Start Of Radiotherapy Research Articles

Geriatric assessment with management for older patients with cancer receiving radiotherapy. Protocol of a Norwegian cluster-randomised controlled pilot study

About 50% of patients with cancer are expected to need radiotherapy (RT), and the majority of these are older. To improve outcomes for older patients with cancer, geriatric assessment (GA) with management (GAM) is highly recommended. Evidence for its benefits is still scarce, in particular for patients receiving RT. We report the protocol of a cluster-randomised pilot study designed to test the effect, feasibility and health economic impact of a GAM intervention for patients ≥65 years, referred for palliative or curative RT. The randomising units are municipalities and city districts. The intervention is municipality-based and carried out in collaboration between hospital and municipal health services from the start of RT to eight weeks after the end of RT. Its main constituents are an initial GA followed by measures adapted to individual patients' impairments and needs, systematic symptom assessments and regular follow-up by municipal cancer nurses, appointed to coordinate the patient's care. Follow-up includes at least one weekly phone call, and a house call four weeks after the end of RT. All patients receive an individually adapted physical exercise program and nutritional counselling. Detailed guidelines for management of patients' impairments are provided. Patients allocated to the intervention group will be compared to controls receiving standard care. The primary outcome is physical function assessed by the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire C-30. Secondary outcomes are global quality of life, objectively tested physical performance and use of health care services. Economic evaluation will be based on a comparison of costs and effects (measured by the main outcome measures). Feasibility will be assessed with mixed methodology, based on log notes and questionnaires filled in by the municipal nurses and interviews with patients and nurses. The study is carried out at two Norwegian RT centres. It was opened in May 2019. Follow-up will proceed until June 2022. Statistical analyses will start by the end of 2021. We expect the trial to provide important new knowledge about the effect, feasibility and costs of a GAM intervention for older patients receiving RT.Trial registration: ClinTrials.gov, ID NCT03881137, initial release 13th of March 2019.

Predicting Feeding Tube Placement in Head and Neck Cancer Patients Receiving Radiation Therapy With Machine Learning

During radiation therapy (RT) for head and neck malignancies, patients often experience weight loss secondary to odynophagia, dysphagia, and dysgeusia, which may necessitate enteral nutrition. Prophylactic feeding tube (FT) placement in every patient is not cost effective, and the procedure is not without complications. Additionally, FT placement has been associated with significant delay in a return to a normal diet. Machine learning models may help facilitate early identification of patients requiring early FT placement, augmenting outcomes and quality of life in these patients.A retrospective cohort of 283 patients from a single institution were included that received definitive or adjuvant RT for head and neck cancer from 2016-2020, and that did not receive > 3 Gy/fraction or FT < 10 days after start of RT. The outcome predicted was FT placement or > 10% weight loss after start of RT if a patient declined FT recommendation. The majority of patients were ECOG 0-1 (51.5%), former/current smokers (67.5%), white (65.7%) and had oropharyngeal/nasopharyngeal disease (60.4%). Definitive chemoRT or RT was received by 91.5% of patients. One hundred twenty-seven patients either had a FT placed (majority) or had > 10% weight loss following the start of RT. Sixty percent of patients were used as training; 20% and 20% were used for validation and testing. Over 50 clinical features were obtained for each patient. Recursive feature analysis was performed to select top performing features in the validation dataset. Hyperparameters were selected for logistic regression (LR), support vector machine (SVM), and explainable boosting machine (EBM) models using Optuna. Separate models were created that used five, six, seven, and eight selected clinical features.The top performing 5-8 feature models for LR, SVM, and EBM are reported using test data as follows. The LR models obtained areas under the receiver operating curve (AUCs) of 0.653-0.685 with the following clinical variables: chemotherapy regimen, ECOG status, RT laterality (unilateral vs bilateral), ethnicity, T stage, smoking status, and pre-RT weight. The SVM models obtained AUCs of 0.530-0.669 with T/N stage, ethnicity, RT laterality, pre-RT pain medications, RT regimen, chemotherapy regimen, primary site, ECOG status, pre-RT weight. The EBM models obtained AUCs of 0.630-0.723 with chemotherapy regimen, T/N stage, RT laterality, RT regimen, gender, age, and ethnicity.The explainable EBM models outperformed LR and SVM models on the test set with consistent use of similar features within the 5-8 feature models. Clinical features most commonly utilized in the models were chemotherapy regimen, RT laterality, and ethnicity.

