Treatment of Internal Mammary Nodes is Associated With Improved Overall Survival in Breast Cancer: A Meta-Analysis.

INTRODUCTION: The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer. METHODS: Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise. RESULTS: Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups. CONCLUSION: Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.

Explainable Artificial Intelligence to Identify Dosimetric Predictors of Toxicity in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Secondary Analysis of RTOG 0617.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Influence of Dexamethasone Premedication on Acute Lung Toxicity in Lung SBRT.

Introduction: The cooperative group experience of thoracic sterotactic body radiation therapy (SBRT) in medically inoperable patients with early stage non-small cell lung cancer (NSCLC) historically utilized corticosteroid premedication. Patterns of care have been mixed as to whether premedication adds benefit in terms of improved lung toxicity and treatment tolerance. Methods: Patients treated for NSCLC from 2014 to 2017 with definitive thoracic SBRT (BED10≥100) at a single institution, in a prospectively collected database were evaluated. Pretreatment clinicopathologic characteristics, including Eastern Cooperative Oncology Group (ECOG) performance status, PFT parameters of FEV1, and diffusing capacity for carbon monoxide (DLCO) were collected. Treatment and dosimetric characteristics were collected, and patients were scored as to whether dexamethasone was prescribed and utilized with each fraction. Toxicity was graded on multiple domains including lung as during and 30 days after completion of treatment using Common Terminology Criteria for Adverse Events Version 4. Univariate analysis was performed with Fisher's exact test for categorical variables and two-tailed Student's t-test for continuous variables. Multivariate analysis was performed with Cox proportional hazards model to adjust for age, pretreatment DLCO, ECOG, tumor size, central versus peripheral location, and biological effective dose. Results: A total of 86 patients treated with thoracic SBRT with 54-60 Gy in 3-8 fractions met inclusion criteria, with the majority (70%) receiving 5 fractions. Of these patients, 45 (52%) received 4 mg dexamethasone premedication prior to each fraction of SBRT and 41 (48%) were treated without dexamethasone premedication. Overall acute lung toxicity was low in both groups. Between the two groups of patients, 5/45 (11%) developed grade 2 or higher lung toxicity including hospital admission in the dexamethasone premedication arm vs. 2/41 (5%) without premedication (p = 0.4370, Fisher's exact test). Freedom from acute SBRT lung toxicity was no different between dexamethasone premedication arm and no premedication (Log rank, p = 0.45). On multivariate Cox proportional hazard modeling adjusting for age, ECOG, tumor size, central vs. peripheral location, pretreatment DLCO, and BED, there was no difference in freedom from acute lung toxicity without dexamethasone premedication (HR: 0.305; 95% CI: 0.033, 2.792; p = 0.293). Conclusions: In this retrospective analysis, pretreatment steroid prophylaxis with dexamethasone confers a similar acute toxicity profile and no added clinical benefit to treatment without pretreatment steroid prophylaxis.

Is Radiation Therapy Cost-Effective in the Positron Emission Tomography/Computed Tomography Era for Early-Stage Favorable Hodgkin Lymphoma With Alternative Payment Models?

PURPOSE: Despite multiple randomized trials, variation in practice remains regarding the most effective treatment for early-stage, favorable-risk Hodgkin lymphoma. With increasing emphasis on alternative payment models, we investigate the cost-effectiveness of chemotherapy alone versus combined modality therapy (CMT). METHODS AND MATERIALS: A Markov model was formed to compared 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) to 2 cycles of ABVD followed by 20 Gy in 10 fractions involved-site radiation therapy. Modalities were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs) and evaluated with a willingness to pay a threshold of $100,000 per QALY gained. RESULTS: The base case analysis showed that CMT is cost-effective compared with ABVD alone, with an incremental cost-effectiveness ratio of $8028 per QALY gained and an incremental cost of $236 gaining 0.029 QALYs. On sensitivity analyses, the results were the most sensitive to changes in recurrence rates. If the recurrence rate differences were ≥6%, CMT was cost-effective. CONCLUSIONS: CMT is a cost-effective strategy for early-stage, favorable-risk Hodgkin lymphoma based on currently available evidence. However, small variations in recurrence-rate estimates dramatically affect strategy cost-effectiveness.

