Completion Of RT Research Articles

Carotid ultrasound to identify head and neck cancer survivors with high cardiovascular risk after radiation therapy: rationale and design of a prospective, cross-sectional pilot study.

Background: Radiation therapy is an integral component of treatment that can predispose to carotid artery stenosis (CAS) and increase the risk of cerebrovascular events for head and neck cancer survivors. The utility of screening for CAS with carotid ultrasound in asymptomatic head and neck cancer survivors is unclear.Methods: In this prospective, cross-sectional pilot study, 60 patients who have no evidence of cancer at least 2years from completion of RT will undergo screening carotid ultrasound to identify patients with high risk of cardiovascular events.Results: Outcomes will include clinically significant CAS, carotid intima-media thickness, acceptability/feasibility of screening, barriers to care and preliminary data on changes to medical management because of screening. Correlative multi-omics analyses will examine biomarkers of CAS after radiation therapy.Conclusion: The results of this study will provide valuable data on the prevalence of CAS and preliminary patient-centered data that will inform the design of a future large-scale, multi-site clinical trial.Clinical Trial Registration: NCT05490875 (ClinicalTrials.gov).

Abstract PO3-02-11: Impact of Tumor Volume on Oncologic Outcomes in Patients with T1 Breast Cancer: A Retrospective Analysis

Abstract Backgrounds: Measuring the extent of tumor cell accretion in the primary organ typically involves assessing the longest diameter, an important component of the widely employed TNM staging system. The largest tumor diameter is considered indicative of the risk of cancer metastasis and the likelihood of distant recurrences. However, relying solely on the unidimensional diameter to determine the degree of cancer cell accretion can be inadequate since each tumor has a unique three-dimensional shape, thus leading to different tumor volumes. Purpose: The aim of this study was to investigate the impact of tumor volume on oncologic outcomes in patients with T1-2 breast cancer. Method: We retrospectively reviewed the medical records of 1,018 patients diagnosed with invasive breast cancer who underwent breast-conserving surgery at Seoul National University Bundang Hospital from 2010 to 2015. Patients with multiple tumors, positive margins leading to mastectomy, or those who received neoadjuvant chemotherapy were excluded. Tumor volume was defined as the product of the length of the three axes to simplify the calculation. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier analysis. Result: The median value for tumor volume was 7.502 cm³. Out of 1,018 patients, 124 patients exhibited tumor volumes greater than the median value. Higher tumor volume was associated with pathologic T stage (P < 0.001), pathologic N stage (P = 0.004), histologic grade (P < 0.001), and luminal B subtype (P = 0.008). In multivariable logistic regression analyses for recurrence, higher tumor volume (OR 3.532, 95% CI 1.708-7.303, P = 0.001), CEA elevation (OR 6.129, 95% CI 1.497-25.092, P = 0.012), pN stage (OR 2.038, 95% CI 1.005-4.132, P = 0.048), and luminal B subtype (OR 2.407, 95% CI 1.060-5.470, P = 0.036) were shown to be predictive factors for recurrence, while completion of radiation therapy (OR 0.142, 95% CI 0.050-0.402, P < 0.001) and completion of hormone therapy (OR 0.200, 95% CI 0.047-0.849, P = 0.029) were identified as protective factors. The 5-year RFS was significantly lower in patients with higher tumor volume compared to those with lower volume (97.4% vs. 91.9%; p < 0.001). In multivariable Cox regression analysis, tumor volume (HR 3.056, 95% CI 1.572-5.940, P = 0.001), CEA elevation (HR 4.934, 95% CI 1.437-16.935, P = 0.011), luminal B subtype (HR 2.336, 95% CI 1.076-5.073, P = 0.032), completion of RT (HR 0.131, 95% CI 0.053-0.325, P < 0.001), and completion of HTx (HR 0.199, 95% CI 0.060-0.655, P = 0.008) were identified as independent prognostic factors for RFS. Conclusion: In the current study, we showed higher tumor volume results in poorer oncologic outcomes in patients with T1-2 breast cancer. Therefore, the T stage based on tumor volume, which includes all three-dimensional measurements, can better predict the prognosis in breast cancer patients than the traditional T stage that is solely dependent on the unidimensional longest tumor diameter. Citation Format: Hyoung Won Koh, Eun-Kyu Kim, Hee-Chul Shin. Impact of Tumor Volume on Oncologic Outcomes in Patients with T1 Breast Cancer: A Retrospective Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-11.

Noninferiority of Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Genitourinary and Gastrointestinal Symptoms

No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy. To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years. In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed. Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT). The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events. Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28). In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy. ClinicalTrials.gov Identifier: NCT03274687.

