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The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P =.005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P =.65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P <.001). Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach. [ABSTRACT FROM AUTHOR]

Anal cancer (AC) is a rare disease with scarce evidence from developing countries. We performed a population-based cohort study to investigate the relationship between tumor, patient, and social determinants of health with treatment outcomes of AC treated by chemoradiation (CRT). Patients who received a diagnosis of AC from 1999 to 2020 were identified from the Fundação Oncocentro de São Paulo database. Only patients with AC stage I-III treated by CRT were included. Age, sex, tumor category (T), nodal category (N), education level, practice setting, time to radiation therapy, histology, and treatment local data were extracted. With the Cox proportional hazard model, the hazard ratio and 95% confidence interval were used to test the relationship between tumor, patient, and social factors with overall survival (OS) and cancer-specific survival (CSS). With 1462 patients assessed, the median follow-up was 72 months, and the OS and CSS at 5/10 years were 61%/46% and 67%/60%, respectively. In the univariate analysis, T category, N category, sex, practice setting, and education level were associated with OS and CSS (P <.05). In the multivariate analysis, female sex, T1/2 category, N0 category, and private service were independently associated with OS (P <.05). For CSS, female sex, T1/2 category, private service, and N0 category remained significant (P <.05). CRT produced satisfactory rates of OS and CSS in patients with AC, with tumor, patient, and social determinants of health influencing the outcomes. These data could help mitigate the effects of social distortions on the survival of AC. [ABSTRACT FROM AUTHOR]

Purpose: With the increasing use of stereotactic body radiation therapy (SBRT) for primary and metastatic cancer, use of multitarget thoracic (MTT) SBRT is rising. Given the limited safety and efficacy data, we report the experience of this strategy from a large academic center.Methods and Materials: Between 2012 and 2021, patients who received SBRT for ≥2 thoracic targets separated by ≤1 year were retrospectively reviewed. The primary endpoint was clinically significant radiation pneumonitis (CSRP) requiring steroids, oxygen, or intubation. Secondary endpoints included local failure (LF), initiation or change of systemic therapy (ICST), progression-free survival, and overall survival. Competing risk analysis was used to evaluate the cumulative incidence of CSRP, LF, and ICST. Univariate and multivariable analyses were performed to look for clinical and dosimetric predictive factors of CSRP and LF.Results: One hundred ninety patients (481 lesions) were treated with MTT SBRT with a median follow-up of 19.7 months. Indications for SBRT were oligometastases (n = 70; 36.8%), oligoprogression (n = 62; 32.6%), curative intent in patients with primary lung cancer (n = 37; 19.5%), and control of dominant areas of metastatic progression (n = 21; 11.0%). The number of irradiated tumors ranged from 2 to 7 and the majority of SBRT courses were delivered simultaneously (88.2%). Overall, 14 patients (7.4%) had CSRP, with 5 cases requiring oxygen. The cumulative incidence of CSRP at 6 and 12 months was 5.3% and 7.6%, respectively. The cumulative incidence of LF at 2 years was 10.5%. The cumulative incidence of ICST at 2 years was 41.1%. Median progression-free survival was 11.8 months and median overall survival was 51.3 months. On multivariable analysis, a higher lung V35Gy (hazard ratio, 2.59; P = .02) was a statistically significant predictor of CSRP and colorectal histology predicted for higher LF (hazard ratio, 2.12; P = .02).Conclusions: In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Optimizing plans to lower the lung V35Gy may decrease the risk of CSRP. [ABSTRACT FROM AUTHOR]

Purpose: Prolonged survivorship is increasingly observed in patients with oligometastases (OM) treated with stereotactic body radiation therapy (SBRT). The purpose of this study was to study the conditional survival of patients with OM, which can provide more detailed prognostic information over time by considering time already survived.Methods and Materials: A multi-institutional database consisting of 1033 patients with OM (≤5 metastases) treated with SBRT between 2006 and 2017 was analyzed. Conditional overall survival (OS) and progression-free survival (PFS) in 3 years were obtained at multiple time points for all patients and by primary cancer type. Cox regression was used to determine trends in conditional OS and PFS. Changes in the predictors of OS and PFS over time were also determined by multivariable Cox regression.Results: The median follow-up was 24 months (0.3-105 months). Three-year OS and PFS at baseline were 56.7% and 23.2%, respectively. The OS in 3 years conditional on having survived for 3, 6, 12, and 24 months did not significantly change over time (56.7%, 55.4%, 55.8%, and 50.6%, respectively; P = .60). In contrast, the probability of PFS in 3 years conditional on having survived progression-free for 3, 6, 12, and 24 months significantly increased over time (23.6%, 27.3%, 35.1%, and 48.8%, respectively; P < .001). When stratified by primary site, conditional PFS significantly increased over time for patients with colorectal, breast, or kidney cancer. Conditional OS remained stable for patients with non-small cell lung cancer or kidney cancer but significantly decreased over time for patients with prostate, breast, or colorectal cancer. Changes in significant prognostic factors of OS and PFS over time were also observed.Conclusions: Analysis of conditional survival among patients with OM showed that as patients survived longer, their prognosis for further survival remained stable or decreased. However, patients who survived longer without disease progression had increased probability of PFS over time. [ABSTRACT FROM AUTHOR]

Purpose: Patients with breast cancer and ipsilateral axillary and internal mammary (IM) lymph node involvement (cN3b) often forgo IM node resection. Therefore, radiation is important for curative therapy. However, prognosis is not well described in the era of modern systemic therapy, and limited data exist to guide optimal locoregional treatment recommendations.Methods and Materials: We retrospectively reviewed 117 patients with nonmetastatic cN3b breast cancer treated at our institution between 2014 and 2019. Staging included ultrasound evaluation of all regional nodal basins. All patients received neoadjuvant chemotherapy, resection of the breast primary, and axillary nodal dissection, followed by adjuvant radiation to the breast/chest wall and regional nodes. Institutional guidelines recommend a 10-Gy boost to radiographically resolved nodes, and a 16-Gy boost to unresolved nodes. Overall survival, recurrence-free survival (RFS), locoregional RFS, internal mammary RFS, and distant metastasis-free survival were evaluated with Kaplan-Meier analysis. A multivariable model for RFS was constructed.Results: Median follow-up for 117 patients was 3.82 years. Median age at diagnosis was 46 years and 56 patients (48%) were receptor group ER+/HER2-. Mastectomy was performed in 96 patients (82%), 38 (32%) had biopsy-confirmed IMC involvement, and 8 (7%) had IM node dissection. The median initial radiation dose was 50 Gy (range, 50-55 Gy) and IMC boost 10 Gy (range, 0-16 Gy). The 5-year overall survival, IM RFS, locoregional RFS, distant metastasis-free survival, and RFS were 74%, 98%, 89%, 68%, and 67%, respectively. On multivariable analysis, a clinical complete response of the IM nodes or ypN0 (pathologic complete response of nodes) status had improved 5-year RFS with hazard ratios of 0.24 (P = .006) and 0.27 (P = .05), respectively. Extranodal extension or lymphovascular invasion were associated with worse 5-year RFS with hazard ratios of 4.13 (P = .001) and 2.25 (P = .04), respectively.Conclusions: Multimodality therapy provides excellent locoregional control of 89% at 5 years for patients with cN3b breast cancer. Adjuvant radiation yields a 5-year IM RFS of 98%. Clinical and pathologic response of IM nodes are independently prognostic for RFS. [ABSTRACT FROM AUTHOR]

Purpose: Patients with breast cancer and ipsilateral supraclavicular (SCV) node involvement at the time of diagnosis (TNM cN3c) have historically had poor outcomes. Radiation therapy (RT) has an important role because SCV nodes are not routinely surgically dissected. However, optimal locoregional management, contemporary outcomes, and prognostic factors are not well defined.Methods and Materials: We reviewed the data of patients with cN3c breast cancer treated at our institution between 2014 and 2019 with curative intent, including neoadjuvant chemotherapy, surgery, and adjuvant RT. All patients received comprehensive regional RT, including to the SCV nodes. Institutional guidelines recommend a 10-Gy or 16-Gy boost to resolved and unresolved N3 nodes, respectively. Overall survival (OS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and supraclavicular recurrence-free survival (SCRFS) were analyzed.Results: Data from 173 consecutive patients were analyzed with a median follow-up time of 2.8 years. The median age was 54 years, 76 patients (44%) were estrogen receptor positive/human epidermal growth factor receptor 2 negative, 100 patients (58%) had T3/4 disease, and 10 patients (6%) underwent a neck dissection. In addition, 156 patients (90%) received a cumulative SCV dose of ≥60 Gy. The 5-year OS, SCRFS, LRRFS, and RFS rates were 73%, 95%, 86%, and 50%, respectively. The 5-year OS rate for a cumulative SCV dose of ≥60 Gy versus <60 Gy was 75% versus 39% (P = .04). In the multivariable analysis, a cumulative SCV dose of ≥60 Gy, extranodal extension, receptor status, and Eastern Cooperative Oncology Group performance status were associated with OS. The 5-year SCRFS rates with and without neck dissection were 100% versus 95% (P = .57). Among patients with a postchemotherapy SCV node size of ≥1 cm without neck dissection, the 5-year SCRFS rate was 83%.Conclusions: In one of the largest series of patients with cN3c breast cancer, multimodality therapy using adjuvant RT with a SCV boost resulted in a 5-year LRRFS rate of 86%. There is a limited role for neck dissection as the 5-year SCRFS rate was 95% overall and 83% for residual SCV disease ≥1 cm after chemotherapy with RT alone. A cumulative SCV dose of ≥60 Gy was associated with improved OS, but not SCRFS, LRRFS, or RFS. A SCV boost should be considered in these patients as treatment was well-tolerated. Despite advances in systemic therapy, nearly half of patients developed distant metastases, highlighting the need for close observation after treatment. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based radiomics for the treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT). This retrospective study included 122 locally advanced ESCC patients who received dCRT. Eligible patients were randomly divided into training cohort (n = 85) and validation cohort (n = 37). Least absolute shrinkage and selection operator (LASSO) regression was performed to select optimal radiomic features to calculate Rad-score for predicting overall survival (OS) in the training cohort. Univariate and multivariate analyses were performed to identify the predictive clinical factors and hematologic parameters for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy. Tenradiomic features were selected by LASSO regression analysis to calculate Rad-score for predicting OS. The patients with Rad-score>0.47 had high risk of death, and those with a Rad-score≤0.47 had low risk of death. Tumor location and neutrophil-to-monocyte ratio (NMR) were significantly associated with OS in univariate analysis. Multivariate analysis showed that NMR and Rad-score were independent predictive factors for OS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.619 (95% CI 0.518-0.720) in training cohort and 0.573 (95% CI 0.385-0.760) in validation cohort. The 2-year OS rate predicted by the nomogram model was highly consistent with the actual 2-year OS rate both in training and validation cohorts. We developed and validated a prediction model based on radiomic features and hematologic parameters, which could be used to predict OS of ESCC patients after dCRT. This model is conducive to identifying the patients with ESCC benefited more from dCRT. [ABSTRACT FROM AUTHOR]