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies.

PURPOSE: Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls. METHODS AND MATERIALS: Meta-analysis of Observational Studies in Epidemiology guidelines were used to perform a comprehensive search identifying case-control or randomized studies reporting RT toxicity outcomes for patients with CVD versus controls. Data were synthesized from studies reporting grade 2 to 3 or more (G2/3 +) acute and late RT toxicities. Results were analyzed with fixed effects meta-analysis on the random-effects model for between-study heterogeneity; otherwise, the fixed-effects model was used. Hazard ratio or odds ratio (OR) were the effect-size estimators, as appropriate. RESULTS: Ten studies were included, with 4028 patients (CVD: 406, control: 3622). Patients with CVD had higher rates of acute G2/3 + toxicity (26.2% vs 16.5%, OR [odds ratio] 2.01; P < .001) and late G2/3 + toxicity (18.4% vs 10.1%, OR 2.37; P < .001). Higher rates of late G2/3 + toxicity were observed for CVD patients with systemic lupus erythematous (21% vs 9.7%; OR 2.55, P = .03), systemic scleroderma (31.8% vs 9.7%, OR 3.85; P = .03), rheumatoid arthritis (11.7% vs 8.4%, OR = 2.56; P = .008), and those irradiated to the pelvis/abdomen (32.2% vs 11.9%, OR 3.29; P = .001), breast (14.7% vs 4.4%, OR 3.51; P = .003), thorax (12.5% vs 8.7%, OR 3.46; P < .001), and skin (14.6% vs 5.2%, OR 2.59; P = .02). Late grade 5 toxicities were significantly higher for patients with CVD, although absolute rates were low (3.9% vs 0.6%, OR = 7.81; P = .01). CONCLUSIONS: Moderate and severe toxicities are more likely in patients with CVD, with variable risk depending on toxicity grade, CVD subtype, treatment site, and dose. Severe toxicities are uncommon. These factors should be considered when informing patients of treatment-related risks and monitoring for morbid treatment sequelae.

Outcome of Surgical Management of Sacrococcygeal Pilonidal Sinus Disease with Rotation Flap in 52 Patients-A Retrospective Study.

Background Surgical treatment of sacrococcygeal pilonidal sinus disease (SPSD) consists of radical excision of the entire tract and treatment of the resultant raw area. Here, the authors have reviewed the results of the rotation flap for closure of the SPSD. Aim This study aims to evaluate the outcomes following SPSD excision and rotation flap closure. Materials and Methods All patients were treated for SPSD with excision and closure using a rotation flap from January 2010 to September 2018. Cases having a follow-up of at least 6 months post surgery were evaluated. Result A total of 52 patients were included in the study; 42 cases were of primary disease while 10 were of recurrent disease. The patients' follow-up records on the 3rd day, 10th day, 1 month, and 6 months were evaluated. None of the patients showed any signs of recurrence on follow-ups. One patient developed a hematoma on the third day post surgery which was treated conservatively. One patient developed a seroma in the perianal region on the fifth postoperative day which required aspiration. Both these patients healed well subsequently. Conclusion Rotation flap is a (simple and reliable) treatment option for closure of postexcision SPSD defect. It not only takes the tension away from suture line, but also pushes the gluteal fat from the sides into the midline, obliterating the deep crevice of the natal cleft which is believed to be one of the important factors in the causation of SPSD, thus minimizing recurrence.

Compassion Inequities and Opioid Use Disorder: A Matched Case-Control Analysis Examining Inpatient Management of Cancer-Related Pain for Patients With Opioid Use Disorder.