Skin dose-volume predictors of moderate-severe late side effects after whole breast radiotherapy

BackgroundToxicity after whole breast Radiotherapy is a relevant issue, impacting the quality-of-life of a not negligible number of patients. We aimed to develop a Normal Tissue Complication Probability (NTCP) model predicting late toxicities by combining dosimetric parameters of the breast dermis and clinical factors. MethodsThe skin structure was defined as the outer CT body contour's 5 mm inner isotropic expansion. It was retrospectively segmented on a large mono-institutional cohort of early-stage breast cancer patients enrolled between 2009 and 2017 (n = 1066). Patients were treated with tangential-field RT, delivering 40 Gy in 15 fractions to the whole breast. Toxicity was reported during Follow-Up (FU) using SOMA/LENT scoring. The study endpoint was moderate-severe late side effects consisting of Fibrosis-Atrophy-Telangiectasia-Pain (FATP G ≥ 2) developed within 42 months after RT completion. A machine learning pipeline was designed with a logistic model combining clinical factors and absolute skin DVH (cc) parameters as output. ResultsThe FATP G2 + rate was 3.8 %, with 40/1066 patients experiencing side effects. After the preprocessing of variables, a cross-validation was applied to define the best-performing model. We selected a 4-variable model with Post-Surgery Cosmetic alterations (Odds Ratio, OR = 7.3), Aromatase Inhibitors (as a protective factor with OR = 0.45), V20 Gy (50 % of the prescribed dose, OR = 1.02), and V42 Gy (105 %, OR = 1.09). Factors were also converted into an adjusted V20Gy. ConclusionsThe association between late reactions and skin DVH when delivering 40 Gy/15 fr was quantified, suggesting an independent role of V20 and V42. Few clinical factors heavily modulate the risk.

Volumetric brain assessment of long-term head and neck cancer survivors

BackgroundRadiation therapy (RT) for locally advanced head and neck cancer (HNC) often exposes subcortical brain structures to radiation. We performed this study to assess region-specific brain volumetrics in a population of long term HNC survivors. Methods and MaterialsForty HNC survivors were enrolled at a mean of 6.4 years from completion of RT. Patients underwent a research MRI protocol that included a 3D T1- weighted whole-brain scan on a 3 Tesla MRI scanner. Voxel based morphometry was performed using the Computational Anatomy Toolbox with the Neuromorphometrics atlas. Healthy controls from the Human Connectome Project were used as a comparison cohort. Study participants also completed a comprehensive neurocognitive assessment. ResultsThe final study cohort consisted of 38 participants after excluding 2 participants due to image quality. HNC survivors displayed widespread reduction in gray matter (GM) brain region volumes that included bilateral medial frontal cortex, temporal lobe, hippocampus, supplemental motor area, and cerebellum. Greater radiation exposure was associated with reduced GM volume in the left ventral diencephalon (r = -0.512, p = 0.003). Associations between cognition and regional GM volumes were identified for motor coordination and bilateral cerebellum (left, r = 0.444, p = 0.009; right, r = 0.372, p = 0.030), confrontation naming and left amygdala (r = 0.382, p = 0.026), verbal memory and bilateral thalamus (left, r = 0.435, p = 0.010; right, r = 0.424, p = 0.012), right amygdala (r = 0.339, p = 0.050), and right putamen (r = 0.364, p = 0.034). ConclusionsReductions in GM were observed within this cohort of primarily non-nasopharyngeal HNC survivors as compared to a control sample. GM volumes were associated with performance in multiple cognitive domains. Results of this exploratory study support the need for investigation of anatomic brain changes as an important translational corollary to cognitive problems among HNC survivors.

Dosiomics and radiomics improve the prediction of post-radiotherapy neutrophil-lymphocyte ratio in locally advanced non-small cell lung cancer.

To develop and validate a dosiomics and radiomics model based on three-dimensional (3D) dose distribution map and computed tomography (CT) images for the prediction of the post-radiotherapy (post-RT) neutrophil-to-lymphocyte ratio (NLR). This work retrospectively collected 242 locally advanced non-small cell lung cancer (LA-NSCLC) patients who were treated with definitive radiotherapy from 2012 to 2016. The NLR collected one month after the completion of RT was defined as the primary outcome. Clinical characteristics and two-dimensional dosimetric factors calculated from the dose-volume histogram (DVH) were included. A total of 4165 dosiomics and radiomics features were extracted from the 3D dose maps and CT images within five different anatomical regions of interest (ROIs), respectively. Then, a three-step feature selection method was proposed to progressively filter features from coarse to fine: (i) model-based ranking according to individual feature's performance, (ii) maximum relevance and minimum redundancy (mRMR), (iii) select from model based on feature importance calculated with an ensemble of several decision trees. The selected feature subsets were utilized to develop the prediction model with GBDT. All patients were divided into a development set and an independent testing set (2:1). Five-fold cross-validation was applied to the development set for both feature selection and model training procedure. Finally, a fusion model combining dosiomics, radiomics and clinical features was constructed to further improve the prediction results. The area under receiver operating characteristic curve (ROC) were used to evaluate the modelperformance. The clinical-based and DVH-based models showed limited predictive power with AUCs of 0.632 (95% CI: 0.490-0.773) and 0.634 (95% CI: 0.497-0.771), respectively, in the independent testing set. The 9 feature-based dosiomics and 3 feature-based radiomics models showed improved AUCs of 0.738 (95% CI: 0.628-0.849) and 0.689 (95% CI: 0.566-0.813), respectively. The dosiomics & radiomics & clinical fusion model further improved the model's generalization ability with an AUC of 0.765 (95% CI: 0.656-0.874). Dosiomics and radiomics can benefit the prediction of post-RT NLR of LA-NSCLC patients. This can provide a reference for evaluating radiotherapy-relatedinflammation.

