Cumulative Incidence Of Local Failure Research Articles

Outcomes of repeated endoscopic submucosal dissection for superficial Esophageal squamous cell carcinoma on endoscopic resection scar.

Endoscopic submucosal dissection (ESD) can be performed for superficial esophageal cancer. However, performing ESD for superficial esophageal cancer on a previous endoscopic resection scar may be difficult. We compared the outcomes between ESD for superficial esophageal cancers on previous endoscopic resection scar (group A) and that for naïve lesions (group B). The study included outcomes of ESD, cumulative incidence of local failure, and predictors of the occurrence of local failure in ESD patients with squamous cell carcinoma (SCC). The outcome variables evaluated were en bloc resection rates, procedure times, adverse events, and overall survival rates. Overall, 220 lesions were extracted (groups A and B: 23 and 197 lesions, respectively). In groups A and B, the complete resection rates were 60.9 and 92.9% (P < 0.001), and the mean procedure times were 79 and 68min (P = 0.15), respectively. The perforation rates in groups A and B were 4.3 and 1% (P = 0.28). The 1-year cumulative local failure rates were 22 and 1% (P < 0.001), respectively. In the multivariate Cox proportional hazards analysis, superficial esophageal SCC on a previous endoscopic resection scar was a strong predictor of local failure (hazard ratio = 21.95 [3.99-120.80], P < 0.001). The 3-year overall survival rates in groups A and B were 95 and 93% (P = 0.99), respectively. Repeated ESD on scar is an option for treating superficial esophageal SCC with an acceptable rate of adverse events. Because of the low complete resection rate and high local failure compared with conventional ESD, strict endoscopic follow-up is required after repeated esophageal ESD.

Assessment of minimum target dose as a predictor of local failure after spine SBRT

ObjectivesMetastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. MethodsSpine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20–24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27–36 Gy and 21–24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. Results522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3–54.4). The cumulative incidence of local failure was 10.5 % (7.4–13.4) at 1 year and 16.3 % (12.6–19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 – 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6–9.4) vs. 14.2 % (8.3–19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). ConclusionsSpine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14–15.3 Gy with single fraction SBRT is recommended whenever possible.

Clinical outcomes of multisite moderate to high dose radiotherapy for patients with metastatic melanoma

AbstractBackground and purposeThis study aimed to summarize the clinical outcomes of patients with metastatic melanoma who received high‐dose radiation prior to or during systemic therapy at a single academic institution.MethodsWe identified patients with metastatic melanoma who underwent high‐dose radiation therapy (HDRT) for extracranial metastases prior to or during systemic therapy from 2010 to 2018. Treatment indications included oligometastases, oligoprogression, and local control. Using the Kaplan‐Meier method, we plotted overall survival (OS), progression‐free survival‐1 (PFS1), and PFS2. Competing risk analysis determined the cumulative incidence of local failure (LF) and the time to start or change systemic therapy (SCST). Univariate and multivariable analyses were used to identify predictive factors.ResultsWe analyzed 34 patients with 79 lesions, with a median follow‐up of 17.4 months. Sixty‐eight percent of patients received systemic therapy after the first HDRT. The median OS was 22 months, with brain metastases before HDRT being a significant predictor in multivariable analysis. The median PFS1 for first‐line HDRT was 4.1 months, and the median PFS2 was 3.9 months. Rates of LF were 10.3% at 12 months and 11.7% at 24 months. The incidence of SCST following HDRT was 59.8% at 12 months and 76.1% at 24 months, with radiation targeted at the lung associated with a lower incidence of SCST.ConclusionHDRT for treating metastatic lesions in melanoma demonstrated excellent local control and may play a role in delaying SCST. Additional courses of HDRT may provide cumulative benefits.

Abstract 1107: Prospective observational study to evaluate the efficacy of oxygen saturation endoscopic imaging for radiotherapeutic response in head and neck squamous cell carcinoma