Brain metastases (BM) are a common occurrence in patients with advanced cancers, and extremely challenging to treat, resulting in short survival periods. Consequently, whole brain radiation therapy (WBRT) remains the standard palliative intervention for patients with BM. The present study set to evaluate the efficacy of WBRT by assessing the quality of life (QoL) and survival outcomes in WBRT-treated patients with BM. It was hypothesized that the WBRT would enhance the QoL through alleviation of symptoms and functionality, and prolong patient survival. This was a prospective, longitudinal, hospital-based single-center study. Consecutive sampling methodology was used to recruit 52 patients with BM undergoing WBRT. Patients were followed up on days 7, 30, 90 and 180 after WBRT. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative care (EORTC QLQ-C15-PAL) was employed to report patient responses in a Likert scale. A descriptive analysis and multi-trait scaling correlation was computed using IBM SPSS Statistics 29.0, 95% confidence interval. The overall survival analysis (Kaplan-Meier) was also performed. The study cohort was predominantly females (82.7%), and accordingly, 65.4% of the respondents had a breast primary tumor. A Shapiro-Wilk test of normality revealed that the data was not normally distributed (sig. < 0.05), however, statistic values (W) closer to 1 suggested a good fit. A goodness-of-fit test ascertained the assumption, yielding non-significant Chi square Pearson (p = 0.325) and Deviance (p = 1.000) residuals. There was a significant correlation (p < 0.001) between physical functioning and emotional functioning. Median overall survival was 180 days (∼6 months). A total of 20 patients (38%) that survived up to 180 days reported alleviated symptoms and better functioning. A significant improvement in physical functioning (p < 0.001) and emotional functioning (p = 0.031) was reported at 180 days post WBRT, compared to baseline. Similarly, a significant improvement in visual disorders (p = 0.002), motor dysfunction (p = 0.031), and communication deficit (p = 0.001) was also reported. A significant alleviation of pain was reported at day 90 (p = 0.042) by 53% of the patients that survived. WBRT is an effective palliative intervention in patients with BM, resulting in improved QoL and prolonged survival. More than 50% of patients that survived 3 months reported a significant alleviation of pain, and 38% of patients that survived for 6 months reported a significantly improved functioning. This demonstrated the effectiveness of WBRT in palliative care and will add to the body of data on the efficacy of radiotherapy. [ABSTRACT FROM AUTHOR]

Definitive chemoradiation is the standard treatment for loco-regionally advanced cervical cancer. One of the major changes in the 2018 FIGO staging update was the inclusion of para-aortic lymph node (PAN) involvement in a new IIIC2 category. However, the impact of the extent of para-aortic involvement on treatment outcomes remains unclear. This study aims to correlate features of PAN metastases with treatment outcomes in order to inform future treatment strategies for these patients. Electronic medical databases were queried to identify all cervical cancer patients with FDG-avid PAN metastases treated with curative intent using extended field radiotherapy +/- concurrent chemotherapy at our institution between 2004 to 2018. Patients with neuroendocrine histology or distant metastases were excluded. We determined the number of FDG-avid PANs; distance between the highest PAN and the renal vessels or aortic bifurcation; and the size of the largest PAN. Analysis of variance, Kaplan-Meier method, log-rank tests, and Cox proportional hazard tests were used for analysis. The 5-year OS of the 102 patients in this study was 42% (95% CI, 32-52%), and the 5-year DMFS was 49% (95% CI, 39-59%). The 5-year OS for patients with non-squamous cancers metastatic to the PANs (N=18) vs. patients with squamous cancers metastatic to the PANs (N=84) were 28% and 45%, respectively (P = 0.075). None of the PAN characteristics studied were significantly associated with OS. However, DMFS was strongly associated with the number of FDG-avid PANs; DMFS of patients with <5 or ≥5 PANs were 56% and 17%, respectively (P = 0.0002). PAN size and the distance between the highest PAN and the renal vessels were not significantly correlated with DMFS. On univariate analysis, age (P = 0.12), BMI (P = 0.91), FIGO 1994 stage (P = 0.35), primary lesion size (P = 0.31), or histologic type (P = 0.99) were not significant predictors of PAN count. None of the 3 patients with more than 5 PAN mets from non-squamous cervical cancers survived. For patients with < 5 positive PANs, those with non-squamous cancers (15 patients) had a 5-year OS of 33%, vs. 44% for 77 patients with squamous histology (P = N.S.). On multivariate analysis, PAN count was significantly associated with 5-year DMFS but not OS. Although the number of FDG+ PANs was correlated with poor DMFS, proximity to the renal vessels and nodal size appear to have less influence on outcome. The presence of both PAN count 5 or higher and adenocarcinoma histology conferred very poor outcomes. Although even patients with extensive PAN metastases are frequently curable with RT, these data suggest that patients with many PAN metastases from non-squamous cervical cancers may benefit from strategies that emphasize systemic treatments. [ABSTRACT FROM AUTHOR]

Promising therapeutic results of immune checkpoint inhibitor (ICI) have been reported in various solid tumors. Radiotherapy (RT) is known to enhance the immunogenic effect. The immunogenic effect of RT is expected to improve the therapeutic effect of ICI. In this study, we aimed to investigate the efficacy and toxicity of combining ICI and RT in hepatobiliary cancer. Patients who received RT and ICI combination therapy for hepatobiliary cancer from January 2020 to December 2021 were retrospectively reviewed. Baseline patient characteristics such as age at diagnosis, stage, previous treatment, radiation dose, tumor volume, and lymphocyte count were recorded. The primary endpoints were in-field and out-field control rate. The secondary endpoint was treatment-related toxicities. Overall survival and progression-free survival were also evaluated. The disease control rate and survival were assessed using the Kaplan-Meier method. In total, 20 patients and 42 treated lesions were included for analysis. The median follow-up period was 6.2 months (range 2.4 – 23 months). Of the 20 patients, 15 were diagnosed hepatocellular carcinoma (75.0%). Sixteen patients had distant metastasis (80.0%). Various treatments were administered to the patients prior to ICI and RT combination treatment. The 6-month overall survival and progression-free survival was 62.8% and 31.5%, respectively. The 6-month in-field control rate was 71.8% and 6-month out-field control rate was 30.2%. Higher BED (≥ 90 Gy) was a significant prognostic factor for both in-field and out-field control, and lymphopenia (≤ 800 /μL) at the time of RT start was a poor prognostic factor for outfield control. Fractional dose of less than 5 Gy showed improved in-field control. Treatment related toxicity occurred in 11 patients (55.0%). The most frequent adverse event was GI disorders such as esophagitis (n=3) and epigastric pain (n=3). Patients who experienced treatment-related toxicity were well recovered after conservative care. There was no grade 3 or 4 toxicity. The combination of ICI and RT showed substantial efficacy with acceptable toxicity in heavily pretreated advanced hepatobiliary cancer patients. Dose per fraction of less than 5 Gy may be appropriate for better efficacy in future study of combining ICI and RT. The results of this study provide a basis for future prospective study in hepatobiliary cancer. [ABSTRACT FROM AUTHOR]

Medicaid insurance is associated with worse oncologic outcomes than private insurance and with similar outcomes as being uninsured, even after accounting for area-level socioeconomic status and stage at diagnosis. However, prior studies have not addressed potential confounding due to individual-level socioeconomic status, which determines Medicaid eligibility. Our objective was to quantify insurance disparities in overall survival after accounting for imputed individual-level federal poverty level. We collected data for patients 18-64 years old diagnosed with cancer in 2014-2016 from the Surveillance, Epidemiology, and End Results (SEER) Program. We analyzed these years as increased Medicaid eligibility income limits after 2014 increase comparability of socioeconomic status between the insurance groups. We imputed individual-level percent Federal Poverty Level (FPL) using a model trained on patients from the general U.S. population who participated in the 2016 Behavioral Risk Factors Surveillance Survey (BRFSS) with covariates also present in SEER: insurance status, age, race/ethnicity, sex, marital status, metropolitan residence, and state. Predictive accuracy was assessed with 5-fold cross-validation. The association of 1-year overall survival (OS) and insurance status was estimated using robust regression models accounting for imputation uncertainty, with and without adjustment for estimated individual-level FPL, cancer site, stage at diagnosis, county income and education, and the aforementioned covariates. A total of 308,557 BRFSS respondents were utilized to establish associations between covariates and FPL. The cross-validated accuracy of the model in predicting FPL <100%, 100-150%, 150-200%, and >250% was 84.9%, 79.6%, 61.6%, and 64.3%, respectively. A total of 416,784 cases in SEER were analyzed. The 1-yr OS for patients with private insurance, Medicaid insurance, and no insurance was 88.7%, 76.1%, and 73.7%, respectively. After adjusting for all covariates except individual-level FPL, there was worse 1-yr OS with Medicaid (-6.0%, 95% CI = -6.3 to -5.6, p<.001) and no insurance (-6.7%, 95% CI = -7.3 to -6.0, p<.001) compared to private insurance. However, after also adjusting for estimated individual-level FPL, there was no difference in 1-yr OS between Medicaid and private insurance (-0.4%, 95% CI = -1.9 to 1.1, p=.68), and uninsured individuals had significantly lower 1-yr OS than those with Medicaid (-2.1%, p<.001) or private insurance (-2.6%, p<.001). Subgroup analyses by cancer site showed similar patterns. These are the first data demonstrating similar cancer outcomes between patients with Medicaid and private insurance after accounting for estimated individual-level FPL and other covariates, more completely controlling for potential social determinants of health. Medicaid coverage may improve outcomes among low-income individuals without access to insurance. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer related death in the US and globally. Stage IV non-small cell lung cancer (NSCLC) is considered incurable with goals of treatment including improving symptoms and prolonging life. In recent years, the addition of targeted therapy and immune checkpoint inhibitors has improved overall survival (OS) of stage IV NSCLC. We undertook this retrospective analysis to assess the impact of modern day therapy on OS of stage IV NSCLC treated in a single institution over more than a decade. This retrospective IRB approved study was conducted using a database of stage IV NSCLC patients treated with systemic therapy or radiation at our institution between 2005 to 2018. Patient charts were reviewed to extract information on age, gender, race, year of diagnosis, treatments and survival. OS was calculated from date of diagnosis until death using Kaplan Meier estimates. The Cox proportional hazards model was used to analyze the association between OS and demographic and tumor factors, as well as treatment periods from 2005-2010, 2010-2015, and 2015-2018. Statistical analysis was performed using R (v. 4.1.2). A total of 973 adults diagnosed with stage IV NSCLC were included in this analysis. The median age was 65 years (20-97). The median follow-up (FU) of living patients was 2.87 years (0-17.5). 52.8% patients were female, 68.6% had adenocarcinoma followed by 14.9% with squamous cell cancer and 13.3% with NSCLC NOS. The majority (64.5%) of patients were Caucasian while 33.0% were African American. 59% of patients received radiation, and 62.6% received systemic therapy. 22.6% of patients were treated between 2005-2010, 36.4% between 2010-2015 and 34.24% after 2015. The median OS for the cohort was 0.84 years with 5-year OS of 9.93%. The median OS of patients diagnosed before 2010, between 2010 and 2015, and after 2015 were 8.2, 9.8, and 13 months respectively (p < 0.0001). The corresponding 2-year OS was 17.2%, 29.4% and 36.7%, for diagnosis before 2010, between 2010-2015 and after 2015. On multivariable analysis, NSCLC NOS histology (1.36, p<0.01) was significant for worse OS, while systemic therapy (0.82, p=0.006) and treatment between 2010-2015 (0.67, p<0.001) and 2015-2018 (0.49, p<0.001) were significant predictors of improved OS. Palliative radiation, age, and gender were not significant. In this single institution study, the OS of stage IV NSCLC was significantly improved based on treatment between 2010-2015 and after 2015. As suggested from clinical trials, real world evidence suggests continued improvement in OS with improvement in systemic therapy and other palliative measures. Additionally, having a histology of NSCLC NOS was significant for worse OS in this study. [ABSTRACT FROM AUTHOR]

Locally advanced, non-metastatic pT4 well-differentiated thyroid cancer (WDTC) diagnosed at age <55 years is considered to be Stage I disease by the American Joint Committee on Cancer (AJCC) 8th edition staging system implying excellent cause-specific survival (CSS) outcomes of ≥95% at 10 years. There are no published outcomes however on this specific cohort of patients, and they may be underrepresented in published outcome series as they comprise of <5% of all WDTC patients. Thus, the objective was to determine the recurrence and survival outcomes of this cohort. We conducted a population-based retrospective study of all patients with pT4 WDTC diagnosed at age <55 years, treated in our province from 1985 to 2013 were extracted. Demographic and treatment factors were extracted. The primary endpoints were cumulative incidence of locoregional recurrence (LRR), cause-specific survival (CSS) and overall survival (OS). Competing risk Fine-Grays analysis and Cox-proportional hazards model was used. There were 218 patients (median follow up 18.2 years) with 137 under the age of 45. Patients were all treated with thyroidectomy. Most patients had papillary histology (95.9%). Adjuvant radioactive iodine was administered in 88% of cases, and 43% received adjuvant external-beam radiotherapy (EBRT). The 15-year LRR was 21%. On multivariate analysis, there was a trend towards EBRT receipt and lower LRR (HR:0.47, p=0.06). Of the patients who did not receive EBRT, but had a LRR (n=19), 11 were salvaged (with RAI, EBRT, and surgery) and only two died of WDTC (both from LRR). For the cohort as a whole, the 15-year CSS was 96%. There were four deaths secondary to LRR and seven deaths from distant disease. Advanced age, larger tumor size, higher T stage, and presence of LVI were associated with worse CSS (all p<0.05), though we note the limited number of events limit the conclusions from our multivariate analysis. The 15-year OS was 93%. Older age, tumor size, and lymphovascular invasion were significantly associated with worse OS (all p<0.05). On multivariate analysis, EBRT receipt was not associated with improved CSS or OS. Despite very locally advanced disease, patients with non-metastatic pT4 WDTC, <55 years at diagnosis, have favorable long-term outcomes. Further prospective studies of adjuvant EBRT are needed in this population. [ABSTRACT FROM AUTHOR]

We at our center practice a PAlliative Split COurse RAdiotherapy (PASCORA) of 22.5Gy in 5 fractions followed by a gap of 4 weeks and then again repeat 22.5Gy in 5 fractions for Locally advanced squamous cell carcinoma patients treated with a palliative intent. Our Primary aim is to determine the symptomatic relief at 3 months after completion of PASCORA regimen. Our secondary objective is to evaluate the Overall Survival (OS) in our patients 49 Patients with histologically proven LAHNSCC between January 2014 to January 2021, planned for PASCORA regimen were evaluated. Retrospectively patient, tumor and treatment characteristics were retrieved. Symptomatic relief was assessed on an objective scale. OS was determined using Kaplan Meir survival curves Median age was 61 years, Multiple comorbidities (37%) were the most commonly documented reason for these patients being treated with a palliative intent. 25% of our patients had an excellent symptomatic relief, 26% of our patients had a good symptomatic relief and 31% had a partial relief. Median OS was 38 months in patients who had an excellent symptomatic relief and 3-8 months in patients with no or partial symptomatic relief (p value=0.000) 6% of our patients had Grade 3 /4 RTOG toxicity PASCORA regimen offers a good symptomatic relief with good local control rates and acceptable level of toxicity and comparable OS. However, a larger prospective study with a greater number of patients and a longer follow up would be required to confirm the same [ABSTRACT FROM AUTHOR]

Cervical cancer is the leading cause of cancer death among women in Botswana. It is well established that persistent human papillomavirus (HPV) infection is the primary risk factor for cervical cancer and that co-infection with human immunodeficiency virus (HIV) further increases the risk for cancer development. Standard of care for locally advanced disease is treatment with chemoradiation (CRT). This study aimed to characterize toxicities, response to treatment, and survival in patients with cervical cancer in Botswana. Patients with histologically confirmed locally advanced cervical cancer eligible for CRT were prospectively enrolled between Jan 2015 and June 2019 to the Ipabalele study in Gaborone, Botswana. Clinical and treatment characteristics, on-treatment toxicities, and treatment response of patients were recorded. Biochemical response to treatment was characterized using SCC-Ag level <2.2ng/ml at the end of treatment and 3 months post treatment. Toxicities were measured during on treatment visits (OTVs) and evaluated using CTCAE 4.0 grading. All patients were followed every 3 months for 2 years. Of 293 women diagnosed with cervical cancer, 73.7% (n=216) were women living with HIV (WLWH). The mean age of diagnosis for cervical cancer was younger in WLWH vs those without HIV (44.9 vs. 47.5, p<0.001). There was no difference in stage at presentation by HIV status, with the most common stage at presentation among both populations as Stage II (46.3% WLWH, 58.84% without HIV, p=0.349). Median CD4 count among WLWH was 467 cells/μL. WLWH had a lower external beam radiation dose (45.76 Gy) compared to women living without HIV (47.09 Gy), p=0.002; however, HIV status did not impact total EQD2 (median 85.7 Gy). HIV status did not impact number of chemotherapy cycles received (median 4 cycles). Seventy three percent (n=106) of all patients had a complete response to treatment by clinical exam and imaging, 65% (n=82) of all patients had a complete response to treatment by SCC-Ag. HIV status did not impact response to treatment by either SCC-Ag or clinical evidence (p=0.718). Two-year overall survival (OS) probability for the cohort was 77.7%. There was no difference in survival by HIV status (OS 75.8% in WLWH; 82.05% in those without HIV, p=0.31). Treatment response by SCC-Ag was associated with OS. Factors associated with OS in a multivariate analysis included cycles of chemotherapy given and stage at presentation. HIV was not significantly related to overall survival. The most common Grade2+ toxicities included anemia (42.8%, n=125), leukopenia (34.6%, n=101), and radiation dermatitis (39.9%, n=101). Importantly, HIV did not impact prevalence of any of the toxicities measured. HIV status impacted age of diagnosis of cervical cancer; however, did not impact stage, treatment received for cervical cancer, or OS. There was no difference seen in chemoradiation associated toxicities of treatment for locally advanced cervical cancer by HIV status. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Patients with locally advanced cervical cancer are at higher risk of para-aortic lymph node recurrence, however, the addition of prophylactic para-aortic irradiation is still controversial. The aim of this study was to evaluate prognostic factors related to para-aortic recurrence in patients with cervical cancer and pelvic lymph node metastasis (2018 FIGO Stage IIIC1).Materials/methods: A retrospective cohort analysis was conducted with patients with cervical cancer and pelvic lymph node metastasis (2018 FIGO Stage IIIC1), that were treated with primary or adjuvant chemoradiotherapy from 2007 to 2018 at a single tertiary cancer center. Clinical and pathological variables were evaluated, as well as radiological and radiotherapy planning factors. Kaplan-Meier method was used to calculate survival and survival comparison between groups with log-rank method. Statistically significant was defined as P ≤ 0.05.Results: Seventy-two patients were included: 56 (77.8%) had primary chemoradiotherapy and 16 (22.2%) adjuvant chemoradiotherapy after radical hysterectomy and lymph node staging. 