/year (p < 0.001), respectively. 40.0% of patients treated with APBI were classified as "suitable", which increased from 2010 to 2017 from 35.3% to 45.3% (slope = 1.51%/year, r 2 = 0.61, p = 0.022). In comparison, 36.0% (36.1% in 2010 to 33.1% in 2017) of patients were classified as "cautionary" (slope = −0.33%/year, r 2 = 0.63, p = 0.019) and 23.9% (28.6% in 2010 to 21.6% in 2017) of patients were classified as "unsuitable" (slope = −1.18%/year, r 2 = 0.67, p = 0.012). While overall APBI utilization has remained stable since 2008, this has been accompanied by a decline in brachytherapy and a rise in IORT. The causes of these trends should be the topic of future research. [ABSTRACT FROM AUTHOR]

Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value. Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model. We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1–3 LNs, 4–5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1–3 LNs, 74.3% for 4–5 LNs (hazard ratio [HR] 1.38; p < 0.001), and 59.9% for 6+ LNs (HR 2.23; p < 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p < 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1–3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p < 0.001). Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement. • Number of involved lymph nodes provides improved prognostic value compared to the existing FIGO staging system. • Number of involved nodes provides predictive value to response to adjuvant treatment in endometrial cancer. • Machine learning algorithms can be used to identify prognostic thresholds. • Future staging systems for endometrial cancer should consider incorporating nodal burden. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate for age, racial, and ethnic disparities among clinical studies where patients can potentially receive brachytherapy treatment. Trials involving brachytherapy for breast, cervical, prostate, and uterine cancers were identified using ClinicalTrials.gov. The age, racial, and ethnic breakdown of the identified trials were compared to US population-estimates derived from the Surveillance, Epidemiology, and End Results (SEER) Program. Primary outcomes were gaps between gaps between mean age and race and ethnic proportions in trials and the US population. Secondary outcomes included proportions of racial and ethnic data reporting. Descriptive statistics, t-tests, χ2 tests, and univariate analysis were used to analyze the data. A total of 77 trials with reported data were identified, representing 13,580 patients. The overall difference in mean age in the identified trials compared to US population estimates was -2.29 years (p < 0.001), with the largest difference occurring in prostate cancer at -2.72 years (p < 0.001). With the exception of ethnicity in cervical cancer (p = 0.18), all racial and ethnic distributions were statistically significantly different. Overall, the largest disparity was among Asian (-2.65%) and Hispanic patients (-1.05%). Of the 77 trials, 76 (98.7%) reported age, 36 (46.8%) reported race, and 24 (31.2%) reported ethnicity. Diversity data is underreported among clinical studies where brachytherapy is a potential treatment component. However, among reported trials, disparities are present albeit relatively small compared to previous studies reporting on disparities in clinical trials. Future efforts should emphasize increased reporting of racial and ethnicity data as well as ensuring inclusion of older patients and minorities. [ABSTRACT FROM AUTHOR]

Purpose: Portal vein tumor thrombosis (PVTT) from cancer involving the liver carries a dismal prognosis, with median overall survival (OS) ranging from 2 to 5 months. While treatment with yttrium-90 (90Y) radioembolization alone may improve outcomes, overall prognosis remains poor. We hypothesize that the combination of 90Y radioembolization to the parenchymal component of the tumor and stereotactic body radiation therapy (SBRT) to the vascular component is a safe and effective means of improving outcomes. Materials and Methods: A single center retrospective review identified 12 patients with cancers involving the liver who received both 90Y radioembolization and SBRT to the PVTT between May 2015 to August 2020. Primary endpoint was the 90-day toxicity rate by the Common Terminology Criteria for Adverse Events version 5.0. Secondary endpoints were the best response rate based on the Response Evaluation Criteria in Solid Tumors v1.1, local control rate, portal vein (PV) patency rate, and median OS. Results: Patients received a median 90Y dose of 104.3 Gy (range, 83.3 to 131.7 Gy) and a median 5-fraction SBRT dose of 32.5 Gy (range, 27.5 to 50 Gy). There were no late toxicities reported, and only 7 acute grade 1 toxicities reported: elevation of liver function tests (17%), nausea (17%), fatigue (17%), and esophagitis (8%). Local control was 83%. 58% of patients had a patent PV after treatment. With a median follow-up time of 28 months, 1-year OS was 55% with a median OS of 14 months. Conclusion: Combination 90Y radioembolization and SBRT appears to be safe and effective in the treatment of PVTT. Larger prospective studies are warranted to better evaluate this combination treatment approach. [ABSTRACT FROM AUTHOR]