The Role of Coronary Artery Calcium Score to Assess Risk of Cardiovascular Disease in Irradiated Esophageal Cancer Patients

Coronary artery calcium (CAC) score is an important predictive imaging marker of cardiovascular disease (CVD). While studies have found positive association between CAC score and cardiac toxicity in irradiated lung and breast cancer patients, there are no studies assessing CAC scores in esophageal cancer (EC). While a cardiac-gated CT is required for standard Agatston CAC score, visual assessment of CAC via ordinal scoring on non-gated CT has shown good concordance with Agatston score. In this study, we sought to examine whether visual assessment of CAC, measured on standard of care, non-contrast chest CT, predicts the development of adverse cardiovascular events (ACVE) in irradiated EC patients. This is a single institution retrospective study of EC patients treated with RT from 2010-2021. We included patients with available PET/CT at diagnosis or chest CT simulation scan without contrast, and excluded those with history of percutaneous coronary intervention, coronary bypass surgery, or prior thoracic RT. Pre-treatment characteristics, clinical factors, and grade ≥ 3 (G3+) adverse cardiovascular events (ACVE) (CTCAEv5.0) were evaluated. Visual assessment of CAC was performed using ordinal method (CAC scored from 0 to 12), by a thoracic radiologist. Fine and Gray regression was used to compute hazard ratios for time to first ACVE. Univariate analyses using Cox proportional hazards were used for overall survival (OS). ACVEs were recorded from start of oncologic treatment and OS calculated after completion of RT. A total of 118 patients were analyzed with a median follow-up of 16 months. Median age was 67 years, 65% male, 43% white, 59% with EC of distal esophagus, and 59% had squamous cell carcinoma. Median mean heart dose was 21.93 Gy (range 0.15-36.94). 24% developed G3+ ACVEs: atrial fibrillation 9%, stroke 6%, heart failure 4%, pulmonary embolism 4%, pericardial effusion 3%, myocardial infarction 2%, heart block 2%, and cardiac death 1%. On univariate analyses, CAC >1 vs. CAC ≤ 1 trended towards increased risk of ACVE (HR = 1.95, 95% CI = 0.89-4.26; p = 0.094), however it is not predictive of OS (HR = 1.31, 95% CI = 0.75-2.30; p = 0.343). Proportion of patients with ACVEs was greater in CAC>1 group (Table). When compared to patients with CAC ≤ 1, those with CAC >1 were older (median age 62 vs 72 years, p = 0.0015), less likely to be never smokers (38% vs 30%, p = 0.0437), and more likely to have hypertension (43% vs 64%, p = 0.0197), and hyperlipidemia (30% vs 47%, p = 0.0557). This is the first study to investigate the relationship between CAC score and ACVEs in EC. While the study was underpowered (likely due to low rates of recorded ACVEs), to detect a significant association between CAC score and ACVEs, there was a trend towards increased risk of ACVEs in patients with a CAC score >1 by visual ordinal scoring. Further prospective evaluation with a larger cohort is warranted.

Dosimetry Predictors of Late Skin Reactions after Whole Breast Radiotherapy on a Large Mono-Institutional Cohort of Patients

To develop an NTCP model predicting late skin toxicity using dosimetric parameters from the breast dermis to identify possible RT constraints on such a structure. The skin structure was defined as the 5 mm inner isotropic expansion from the outer CT body contour. It was retrospectively segmented on a large mono-Institutional cohort of early-stage breast cancer patients enrolled between 2009 and 2017 (n = 1066). Patients were treated with tangential-field RT, delivering 40 Gy in 15 fractions without a RT boost. Toxicity was reported during FU using SOMA/LENT scoring. The study endpoint was moderate-severe late toxicity consisting of Fibrosis-Atrophy-Telangiectasia-Pain (FATP G2+) developed within 42 months after RT completion. Automatic delineation of skin and DVH extraction were accomplished by scripting using the MIM_assistant software. Also, the impact of changes in the dose calculation algorithms during enrolment time was quantified. A logistic model was created by combining multifactorial variables, considering both clinical factors and the absolute skin DVH (cc). Variance Inflation Factor (VIF) was performed to reduce the multicollinearity. Repeated 5-fold cross-validation with SMOTE approach to overcome the class unbalance was applied for model feature selection. The predictive model was then developed on the entire population due to the limited G2+ events. The FATP G2+ rate was 3.8% with 40/1066 experiencing late toxicity. Among them, a 40% had already developed acute symptoms after RT completion showing a consequential effect. The multicollinearity analysis selected 27 clinical-treatment-dosimetric factors. After repeated (20 times) 5-fold cross-validation, the best-performing model included Post-Surgery Cosmetic alterations, Aromatase Inhibitors (as a protective factor), V20 Gy (50% of the prescribed dose - DVH plateau region) and V42 Gy (105% of the prescribed dose - DVH high-dose tail). Accuracy and f1-score were 0.76 and 0.58 in both training and test sets, providing good reliability for selected variables. AUC for the final model on the entire population was 0.76+/-0.04. We quantified the association between fibrosis and skin DVH when delivering 40 Gy in 15fr. The model suggested an independent role of V20 and V42 Gy and a heavy risk modulation by surgical effects and aromatase inhibitors. This last factor could interfere with adipose tissue and water-content distribution within the breast. For this purpose, a CT-based densitometry characterization of toxicity patients is ongoing.