58 (80.5%) underwent 3D-conformal, 14 (19.5%) intensity-modulated radiotherapy, and 67 (93%) also had high dose rate vaginal brachytherapy. Only 1 patient did not receive concomitant chemotherapy. Staging PET-CT was available in 23 (31.9%) cases and the remaining ones were staged with MRI or CT scans, Surgical para-aortic staging was not performed. The median follow-up was 42 months (range, 5 to 144 months). Overall, 27 (37.5 %) patients recurred during follow-up, and 7 (26 %) had isolated para-aortic lymph-node recurrence. Distant metastasis and pelvic recurrence were found in 12 (45 %) and 8 (29 %) cases, respectively. Median overall survival, disease free survival, distant metastasis free survival, loco-regional free survival and para-aortic free survival were 56, 52, 52, 51 and 42 months, respectively. In univariate analysis, PET SUV in pelvic lymph nodes higher than 10.2 (P = 0.02) and positive lymph nodes in the left common iliac station (P = 0.05) were identified as predictive factors for isolated para-aortic recurrence. We also identified positive lymph node in the common iliac station as a predictor for distant recurrence (P = 0.002). Tumor size larger than 66 mm (P = 0.046) and positive lymph node in the left common iliac lymph node station (P = 0.02) as predictors for pelvic recurrence. Lymph node > 24 mm was the only prognostic factor associated with overall survival (P = 0.012).Conclusion: In this retrospective cohort, radiological and radiotherapy planning factors as high lymph node's PET SUV and proximal location of positive pelvic lymph nodes were prognostic for para-aortic recurrence in IIIC1 cervical cancer patients. Further prospective and randomized studies are required to validate those risk factors as well as to determine if prophylactic para-aortic irradiation would improve outcomes in these patients.Author Disclosure: P.J. Pinto: None. S.L. Favareto: None. C.F. Souza: None. G. Baiocchi: None. A.A. da Costa: None. A.C. Pellizon: None. C. Abrahao: None. D.G. Castro: None. G.R. Gondim: None. H. Ramos: None. E. Santos Neto: None. R.C. Fogaroli: None. M.G. Silva: None. M.J. Chen: None. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Stereotactic body radiotherapy (SBRT) is recommended only for inoperable patients with early stage (e-stage) non-small cell lung cancer (NSCLC). We compared outcomes between surgery and SBRT in borderline patients for surgery due to impaired pulmonary function (PF).Materials/methods: In our institution, operable patients (i.e., sufficient PF and no serious comorbidity) were generally selected for surgery after discussion among the multidisciplinary team. The inoperable patients decided after discussion among the multidisciplinary team and those who refused surgery were usually selected for SBRT. The total dose of 44 or 48 Gy for tumors with a maximum diameter < 1.5 cm, 48 or 50 Gy for tumors of 1.5-3 cm, and 52 Gy for tumors > 3 cm was prescribed to the isocenter of the planning target volume. Surgery included lobectomy, sub lobar resection (SLR), and wedge resection (WR) by video-assisted thoracic surgery or open thoracotomy at the thoracic surgeons' discretion. We reviewed single-institutional retrospective data of 578 patients with clinically T1-2N0M0 NSCLC treated by surgery or SBRT between 2004 and 2014, and extracted a cohort with borderline impaired PF for surgery, which was defined as predicted postoperative (PPO) forced expiratory volume in 1 second (FEV1) of < 50% and ≥ 30%. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared between surgery and SBRT using propensity score-matching (PSM) to avoid bias.Results: Among a total of 116 eligible patients with a median PPO FEV1 of 45%, PSM identified 25 patients from each group with similar characteristics. After PSM, 17 (68%), 3 (12%), and 5 (20%) patients underwent lobectomy, SLR, and WR, respectively. The median age, pretreatment FEV1, and follow-up durations for the surgery and SBRT groups were 75 and 74 years, 58% and 56%, and 56 and 60 months, respectively. The 5-year OS, CSS, and DFS rates of the surgery vs SBRT groups were 60% vs 63%, 76% vs 81%, and 52% vs 48%, respectively (P = 0.97, 0.81, and 0.99). Among the matched patients, one patient died of massive hemorrhage during lobectomy. The 90-day surgical mortality was 4.0% (1 of 25), but no treatment-related death was observed after SBRT. In the surgery group after PSM, 10 (40%) patients had grade 2 or greater adverse events. In the SBRT group after PSM, 5 (20%) patients had treatment-related grade 2 or greater adverse events. After PSM, the incidence of grade 2 or greater adverse events in the surgery group was twice as high as that in the SBRT group, but this difference was not significant by the χ2 test (40% vs 20%, P = 0.22).Conclusion: Although surgery and SBRT had similar survivals, fewer adverse events were observed after SBRT. Our current study suggests that SBRT is a reasonable option for impaired PF patients borderline for surgery in e-stage NSCLC. However, a prospective study of this specific population is warranted in order to improve patient selection for SBRT or surgery. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): A recent randomized controlled trial for post-operative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) patients with N2 disease has suggested no clinical benefit. However, data regarding the possible correlation between lymph node disease burden and PORT outcomes is lacking.Materials/methods: The National Cancer Database (NCDB) NSCLC participant user file was used to identify patients who received upfront surgical resection and documented pathologic N2 disease. Patients not receiving chemotherapy were excluded. A positive to examined lymph node (PEN) ratio was calculated by dividing the number of positive lymph nodes by the number of examined lymph nodes (range 0 - 1.0). The PEN ratio was then divided into quartiles to compare overall survival (OS) with and without PORT. Cox proportional hazards modeling (CPHM) was used to assess the association between OS and PORT status by quartile group.Results: From 2004 to 2017, 22,354 NSCLC patients received upfront surgery and were found to have pathologic N2 disease. The median number of lymph nodes examined was 11 (Interquartile Range 6, 16). Median OS decreased with increasing PEN ratio: 0-0.16: 58 months, 0.17-0.30: 49 months, 0.31-0.50: 37 months, 0.51-1.0: 29 months, P < 0.001. 10,446 (47%) of this patient population received PORT. The proportion of patients receiving PORT increased by PEN ratio quartile: first quartile 40% versus last quartile 52%, P < 0.001. There was no difference in OS for patients receiving PORT in the first quartile (59 months versus 57 months without PORT, P = 0.3). However, each of the higher quartiles did demonstrate a significant improvement with PORT: 2nd quartile: 51 months versus 47 months, P = 0.01, 3rd quartile: 43 months versus 37 months, P < 0.001, and 4th quartile 33.6 months versus 24 months, P < 0.001. On CPHM, receipt of PORT for patients in the 3rd and 4th quartiles of PEN ratio scores was independently associated with a decreased mortality hazard: 0.88 (0.82 - 0.94), P < 0.001 and 0.79 (0.74, 0.84), P < 0.001, respectively.Conclusion: While a recent prospective clinical trial demonstrated no clinical benefit to PORT in the setting of N2 disease, this analysis shows that there may be a select population of patients that may benefit as the ratio of positive to examined lymph nodes increases. Secondary analyses in prospective trials may help delineate the role of the PEN ratio in treatment selection. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The addition of cisplatin to radiation therapy (RT) results in improved outcomes in oropharyngeal head and neck cancer (OHNC) patients. This comes at the cost of increased toxicities over RT alone and often results in the inability to complete the initially prescribed chemotherapy regimen. In this study, potential predictors of chemotherapy completion and their effect on outcomes were investigated in OHNC patients treated at two different institutions.Materials/methods: We conducted a retrospective chart review of patients with OHNC at two different institutions. Patients were staged according to AJCC 8th Ed and separated into two groups: Completers (able to complete initially prescribed concurrent cisplatin regimen) and Non-Completers (unable to complete all prescribed cycles and/or required change to a different systemic therapy agent). Age, sex, race, ECOG, smoking status, HPV status, and stage were analyzed for ability to predict completion of chemotherapy regimen and for prognostic implication on outcomes. Overall survival (OS) and local control (LC) were calculated from start of RT. Chi-squared was used for associations, Kaplan-Meier estimates were compared using log-rank test, odds ratios (OR) and hazard ratios (HR) were generated from logistic and Cox regression analyses, respectively.Results: Between 2007 and 2019, 271 patients with OHNC were reviewed and included in the study. Most patients were Stage II (60%) and HPV positive (83%). More patients were Completers (61%) than Non-Completers (39%). Mean age was 56.6 years in Completers and 58.0 years in Non-Completers. Comparing Stage I to IV was the only significant predictor of chemotherapy completion (OR 6.139, 95% CI 1.43-26.35). HPV negative status trended towards significance for non-completion (OR 0.520 P = 0.061). Predictors of inferior OS were race (Non-White vs White) HR 2.520 P = 0.001; ECOG (2-3 vs 0-1) HR 2.324 P = 0.018; ever smoker (Yes vs No) HR 2.582 P = 0.001; HPV status (Negative vs Positive) HR 3.584 P < 0.001; and Stage (IV vs I) HR 5.983, 95% CI 1.38, 25.97. Inability to complete chemotherapy was not found to be a predictor of inferior survival (HR 0.737 P = 0.173). OS at 3 years was not statistically different between Completers (81%) and Non-Completers (77%), P = 0.404. LC at 3 years was not statistically different between Completers (93%) and Non-Completers (92%), P = 0.755.Conclusion: In our study of OHNC patients who were mostly HPV positive and early stage, cancer stage was found to be the only significant predictor of chemotherapy completion. Chemotherapy completion was not found to be a predictor of outcome. Provided the Non-Completer group included those who had a change in systemic agent but may have completed the same total number of planned chemotherapy cycles, this study suggests the need for further multivariate analysis and potentially more upfront individualized chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The present study aimed to evaluate prognostic factors, particularly with respect to their role in establishing distinct prognostic subsets of human papillomavirus (HPV)-positive and -negative oropharyngeal cancer (OPC).Materials/methods: This study retrospectively evaluated 101 patients with OPC who underwent radiotherapy (RT) alone or chemoradiotherapy (CRT) at our institution between August 2008 and December 2018. Whole neck RT (44.0-50.0 Gy/22-25 fractions) was delivered by intensity-modulated RT (IMRT), followed by boost IMRT to high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Seventy patients (69.3%) received concurrent chemotherapy. Clinical factors which were potentially associated with prognosis were analyzed. Receiver-operating characteristic curve analysis was adopted to determine the most appropriate cut-off points of hematological biomarkers including the serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/ albumin ratio (CRP/Alb).Results: The median follow-up period of the surviving patients was 68 (range; 8-164) months. The 5-year overall survival rate were 69.8%. Univariate analyses revealed that poor survival was associated with gender of male, smoking≥30 pack years, Eastern Cooperative Oncology Group performance status≥1, tumor-node-metastasis (TNM) stage of III-IV (8th edition), HPV-negative, LDH≥202, CRP/Alb≥0.15, LMR < 2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack years (P < 0.01), LDH ≥202 (P = 0.02). Patients were divided into two groups according to HPV status as HPV-positive and negative OPC and potential prognostic factors were assessed in univariate analyses. In HPV-positive OPC patients, poor survival was significantly associated with smoking ≥30 pack years (P = 0.03), LDH ≥202 (P = 0.04), and LMR < 2.90 (P < 0.01). In HPV-negative OPC patients, gender of male (P < 0.01), smoking ≥30 pack years (P < 0.01), LDH ≥202 (P < 0.01), and CRP/Alb ≥0.15 (P = 0.01) were significant predictors of poor survival.Conclusion: The present study revealed that high LDH levels predicted poor survival after definitive radiotherapy in both HPV-positive and HPV-negative OPC patients. High LDH levels were stronger poor prognostic factor than HPV status and TNM stage in this study. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Surgery remains the foundation of curative therapy for non-metastatic breast cancer, but a substantial proportion of patients do not undergo surgery. Evidence is limited regarding overall survival (OS) outcomes and factors associated with lack of surgery. We sought to measure OS among patients with breast cancer who do not undergo surgery, and assess factors for association with lack of surgery and OS.Materials/methods: Retrospective cohort study of patients in the US National Cancer Data Base from 2004-2016. The dataset comprised 2,696,734 patients; excluding patients with unknown surgical status or stage IV, cT0, cTx, or pIS, metastatic or recurrent disease resulted in 1,192,294 patients for analysis. Descriptive statistics were used to summarize patient characteristics. Chi-square tests and Wilcoxon rank-sum were used to test for differences between variables between groups. OS was analyzed utilizing the Kaplan-Meier method for non-surgical patients diagnosed in 2010-2015 to account for receptor status (Median follow-up time 34 months). The Cox proportional hazards model was used to assess association of risk factors with OS.Results: Of the 1,192,294 patients, 50,626 (4.3%) did not undergo surgery. Socioeconomic factors that were more prevalent in the non-surgical cohort were Black race, age > 50 years, lower income, uninsured or public insurance, and lower education; this group was also more likely to have more comorbidities, higher disease stage, and more aggressive disease biology. Only 3,689 non-surgical patients (7.3%) received radiation therapy (RT). Median OS time for all patients who did not have surgery was 58 months (3-year and 5-year OS rates 63% and 49%). Median OS times were longer for patients who received chemotherapy (80 vs 50 months) and RT (85 vs 56 months). On multivariate analysis, age, race, income, insurance status, comorbidity score, disease stage, tumor subtype treatment facility type and location, and receipt of RT were associated with OS. On subgroup analysis, receipt of chemotherapy improved OS for patients with high-risk (triple-negative, HER2+) disease, whereas receipt of RT led to improved OS for patients with ER+ and favorable (ER+, early-stage, age > 60) disease.Conclusion: More than 4% of women with non-metastatic breast cancer do not undergo surgery for their cancer, particularly those with more aggressive disease, of minority race/ethnicity and lower socioeconomic status. Despite its known benefits, RT was significantly underused. This study provides one of the first benchmarks of survival outcomes for patients who do not undergo surgery for breast cancer, and highlights a potential role for increased use of RT. Additionally this report highlights significant disparities effecting women of minority race/ethnicity and lower socioeconomic status. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Thoracic radiotherapy (TRT) is a mainstay treatment for locally advanced non-small cell lung cancer (LA-NSCLC). Mean heart dose (MHD) and left anterior descending (LAD) receiving ≥15 Gy (LADV15) was shown to predict major adverse cardiac events (MACE) in LA-NSCLC patients receiving TRT. We aim to develop a clinically applicable MACE risk prediction score model, including both cardiac dosimetric and baseline risk factors.Materials/methods: Retrospective data from 748 consecutive patients with LA-NSCLC treated with curative intent between November 1998 to December 2013 were included. The data was split based on diagnosis dates to allow external validation. Model development was performed on 500 consecutive patients diagnosed before December 2010 using multivariable Cox-proportional hazard model; backward elimination scheme (α = 0.05) was used to select the predictors for the final model. Potential predictors were selected a priori based on prior literature: age, pre-existing coronary heart disease (CHD), Framingham Risk, hypertension (HTN), MHD, LADV15, intensity modulated RT (IMRT) use, and interaction between CHD and LADV15 (CHD:LADV15). Model performance was assessed by the Harrell's c-index and internally validated using leave-one out cross validation (LOOCV). The model was applied to the remaining 248 consecutive patients from the initial cohort as the external validation "test" dataset.Results: The development and test cohorts had median age 64 vs 66 years (P = 0.02), 51.0 vs. 50.4% females (P = 0.88), and 89.4 vs 89.1% stage III cancer (P = 0.91). The final model incorporated CHD, HTN, LADV15, and CHD:LADV15 (β coefficients: 2.703, 1.129, 0.043, -0.047; all P < 0.001; c-index 0.773). LOOCV Pseudo R2 = 0.0195. The c-index on the external test dataset was 0.727. Actuarial 3-year MACE rates were 10.7% for development cohort and 15.4% for test cohort. Stratifying development cohort patients into terciles based on MACE risk prediction scores yielded 3-year MACE rates of 0%, 5.7%, and 25.6% for lowest to highest risk-terciles, respectively; among test cohort, the 3-year MACE rates were 4.9%, 10.5%, and 31.9%. Respectively, the 3-year overall survival rates for lowest to highest MACE risk-terciles were 47.3%, 35.2%, and 32.8% among development cohort, and 52.3%, 43.9% and 30.6% within test cohort (both Log-rank P < 0.05).Conclusion: The 3-year MACE rates spans 5% to 32% from lowest to highest risk groups. Both LADV15 and pre-existing cardiac risk factors are important in predicting MACE risk post-TRT. MACE risk score was associated with survival. This tool has the potential to estimate personalized LADV15 constraints based on patient risk factors and acceptable MACE risk thresholds (e.g., 5-10%), thus may help identify patients who may benefit most from the application of advanced RT techniques to further reduce LAD dose as a modifiable risk factor during RT planning. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To evaluate the impact of regional nodal irradiation (RNI) on the loco-regional recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) in breast cancer patients with node positive disease who received neoadjuvant chemotherapy (NAC) and became ypN0.Materials/methods: From January 1st 2016 till December 31st 2019, 231 patients with node positive breast cancer who received NAC and became ypN0 were randomized to receive whole breast irradiation/post mastectomy irradiation with or without RNI. One hundred and twelve patients were included in the regional nodal irradiation arm (RNI+) and 119 patients were included in the no regional nodal irradiation arm (RNI-).Results: Median follow up was 24 months (range, 1-55 months). No regional nodal failures were recorded in both groups. The actuarial LRFS was 98.2% in the RNI+ arm and 100% in the RNI- arm (P 0.28). The actuarial DMFS was 93.6% in the RNI+ arm and 97.4% in the RNI- arm (P 0.93). The actuarial OS was 96.3% in the RNI+ arm and 99.1% in the RNI- arm (P 0.75). Cox univariate regression analysis revealed initial tumor size > 5 cm (HR 1.276, CI 1.054-1.543, P 0.012) was the only factor associated with increased incidence of distant metastases. Age younger than 35 years was associated with worsened survival (HR 0.866, CI 0.760-0.986, P 0.03).Conclusion: In the current interim analysis, omission of regional nodal irradiation did not compromise the outcomes in clinically node positive patients who received NAC and had ypN0 disease. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Locally advanced non-small cell lung cancer (LA-NSCLC) has strong tumor heterogeneity. Postradiotherapy concentration of circulating tumor DNA (ctDNA) has been demonstrated a promising prognostic biomarker of LA-NSCLC and might be helpful in assisting consolidation decision-making. However, it is widely acknowledged that many biomarkers are specific to certain patient populations. Therefore, we performed this prospective study in Chinese patients with LA-NSCLC to evaluate the prognostic role of ctDNA.Materials/methods: We consecutively enrolled patients with unresectable LA-NSCLC. Plasma samples were prospectively collected at different time point if obtained (1) baseline (pretreatment), (2) the fourth week during radiotherapy (RT), and (3) one-month post RT. All plasma specimens were subjected to next-generation sequencing panel of 474 cancer-related genes. Plasma samples with at least 1 variant detected were defined as ctDNA+. A landmark analysis was used to assess predictive value of ctDNA clearance at the time point of one-month post RT. Nonparametric test was used to compare ctDNA concentrations among groups. The Kaplan-Meier method was used to estimate survival distributions, Cox model to estimate hazard ratios and confidence intervals, and log-rank test to estimate P value.Results: A total of 35 patients treated with definitive chemoradiotherapy (CRT) were enrolled. The median follow-up from diagnosis was 16 months. At baseline timepoint, 21 patients with ctDNA+ and 14 patients with ctDNA-. For ctDNA+ patients, ctDNA concentration (ng/ml) was significantly higher with increasing clinical stage (stage IIIA vs stage IIIB vs stage IIIC, 0.345 vs 0.580 vs 3.630, P = 0.007). Both progression free survival (PFS) and overall survival (OS) was not significantly different between ctDNA- and ctDNA+ group at baseline timepoint. However, at the time point of one-month post RT, patients with ctDNA- had significantly higher PFS (median: NA vs 7 months; HR 0.205, 95% CI: 0.066∼0.637; P = 0.002) and OS (HR 0.065, 95% CI: 0.008∼0.541; P = 0.001). Kinetic changes in ctDNA concentrations were analyzed in 16 pts with matching baseline and one-month post RT specimens. Of these 16 cases with detectable ctDNA at baseline, 50% (8/16) became undetectable at one-month post RT ("ctDNA clearance"), all these 8 patients were alive and nonrecurrent during the following-up. ctDNA clearance was associated with significantly higher PFS (P = 0.003) and OS (P = 0.016) compared with ctDNA residual patients.Conclusion: For LA-NSCLC receiving CRT, ctDNA concentration was significantly higher with increasing clinical stage (IIIA vs IIIB vs IIIC). Baseline ctDNA+/- seemed not a prognosis factor, whereas ctDNA- or ctDNA clearance at the time of one-month post RT was associated with significantly superior PFS and OS. More enrolled patients are needed to update and validate these results.Clinical Trial Information: NCT04014465. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Definitive or adjuvant radiotherapy (RT) for vulvar squamous cell carcinoma (VSCC) is associated with significant toxicity that can negatively impact a patient's health-related quality of life (HRQoL). Given the rarity of this disease, data on the incidence of acute and late severe toxicity as well as the real-world late-symptom burden from a modern cohort are lacking.Materials/methods: Patients with VSCC treated with adjuvant or definitive radiotherapy with curative intent from 2009-2020 within our multi-center academic medical system were retrospectively analyzed. Treatment-related acute and late (≥3 months after RT) grade 3 or greater toxicities assessed by CTCAE version 5.0 were recorded. All provider-reported subjective symptoms (PRSS) documented from the date of RT completion to the date of last follow up were recorded. Kaplan-Meier model was used to estimate one-year overall survival (OS) and progression-free survival (PFS).Results: Thirty-nine patients received either definitive (n = 22, 56.4%) or adjuvant (n = 17, 43.6%) RT to a median dose of 64.4 Gy and 59.4 Gy, respectively. Five patients (3 definitive, 2 adjuvant) received a brachytherapy boost with a median total EQD2 of 84.3 Gy. Intensity-modulated or volumetric-modulated arc RT was used in 34 (87.2%) of patients, and 22 patients (56.4%) received concurrent chemotherapy. Median follow up time was 12.5 months (Q1-Q3: 2.8-31.3 months) for all patients and 14.9 months (3.8-33.2) for alive patients. Seventy-four percent of patients (FIGO Stage I; n = 10, II; n = 5, III; n = 10, IVA; n = 4) had a complete response based on clinical (n = 26) or pathologic (n = 3) criteria, including 16 treated with adjuvant RT and 13 treated with definitive RT. The 1-year estimated OS and PFS were 90.4% and 90.5%, respectively. The incidence of acute grade ≥3 toxicity was 35.9% (n = 14). Acute grade ≥3 skin toxicity was most common (n = 10, 25.6%), followed by urinary (n = 1, 2.6%), gastrointestinal (n = 1, 2.6%), hematologic (n = 1, 2.6%), and fatigue (n = 1, 2.6%). Five (12.8%) patients experienced late grade ≥3 toxicity, including 2 patients (5.1%) with grade 3 dermatologic toxicity, 2 patients (5.1%) with grade 4 skin toxicity, and 1 patient (2.6%) with grade 3 gastrointestinal toxicity. Among the 32 patients with PRSS data available, 6 (15.3%) reported dyspareunia or inability to have sexual intercourse, 5 (12.8%) noted skin discoloration or fibrosis, 11 (28.2%) reported long-term vaginal pain or irritation, and 8 (20.5%) required long-term opiate pain medication.Conclusion: RT for VSCC is associated with considerable rates of severe acute and late toxicity as well as PRSS that affect both a patient's physical functioning and HRQoL. Taken together with the high rates of disease control and survival, these data argue for improved patient-reported outcome measures and investigation of therapeutic de-escalation strategies.Author Disclosure: N.S. McCall: Honoraria; PrecisCA.T.Y. Eng: Stock; Amgen. J.W. Shelton: None. S. Hanasoge: None. P.R. Patel: None. A.B. Patel: Honoraria; American College of Radiology. A. McCook: None. J. Switchenko: None. T. Cole: None. N. Khanna: None. C. Han: None. A.N. Gordon: None. K. Starbuck: None. J.S. Remick: None. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The utility of metabolic positron-emission tomography (PET) parameters in patients with cervical cancer who had complete metabolic response (CMR) after chemoradiotherapy (ChRT) is unclear. We investigated the importance of metabolic parameters measured with 18F-FDG-PET/CT for predicting progression-free survival (PFS) and overall survival (OS).Materials/methods: The clinical data of 152 patients with biopsy-proven cervical cancer treated with definitive ChRT at our institution between November 2006 and August 2012 were retrospectively evaluated. The clinical data and PET parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 122 patients having CMR in post-treatment 18F-FDG-PET/CT delivered a median of 3.9 months after ChRT completion were analyzed. The PET parameters were measured for primary tumors (p) and metastatic lymph nodes (ln) separately.Results: With a median follow-up of 8.4 years, 55 patients (45%) presented with disease a median of 19.7 months after ChRT. The cut-off values determined with receiver operating curve analysis for survival were 15.8, 48.7 cm³, 552.3, 8.7, 7.0 cm³, and 24.6 and for disease recurrence were 19.9, 49.8 cm³, 597.4, 9.1, 7.3 cm³, and 25.2 for SUVp, MTVp, TLGp, SUVln, MTVln, and TLGln, respectively. All metabolic PET parameters were significant prognostic factors for OS and PFS in univariate analysis. FIGO stage was predictive of both OS and PFS, while pelvic and/or para-aortic lymph node metastasis were predictive of OS only. In multivariate analysis, FIGO stage ≥IIB [HR = 2.53 (95% CI, 1.02-7.34), P = 0.04], MTVp ≥49.8 cm³ [HR = 4.13 (95% CI, 2.51-6.78), P < 0.001] and TLGp ≥597.4 [HR = 2.21 (95% CI, 1.06-4.61), P = 0.03] were predictive of worse OS. Advanced stage [HR = 4.11 (95% CI, 0.98-7.22) P = 0.05], presence of lymph node metastasis [HR = 1.48 (1.09-2.39), P = 0.04], higher TLGp [HR = 2.31 (95% CI, 1.14-4.68), P = 0.02] and larger MTVln [HR = 2.24 (1.05-4.74), P = 0.04] were significant factors for poor PFS rates.Conclusion: Advanced stage and higher TLGp values were significant predictors for poor survival and higher progression rates. Additional prognostic factors for worse OS were larger MTVp and lymph node metastasis and for disease progression, MTVln. We also found that most disease recurrences presented as distant metastasis, which suggests a need for effective systemic treatment.Author Disclosure: C. Onal: None. O. Guler: None. M. Reyhan: None. A. Yapar: None. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The benefit of radiotherapy (RT) in poor-prognosis patients with leptomeningeal disease (LMD) is not well characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT.Materials/methods: Patients with breast cancer and classic radiographic LMD (36% cytology-confirmed) treated with palliative whole brain and/or partial spine RT between 2000-2020 at a single academic institution were included in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method, and differences in subgroups were determined using the log-rank test. Multivariate Cox proportional hazards models adjusting for estrogen receptor (ER), progesterone receptor (PR), HER2, ECOG performance status (ECOG), and systemic disease status assessed factors associated with OS. Domain-specific and any symptom improvement were ascertained by chart review of patient- and physician-report, and a multivariate logistic regression model developed incorporating ER/PR status, HER2 status, ECOG and steroid use to identify factors associated with symptom benefit.Results: Among 64 patients of median age 50 years (IQR 31-69), the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had concurrent brain metastases, and 57% of patients had ER+ and/or PR+ tumors, 22% HER2+, and 38% triple-negative disease. Among 92% of symptomatic patients whose primary symptom domains were cranial nerve deficit (34%), sensory/motor deficits due to intracranial disease (25%) sensory/motor deficits due to spine disease (27%), and headaches/nausea (14%), 42% had > 1 reported symptom domain. Two-thirds of patients were on steroids prior to RT, and only 13% of patients received intrathecal therapy. Following a median dose of 30 Gy in 10 fractions, symptom improvement in any domain was noted in 59% of patients with symptoms pre-RT, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in > 1 symptom domain. Overall survival was only 2.1 months (95% CI 1.8-3.3) in the triple-negative subgroup, and higher among patients with HER2+ disease (5.2 months, 95% CI 3.8-NR, P = 0.003). On multivariate analysis, ER+ (HR 0.4, 95% CI 0.2-0.8, P = 0.009) and HER2+ (HR 0.4, 95% CI 0.2-0.9, P = 0.018) disease were associated with improved OS. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2-11, P = 0.029).Conclusion: Even in this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yields symptomatic improvement, and may especially be of benefit among better-prognosis patients with hormone receptor-positive or HER2-positive disease.Author Disclosure: J. Takayesu: None. E. Sapir: Research Grant; LipoMedix, BioProtect. Consultant; AstraZeneca, MSD, Belong.Life. J. Xie: None. Y. Sun: None. A. Morikawa: Institutional research; Novartis, Lilly, Takeda, Eisai/H3b, Pfizer/National Comprehensive Cancer Network. L. Junck: Advisory Board; Orbus Therapeutics. D. Leung: None. Y. Umemura: None. J. Heth: None. W. Al-Holou: None. D.R. Wahl: Research Grant; Agios Inc, Innocrin Inc, American Cancer Society, NIH. Stock Options; Lycera Inc. Advisory Board Member; Agios Inc. T.S. Lawrence: None. C. Mayo: None. J.A. Hayman: Research Grant; Blue Cross Blue Shield of Michigan. M.M. Kim: Research Grant; Blue Earth Diagnostics. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Currently prophylactic cranial irradiation (PCI) is recommended for limited stage small cell lung cancer (LS-SCLC) patients with good response after thoracic chemoradiotherapy. However, the role of PCI for LS-SCLC was doubted after Japanese study published, which PCI was not superior to magnetic resonance imaging (MRI) follow up for extensive stage of SCLC. This study was aimed to investigate the role of PCI for LS-SCLC in the MRI era.Materials/methods: We retrospectively evaluated patients with LS-SCLC who without brain metastasis (BM) confirmed by MRI, and had complete response (CR) or partial response (PR) after initial chemoradiotherapy in our Center between 2007 and 2018. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated by Kaplan-Meier method between patients received PCI or not.Results: There were 121 patients enrolled in this study. The median age was 59 years old. Ninety-six patients were male, and 25 patients were female. After initial chemoradiotherapy, 55 patients achieved CR, and 66 patients achieved PR. Eighty-six patients received PCI, and 35 patients did not. For the whole group, patients received PCI had lower 2-year BM (10.8% vs 31.9%, P = 0.02), and better median PFS (58.0 [95% CI: 7.4 - 108.6] months vs 18.0 [95% CI: 11.0 - 25.0] months, P = 0.002) than those did not. However, the difference of median OS between two group was not statistically significant (95.0 [95% CI: 56.5 - 133.5] months vs 56.0 [95% CI: 13.8 - 98.2] months, P = 0.08). For the CR subgroup, patients received PCI had lower 2-year BM (8.6% vs 47.1%, P = 0.04), better median PFS (93.0[95% CI: 54.7 - 131.3] months vs 66.0 [95% CI: 0.0 - 141.6] months, P = 0.04), and better median OS (117.0 [95% CI: 85.4 - 148.6] months vs 68.0 [95% CI: 0.0 - 143.3] months, P = 0.049) than those did not. For the PR subgroup, patients received PCI had better median PFS (31.0 [95% CI: 17.0 - 44.9] months vs 16.0 [95% CI: 5.8 - 26.2] months, P = 0.012) than those did not. However, the difference of median OS between two group was not statistically significant (45.0 [95% CI: 28.4 - 61.7] months vs 56.0 [95% CI: 9.2 - 102.8] months, 2-year BM between two group was not statistically significant (12.8% vs 20.6%, P = 0.53).Conclusion: In the MRI era, LS-SCLC patients with CR after thoracic chemoradiotherapy still benefited from PCI. However, PCI should not be recommended to patients achieved only PR after initial treatment. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Concurrent chemoradiotherapy is the standard treatment for limited-stage small-cell lung cancer patients (SCLC), but the optimal dose and schedule of radiotherapy have not been established.Materials/methods: We retrospectively reviewed the clinical records of limited-stage SCLC patients treated with twice-daily thoracic radiotherapy by intensity modulated radiotherapy (IMRT) or Simultaneous integrated boost IMRT (SIB-IMRT) with concurrent chemotherapy between December 2009 to December 2017. The patients were divided into two groups according to the radiotherapy dose. The patients of SIB-IMRT group received 57Gy at 1.9Gy twice-daily to the gross tumor volume (GTV), 51Gy at 1.7Gy twice-daily to the clinical target volume (CTV) and 45Gy at 1.5Gy twice-daily to the planning target volume (PTV), and the patients of IMRT group received 45Gy at 1.5Gy twice-daily to PTV. A 1:1 propensity score matching (PSM) was applied to balance observable potential confounding factors between two groups. Primary endpoint was progression-free survival (PFS). Overall survival (OS), objective tumor response (ORR) and treatment-related toxicities were also evaluated. Statistical analyses were conducted using SPSS version 22.0 and statistical significance was defined as P < 0.05.Results: A total of 112 patients were enrolled in our study, including 71 patients in IMRT group and 41 patients in SIB-IMRT group. After PSM, the clinical features were well balanced between two groups included 37 patients each. ORR in IMRT group and SIB-IMRT group were 94.6% (35/37) and 97.3% (36/37), respectively. Median PFS was 17.54 months in IMRT group vs 34.92 months in SIB-IMRT group (P = 0.047). Median OS was 38.52 months in IMRT group vs 63.41 months in SIB-IMRT group (P = 0.261). The incidence of grade 3-4 treatment-related toxicities was 43.24% (32/74), and there was no significant difference between two groups (P = 0.639).Conclusion: Compared with IMRT, the high dose of twice-daily thoracic radiotherapy by SIB-IMRT approach with concurrent chemotherapy for the patients with limited-stage SCLC were well-tolerated and may improve PFS, but PFS improvement didn't result in significant advantage in OS. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): In consideration of the results of the RTOG0617 study, researchers began to adopt a prudent policy to high-dose radiotherapy. Based on the assume that radiation dose escalation to the primary tumor can improve local control and therefore producing survival benefits under the condition of limiting the dose to the organ at risk (OAR), we launched the study to evaluate the effect of simultaneous Integrated boost (SIB) radiotherapy implemented on the stage III local-advanced non-small cell lung cancer (LA-NSCLC) patients.Materials/methods: 42 Patients with stage III LA-NSCLC who were eligible for definite concurrent chemoradiotherapy were prospectively given the radiation regimen of single dose of 2.0Gy for PTV, 2.2Gy for CTV, and 2.4 -2.8Gy for GTV with 25 fractions. Other stage III LA-NSCLC patients retrospectively collected with routinely radiotherapy were matched through PSM. 2 Cycles of platinum based concurrent chemotherapy were carried on patients in both groups. The primary endpoints were progression-free survival (PFS), toxic effects and dose for normal tissues, with the secondary end point of overall survival (OS). The Kaplan-Meier method was used to evaluate PFS and OS, and the Mann-Whitney U test for toxic effects and the dose for normal tissues.Results: The median PFS time was 20.6 vs 9.0 months (P = 0.01), and the median OS was 40.0 vs 24.5 months (P = 0.02) in the SIB group and the control group respectively, all were obviously longer in the SIB group. No significant differences of radiation-related pneumonitis (P = 0.95) and myelosuppression (P = 0.40) have been observed between the two groups, as well as nausea, vomiting, esophagitis and dyspnea. The dose and the radiation-effected volume to the surrounding normal tissues also did not show the tendency of increasement in the SIB group.Conclusion: The results of our research has revealed that the dose escalation did improve the PFS and OS while not increased the dose to the surrounding normal tissues and the occurrence of toxic effects. Simultaneous integrated boost radiotherapy to the primary tumor might be a safe and feasible regimen to improve survival benefit for the stage III LA-NSCLC patients eligible for definite concurrent chemoradiotherapy in the future. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Whether thoracic radiotherapy (TRT) could be applied to interstitial lung diseases and lung cancer (ILD-LC) patients safely remains unclear. This retrospective study aims to evaluate the efficacy and safety of definitive TRT in locally advanced non-small cell lung cancer (LA-NSCLC) patients with pre-existing ILD, and to analyze the associated risk factors for radiation induced lung toxicities (RILTs) in the clinical setting.Materials/methods: Patients with histologically confirmed LA-NSCLC and pre-existing ILD treated definitive TRT between 2010 and 2019 were retrospectively reviewed. Patient, tumor, and treatment characteristics were evaluated to determine the risk factors for RILTs. Pre-radiation CT of all patients were reviewed by two radiologists and one pulmonologist and are scored according to Müller's thin-section CT scoring system for IPF: 0-no discrete honeycombing, with interlobular septal thickening; 1-honeycombing involving 0-5% of the lobe; 2-honeycombing 6-24%; 3-honeycombing 25-49%; 4-honeycombing 50-74%;5-honeycombing > 75%. Univariate and multivariate analyses with logistic regression models and cox proportional hazards approach were performed to identify the risk factor(s) of RILTs and overall survival (OS) respectively.Results: Among 1261 LA-NSCLC patients, 85 were found with pre-existing ILD and enrolled in the analysis. 36.5% of them were scored more than 1 point on CT. 20% patients developed G3+ RILTs within 1 year after the last irradiation, with remarkably 11.8% dying from lung toxicities. And the incidence of symptomatic (G3+) RILTs abruptly dropped to 11.1% (6/54), 3.8% (1/26), and 0% (0/19) for patients with CT score ≤1, V20 < 20%, or neither, respectively. Multivariate analysis showed that CT score > 1 and V20 ≥ 20% were independently associated with higher risk of G3+ RILTs. The median OS and PFS were 14.0 months and 7.4 month respectively. In the univariate analysis for OS, clinical stage and G3+RILT were evaluated as risk factors while patients in low-risk group, defined as honeycombing score < 1 and V20 < 20%, had shown a protective tendency (HR = 0.52, 95% CI: 0.27-1.04, P = 0.063). In multivariate analysis, G3+RILT was the only independent risk factor associated with OS (HR = 2.40, 95% CI: 1.32-4.36, P = 0.004). However, the median OS of low-risk group was quite longer than the whole group (26.5 months versus 14.5 months), indicating that patients at low risk might benefit from thoracic radiation therapy.Conclusion: Honeycombing score > 1 and V20 ≥ 20% were significantly associated with high incidence of severe lung toxicities, leading to poor survival. However, patients at low risk might benefit from TRT with a considerable overall survival. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To retrospectively investigate the patterns of failure and potential benefits of local therapy for patients with metastatic non-small cell lung cancer (NSCLC) receiving immunotherapy.Materials/methods: This single institution, retrospective analysis included 118 patients diagnosed with stage IV NSCLC from January 2015 to May 2020 who received at least one cycle of pembrolizumab, with or without concurrent chemotherapy, and had radiographic follow up of at least 3 months. Patterns of failure were identified by first disease progression event after initiation of immunotherapy. Progression was defined by radiographic evidence of tumor growth and/or development of new sites of disease. Failure events were grouped into the following categories: local, regional, distant, or combined (any combination of synchronous local, regional, or distant disease progression). Overall survival (OS), progression-free survival (PFS) and time to treatment failure (TTF) were calculated using the Kaplan-Meier method.Results: The median follow up time for the 118 patients included in the analysis was 8.5 months. Overall, 70 patients (59.3%) developed progression of disease while on immunotherapy. Of these, 15 (12.7%) progressed locally alone, 2 (1.7%) progressed regionally alone, 17 (14.4%) progressed distantly alone, and the majority (36 (30.5%)) experienced a combined progression. Of the 36 patients who developed synchronous combined progression, 31 (86.1%) shared distant failure with either a local and/or regional failure. The median OS, PFS, and TTF for the entire cohort were 15.8 months, 6.3 months, and 7.3 months respectively. When stratified by patterns of failure, the median OS for local, regional, distant, combined and no progression were 12.4, 18.3, 13.5, 10.7, and 41.7 months respectively (P = 0.024). The median PFS for the same groupings were 3.5, 16.8, 4.2, 3.5, and 41.7 months respectively (P < 0.0001). Of the 41 patients with only local progression or a combination of local and another site of progression, 18 received extracranial radiation concurrently with pembrolizumab (12 palliative RT, 6 consolidative SBRT). There was a statistically significant improvement in OS for this cohort of patients (any local progression) favoring those who received radiation concurrently with immunotherapy (15.8 vs 8.7 months; P = 0.039), but there was no PFS benefit (P = 0.098).Conclusion: Approximately 60% of patients in this retrospective analysis experienced progression of disease after initiation of pembrolizumab. The most common pattern of failure was a combination of local, regional, and/or distant progression. Additional study of the potential benefits of adding local therapy (radiation) to immunotherapy for these patients is warranted. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To compare the outcomes of W&W strategy in patients with locally advanced rectal cancer who achieve complete clinical response (cCR) after neoadjuvant therapy, with those pathological complete response (pCR) after total mesorectal excision (TME).Materials/methods: This is a retrospective cohort analysis study. 