Abstract Background: Radiotherapy (RT) has a pivotal role in the management of head and neck squamous cell carcinoma (HNSCC), providing effective tumor control and functional preservation. Hypoxia is a cause of radioresistance in HNSCC. We have developed an oxygen saturation endoscopic imaging (OXEI) method to assess real-time tissue oxygenation levels. However, the clinical significance of OXEI in patients with HNSCC receiving RT remains unclear. We evaluated the association between pretreatment tumor oxygen saturation (StO2) quantified by OXEI and clinical outcomes of patients with HNSCC receiving RT. Methods: We prospectively recruited patients with HNSCC scheduled to receive RT at 2 institutions. The primary endpoint was the association between pretreatment tumor StO2 and complete response (CR) rate 8 weeks after completion of RT. Secondary endpoints evaluated the impact of StO2 on 1-year overall survival (OS) and progression-free survival (PFS) rates after RT initiation. We also evaluated the cumulative incidence of local failure (LF). To explore the relationship between tumor hypoxia assessed by OXEI and gene expression profile, we performed RNA sequencing of 4 tumor samples collected from 2 patients (2 samples/patient) before RT. The hypoxia score for each sample was calculated by gene set variation analysis based on HNSCC mRNA-based hypoxia signatures. We performed gene set enrichment analysis (GSEA) to evaluate whether the biological pathways (Hallmark, Reactome, and KEGG gene sets) showed significant associations with tumor hypoxia. Results: Of the 50 patients enrolled from March 2019 to February 2022, we analyzed 37 who underwent RT and OXEI. Thirty-six (97%) patients received current platinum-based chemotherapy. The median (range) pretreatment tumor StO2 of 60 (45-84)% was lower than that of normal mucosa, 66 (56-84)% (P &amp;lt; 0.01). Patients with tumor StO2 &amp;lt; 60% were classified as the hypoxia group (n =19), and those with tumor StO2 ≥ 60% as the non-hypoxia group (n =18). The CR rate 8 weeks after RT was not significantly different between the hypoxia and non-hypoxia groups (84% vs. 100%, respectively; P = 0.23). After a median (range) follow-up of 33 (9-45) months, the hypoxia group had worse 1-year PFS (74% vs. 94%, P = 0.017) and OS (89% vs. 100%, P = 0.015) and higher LF rates (21% vs. 6%, P = 0.036) compared with the non-hypoxia group. RNA sequencing confirmed that tumor StO2 reflected expression-based hypoxia scores. GSEA showed upregulation of reactive oxygen species (ROS) and KEAP1-NFE2L2 pathways in hypoxic samples (StO2 of 59%) compared with non-hypoxic samples (StO2 of 70%; adjusted P &amp;lt; 0.01), consistent with the fact that hypoxic stress increases ROS production. Conclusion: Our findings suggest that pretreatment tumor StO2 quantified by OXEI correlates with 1-year PFS, OS, and LF rates of patients with HNSCC receiving RT. Citation Format: Kento Tomizawa, Atsushi Motegi, Hidenari Hirata, Hiroki Yamashita, Hironori Sunakawa, Wataru Okano, Tomohiro Enokida, Takeshi Fujisawa, Sadamoto Zenda, Masaki Nakamura, Hidehiro Hojo, Seiichiro Abe, Madoka Sakuramachi, Hiroshi Igaki, Yutaka Saito, Kazuto Matsuura, Makoto Tahara, Tomonori Yano, Tetsuo Akimoto. Prospective observational study to evaluate the efficacy of oxygen saturation endoscopic imaging for radiotherapeutic response in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1107.

Intraoperative radiation therapy for pediatric sarcomas and other solid tumors.

To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST). A single-institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan-Meier method, both from the day of surgery. Median age at time of IORT was 8years (range: 0.8-20.9years). Median follow-up for all patients and surviving patients was 16months and 3years, respectively. The most common histologies included rhabdomyosarcoma (n=42), Ewing sarcoma (n=10), and Wilms tumor (n=9). Most (95%) received chemotherapy, 37% had prior external beam radiation therapy to the site of IORT, and 46% had a prior surgery for tumor resection. About half (54%) were treated with upfront IORT to the primary tumor due to difficult circumstances such as very young age or challenging anatomy. The median IORT dose was 12Gy (range: 4-18Gy), and median area treated was 24cm2 (range: 2-198cm2). The cumulative incidence of LF was 17% at 2years and 23% at 5years. Toxicity from IORT was reasonable, with postoperative complications likely related to IORT seen in 15 (16%) patients. Our study represents the largest and most recent analysis of efficacy and safety of IORT in pediatric patients with ST. Less than one quarter of all patients failed locally with acceptable toxicities. Overall, IORT is an effective and safe technique to achieve local control in patients with challenging circumstances.

Abstract 7396: Development of deep neural networks that guide more individualized radiotherapy to the lung