Systematic Review and Pooled Analysis of the Impact of Treatment-Induced Lymphopenia on Survival of Glioblastoma Patients

Lymphopenia is a known toxicity of chemotherapy and radiation therapy (RT), part of the standard treatment for glioblastoma (GBM). Given the immune system's role in cancer control and general health, a number of single-institution studies have examined the association between treatment-related lymphopenia and survival outcomes of GBM patients. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemoRT.Following PRISMA guidelines, a systematic review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. Inclusion criteria included: (1) retrospective/prospective studies of human subjects (2) GBM patients (3) treated with chemoRT (4) reported lymphopenia and OS outcomes (5) analyzed lymphopenia and OS association. Analysis was conducted using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS.104 studies were identified, with 11 studies meeting the inclusion criteria, representing 2,196 unique patients. The threshold of lymphopenia varied between studies (lymphocyte count cutoff value range of 400 - 1200 cells/uL; mode 500 cell/uL). The time of lymphopenia onset was dichotomized into two groups (time-point vs time-range), with 6 studies tabulating the incidence of lymphopenia defined at a fixed time point approximately 2-months after the start of RT, while 5 studies utilized a time-range, tabulating the incidence of lymphopenia defined as any occurrence of lymphopenia from the start of RT to approximately 2-months after the start of RT. The mean overall pooled incidence of lymphopenia for all 11 studies was 32.4%, and was 21.1% vs 41% for time-point studies and time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI: 1.46 - 2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI: 1.24 - 1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies (P = 0.6 for time-point and P = 0.5 for time-range studies). Available pooled analysis of MVA estimates of HR for the time-range studies were confirmatory, with pooled HR of 1.36 (95% CI: 1.12 - 1.65, P < 0.002), with significant heterogeneity between studies, P = 0.02.These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between treatment-related lymphopenia with decreased OS in GBM patients, highlighting lymphopenia as a poor prognostic factor. These results are hypothesis generating, stimulating a better understanding regarding causality and underscores the need for investigations into strategies to mitigate lymphopenia. Such insights may improve outcomes and possibly shed light on the limited efficacy of immunotherapy for the treatment of GBM.A. Saeed: None. S.M. Bentzen: Travel Expenses; University of Copenhagen. M.V. Mishra: Employee; Orthofix. Research Grant; ASTRO, Keep Punching. Advisory Board; Patient Centers Outcomes Research Institute (PCORI. Travel Expenses; Patient Centers Outcomes Research Institute (PCORI.

Final Report of NRG Oncology RTOG 0022: A Phase I/II Study of Conformal and Intensity Modulated Radiation for Oropharyngeal Cancer

Final Report of NRG Oncology RTOG 0022: A Phase I/II Study of Conformal and Intensity Modulated Radiation for Oropharyngeal Cancer

Impact of Diabetes on Radiotherapy-Related Infection

Impact of Diabetes on Radiotherapy-Related Infection

Predictors of Ability to Complete Prescribed Concurrent Cisplatin Chemotherapy Regimen and Effect on Outcomes in Oropharyngeal Head and Neck Cancer Patients Treated With Radiotherapy

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.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.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.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.

Survival and Local Control Outcomes Following Palliative Radiation for Malignant Airway Obstruction

Palliative radiation may be beneficial for patients with metastatic or locally advanced disease causing malignant airway obstruction (MAO). However, the subset of patients most likely to benefit from palliative airway radiation is unknown. In this study, we seek to report local control and survival outcomes for patients treated with palliative radiation for MAO and provide prognostic factors for improved overall survival.An IRB approved single institution retrospective review of patients treated with palliative thoracic radiation for MAO from 2008-2016 was undertaken. The primary study endpoint was overall survival (OS) and secondary endpoints included local response and airway specific progression free survival. Kaplan-Meier survival, and Cox proportional hazards regression analyses were performed to identify factors associated with OS. Variables with clinical and univariate significance were modelled using multivariate logistic regression analysis.Palliative radiation for MAO was identified for 237 patients (median age of 63.8 yrs). 88.6% of patients were treated for primary lung cancer and 41.6% of those patients had adenocarcinoma histology. At time of analysis, 78.5% patients had died. Median follow-up was 2 months. Out of 116 patients with imaging follow-up: 31.0% had airway specific progression, 68.9% had complete or partial response at last follow up. For those patients with palliative tumor response, median time to progression was 5.0 (Range 1.1-17.8) months. Kaplan-Meier estimate of median overall survival following start of radiation therapy was 5.0 (95% CI 3.8-5.8) months. In multivariable analyses, there was a marginally increased hazard ratio for patients who had dyspnea at rest HR 2.09 (95% CI 0.78-5.62), oxygen requirement at presentation HR 1.28 (95% CI 0.81-2.01), and higher ECOG level 2-4 HR 1.21 (95% CI 0.81-1.80). Conversely, squamous cell histology and treatment with BED10 greater than or equal to 39 (equivalent to the commonly used 30Gy in 10 fraction regimen) were significantly predictive of improved OS, HR 0.56 (95% CI 0.32-0.97) and HR 0.42 (95% CI 0.28-0.64) respectively.To our knowledge, this analysis is the largest collection of patients receiving palliative thoracic radiotherapy for MAO. These data show that MAO is a poor prognostic feature for survival, but treatment responses are seen. Increased BED delivered and squamous cell carcinoma, a radiosensitive tumor histology, were associated with improved survival. These results may help to inform optimized patient selection for and outcomes of patients with MAO receiving palliative RT.