1014 Patients of histologically proven with locally advanced rectal adenocarcinoma who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing long-course concurrent chemoradiotherapy or short-course sequential chemoradiotherapy, no distant metastases within 6 months after treatment, follow-up ≥1 year, and patients who did not have cCR but pCR after TME. The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (non- regrowth DFS), and organ preservation rate. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results: 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (IQR 12.1-79.9). No difference in 3-year OS (97.1% vs 96.7%) and 5-year OS (93.8% vs 90.9%, P = 0.696) between W&W and pCR, but patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs 43.5%, P < 0.0001). Six patients had local regrowth managed by W&W, while no local recurrence in the pCR group, which had better 3-year DFS (83.6% vs 97%) and 5-year DFS (83.6% vs 91.2%, P = 0.047). However, after salvage surgery, no significantly difference in 3-year non-regrowth DFS (95.9% vs 97%) and 5-year non-regrowth DFS (92.8% vs 97%, P = 0.407) between these two groups. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs 26.5%, P < 0.0001) were noted in the W&W group, but no differences in other survival between groups. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19 vs 9.8 wk, P < 0.0001).Conclusion: The long-term outcomes of W&W strategy in patients with locally advanced rectal cancer were not inferior to that of those with pCR. 87.7% of patients had successful rectum preservation in W&W group, although patients may require a longer interval for efficacy assessment. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Breast cancer patients with clinical N3c (cN3c) disease at diagnosis have poor outcomes relative to other breast cancer patients. Radiotherapy (RT) has an important role in the management of these patients as the supraclavicular (SCV) nodes are not routinely surgically dissected. However, outcomes and prognostic factors in the era of modern neoadjuvant chemotherapy (NAC) are not well-described.Materials/methods: We reviewed breast cancer patients with non-metastatic cN3c disease treated at our institution from 2014-2019 with curative intent NAC, surgery, and adjuvant RT. All patients received nodal RT including the SCV, infraclavicular, and internal mammary nodes. Institutional guidelines recommend a 10 Gy boost to clinically resolved N3 nodal basins and 16 Gy to unresolved N3 nodes. Variables including initial and boost dose, pathologic response, and type of nodal dissection were collected. Local (LC) and regional control (RC), freedom from distant metastases (FFDM), and overall survival (OS) were analyzed with the Kaplan Meier method. A saturated multivariable Cox proportional hazards model of OS with backward elimination identified clinical variables associated with OS at P < 0.10.Results: A total of 176 consecutive patients were analyzed. The median follow-up time was 2.83 years. The median age was 54 years, 76 (43%) were ER+/HER2-, 20 (11%) ER+/HER2+, 26 (15%) ER-/HER2+, and 54 (31%) ER-/HER2-. 102 (57%) had T3/4 disease, 41 (23%) underwent lumpectomy, 142 (81%) had pathologic confirmation of N3c, and 10 (6%) had a neck dissection. The median initial radiation dose was 50 Gy (range, 44-56.25), SCV boost 10 Gy (range, 6-16), and 156 (89%) received cumulative SCV dose ≥60 Gy. The 3-year OS, FFDM, RC, and LC were 79%, 64%, 93%, and 96%, respectively. For cumulative SCV dose of ≥60 Gy vs. < 60 Gy, the 3-year OS was 81% vs. 61% (P = 0.03). Among patients with a nodal pCR after NAC, the 3-year OS for SCV dose ≥60 Gy vs. < 60 Gy was 93% vs. 53% (P = 0.03). In multivariable analysis, cumulative SCV dose ≥60 Gy, extranodal extension, ER status, HER2 status, number of dissected lymph nodes, and ECOG status were associated with OS (Table 1).Conclusion: In a large, modern cohort of non-metastatic cN3c breast cancer patients treated with multimodality therapy, cumulative SCV dose ≥60 Gy was found to be associated with improved OS. Although optimal radiation dosing cannot be established from this data, a SCV radiation boost should be considered in cN3c patients treated with curative intent respecting normal tissue constraints. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The role of prophylactic extended-field radiation therapy (EFRT) has not been established, and the indications for prophylactic EFRT in patients with cervical cancer are not clear. In the present study, we compared the survival rates and toxicities of prophylactic EFRT and pelvic radiation therapy (PRT) among cervical cancer patients with 2018 FIGO stage IIIC1 disease.Materials/methods: We retrospectively analyzed patients with 2018 FIGO stage IIIC1 disease who were treated with definitive concurrent chemoradiotherapy at our institute between 2011 and 2015. A dose of 50.4 Gy in 28 fractions was delivered to the pelvic region (by PRT) or the pelvic plus para-aortic lymph node region (by EFRT) with intensity-modulated radiation therapy. The first-line regimen of concurrent chemotherapy was weekly cisplatin. As the baseline characteristics were not balanced between the two groups, we conducted propensity score matching.Results: A total of 280 patients were included, with 161 patients treated with PRT and 119 patients treated with EFRT. The median follow-up periods were 47.2 months. After propensity score matching (1:1), 71 pairs of patients were selected. The 5-year rates of the patients treated with PRT and EFRT were 61.9% and 85.0% for overall survival (OS, P = 0.025), 53.0% and 77.9% for disease-free survival (DFS, P = 0.004), 89.7% and 98.4% for para-aortic lymph nodes (PALN) control (P = 0.053). In the subgroup analysis, patients were grouped into a high-risk group (122 patients) and a low-risk group (158 patients) based on three factors: positive common iliac lymph nodes, 3 or more pelvic lymph nodes and T3 disease. Patients with one or more risk factors were grouped to the high-risk group. In high-risk group, 32 pairs of patients were selected after matching. Over 5 years, the rates for patients treated with PRT and EFRT after matching were 65.1% and 84.3% for OS (P = 0.135), 54.9% and 84.4% for DFS (P = 0.018), 91.8% and 100.0% for PALN control (P = 0.132). In low-risk group, 39 pairs of patients were selected after matching. Over 5 years, the rates for patients treated with PRT and EFRT after matching were 61.8% and 91.1% for OS (P = 0.028), 53.8% and 80.3% for DFS (P = 0.017), 88.4% and 100.0% for PALN control (P = 0.043). The rates of grade 3 or greater chronic toxicities were 1.2% and 5.9% in the PRT and EFRT groups, respectively (P = 0.067).Conclusion: Compared to PRT, prophylactic EFRT improved OS, DFS and PALN control in cervical cancer patients with pelvic MLNs. In the subgroup analysis, patients in both the high-risk group and low-risk group benefited from prophylactic EFRT. The incidence of grade 3 or higher toxicities was higher in the EFRT group than in the PRT group, although the difference was not significant. 2018 FIGO stage IIIC1 can be used as an inclusion criterion in clinical trials comparing PRT to prophylactic EFRT in patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Immune-related markers from the peripheral blood and radiation dose to the immune system have been associated with outcomes in locally-advanced non-small cell lung cancers (LA-NSCLC) patients treated with concurrent chemoradiation (cCRT). We assessed if the neutrophil-to-lymphocyte ratio (NLR), and risk scores from two dose models (Estimated Dose of Radiation to Immune Cells (EDRIC) and the RTOG 0617 overall survival (OS) model including cardiopulmonary dose) are also associated with outcomes in patients treated with cCRT and durvalumab.Materials/methods: Consecutive LA-NSCLC patients treated with platinum-based cCRT and at least one dose of durvalumab between November 2017 and December 2019 were evaluated. The pre-cCRT and pre-durvalumab NLR were calculated using samples most proximal to RT and durvalumab start (NLRpre-cCRT, NLRDurvalumab). Mean body dose, mean heart dose and mean lung dose (MLD) were extracted to calculate EDRIC; atria D45, mean of the hottest 5% of the ventricle dose (MOH5), pericardium MOH55 and MLD were used to calculate OS risk scores from the 0617 model. Progression-free survival (PFS) was defined from the start of cCRT. NLRpre-cCRT, NLRDurvalumab, risk scores from the two dose models, and patient characteristics (stage, age, PD-L1, ECOG status) were associated with PFS using bootstrapped Cox proportional hazards modeling. A Bonferroni-corrected P≤0.006 was considered statistically significant.Results: A total of 105 patients with a median follow-up of 20 months (IQR: 13-27) were included. Median age was 67 years, 60% were male, and 45% were ECOG 1. Most patients had adenocarcinoma histology (n = 64) and stage IIIB/IIIC disease (n = 71). PD-L1 expression was available for 75% of patients, of which 66% had PD-L1 expression ≥1%. Patients were treated with a median of 7 (IQR: 2-12) months of durvalumab that started a median of 7 (5-9) weeks from end of cCRT. Twenty-eight (27%) patients discontinued durvalumab due to toxicity after a median of 2 (IQR: 1-4) months. In total, 41 patients had a progression event at a median of 8 (IQR: 6-11) months. The 12- and 18-months PFS estimates were 69% (95% CI: 60-78%) and 62% (52-72%), respectively. The median NLRpre-cCRT was 3.4 (IQR: 2.2-4.7), NLRDurvalumab was 5.5 (IQR: 3.6-7.4). The median risk score for EDRIC was 5.3 (IQR: 3.9-6.6) and 0.82 (IQR: 0.62-1.1) for the 0617 model. Among the investigated variables only NLRpre-cCRT reached significance in predicting PFS (HR: 1.10, 95% CI 1.05-1.16, P = 0.0002). Further, NLRpre-cCRT was not strongly correlated with age, stage, PD-L1 expression or ECOG status (Spearman's rho range: -0.22, 0.22).Conclusion: This study represents the first effort focusing on immune-related markers and dose models in LA-NSCLC treated with cCRT and durvalumab and finds the pre-cCRT NLR as the best predictor of disease outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relationship between prostate-specific antigen (PSA) failure and cause-specific and overall survival in prostate cancer patients treated with radical radiotherapy.Methods and materials: Patients with and without PSA failure were compared with respect to overall survival and cause-specific survival in a cohort of 1786 patients. The relationship between PSA failure and survival was further investigated among six subgroups defined by three tumor risk groups (high, intermediate, and low risk based on T stage, Gleason score, and presenting PSA) and two age groups (<75 years and ≥75 years).Results: The 5-year overall survival among patients who had PSA failure was 79.5% vs. 87.5% among patients who had not failed (p = 0.0003). The corresponding 5-year cause-specific survival was 84.4% vs. 99.0% (p <0.0001). When the six subgroups are considered separately, PSA failure was associated with a worse cause-specific survival in the groups with intermediate- and high-risk disease. PSA failure was only associated with a worse overall survival in one subgroup: patients younger than 75 with high-risk disease. Deaths from nonprostate causes made the survival curves of patients with and without PSA failure in the other subgroups almost identical.Conclusion: PSA failure in prostate cancer patients treated with radiotherapy was associated with a poorer overall survival, which is seen mainly in younger patients with high-risk disease. [Copyright &y& Elsevier]