Abstract Introduction: Radiotherapy is dependent on an expert-based model that impedes implementation of many potentially useful applications that could aid decision makers. This model is a barrier to a learning healthcare system due to noise introduced by decision-maker variation. Surmounting this barrier will require compelling clinical outcome data and highly useful and accurate information systems. We sought to develop new augmented-intelligence capabilities to better predict both high-dose lung irradiation treatment efficacy (i.e., local tumor control) and toxicity (i.e., radiation-induced pneumonitis). Methods: We curated one of the largest datasets of lung stereotactic body radiotherapy (SBRT) datasets globally (~1200 cases). We input pre-therapy lung computed tomography (CT) images using a bounding box approach that captures the gross tumor volume and adjacent normal lung into a multi-task deep neural network to generate an image fingerprint that predicts local failures after treatment. Separately, we input axial slices from CT scans of the lung into convolutional neural network (CNN) and trained using an outcome per slice method. We then aggregated intra-patient slices into a recurrent neural network (RNN) to estimate individual patient risk for pneumonitis. We validated our findings with the independent study cohort. Risk scores for local failure and pneumonitis were combined with clinical variables to assess the relative contribution of the deep learning-derived image risk scores. Results: A total of 1045 patients met our eligibility criteria. Radiation treatments in patients with high local failure risk scores failed at a significantly higher rate than in patients with low scores; 3-year cumulative incidence of local failure in the internal study cohort was 20·3% (16·0-24·9) in patients with high scores and 5·7% (95% CI 3·5-8·8) in patients with low scores (hazard ratio [HR]=3·64 [95% CI 2·19-6·05], p&amp;lt;0·0001). Models that included the local failure risk score and clinical variables predicted treatment failures with a concordance index (C-index) of 0·72 (95% CI 0·67-0·77), a significant improvement compared with classical radiomics (p&amp;lt;0·0001) or clinical variables (p&amp;lt;0·0001) alone. Radiation pneumonitis risk scores were highly predictive of toxicity, with an accuracy and CI of 0.78 (95% CI 0.72-0.85). A model that includes dosimetry variates (V20), improved the CI to 0.85 (95% CI 0.80-0.90). Conclusions: The image-based deep learning frameworks developed herein represent the first opportunity to use medical images to individualize radiotherapy dose and toxicity predictions. Our results signify a new roadmap for deep learning-guided predictions and treatment guidance in the image-replete and highly standardized discipline of radiation oncology. A phase 2 study assessing machine-derived dose predictions is currently enrolling patients. Citation Format: Mohamed Abazeed. Development of deep neural networks that guide more individualized radiotherapy to the lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7396.

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Less than whole uterus irradiation for patients with locally advanced cervical cancer

IntroductionCurrent consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation. MethodsWe identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point. ResultsThe median follow-up time was 65 months (range 3–352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3–9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups. ConclusionsIncluding less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity.

Stereotactic Body Radiation Therapy for Sacral Metastases: Deviation From Recommended Target Volume Delineation Increases the Risk of Local Failure

PurposeAlthough spine stereotactic body radiotherapy (SBRT) is considered a standard of care in the mobile spine, mature evidence reporting outcomes specific to sacral metastases is lacking. Furthermore, there is a need to validate the existing sacral SBRT international consensus contouring guidelines to define the optimal contouring approach. We report mature rates of local failure (LF), adverse events, and the impact of contouring deviations in the largest experience to date specific to sacrum SBRT. Methods/MaterialsConsecutive patients who underwent sacral SBRT from 2010-2021 were retrospectively reviewed. Primary endpoint was magnetic resonance imaging-based LF with a specific focus on adherence to target volume contouring recommendations. Secondary endpoints included vertebral compression fracture (VCF) and neural toxicity. ResultsOf the 215 sacrum segments treated in 112 patients, most received 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Sixteen percent of segments were non-adherent to the consensus guideline with a more restricted target volume (under-contoured). The median follow-up was 21.4 months (range, 1.5-116.9). The cumulative incidence of LF at 1 and 2 years was 18.4% and 23.1%, respectively. In those with guideline adherent vs. non-adherent contours, the LF rate at 1 year was 15.1% vs. 31.4% and at 2 years 18.8% vs. 40.0% (HR=2.5, 95% CI 1.4-4.6, p=0.003), respectively. On multivariable analysis, guideline non-adherence (HR=2.4, 95% CI 1.3-4.7, p=0.008), radioresistant histology (HR=2.4, 95% CI 1.4-4.1, p<0.001), and extraosseous extension (HR=2.5, 95% CI 1.3-4.7, p=0.005) predicted for an increased risk of LF. The cumulative incidence of VCF was 7.1% at 1 year and 12.3% at 2 years. Seven patients (6.3%) developed peripheral nerve toxicity, of which 4/7 had been previously radiated. ConclusionsSacral SBRT is associated with high efficacy rates and an acceptable toxicity profile. Adhering to consensus guidelines for target volume delineation is recommended to reduce the risk of LF.