Pediatric Patient-Reported Quality of Life Before and after Radiotherapy: A Prospective Registry Study

Pediatric Patient-Reported Quality of Life Before and after Radiotherapy: A Prospective Registry Study

Use of Angiotensin Converting Enzyme Inhibitors and Risk of Late Bladder Toxicity Following Radiotherapy for Prostate Cancer

Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) near AGT associated with late hematuria following radiotherapy (RT) for prostate cancer. AGT encodes angiotensinogen and, in pre-clinical models, angiotensin pathway inhibition protects against late radiation toxicity in some tissues. Effects on the bladder have not been investigated. We tested the hypothesis that angiotensin converting enzyme inhibitors (ACEi) reduce risk of late hematuria following RT. We additionally investigated the effect of genetically-defined hypertension on hematuria.Prostate cancer patients (N = 268) undergoing curative RT (alone or with surgery and/or androgen deprivation therapy) were enrolled from each of two cancer centers pre-RT and followed prospectively for development of hematuria for up to four years using patient reported outcome questionnaires. Hematuria was defined as gross bleeding or medication use for hematuria. Demographic, treatment, and medication data were abstracted from medical records. The cumulative probability of hematuria was estimated by Kaplan-Meier methods, and the log rank test assessed differences by ACEi/ARB, use stratified by enrollment center. Multivariable analyses used Cox models of time to onset of hematuria stratified by enrollment center. A polygenic risk score (PRS) comprising 882 SNPs previously associated with blood pressure was tested for association with time to onset of hematuria in our Radiogenomics Consortium GWAS cohorts (N = 3,608).The cumulative probability of hematuria among all participants was 17.1% (N = 19) at four years (median follow-up of two years). Hematuria was seen in 1.4% of those taking vs 22.9% in those not taking ACEi (P = 0.01) at the start of RT, resulting in a hazard ratio (HR) of 0.11 (95% CI 0.01 to 0.83). The protective effect of ACEi on hematuria remained when adjusted for factors associated with ACEi use, including body mass index, hypertension, or diabetes. The protective effect also remained after stratifying by risk factors for hematuria, including prior transurethral prostate resection, smoking status, or prior prostatectomy. A blood pressure PRS was strongly associated with hypertension (odds ratio per standard deviation 1.40, 95% CI 1.30 to 1.50, P < 0.001) but not with hematuria (HR per standard deviation 0.97, 95% CI 0.87 to 1.07, P = 0.52).Our study is the first to show a radioprotective effect of ACEi on bladder toxicity. This effect appears distinct from presence of hypertension, which is not itself a risk factor. These results point to a promising radioprotector readily available for testing in a randomized clinical trial. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects normal tissues to reduce RT toxicity.

Dose Escalated Radiotherapy (RT) Alone or in Combination With Short-Term Total Androgen Suppression (TAS) for Intermediate Risk Prostate Cancer: Patient Reported Outcomes (PROs) From the NRG Oncology/RTOG 0815 Randomized Trial

<h3>Purpose/Objective(s)</h3> To report the PROs of a phase III randomized trial evaluating TAS combined with dose-escalated RT for patients with intermediate risk prostate cancer. <h3>Materials/Methods</h3> Eligible patients had intermediate risk prostate cancer defined as harboring ≥ 1 of these risk factors: clinical stage T2b-T2c, Gleason score 7, or PSA > 10 to ≤ 20 ng/mL. Patients were randomized to dose-escalated RT alone (Arm 1) or RT plus TAS (Arm 2) consisting of LHRH agonist/antagonist with oral antiandrogen for 6 months. Validated PROs included the Expanded Prostate Cancer Index Composite (EPIC-50) and Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue short form. PRO change scores, calculated for each patient as the follow-up score minus baseline score (at end of RT, 6, 12, and 60 months from start of RT) were compared between treatment arms using a two-sample <i>t</i> test. An effect size (ES) of 0.50 SD (standard deviation) of the baseline measure was considered clinically meaningful. For the PRO sample size, 200 patients per arm would provide 90% statistical power to detect an ES < 0.50 if the completion rate was only 60%. Mixed effect regression models were also utilized. Clinical outcomes are reported in a separate abstract. <h3>Results</h3> Of the 402 initial planned subset of trial patients who completed baseline PROs, PRO compliance was approximately 96%, 89%, 86% and 87% at end of RT, 6, 12 and 60 months, respectively. There were no significant differences between these 402 patients and the remaining patients on this trial with respect to age, race, performance status, # risk factors, or comorbidity score. While EPIC urinary and bowel scores decreased significantly by the end of RT in both arms, no clinically meaningful differences between arms were detected over time. For the EPIC hormonal and sexual domains, however, there were clinically meaningful differences between the two arms with greater (<i>P</i> < 0.0001) deficits in the RT + TAS arm. These differences improved over time, with ∼50% resolution by one year after treatment and no clinically meaningful differences by 5 years between arms. PROMIS-fatigue scores increased from baseline in both arms and were significantly higher in arm 2 at the end of RT (<i>P</i> = 0.016), though slightly lower at 12 and 60 months. <h3>Conclusion</h3> The addition of TAS to dose-escalated RT demonstrated significant clinically meaningful declines in the EPIC hormonal and sexual domains, and increases in the PROMIS-fatigue scores, compared to RT alone. These scores gradually improved over time, with no clinically meaningful differences between arms in fatigue by one year, or in hormonal and sexual domains by 5 years. Beyond the clinical outcomes, these PRO results directly from patients provide added value to help patients make informed decisions among treatment options.