Utility of Stereotactic Body Radiation Therapy (SBRT) in Establishing Local Control for Invasive Breast Cancer Patients Not Undergoing Definitive Surgery

Breast cancer (BC) treatment involves a multi-modal approach where surgical resection is the backbone of therapy. However, due to medical comorbidities precluding surgery, unresectable disease, or patient preference, some patients do not undergo surgery. In the absence of resection, it is paramount to improve local control (LC) of the primary tumor. To that end, this study explored the role of ablative RT dose delivered with SBRT. Between 2015-2022, 21 patients (10 metastatic, 11 stage IA-IIIC) received 23 SBRT courses to primary BC lesions without planned surgery at our institution. One patient had undergone whole breast RT 20 years prior to SBRT. 7 patients were analyzed retrospectively; 15 are currently enrolled in a prospective study. SBRT dose was 40 Gy/5 fractions delivered every other day. Follow-up imaging (PET, CT, MRI, MMG/US) was reviewed to evaluate the response. CTCAE v.3 was used to document any acute (≤3 months) and late toxicities. Kaplan-Meier curves were used to estimate local control (LC) and overall survival (OS). Median age was 78.4 (45.9-97.3) years. Median follow-up was 14.7 (3.3-70.3) months after RT completion. Initial post-treatment imaging was available for all cases and was performed at a median of 4.0 (0.6-11.9) months after SBRT. The median pre-SBRT index lesion size was 3.1 (0.5-14.5) cm and PTV was 32.4 (11.5-522.4) cc. At a median 4 months post-SBRT, the median decrease in index lesion size was 20.8 (0-100) % and SUV reduction was 65.2 (20.8-100) %. Further improvement was seen on the 2nd follow-up scans at a median 7.8 months post-SBRT, with 62 (0-100) % and 88 (33.3-100) % median reduction in the tumor size and SUV, respectively, compared to pre-SBRT values. The estimated LC rate was 100% at 6 months and 93.3% at 12 months. The sole case of local progression occurred 9.5 months after SBRT, after an initial interval decrease in the primary lesion. Among the patients with available systemic follow-up scans, regional progression occurred in 4 (17.4%) cases at a median 18.6 (5.2-22.7) months post-SBRT. Six (37.5%) patients developed distant progression at a median 4.8 (0.9-16.2) months, all of whom had metastatic disease at diagnosis. The estimated OS was 85.7% at 6 months and 63.8% at 12 months. Most patients tolerated the treatment well. There was no grade 4 toxicity. Complete acute toxicity data is presented in Table 1. Only one patient experienced late grade 2 breast edema. Based on our preliminary results, definitive SBRT to the primary BC appears to have a role in providing LC in the treatment of non-surgical patients and is well-tolerated. Since the disease progression tends to occur outside the treated primary tumor, additional approaches to improve regional and distant control should be investigated.

Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study.

Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

Pelvic insufficiency fractures after intensity modulated radiation therapy combined with chemotherapy for cervix carcinoma: Incidence and impact of bone mineral density

Background and PurposeThe aim of this study was to evaluate the incidence and predictive factors of Pelvic Insufficiency Fractures (PIFs) occurring after Intensity Modulated Radiation Therapy (IMRT) combined with chemotherapy for locally advanced cervical cancer (CC).Material and methodsMedical records of patients receiving radio-chemotherapy with IMRT between 2010 and 2020 for advanced CC were reviewed. PIFs were detected during follow-up on pelvic Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The cumulative incidence rate of PIFs and its confidence interval were calculated at 2 and 5 years of follow-up. Pre-therapeutic Bone Mineral Density (BMD) (g/cm3) was evaluated on CT simulation for sacrum and the fourth lumbar (L4) vertebrae. Sacrum dosimetric parameters (V30Gy, V40Gy, D50%, Dmean) were analyzed.Results136 patients were included. The median follow-up was 4.4 years. Median dose of D50% and V40Gy sacrum were 35.2 Gy (20.6–46.4) and 32.2% (7.2–73.4) respectively. The 2-year and 5-year cumulative incidence rates were 15.7% (95% CI: 9.88–22.71) and 22% (95% CI: 14.58–30.45) respectively. Median time interval between RT completion and PIFs’ detection was 11.5 months (IQR: 7.4–22.3). Univariate analysis showed that older age (p < 0.01), postmenopausal status at baseline (p < 0.01), and lower sacral and spinal BMD at baseline (respectively p < 0.001 and p < 0.01) were significantly associated to all sites of PIFs, and lower sacral BMD with sacral fractures (p < 0.001).ConclusionPost-IMRT PIFs were detected in 18.4% of patients with locally advanced CC. Individual predisposing factors as older age, postmenopausal status, decreased bone density on the CT simulation were mainly predictive.