Purpose: The significance of radiation dose to the host immune system during the treatment of stage III non-small cell lung cancer (NSCLC) is unknown, but higher doses were associated with worse tumor control and overall survival (OS) in a secondary analysis of RTOG 0617. In this study, we sought to assess the impact of the estimated dose of radiation to immune cells (EDRIC) on cancer-specific outcomes in an independent cohort of patients treated at our institution.Methods and Materials: We retrospectively identified 117 patients with stage III NSCLC treated with definitive fractionated radiation from 2004 to 2017 at a single academic center (median dose of 60 Gy; 60% underwent intensity modulated radiation therapy and 92% received concurrent platinum-based chemotherapy). EDRIC was calculated as a function of the number of radiation fractions and mean doses to the lung, heart, and remaining body based on a model developed by Jin et al.Results: Median follow-up was 16 months with 77% of patients followed until death. In the entire population, 5-year OS was 11.2% with a median survival of 17.3 months. Median EDRIC for the entire cohort was 6.1 Gy (range, 2.5-10.0 Gy). A higher EDRIC was correlated with greater risk of grade ≥3 lymphopenia (P = .004). On multivariate analysis including total prescription radiation dose, planning target volume, and chemotherapy utilization, EDRIC was independently associated with OS (hazard ratio [HR] 1.17, P = .03), local progression-free survival (HR 1.17, P = .02), and disease-free survival (HR 1.15, P = .04). The median OS for patients with an EDRIC above 7.3 Gy (fourth quartile) and below 5.1 Gy (first quartile) was 14.3 and 28.2 months, respectively.Conclusions: Higher doses of radiation to the immune system were associated with tumor progression and death after the definitive treatment of stage III NSCLC. Tailoring radiation therapy to spare the immune system may be an important future direction to improve outcomes in this population. [ABSTRACT FROM AUTHOR]

Simple Summary: Brachytherapy is a key component of radiation treatment in the curative treatment of locally advanced cervical cancer. To improve the delivery of brachytherapy, recent studies have explored the use of imaging, such as magnetic resonance imaging (MRI), in treatment planning. In this review, we reviewed the current evidence for image-guided brachytherapy and discussed future directions for research. Purpose: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. Methods: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried "cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy". Discussion: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. Conclusions: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy. [ABSTRACT FROM AUTHOR]