Impact of the COVID-19 Pandemic on Radiotherapy Patterns of Practice for Curative Intent Breast Cancer Patients

Purpose/Objective(s)In response to the COVID-19 pandemic, radiotherapy (RT) departments around the world created new policies as a means of reducing risk of exposure for patients and staff, while attempting to maintain high-quality RT. We aim to describe the impact of the pandemic on changes in breast cancer RT patterns of practice for new patient referrals at a tertiary cancer center.Materials/MethodsNewly diagnosed breast cancer patients referred to our department from March 17-June 30, 2020 were included. Referrals for palliative RT were excluded. Demographic characteristics, COVID-19 status (if available) and RT treatment information, including deviations from usual practice because of the pandemic, were extracted from medical records by independent reviewers, and validated by the treating radiation oncologist. Descriptive statistics were used to summarize the data. The results were compared to breast cancer patients treated from March 17-June 30, 2019.ResultsA total of 271 and 306 patients met selection criteria for the 2020 and 2019 cohorts, respectively. The majority of consultations in 2020 were virtual (96%), conducted via telephone or videoconference, whereas in 2019 all were conducted in-person. Median age of the cohorts was similar: 58 years (range: 24-86) in 2020 and 59 years (range: 26-88) in 2019. Of those treated with adjuvant RT (n = 209), 56% of patients received whole breast (WB), 36% regional nodal irradiation (RNI) and 8% partial breast (PB) RT in 2020, whereas in 2019 (n = 284), 60% received WB, 31% RNI and 9% PB (Chi-squared test P = 0.43). As a result of the pandemic, 78% of cases (n = 211) received one or more deviations in RT practice compared to pre-pandemic institutional policies. The most common was an “altered dose/fractionation protocol” (n = 197; 93%), such as use of hypofractionated RNI (2020: 97%, 74/76 cases vs. 2019: 3%, 3/87 cases) or the FAST Forward regimen (2020: 43%, 57/134 WB/PB cases vs. 2019: 0/197 cases). Other deviations included a delay in RT start (defined as > 12 weeks post-op) noted in 11% (n = 29) and omission of RT in only 8% (n = 17), both were recommended when the risks associated with COVID-19 were felt to outweigh the benefit of RT. One patient had a deviation in RT as a result of testing positive for COVID-19.ConclusionIn order to minimize hospital visits in response to the COVID-19 pandemic, a substantial proportion of breast cancer patients were seen virtually and treated with newer hypofractionated dose schedules, while total omission of adjuvant RT was infrequently observed. Continuously tracking patterns of practice provides an opportunity to evaluate the impact of the pandemic on clinical outcomes and help inform post-pandemic value-enhancing practices.

IDO Immune Status After Radiotherapy in Patients With IV Stage Non-Small Cell Lung Cancer: An Exploratory Study

<h3>Purpose/Objective(s)</h3> Host immunity has a significant impact on radiotherapy (RT) outcomes in cancer. We have previously demonstrated that Indoleamine 2, 3-dioxygenase (IDO), a known immunoinhibitory kinase, predicts the survival of patients with stage I/II after RT alone and stage III non-small cell lung cancer (NSCLC) after chemoradiation. We hypothesize that the IDO activity levels in the blood also change in patients with stage IV NSCLC following radiotherapy. <h3>Materials/Methods</h3> This was part of a prospective study of circulating immune biomarkers for prognosis and prediction. Newly diagnosed or recurrent stage IV NSCLC patients were eligible. Blood samples were obtained before and after RT start and platelet-poor plasma samples were used for the kynurenine (Kyn) and tryptophan (Trp) measurement by high-performance liquid chromatography. Kyn and Trp was detected on a UV/vis channel at 360 nm and 285 nm, respectively, with more than 95% re-productivity. IDO activity was defined as the ratio between Kyn and Trp in synchronization. Student T-test was applied for group comparison. Data are presented as mean and 95% confidence interval (CI). <i>P</i> value < 0.05 was considered as statistical significance. <h3>Results</h3> Between July 2019 and Dec 2020, a total of 54 patients with stage IV NSCLC treated with radiotherapy was recruited. RT dose ranged from 20-60 Gray in 5-30 fractions, covering thoracic, spines or brain. Higher concentration of Kyn (mean = 1.88, CI = 1.48-2.27 mM) was detected before RT, compared with the Kyn concentration (mean = 1.20, CI = 0.70-1.70 mM) after RT (<i>P</i> = 0.052). The mean concentration of Trp was 20.81 (CI = 17.01-24.62) mM before RT, compared with 19.01 (CI = 17.03-21.00) mM after RT with no significant change (<i>P</i> = 0.982). In addition, the IDO activity (mean = 0.11, CI = 0.08-0.14) before RT was higher than the IDO activity after RT (mean = 0.08, CI = 0.05-0.10) with <i>P</i> = 0.130. Furthermore, a subgroup analysis of the IDO activity in patients with distant metastasis (n = 31) was conducted. The mean concentration of Kyn was significantly decreased from 1.78 (CI = 1.67-2.67) mM before RT to 0.68 (CI = 0.28-2.09) mM after RT (<i>P</i> = 0.028). The mean concentration of Trp was 18.12 (CI = 15.39-20.84) mM before RT versus 18.64 (CI = 14.41-22.86) mM after RT (<i>P</i> = 0.847). Besides, the IDO activity was also reduced from 0.15 (CI = 0.09-0.20) before RT to 0.07 (CI = 0.01-0.13) after RT (<i>P</i> = 0.051). <h3>Conclusion</h3> This study reveals that the plasma kynurenine and IDO activity is reduced after RT, suggesting that potential roles of RT in releasing immune suppression status of the host that can be simply tested by IDO activity in patients with stage IV NSCLC.