Single-Institution Prospective Evaluation of Moderately Hypofractionated Whole-Breast Radiation Therapy With Simultaneous Integrated Boost With or Without Lymphatic Drainage Irradiation After Breast-Conserving Surgery

We report treatment outcomes for patients who received adjuvant moderate hypofractionated whole-breast radiation therapy with simultaneous integrated boost (SIB-mhWBRT) after breast-conserving surgery. SIB-mhWBRT for patients with breast cancer was introduced in our department in July 2017. This prospective evaluation includes 424 consecutive patients treated with SIB-mhWBRT for stage I-III invasive breast cancer (n=391) and/or ductal carcinoma in situ (n=33) until December 2021. SIB-mhWBRT was applied with 40 Gy in 15 daily fractions over 3 weeks according to the START B trial, with an SIB dose to the tumor bed of 48 Gy according to Radiation Therapy Oncology Group 1005/UK-IMPORT-HIGH, delivered as 3-dinemsional conformal radiation therapy (RT; n=402), intensity modulated RT (n=4), or volumetric modulated arc therapy (n=18). The mean patient age was 60 years (range, 27-88). Since May 2018, patients with indications for lymphatic pathway RT were included (n=62). Baseline parameters and follow-up data were recorded and reported, including objective assessment of treatment-related outcomes and subjective patient-reported outcome measures (PROMs). Mean/median follow-up was 29/33 months (range, 2-60). Acute toxicity grade 0, 1, 2, and 3 was observed in 25.0%, 61.4%, 13.3%, and 0%, respectively, at the completion of RT. Data of 281, 266, 243, 172, and 58 patients were available for 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Grade 2 late effects were identified in 8.5%, 6.0%, 4.9%, 2.2%, and 10.2% and grade 3 in 2.8%, 1.1%, 1.2%, 0%, and 0% of patients at 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Medical treatment of breast edema was the only grade 3 late effect observed. PROM cosmesis results were evaluated as excellent-good, fair, and poor in 97.2%, 2.5%, and 0.4%; 96.5%, 3.1%, and 0.4%; 97.4%, 2.2%, and 0.4%; 97.5%, 2.5%, and 0%; and 96.5%, 3.5%, and 0.0% at 6 months and 1, 2, 3, and 4 years post-RT, respectively. For all patients, the 3-year overall, cancer-specific, and disease-free survival rates were 98.2%, 99.1%, and 95.9%, respectively. Three-year risk of any locoregional recurrence was 0.6%. No mortality or relapse was observed in patients with ductal carcinoma in situ. SIB-mhWBRT demonstrated very favorable side effect profiles and cosmesis/PROMs. Three-year results demonstrate excellent locoregional control. This short-term regimen offers substantial patient comfort and improves institutional efficacy.

Radiation-induced circulating microRNAs linked to echocardiography parameters after radiotherapy.

Patients treated with radiotherapy to the chest region are at risk of cardiac sequelae, however, identification of those with greatest risk of complications remains difficult. Here, we sought to determine whether short-term changes in circulating miRNA expression are related to measures of cardiac dysfunction in follow-up. Two parallel patient cohorts were enrolled and followed up for 3 years after completion of RT to treat left-sided breast cancer. In the primary group (N=28) we used a a panel of 752 miRNAs to identify miRNAs associated with radiation and cardiac indices at follow up. In the second, independent cohort (N=56) we validated those candidate miRNAs with a targeted qPCR panel. In both cohorts. serum samples were collected before RT, 24h after the last dose and 1 month after RT; cardiac echocardiography was performed 2.5-3 year after RT. Seven miRNAs in the primary group showed marked changes in serum miRNAs immediately after RT compared to baseline and associations with cardiopulmonary dose-volume histogram metrics. Among those miRNAs: miR-15b-5p, miR-22-3p, miR-424-5p and miR-451a were confirmed to show significant decrease of expression 24 hours post-RT in the validation cohort. Moreover, miR-29c, miR-451 and miR-424 were correlated with the end-diastolic diameter of the left ventricle, which was also confirmed in multivariable analysis adjusting for RT-associated factors. We identified a subset of circulating miRNAs predictive for cardiac function impairment in patients treated for left-sided breast cancer, although longer clinical observation could determine if these can be used to predict major clinical endpoints.

74MO Clinical outcomes for pelvic node-positive vulvar carcinoma in the PET and IMRT era: Reassessing the stage IVb designation

Pelvic node-positive (PNP) vulvar carcinoma has historically had poor outcomes; 2-year DFS was 27% in GOG 37. Studies in this cohort were performed prior to widespread PET staging and intensity modulated radiotherapy (IMRT). We assessed clinical outcomes and prognostic factors in FIGO IVb patients in the PET and IMRT era, hypothesizing that PET staging and IMRT treatment may improve outcomes. Following IRB approval, we reviewed all patients with PNP vulvar squamous cell carcinoma (SCC) who received IMRT from 2012-2022. Patients treated palliatively were excluded. Eligible patients met stage IVb criteria and received simultaneous integrated boost (SIB) to radiologically positive lymph nodes (LN). Tumor size, grade, PET primary and LN SUVmax, largest LN size, LN anatomic location, p16 status, chemotherapy (CHT), and RT completion were recorded, as were survival (OS), disease free survival (DFS), local (LRFS)/regional (RRFS) recurrence and distant metastasis (DMFS). Patterns of recurrence and survival were examined via Kaplan Meier, with univariate analysis (UVA) via log-rank t-test. Multivariate analysis (MVA) was performed via Cox regression. 198 patients received RT for vulvar SCC, and 31 met inclusion criteria. Median follow up was 26 months (IQR 9-49) for patients completing RT (n=25) and 3 months (IQR 1-9) for patients not completing RT (n=6). 93.5% (n=29) had PET staging, with avid LN at external iliac (74.2%, n=23), common iliac (16.1%, n=5) and para-aortic (9.7%, n=3) echelons. RT was majority definitive/neoadjuvant (83.9%, n=26); 93.5% (n=29) received concurrent CHT. 22.5% (n=7) underwent LN dissection, with median 3 LN resected and 2 LN positive. With RT completion, 3-year OS and DFS were 64.1% and 69.6%, with 82.6% LRFS, 83.1% RRFS, and 77.5% DMFS. On UVA, LN SUVmax correlated with worse DFS, RRFS, and DMFS, and p16- status with worse OS, RRFS, and DMFS (p<0.05). LN SUVmax retained significance for DFS (p=0.045) and DMFS (p=0.041) on MVA. Clinical outcomes for PNP vulvar SCC have substantially improved in the PET and IMRT era, challenging the FIGO IVb designation. PET LN SUVmax may help predict patients at higher risk of DM, and p16+ status those with more favorable outcomes.