CONTEXT: The opioid epidemic spurred guidelines intended to reduce inappropriate prescribing. Although acute cancer-related pain was excluded from these recommendations, studies demonstrate reduced opioid prescribing for patients hospitalized with advanced cancer. OBJECTIVES: We performed a matched case-control analysis to determine how a history of opioid use disorder (OUD) affects inpatient management of cancer pain. METHODS: Charts of patients with OUD admitted for cancer pain from 2015-2020 were retrospectively reviewed. Hospitalizations were matched 1:1 by patient age and sex. Home milligram-morphine equivalent per day (MME/day) was calculated from the home medication list. Admission MME/day was the average MME/day administered during hospitalization. RESULTS: A total of 80 hospitalizations (40:40) were matched for 25 patients with a history of OUD and 31 patients with no history of OUD. Cancer was metastatic/relapsed for 70% of admissions. The median overall survival was 2.3 months (95% CI 0-5.21, P = 0.13). Patients with OUD had a significantly lower change from Home to Admission MME/day (-3 vs. 37, P < 0.01) and were less likely to have any increase in Admission MME/day (OR 0.1, 95% CI 0.02-0.43, P < 0.01). When considering opioids administered after pain specialty consultation, there was no difference between groups. CONCLUSION: Our results suggest that patients with OUD receive lower quality inpatient management of cancer-related pain. Provider education and early involvement of pain specialists are crucial in delivering equitable and compassionate end-of-life care for patients with OUD.

Intraoperative Radiation Therapy Versus Whole Breast Radiation for Early-Stage Breast Cancer Treatment in Rural Appalachia.

BACKGROUND: Intraoperative radiation therapy (IORT) is an alternate accelerated form of radiation following breast-conserving surgery (BCS). Lack of data regarding long-term outcomes has limited adoption. We report our experience with IORT in patients undergoing BCS versus whole breast radiation therapy (WBRT). METHODS: Retrospective review of patients undergoing BCS with IORT versus WBRT (2012-2017). Inclusion: low grade, T1-2N0M0, estrogen receptor/progesterone receptor positive, and Her2-negative infiltrating ductal carcinomas. IORT was delivered as a single fraction of radiation (20 Gy) intraoperatively. Outcomes were compared using Fisher's test for discrete variables or Wilcoxon signed-rank test for continuous variables. Kaplan-Meier method was used to estimate disease-free survival (DFS). RESULTS: Fifty-one patients (44%) received IORT, and 66 (56%) received WBRT. There was no difference in age, tumor size, receptor status, or in-breast recurrence (1.9% vs 0%, all P > .05). Length of follow-up was longer in the WBRT group due to time to inception of IORT (mean ± SD: 44 ± 8.1 vs 73 ± 13 months, P < .001). There was no difference in DFS between the 2 groups (HR 2.5; P = .44). IORT patients experienced delay to BCS (mean ± SD: 38 ± 12.7 vs 27 ± 12.2 days, P < .001) likely due to coordination of care. Analysis demonstrated IORT patients would have traveled a mean distance of 20 miles to the closest WBRT center (range 1-70, miles) for a mean travel time of 31 minutes (range 4-90, minutes) per WBRT treatment. DISCUSSION: IORT produces noninferior oncologic outcomes and decreased skin toxicity compared with WBRT. It can be convenient for patients in rural regions with limited health care access.

Consolidation radiotherapy following positron emission tomography complete response in early-stage Hodgkin lymphoma: a meta-analysis.

Despite a number of randomized trials, there is clinical equipoise whether de-escalation with the omission of radiotherapy (RT) in positron emission tomography (PET) responders is safe in early-stage Hodgkin lymphoma (HL). A comprehensive Medline and conference abstracts search was performed to identify prospective studies with the following criteria: early-stage (stage I/II) HL treated with anthracycline-based chemotherapy with PET-directed randomization to ± consolidation RT. Four studies were meta-analyzed with a total of 2267 patients (RT: n = 1136, no RT: n = 1131). Pooled analysis showed a significant progression-free survival (PFS) benefit with RT (HR = 2.08, 95% CI 1.27- 3.43 p = .004, RE). There was no statistically significant overall survival (OS) benefit with RT for all patients (HR = 0.92, 95% CI 0.37-2.30, p = 0.85), nor in favorable (HR = 0.90, p = .89) or unfavorable risk (HR = 1.01, p = .99). In early-stage PET-negative HL, consolidative RT consistently improves PFS across risk stratifications over PET-directed omission of RT, with no significant impact on OS.