Rectal Volume and Quality of Life in Prostate Cancer Patients Receiving Pediococcus-Based Probiotics and Radiation Therapy: A Prospective Randomized Trial

Previous research identified Lactobacillus-based probiotic administration significantly reduced median and percent rectal volumes in prostate cancer (PC) patients undergoing daily radiation therapy (RT). However, Lactobacillus is sensitive to the acidic environment in the stomach. Pediococcus-based probiotics are resistant to pH as low as 1.5. We designed a prospective randomized trial to determine if administration of a Pediococcus-based probiotic therapy is feasible in patients undergoing prostate RT. An exploratory aim was to determine if probiotic therapy decreased rectal volumes throughout RT for PC compared to placebo.This was a single-institution prospective randomized study for men with PC undergoing prostate-only RT. Patients were randomized 1:1 to probiotic (2 gelatin capsules containing 4 × 109 colony-forming units of Pediococcus-based probiotics) or placebo. Administration of study agent was initiated 10 days prior to the start of daily RT. Quality of life (QOL) EPIC - Bowel Domain only surveys were completed at baseline, midway during RT, end of RT, and 1-month follow-up. Toxicities were recorded in accordance with CTCAE v5. Rectal volumes were contoured per the Radiation Therapy Oncology Group guidelines on the initial CT simulation, week 2, and week 6 using quality assurance CTs or cone-beam CTs, and compared using an independent samples Mann-Whitney U-test.Thirty patients were enrolled to the study. Two patients withdrew prior to initiating treatment, leaving 28 patients with evaluable data. Seven patients withdrew from the study for a completion rate of 75%. Of the patients that withdrew, 6 of 7 were on the placebo arm. In the placebo arm, one withdrew before starting the pills and five cited inconvenience as the reason for discontinuation. In the probiotic arm, one participant reported "increased blood pressure" which did not resolve with cessation; this was the only protocol-related toxicity. There were no differences in QOL in bowel function or bother scores between the two groups relative to each patient's baseline. The relative rectal volumes at week 2 (RV2) and 6 (RV6) were not significantly different between probiotic and control arms. RV2 averaged across all patients in each of the two trial arms was 9.9% larger in the probiotic arm compared with controls, RV2p/RV2c = 1.099 with 95% significance limits 0.82 and 1.47, P = 0.51. At 6 weeks, RV6p/RV6c = 0.868, 95% CI 0.654 to 1.152, P = 0.31.While feasible and with rare protocol-related toxicity, compliance with daily capsule administration during conventionally fractionated prostate RT proved difficult, with 25% of patients withdrawing before study completion. Within the limitations of this pilot study, Pediococcus-based probiotic administration did not significantly alter QOL metrics or rectal volumes.