The Effect of the Time Interval between Temozolomide and Radiotherapy in Adjuvant High-Grade Glioma Treatment

<h3>Purpose/Objective(s)</h3> The standard of care for high grade glioma (HGG) treatment consists of postoperative radiotherapy and temozolamide (TMZ). The effect of time between TMZ administration and RT on treatment outcomes is not well defined. The purpose of this study was to examine the interval between oral administration of TMZ and RT, and its effect on treatment outcomes in patients with HGG. <h3>Materials/Methods</h3> The clinical data of 277 patients with HGG treated between 2009 – 2021 at four centers were retrospectively analyzed. The following are the inclusion criteria: Pathologically proven grade ≥3 glial tumors, ≥18 years old, and completion of curative RT with concurrent oral 75 mg/m²/day TMZ. Patients who were unable to take oral TMZ, or had previously been treated with TMZ and/or RT were excluded. The TMZ to RT interval (TRI) was calculated from the time of oral TMZ administration to the time of RT fraction. In relation to the TMZ half-life, the interval time was divided into <2 h and ≥2 h groups. Progression free survival (PFS) is calculated as the time between the end of RT and clinical or radiological progression. Overall survival (OS) is calculated from the time of diagnosis to the last follow-up. <h3>Results</h3> The median age was 58 years (range: 19–81). 159 patients (57.4%) were male, while 118 (42.6%) were female. 75.4% of patients had an ECOG performance score (ECOG PS) of 0–1, and 54.5% had gross total resection (GTR). The median fraction and total RT doses were 2 Gy (1.8–3) and 60 Gy (40–60), respectively. The median follow-up was 15.2 months (range: 1.9–75.1) for the entire cohort. Two-year OS and PFS rates were 35% and 15%, respectively. After completion of RT, disease progression occurred in 255 patients (92.1%) at a median of 6.4 months (range, 0.2–64.9). The 2-year OS was 42.8% for patients with a TRI >2 hours and 32% for patients with a time interval of ≤2 hours (p = 0.18). Similarly, there was no statistically significant difference in 2-year PFS between the two groups (12.8% vs. 9%; p = 0.95). Age, ECOG PS, and type of surgery were all significant prognostic factors for OS and PFS in univariate analysis. In multivariate analysis, advanced age [HR = 1.03 (95% CI, 1.01 – 1.04); p<0.001], poor ECOG PS [HR = 2.14 (95% CI, 1.56 – 2.94); p<0.001], and incomplete surgical resection [HR = 1.39 (95% CI, 1.06–1.84); p = 0.02] were independent predictors of poorer OS. Similarly, age [HR = 1.02 (95% CI, 1.01 – 1.03); p = 0.002], ECOG PS [HR = 1.57 (95% CI, 1.17 – 2.09); p = 0.002], and type of surgery [HR = 1.41 (95% CI, 1.10 – 1.80); p = 0.006] were all significant prognostic factors for PFS in multivariate analysis. <h3>Conclusion</h3> We found that advanced age, poor performance status, and incomplete surgical resection were all predictive of poor OS and PFS in this current study. However, we were unable to detect a statistically significant effect of the time interval between oral administration of TMZ and RT. Validation of our findings will require a longer follow-up period and randomized trials.

Real World Rates and Predictive Factors of Pneumonitis in Advanced, Non-Resectable NSCLC Treated with Concurrent Chemoradiation and Durvalumab