Brachytherapy (BT) is a critical component of the standard-of-care curative regimen for women with locally advanced cervical cancer (LACC). However, existing literature suggests a sizeable proportion of patients will not receive the BT boost. Although predictive models such as logistic regression have been able to help identify characteristics of patients who are most at-risk for omission of BT boost, its predictive performance could be improved. Therefore, we utilized machine learning (ML) combined with explainable artificial intelligence to characterize this treatment disparity, with an emphasis on more recent trends that might be attributable to the COVID-19 pandemic. Patients with LACC diagnosed from 2004-2020 were identified in the National Cancer Database. The query was subsequently limited to patients who received definitive radiation. Five ML models were trained to predict if a patient received a BT boost. Model performance, measured using area under the curve (AUC), was compared to multivariable logistic regression. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To permit more traditional statistical understanding, SHAP values were converted into odds ratios (OR) and used to identify how model features influenced predictions. To identify trends that may be attributable to the COVID-19 pandemic, the previous analysis was repeated and limited to the years 2019-2020. A total of 54,896 patients with LACC were identified; 8298 were diagnosed from 2019-2020. Of these patients, 54.8% received a BT boost, with 70.5% of patients diagnosed in 2019-2020 receiving a boost. The majority of the increase occurred from 2018 onward, with rates every year prior being a maximum of 57.0%. The Extreme Gradient Boosting model outperformed all other models with an AUC of 0.61 (95%CI: 0.57-0.65) compared to 0.56 (95%CI: 0.52-0.60) for logistic regression. SHAP values > zero represent greater probability of BT boost. SHAP summary plots of the ML models from 2004-2020 and 2019-2020 are shown in Figure 1A and 1F, respectively. SHAP dependence plots of the ML models from 2004-2020 and 2019-2020 are shown in Figure 1B-E and 1G-J, respectively. Overall, a more recent year of diagnosis (OR: 1.08; 95%CI: 1.07-1.08; p<0.001) and lower Charlson Deyo score (2+ vs 0; OR: 1.27; 95%CI: 1.17-1.38; p<0.001) were strong predictors of receiving a BT boost. Other factors associated with BT boost receipt included younger age, private insurance, and white (vs black) race. When examining the years 2019-2020, year of diagnosis (OR: 0.98; 95%CI: 0.92-1.01; p=0.31) and Charlson Deyo score (2+ vs 0; OR: 1.07; 95%CI: 0.99-1.22; p=0.19) were no longer significant. It does not appear that a COVID-19 diagnosis during radiation adversely impacted rates of BT utilization, with 24 of 34 (70.5%) patients who tested positive for COVID-19 during their radiation course receiving a boost. There were slight delays reflected in total treatment duration relative to national recommendations of 8 weeks, lasting a median of 10.7 weeks. This study illustrates how ML can be used to examine practice patterns and identify areas of underutilization. ML approaches yielded improved performance, relative to logistic regression, at predicting receipt of BT boost. To our knowledge, this is the first time SHAP values have been converted to OR, CI, and p-values to describe such models. An increase in BT boost utilization has been noted since 2018, which fortunately did not seem to be significantly impacted by the onset of the COVID-19 pandemic. ML should be considered to better identify health disparities across patient populations where BT is underutilized, which can provide actionable feedback for improving access. [ABSTRACT FROM AUTHOR]

The complexity of cancer care requires integrated and continuous support to deliver appropriate care. An expert network with complementary expertise and the capability of multidisciplinary care is an integral part of contemporary oncology care. Appropriate infrastructure is necessary to empower this network to deliver personalized precision care to their patients. Providing decision support as cancer care becomes exponentially more complex with new diagnostic and therapeutic choices remains challenging. City of Hope has developed a Pyramidal Decision Support Framework to address these challenges, which were exacerbated by the COVID pandemic, health plan restrictions, and growing geographic site diversity. Optimizing efficient and targeted decision support backed by multidisciplinary cancer expertise can improve individual patient treatment plans to achieve improved care and survival wherever patients are treated. [ABSTRACT FROM AUTHOR]

Geometric and nomenclature errors are commonly encountered in automated treatment planning. We describe a novel algorithm to extract organ geometry relationships from patient structure DICOM data to construct a database that can be used to detect organ contour inaccuracies including relational and naming errors. Twenty-five sets of head and neck patients' treatment plan data (CT, structures) were retrospectively retrieved from our institution. For each dataset, various organs were contoured and verified by experienced physicians. The relative position and orientation between organs were extracted from each patient and the data were used to construct an organ relationship database model. The model was tested using a dataset originating from an in-house organ renaming software that often-introduced organ contour naming mismatches. As part of the validation test, the renamed organs relative positions were compared with the database model to identify mismatches. Within the forty head and neck patients, we extracted the geometric relationship between 201 organ pairs. The average number of unique types of organ pairs (for example, left parotid with left eye is one type of organ pair) stored in the database was 12. Fifteen head and neck structure sets automatically renamed using our in-house organ renaming tool was used as validation data. All of the 30 random assigned wrong name labels present in these structure sets were identified using the established organ geometry relationship database. We successfully constructed a head and neck organ geometry relationship database and validated it in a contour naming quality assurance process. This novel scheme can be expanded to the entire body and shows a great potential in automatic plan physics QA procedure. It should be one essential QA step in an autonomous treatment planning process. [ABSTRACT FROM AUTHOR]