Oropharyngeal Cancer Early Outcomes and Challenges During the COVID-19 Pandemic

Purpose/Objective(s)The COVID-19 pandemic triggered a national emergency which drastically affected the practice of medicine. Studies have already shown that delays in cancer screening/diagnosis/treatment have ensued, and some project this will translate into increased mortality. We aimed to evaluate if early oropharyngeal cancer (OPC) outcomes with radiation therapy (RT) were affected.Materials/MethodsOn 3/17/2020, in response to the crisis in New York City, telemedicine consultations were implemented at our institution and patients followed prospectively. The Covid cohort (COV) includes new patients through July 2020. They were compared to a contemporary pre-Covid (PC) historical cohort of new patients from November 2019 to 3/16/2020. We reviewed medical records and collected clinicopathologic factors for OPC patients treated with curative intent RT. The Kaplan-Meier method was used to estimate time-to-event outcomes.ResultsMedian follow-up was 8.6 [1.0-13.8] months for all (5.8 months COV, 10.1 months PC). Both cohorts encompassed ∼19 weeks, but half as many consults were seen during the pandemic (n = 38 COV, n = 78 PC). The COV cohort included: 74% telehealth, 92% definitive RT (no surgery), and 89% chemoRT. The PC cohort included: 0% telehealth, 88% definitive RT (no surgery), and 94% chemoRT. There was no difference in COV vs. PC median times from consultation to simulation (1.1 [0-6.4] weeks vs. 1.4 [0-10.6] weeks) or simulation to RT start (2.1 [1.3-4.9] weeks vs. 2.0 [1.1-9.9] weeks). There was no difference in 6 month outcomes between COV vs. PC cohorts: local control (100% vs. 100%, P = 0.70), regional control 100% vs. 100%, P = 0.70), distant control (95.2% vs. 97.2%, P = 0.91), cancer-specific survival (100% vs. 98.7%, P = 0.48). There was no difference in outcomes between telemedicine vs. in-person consults. There were numerically more patients with very advanced disease during the pandemic: T4 (13.2% COV vs. 7.7% PC) or N3/M1 (5.2% COV vs. 2.6% PC), but differences were not statistically significant due to limited numbers. More patients treated during the pandemic developed grade 3 dysphagia requiring feeding tubes (10.5% COV vs. 5.1% PC), not significant due to limited numbers. No patients diagnosed with COVID (1 before, 2 during, and 5 after RT) had recurrence at last follow-up.ConclusionThere was no difference in early 6 month outcomes between COV and PC cohorts, no difference in outcomes with telemedicine, and RT delivery was sustained at pre-pandemic timelines. Several important clinical trends were identified in the COV cohort: about half as many consultations were seen during the pandemic, patients appeared more likely to present with very advanced disease, and more patients required feeding tubes during treatment. These findings may have important post-pandemic healthcare delivery implications related to delays in diagnosis, threats to long-term outcomes, and increased supportive care needs.

Using Inflammatory Blood Markers as Useful Prognostic Factors in Patients Undergoing Neo-Adjuvant Therapy for Stage II-III Breast Cancer

<h3>Purpose/Objective(s)</h3> The prognostic value of inflammatory blood markers (IBMs) in breast cancer patients have been an area of growing interest. Most of the studies took parameters from one defined point, usually the pretreatment ones. Current study aims to investigate the potential prognostic significance of IBMs among patients with stage II-III breast cancer receiving neo-adjuvant therapy (NAT). <h3>Materials/Methods</h3> Patients with stage II-III breast cancer who received NAT and postoperative radiotherapy (RT) at a single institute from Jan 2009 to Dec 2016 were retrospectively reviewed. The neutrophil, lymphocyte, platelet and monocyte count were collected at different stages of treatment, after NAT but before surgery, before and after RT, respectively. LMR and SII was calculated for each patient. The breast cancer specific survival (BCSS) and locoregional recurrence free survival (LRRFS) were defined from the date of the start of RT until last follow up. Univariate and multivariate Cox regression analysis was performed to identify independent predictors for BCSS and LRRFS. Model performance was evaluated by the concordance index (c-index). <h3>Results</h3> In total, 205 patients were enrolled. After a median follow-up of 65 months, 19 BCSS events were identified. The optimal cutoff value of SII and LMR after NAT but before surgery by receiver operating characteristic curve were 467.76 × 10⁹ (AUC = 0.63) and 1.57 (AUC = 0.65). The five-year BCSS of the group with lower LMR (LMR≤1.57) and higher LMR (LMR > 1.57) were 74.2% and 93.7%, respectively (P = 0.001). The 5-year risk of BCSS in patients with high SII value (SII > 467.76 × 10⁹) and low SII value (SII≤467.76 × 10⁹) were 81.5% vs 96.4%, respectively, <i>P</i> = 0.003. The multivariate analysis found that in addition to the traditional prognostic factors including hormone receptor, ypT, ypN stage and lymphovascular invasion, both post-NAT LMR (HR = 0.28, 95% CI = 0.10-0.81, <i>P</i> = 0.02) and SII (HR = 4.06, 95% CI = 1.37-12.00, <i>P</i> = 0.01) were independent predictors for BCSS. The C-index of the multivariate model of Neo-Bioscore for BCSS was 0.71(95% CI = 0.83-0.59), which was improved to 0.80((95% CI = 0.94-0.67) by adding LMR and SII. The prognosis of pre-RT and post-RT SII on LRRFS was analyzed in124 patients. The optimal cutoff value of SII before and after RT were 412.2 × 10⁹ (AUC = 0.71) and 571.48 × 10⁹ (AUC = 0.69) respectively. Patients with pre-RT SII > 412.2 × 10⁹ or post-RT SII > 571.48 × 10⁹ had a higher rate of locoregional failure (<i>P</i> = 0.02 and <i>P</i> = 0.01). After adjusting for cT, cN stage and age, post-RT SII remained predictive of locoregional failure (HR = 10.22, 95% CI = 1.25-83.45, <i>P</i> = 0.03). <h3>Conclusion</h3> IBMs after NAT was useful prognostic factor for stage II-III breast cancer patients. Adding LMR and SII to Neo-Bioscore can further stratify the prognosis of BCSS. High level of SII after RT had a negative impact on local-regional control, whether it reflects preclinical studies of post-RT inflammation-mediated tumor recurrence needs further study.