<h3>Purpose/Objective(s)</h3> Real world outcomes related to pneumonitis in patients with locally advanced (LA) non-resectable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation (chemoRT) and consolidative durvalumab (D) may differ from those seen in prospective trials given selection biases and other variables in clinical trials. We aimed to assess the real-world incidence of pneumonitis for LA NSCLC patients and identify clinical or dosimetric predictors of pneumonitis. <h3>Materials/Methods</h3> We retrospectively identified consecutive patients with locally advanced NSCLC treated with chemoRT and D at a single institution from 4/2017 to 6/2019 from our prospectively maintained institutional database. The actuarial incidence of pneumonitis was estimated using the Kaplan-Meier method and compared using log-rank tests. Toxicity was evaluated via retrospective examination of clinical documents and prescription records (i.e., steroids or oxygen) and graded according to Common Terminology Criteria for Adverse Events, version 5.0. Logistic regression was used to assess associations between pneumonitis and relevant clinical and dosimetric variables. Patients were followed with clinical examination and surveillance computed tomography scans every 3 months for 2 years and every 6 months afterwards. <h3>Results</h3> We identified 61 patients with locally advanced NSCLC that were consecutively treated with a median RT dose of 66 Gy (range 60-70Gy). Median follow up was 29 months (range 4-55). Intensity-modulated radiation therapy (IMRT) was used in 36 (59%) patients, and 25 (41%) patients received 3D-conformal RT (3DCRT). Twenty-three (37.7%) patients developed pneumonitis. Highest grade pneumonitis was 2 (n=17, 27.9%), and 3 (n=5, 8.2%). Of patients who developed pneumonitis, the median time to onset was 3.2 months from completion of RT (range 1.2-9.1), with a 1-year actuarial rate of 43.5% for all grade pneumonitis. On logistic regression, significant predictors of any grade pneumonitis were higher mean lung dose, V5, V10, V15, V20 and V25. There was no association between time to pneumonitis and the volume of the planning target volume (PTV) or use of 3DCRT vs IMRT (p > 0.05). <h3>Conclusion</h3> In real-world patients with locally advanced NSCLC treated with concurrent chemoRT and consolidative durvalumab, the incidence of any grade and grade 3 pneumonitis may be higher than previously observed in prospective clinical trials. Several dosimetric parameters (MLD, V5, V10, V15, V20 and V25) predicted development of pneumonitis, emphasizing the global importance of minimizing dose to normal lung tissue.

Comparison of Overall Response to Neoadjuvant Short Course Radiotherapy Followed by Consolidation Chemotherapy with Long Course Chemoradiotherapy in Locally Advanced Rectal Cancer

<h3>Purpose/Objective(s)</h3> Primary objective of this study was to compare the clinical and radiological response rates between patients receiving pre-operative Short Course Radiotherapy (SCRT) followed by chemotherapy versus conventional long course CRT in patients with locally advanced rectal cancer. secondary objectives included comparison of rates of pCR and acute toxicities among the 2 groups of patients. <h3>Materials/Methods</h3> 33 patients with locally advanced rectal cancer were randomized to standard long course CTRT arm (arm A) and SCRT followed by sequential chemotherapy (arm B) arm (17 and 16 patients respectively). Patients in arm A received long course RT at dose 45 Gy in 25 fractions over 5 weeks with concurrent oral capecitabine on days of radiotherapy. Patients in arm B was prescribed short course radiotherapy at dose 25 Gy in 5 fractions over 1 week. 3 cycles of 3 weekly CAPOX chemotherapy was followed. Patients were planned with 3DCRT technique in Versa HD with 6 MV and 15 MV photons. Clinical response assessment was done by comparing the 2 arms in terms of per rectal examination findings before starting radiotherapy and after completion of RT, right before surgery. The parameters used for assessment were palpability of lesion, tone, mobility, distance from anal verge and location of the lesion. Radiological response assessment was done by comparing 5-point tumor regression grades (TRG) post treatment in the 2 treatment arms. <h3>Results</h3> Radiological tumor regression showed statistically non-significant trend favoring the experimental arm (rates of complete tumor regression 35.7% in SCRT followed by chemotherapy arm versus 23.1% in long course CTRT arm, higher percent of patients with greater tumor regression in SCRT+CT arm). pathological tumor regression also favored experimental arm without showing statistical significance (pCR rates 20% in long course CTRT versus 30% in SCRT+CT). Most of patients in the interventional arm presented with higher pathological tumor regression (TRG 0 and TRG 1) while the most common TRG in the long-course CTRT arm was TRG 3. Higher rate of acute grade 3 bowel toxicities was seen in the interventional arm. Grade 3 acute skin toxicity occurred in the standard arm compared no skin toxicity in the interventional arm. This difference was also not statistically significant. <h3>Conclusion</h3> Short course radiotherapy followed by 3 cycles of CAPOX chemotherapy is comparable to Long-course CTRT in terms of tumor regression. In resource limited setting, short course radiotherapy and chemotherapy is favored due to smaller radiotherapy duration and lesser chances of treatment interruption