Background: The RefleXion X1 is a novel radiotherapy delivery system on a ring gantry equipped with fan‐beam kV‐CT and PET imaging subsystems. The day‐to‐day scanning variability of radiomics features must be evaluated before any attempt to utilize radiomics features. Purpose: This study aims to characterize the repeatability and reproducibility of radiomic features produced by the RefleXion X1 kV‐CT. Materials and Methods: The Credence Cartridge Radiomics (CCR) phantom includes six cartridges of varied materials. It was scanned 10 times on the RefleXion X1 kVCT imaging subsystem over a 3‐month period using the two most frequently used scanning protocols (BMS and BMF). Fifty‐five radiomic features were extracted for each ROI on each CT scan and analyzed using LifeX software. The coefficient of variation (COV) was computed to evaluate the repeatability. Intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) were used to evaluate the repeatability and reproducibility of the scanned images using 0.9 as the threshold. This process is repeated on a GE PET‐CT scanner using several built‐in protocols as a comparison. Results: On average, 87% of the features on both scan protocols on the RefleXion X1 kVCT imaging subsystem can be considered repeatable as they met COV < 10% criteria. On GE PET‐CT, this number is similar at 86%. When we tighten the criteria to COV <5%, the RefleXion X1 kVCT imaging subsystem showed much better repeatability with 81% of features on average whereas GE PET‐CT showed only 73.5% on average. About 91% and 89% of the features with ICC > 0.9 respectively for BMS and BMF protocols on RefleXion X1. On the other hand, the percentage of features with ICC > 0.9 on GE PET‐CT ranges from 67% to 82%. The RefleXion X1 kVCT imaging subsystem showed excellent intra‐scanner reproducibility between the scanning protocols much better than the GE PET CT scanner. For the inter‐scanner reproducibility, the percentage of features with CCC > 0.9 ranged from 49% to 80%. between X1 and GE PET‐CT scanning protocols. Conclusions: Clinically useful CT radiomic features produced by the RefleXion X1 kVCT imaging subsystem are reproducible and stable over time, demonstrating its utility as a quantitative imaging platform. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer management continues to evolve with improvements in survival across all stages. The review highlights the current data supporting screening and discusses barriers to screening and potential opportunities to improve screening access. Further, the review discusses the current challenges in diagnosis and biomarker testing in early stage lung cancer and ways in which these can be improved upon. Management of lung cancer has transformed over the past decade and is no longer considered a singular disease as it now has multiple sub-classifications based on molecular markers. The current treatment paradigm requires a multidisciplinary approach. One of the most important facets of lung cancer outcomes however relies on early detection. Early detection has become crucial, and recent effects have shown success in lung cancer screening programs and early detection. In this narrative review, we evaluate low-dose computed tomography (LDCT) screening and how this screening modality may be underutilized. The barriers to broader implementation of LDCT screening is also explored as well as approaches to address these barriers. Current developments in diagnosis, biomarkers, and molecular testing in early-stage lung cancer are evaluated as well. Improving approaches to screening and early detection can ultimately lead to improved outcomes for patients with lung cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of curative intent concurrent chemoradiation (CCRT) vs radiation (RT) alone for T1-T3N0 HPV-positive and HPV-negative oropharyngeal squamous cell cancer (OPSCC).Methods: The NCDB was queried for patients diagnosed between 2010 and 2017 with cT1-3N0M0 OPSCC treated with definitive RT or CCRT. Univariable analysis (UVA) and multivariable analysis (MVA) Cox regression analysis was performed with OS as the endpoint. Propensity score matching (PSM) 1:1 was performed. Interaction test to assess heterogeneity of treatment effect.Results: A total of 2830 patients were queried. On MVA, CCRT was associated with improved OS for T3N0 tumors (HR 0.49; 95% CI 0.39-0.63) but not for T1N0 (HR 1.43; 95% CI 0.99-2.07) and T2N0 (HR 0.92; 95% CI 0.75-1.13). For T3 patients, CCRT improved OS for HPV-negative (HR 0.43; 95% CI 0.31-0.59) and HPV-positive tumors (HR 0.39; 95% CI 0.25-0.61). After PSM, CCRT was not statistically different to RT for patients with T1-2N0 HPV-negative tumors (HR 1.10; 95% CI 0.85-1.43; p = 0.48) and T1-2N0 HPV-positive tumors (HR 1.15; 95% CI 0.79-1.68; p = 0.45). After PSM, CCRT improved OS compared to RT alone for patients with T3N0 HPV-negative (HR 0.43; 95% CI 0.31-0.59; p < 0.01) and HPV-positive tumors (HR 0.39; 95 %CI 0.25-0.61; p < 0.01).Conclusions: CCRT is associated with improved OS in HPV-positive and HPV-negative T3N0 OPSCC. RT alone vs. CCRT demonstrated similar OS for T1-T2N0 OPSCC for both HPV negative and HPV positive tumors. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to sample the opinions of radiation oncologists and trainees in the United States regarding residency expansion, what action(s) should be taken to limit residency supply, if any, and the proposed Accreditation Council for Graduate Medical Education (ACGME) changes.Methods and Materials: An online survey was distributed to 1048 attending radiation oncologists by e-mail and approximately 800 residents through their program coordinators. The survey asked respondents to rank how strongly they agreed with certain statements regarding residency supply, possible solutions to address any perceived oversupply, and the proposed ACGME changes on a 1-to-10 disagreement-to-agreement scale. The 16% response rate yielded 294 responses for analysis.Results: Of the respondents, 90 (30%) were residents, and 204 (70%) were attendings, of whom 117 (57%) were academic and 87 (43%) were nonacademic. Eighty-six percent agreed that there is a residency oversupply issue, and 91% agreed that actions should be taken to limit residency expansion. On χ2 test, residents and attendings were similarly likely to agree that there is a residency oversupply issue (93% and 89%, P = .27), although residents were more likely to agree that this oversupply should be acted upon compared with attendings (100% and 88%, P < .01). Regarding possible solutions, respondents were most likely to agree that further expansion should be limited (90%), program requirements should be made more stringent (76%), and the use of the Supplemental Offer and Acceptance Program should be limited (69%). Proposed ACGME changes that respondents were most likely to agree with included requiring that programs have modern image guidance, stereotactic radiation therapy, and brachytherapy techniques (98%) and have 4+ faculty members and maintain a faculty-to-resident ratio of >1.5:1 (86%). Case log minimums most supported to be increased were 4 uterus (65%) and 11 postmastectomy breast (61%) simulations.Conclusions: The majority of respondents agree that there is a residency oversupply issue and that actions should be taken to limit residency expansion and make program requirements more stringent. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the impact on dose distribution and radiobiological metrics of common high-dose-rate vaginal brachytherapy treatment parameters and to analyze multiinstitutional data for clinically significant impact on outcomes in early-stage endometrial cancer. Treatment plans were created for all combinations of prescription parameters and used to quantify the dosimetric impact of each parameter and to estimate the dose delivered using common voxel-integrated radiobiological metrics. A rating system, based on risk grouping from GOG and PORTEC trials, was used to consolidate staging information into a cancer "aggressiveness" measure. Correlations between the rating, toxicity, disease recurrence, and plan parameters were investigated. When prescribing to 5 mm depth, the variation caused by the diameter was very large across all dose metrics, ranging from 51% to 175% increase with the most divergence in BED max. For surface prescription, changing the cylinder diameter from 4 cm to 2 cm caused the dose metrics of BED min , D min , and gBEUD (a = −3) to increase by 117%, 67%, and 52%, respectively. Prescription to 5-mm depth caused changes across all dose metrics of 260% compared with surface prescription for a 2-cm cylinder. Deeper prescription point (p = 0.005) and longer treatment length (p = 0.01) were correlated with increased stenosis rates. No correlation between recurrence and any plan parameter was found. Dramatic differences in dose distributions arise by small variations of plan parameters, with large impact on rates of vaginal stenosis, but no clear relation with local recurrence. To help radiation oncologists interpret the magnitude of these effects for their patients, we created a tool that allows comparison between dose and fractionation parameters. [ABSTRACT FROM AUTHOR]

Erratum: "Evaluation of repeatability and reproducibility of radiomic features produced by the fan-beam kV-CT on a novel ring gantry-based PET/CT linear accelerator" https://10.1002/mp.16399 In Ketcherside et al., 1 the COI disclosure statement missed disclosing three authors who are from commercial companies, thus the COI disclosure statement is corrected. CONFLICT OF INTEREST STATEMENT David Leung, Andrew Sundquist, and Calvin Huntzinger are employed by Reflexion Medical. [Extracted from the article]