Comparative Analyses of Two Established Scores to Assess the Stability of Spinal Bone Metastases Before and After Palliative Radiotherapy.

Background and PurposeTo compare two validated spinal instability scores regarding the stabilizing effects and skeletal-related events (SREs) of palliative radiotherapy (RT) in patients with spinal bone metastases (SBM).Materials and MethodsTwo hundred eighty-two osteolytic SBM of lung or breast cancer patients were analyzed for stability before and following RT based on the Spinal Instability Neoplastic Score (SINS) or the Taneichi score. Score concordance was quantified by absolute agreement and Cohen’s kappa coefficient. SREs were defined as fractures or local progression after RT. OS was quantified as the time between the start of RT and death from any cause.ResultsAt 3 and 6 months after RT, 35 and 50% of initially unstable SBM were re-stabilized according to SINS in patients still alive. Corresponding Taneichi score-based stabilization proportions were 25 and 46%, respectively. Comparison of both stability scores showed high absolute agreement for all time-points (range 71–78%, kappa range 0.35–0.44). SRE occurred more frequently in initially unstable SBM compared to stable SBM according to SINS (14 vs. 5%), but no such association could be shown for the Taneichi-based instability criterion. Poor general condition of patients was negatively associated with SINS-measured re-stabilization after 6 months, but no predictive factor for re-stabilization could be found for the Taneichi score.ConclusionsDespite the relatively high agreement between both stabilization scores, the SINS should be considered the standard for future studies on the stabilization effects of RT in SBM.

Patient Reported Outcomes and Financial Toxicity in Head and Neck Cancer (PaRTNer): Baseline financial toxicity and attitudes toward costs from a pilot study.

56 Background: Cancer patients face considerable financial burden, but few studies have explored associations between radiation therapy (RT) and financial toxicity. This study assessed financial toxicity, patient-reported outcomes, and attitudes/perspectives on the role of cost in treatment decisions. Methods: In a prospective, survey-based, longitudinal study (NCT3506451), eligible patients were adults with newly diagnosed non-metastatic head and neck cancer (HNC) undergoing RT as part of their definitive cancer treatment. Surveys collected demographics, cancer details, the COmprehensive Score for financial Toxicity (COST) score to measure financial toxicity, and patient attitudes regarding cost conversations. Results: 60 patients were enrolled (2019-2021), and 58 completed the baseline survey prior to the start of RT. Most were white (75.9%) and non-Hispanic (98.1%). Median age was 61 (range 42-86). Most were married or in long term partnerships (67.0%), had completed at least some college (70.7%), and had employer sponsored private insurance (55.2%). Half were working at least part time, and most earned &gt; $60,000/yr (55.4%). Oropharynx (48.3%) was the most common disease site; almost half (48.1%) received concurrent chemotherapy. Median baseline COST score was 25 (range 0-44), indicating borderline financial toxicity. 37.7% had reduced spending on leisure items, and 30.9% had reduced spending on basics like food or clothing to pay for cancer care. 10.5% had skipped doses of medications to make them last longer, and 21.1% had not filled a prescription because it was too expensive. 19.6% had borrowed money, and 36.4% had used either all or part of their savings (or had no savings at all) to pay for care. Of those employed at diagnosis, 38.9% took extended leave or reduced hours to part time. 25.9% felt their treatment costs/financial situation should be a factor in treatment decisions. 50.8% wanted the less costly treatment, assuming equal effectiveness. 46.6% felt they should receive cost information from their doctor, and 63.8% wanted a financial assistance counselor or social worker to provide cost information. 46.6% felt that discussing their costs would make them feel more involved in their care. While 43.1% felt that talking about cancer-related costs would reduce their anxiety, 36.2% felt it would increase their anxiety. The majority (63.8%) had little or no understanding about the costs of their cancer care, and 69.0% felt that educational materials about costs would be helpful. Conclusions: Despite borderline baseline financial toxicity scores, some HNC patients had already made significant sacrifices in order to afford care before RT had even started. There was little baseline knowledge of cancer costs and overall mixed attitudes toward cost conversation. Most patients felt that cost education would be helpful. Clinical trial information: NCT03506451.