A Study to Evaluate the Efficacy of Purely Accelerated 6 Fraction-per-Week Radiotherapy in Post-Operative Oral Cavity Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> To determine the efficacy of pure modestly accelerated fractionated radiotherapy (PM-ART) in postoperative setting in patients of squamous cell carcinoma of oral cavity (OCSCC) in terms of Locoregional control (LRC), Overall survival (OS), and Disease-free survival (DFS). <h3>Materials/Methods</h3> 40 post-operative OCSCC patients with one or more high risk features (pT3 or higher, close margins, DOI >10 mm, lymphovascular invasion, perineural invasion, >1 node positive, extra capsular extension) were treated between May 2015 and July 2016 with adjuvant PM-ART alone (60Gy in 30 fractions @ 2Gy per fraction; 6 fractions per week, over 5 weeks by three-dimensional conformal technique on a linear accelerator). Primary endpoint of the present study was to evaluate the efficacy of PM-ART and secondary endpoint was late toxicity assessment. <h3>Results</h3> 40 patients were followed up till July 2021 of which four were lost to follow up. At a Median follow up of 45.5 months (range 4-70 months), 3-year LRC was 75%. Out of 40 patients, 17 patients had expired at the time of analysis of which 3 deaths occurred due to other competing causes after the completion of RT. DFS rate at 3 years was 64.8% and median DFS was 64.2 months; 3-year OS rate was 59%, and median OS was not yet reached. 23 patients were available for evaluation of late toxicity at the time of analysis. Xerostomia and subcutaneous fibrosis were the main late toxicities observed as follows – xerostomia grade 2 in 2 patients (9%), grade 1 in 11 patients (48%), subcutaneous fibrosis grade 2 was seen in 2 patients (9%), and grade 1 in 12 patients (52%). There was no grade 3 or higher late toxicities recorded. <h3>Conclusion</h3> Intensification of treatment by using PM-ART (6 fractions per week) was found to have good locoregional control rates and survival outcomes with acceptable late toxicities and needs to be evaluated in the context of randomized controlled trials to validate the findings.

Dosiomics and Radiomics Features-Based Model to Predict the Neutrophil-Lymphocyte Ratio in Locally Advanced Non-Small Cell Lung Cancer Treated with Definitive Radiotherapy

<h3>Purpose/Objective(s)</h3> The neutrophil-to-lymphocyte (NLR) is a marker of systemic inflammatory that may predict clinical outcomes of many malignancies. This study therefore developed and validated a dosiomics and radiomics model based on three-dimensional (3D) dose distribution map and planning computed tomography (CT) images to predict the post-radiotherapy (post-RT) NLR. <h3>Materials/Methods</h3> We retrospectively collected 242 locally advanced non-small cell lung cancer (LA-NSCLC) patients. These patients were treated with definitive radiotherapy from 2012 to 2016. The model was developed and validated to predict the NLR collected one month after the completion of RT. Patients were randomly assigned (2:1) into development set and independent testing set. We extracted dosiomics features from 3D dose maps and radiomics features from CT images within different region of interest (ROIs). We developed the prediction model with gradient boosting tree (GBDT) using the features with good discriminability and low redundancy. We tuned the hyperparameters of GBDT model by using five-fold cross-validation. At last, we developed a fusion mode which combined dosiomics, radiomics and clinical features with weighted sum of different model's prediction probability. The model's discriminability was evaluated by receiver operating characteristic curve (ROC) and area under the curve AUC). Kaplan-Meier (KM) curves were used to explore the association between the predicted NLR and patient's survival. <h3>Results</h3> The clinical-based model and DVH-based model achieved an AUC of 0.632 and 0.621 in the testing set, respectively. The 8 features-based dosiomics and 4 features-based radiomics model achieved an AUC of 0.730 (95% CI: 0.599 – 0.860) and 0.701 (0.576 – 0.827). The dosiomics and radiomics and clinical fusion model improved the model's generalization ability with an AUC of 0.751 (95% CI: 0.623 – 0.880), sensitivity of 60.9% and specificity of 80.7% in the testing set. Moreover, the fusion model can significantly divide patients into high-risk and low-risk groups of progression free survival (PFS) and overall survival (OS) (log-rank test, p = 0.0056 and 0.0013). <h3>Conclusion</h3> In patients with LA-NSCLC treated with definitive radiotherapy, the dosiomics and radiomics can improve the prediction of the post-RT NLR.

Impact of Facility Case Volume on Radiation Schema and Outcomes in Palliative Radiation of Osseous Metastases

<h3>Purpose/Objective(s)</h3> To compare how facility volume impacts palliative RT practices in patients with osseous metastases, radiation schema used, and outcomes of the applied therapies by analyzing the percentage of remaining life spent receiving RT (PRLSRT) and RT completion rates. <h3>Materials/Methods</h3> A retrospective analysis was conducted using the National Cancer Database (2010-2016). Facilities were grouped and analyzed according to case volume of patients treated with palliative RT for bone mets. Facilities were grouped by case volume (<10, 10-24, 25-49, 50-74, 75-99, 100-149, ≥150). Patterns of palliative RT schemes (extended fractionation (>10 fx), hypofractionation (5 or fewer), and single fraction (8 Gy)) and outcomes were evaluated for facilities based on case volume. PRLSRT and course completion rates were calculated. <h3>Results</h3> 52,864 patient cases from 1,312 facilities were included. Higher facility case volume was associated with facility type (Academic > Comprehensive Community > Integrated Network > Community Cancer Program), higher population areas, higher distance traveled for treatment, lower comorbidity, younger age, and private insurance. Higher volume facilities were associated with the use of higher dose per fraction, resulting in increased use of single fraction, hypofractionation, and less use of extended fractionation regimens (see Table 1). The use of shorter courses at high volume centers resulted in increased radiation completion rates, and remaining life spent receiving radiation. <h3>Conclusion</h3> For palliative treatment of osseous metastases, facilities with higher case volumes favor shorter courses of RT and have better outcomes measured by PRLSRT and higher rates of treatment completion. It should be considered whether facility volume and experience influence the adoption of hypofractionation for palliative treatment of bone mets and how to improve adoption of shorter courses among all volume facilities.