Salvage radiation therapy for postoperative locoregionally recurrent non-small cell lung cancer: a single-center experience

PurposeTo determine the effectiveness of salvage radiation therapy (RT) in patients with locoregional recurrence (LRR) following initial curative resection of non-small cell lung cancer (NSCLC) and identify the prognostic factors affecting survival.Materials and MethodsBetween January 2009 and January 2019, 54 patients with LRR after NSCLC surgery were treated with salvage RT (83.3%) or concurrent chemoradiation therapy (16.7%). Twenty-three (42.6%), 21 (38.9%), and 10 (18.5%) patients had local, regional, and both recurrences, respectively. The median RT dose was 66 Gy (range, 37.5 to 70 Gy). The radiation target volume included recurrent lesions with or without regional lymphatics depending on the location and recurrence type.ResultsThe median follow-up time from the start of RT was 28.3 months (range, 2.4 to 112.4 months) and disease-free interval (DFI) from surgery to recurrence was 21.0 months (range, 0.5 to 92.3 months). Tumor response after RT was complete response, partial response, stable disease, and progressive disease in 17, 29, 5, and 3 patients, respectively. The rates of freedom from local progression at 1 and 2 years were 77.2% and 66.0%, respectively. The median survival duration after RT was 24.8 months, and the 2-year overall survival (OS) rate was 51.1%. On univariate analysis, initial stage, recurrence site, DFI, and tumor response after RT were significant prognostic factors for OS. DFI ≥12 months and tumor response after RT were statistically significant factors on multivariate Cox analysis for OS.ConclusionOur results demonstrated the effectiveness of salvage RT for LRR of NSCLC following curative surgery.

Survival impact of increasing time to IMRT initiation following induction chemotherapy in nasopharyngeal carcinoma: A propensity score-matched analysis

PurposeTo explore the prognostic impact of waiting time for radiotherapy (RT) after induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). Methods and materialsA total of 648 NPC patients receiving IC between 2009 and 2011 were included. Propensity score matching (PSM) was performed to balance the variables. Survival outcomes were compared in subgroups based on time to RT (TTR) after IC. ResultsThe optimal cutoff point for TTR was 28 days. A total of 330 patients were selected by 1:2 PSM. Stratified and dichotomized TTRs were both strongly correlated with prognosis. Patients with TTR > 28 days had significantly worse 5-year LRFS, DMFS, DFS and OS than those with TTR ≤ 28 days (P < 0.05). In multivariate analysis, TTR > 28 days was an independent predictor of worse LRFS [HR=2.08; 95% CI, 1.18-3.66; P = 0.011), DMFS (HR=1.65; 95% CI, 1.04-2.62; P = 0.033), DFS (HR=1.86; 95% CI, 1.35-2.62; P < 0.001) and OS (HR=1.90; 95% CI, 1.26-2.85; P < 0.001). High-risk patients with T4 or N2-3 disease were highly susceptible to RT delay with impaired DFS and OS. In high-risk patients with TTR > 28 days, concurrent chemotherapy yielded better DMFS (70.9% vs. 52.0%, P = 0.041), DFS (52.5% vs. 34.3%, P = 0.039) and OS (70.3% vs. 53.2%, P = 0.048). ConclusionsProlonged waiting is detrimental to survival in NPC, and it is strongly recommended to start RT within 28 days after IC. T4/N2-3 NPC has a higher risk of treatment failure with delayed RT. With potential protection against RT delay, concurrent chemotherapy should be performed in high-risk patients as salvage therapy.

Influence of Timing Between Androgen Deprivation Therapy and External Beam Radiation Therapy in Patients With Localized, High-Risk Prostate Cancer

PurposeTreatment with long-term androgen deprivation therapy (ADT) and radiation therapy (RT) is the nonsurgical standard-of-care for patients with high- or very high-risk prostate cancer (HR-PC), but the optimal timing between ADT and RT initiation is unknown. We evaluate the influence of timing between ADT and RT on outcomes in patients with HR-PC using a large national cancer database. Methods and MaterialsData for patients with clinical T1-T4 N0, M0, National Cancer Comprehensive Network HR-PC who were treated with definitive external RT (≥60 Gy) and ADT starting either before or within 14 days after RT start were extracted from the National Cancer Database (2004-2015). Patients were grouped on the basis of ADT initiation: (1) >11 weeks before RT, (2) 8 to 11weeks before RT, and (3) <8 weeks before RT. Kaplan-Meier, propensity score matching, and multivariable Cox proportional hazards were performed to evaluate overall survival (OS). ResultsWith a median follow-up of 68.9 months, 37,606 patients with HR-PC were eligible for analysis: 13,346 (35.5%) with >11 weeks of neoadjuvant ADT, 11,456 (30.5%) with 8 to 11 weeks of neoadjuvant ADT; and 12,804 (34%) patients with <8 weeks of neoadjuvant ADT. The unadjusted 10-year OS rates for >11 weeks, 8 to 11 weeks, and <8 weeks neoadjuvant ADT groups were 49.9%, 51.2%, and 46.9%, respectively (P = .002). On multivariable and inverse probability of treatment weighting analyses, there was a significant OS advantage for patients in the 8 to 11 weeks neoadjuvant ADT group (adjusted hazard ratio 0.90; 95% confidence interval, 0.86-0.95; P < .001) but not the >11 weeks group. ConclusionsNeoadjuvant ADT initiation 8 to 11 weeks before RT is associated with significantly improved OS compared with shorter neoadjuvant ADT duration. Although prospective validation is warranted, this analysis is the largest retrospective study suggesting an influence of timing between ADT and RT initiation in HR-PC.