Intraoperative Radiation Therapy for Relapsed or Refractory High-Risk Neuroblastoma: A 27-Year Experience

To evaluate outcomes after intraoperative radiation therapy (IORT) in high-risk neuroblastoma (NB), including local control, overall survival, and toxicity. This was a single institution retrospective study of 92 pediatric patients with NB treated with IORT from 1995 to 2022. Each IORT application was considered a separate event for a total of 110 sites treated. Local failure was calculated using the cumulative incidence function and survival by Kaplan-Meier method from the day of surgery. All patients had high-risk relapsed or treatment refractory disease. Median age was 6 years (range, 2-34 years). Median follow-up for all patients and surviving patients was 16 months and 4 years, respectively. All patients previously received chemotherapy, 93% had prior external beam radiation therapy to the site of IORT (median dose, 21.6 Gy; range, 10-36 Gy), and 94% had a prior surgery for tumor resection. The median IORT dose was 12 Gy (range, 8-18 Gy) and median area treated was 18 cm2 (range, 2.5-60 cm2). The cumulative incidence of local failure was 23% at 2 years and 29% at 5 years. The overall survival (OS) was 44% at 2 years and 29% at 5 years. Local failure after IORT was associated with worse OS (hazard ratio, 1.74; 95% CI, 1.07-2.84; P = .0267). Toxicity from IORT was rare, with postoperative complications likely related to IORT seen in 7 (8%) patients. Our study represents the largest, most recent analysis of the efficacy and safety of IORT in patients with relapsed or refractory NB. Less than one-third of patients failed locally at 5 years, and achieving local control affected overall survival. Minimal toxicities directly related to IORT were observed. Overall, IORT is an effective and safe technique to achieve local control in high-risk relapsed or refractory neuroblastoma.

Radiation therapy dose escalation achieves high rates of local control with tolerable toxicity profile in pediatric and young adult patients with Ewing sarcoma.

Local control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors ≥8cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS. Eligible patients ≤30years old with newly diagnosed EWS ≥8cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity. Thirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8Gy (range, 59.4-69.4Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy. This study demonstrates that definitive RT for pediatric and young adult patients with EWS ≥8cm provides high rates of local control, while maintaining a tolerable toxicity profile.

Safety and efficacy of external beam radiotherapy in hepatocellular carcinoma patients previously treated with yttrium-90 radioembolization.

523 Background: Data on the safety and efficacy of external beam radiation (EBRT) after Yttrium-90 (Y-90) radioembolization for hepatocellular carcinoma (HCC) is limited. We report our experience using EBRT to treat HCC patients who were previously treated with Y-90. Methods: We analyzed 31 HCC patients who received EBRT following Y-90 treatment. Eighteen were treated with photon therapy (40-50 Gy in 5 fractions), and thirteen with proton therapy (42-67.5 Gy in 15 fractions). Twenty-four patients underwent Y-90 segmentectomies, while seven received Y-90 lobar treatment. The median administered Y-90 activity was 44.4 mCi (range 8.3-114.4). Results: Patients had received 1 (n=14), 2 (n=7), or ≥3 (n=10) prior Y-90 treatments. EBRT was administered for various reasons: poor Y-90 response in two patients, technical limitations in 25 patients, and other reasons in four patients. Ten patients had previously received Y-90 within the EBRT area, thirteen outside the EBRT area, and eight in both regions. The median tumor size was 3.8 cm (range 1.6-19.4). Twenty-seven patients had Child-Pugh (CP)-A score, three had CP-B, and one had CP-C baseline liver function. With a median follow-up of 21 months, the 2-year progression-free survival, and overall survival rates were 28%, and 43%, respectively. The 2-year cumulative incidence of local failure was 7%. CP+2 progression was observed in five patients (16%): three had Y-90 delivered outside the EBRT area and two within the EBRT area. Three patients had possible RILD-related deaths. Grade 3+ biliary complications occurred in three patients (10%): one biloma, one liver abscess, and one biliary stricture which resulted in a possible treatment-related death. All three patients had received at least two prior Y-90 treatment overlapping with the area treated with EBRT and had tumors located near the porta hepatis. Conclusions: EBRT for HCC patients previously treated with Y-90 is feasible and offers excellent local control. Hepatic function and biliary toxicities are potential complications and should be weighed against the clinical benefits.

Locoregional Ablative Radiation Therapy for Patients With Breast Cancer Unsuitable for Surgical Resection

Breast cancer patients unsuitable for surgical resection are typically managed with palliative systemic therapy alone. We report outcomes of 5-fraction ablative radiotherapy for non-resected breast cancers. Retrospective analysis of an institutional registry of breast cancer patients unsuitable for resection who underwent 35-40 Gy/5 fractions to the primary breast tumour and/or regional lymph nodes from 2014-2021. Primary outcomes were cumulative incidence of local failure (LF) and grade ≥3 toxicity (CTCAE v5.0). We reviewed 57 patients who received 61 treatment courses (median age of 81 years, range 38-99). Unresectable tumour (10%), patient refusal (18%), medical inoperability (35%), and metastatic disease (37%) were the causes of not having surgery. Five patients (8%) had previously undergone adjuvant locoregional radiotherapy. Fifty-four percent (n=33/61) of treatment courses targeted the breast only, 31% (n=19/61) both the breast and lymph nodes, and 15% (n=9/61) the lymph nodes only. Sixty-seven percent (n=35/52) of the courses that targeted the breast were delivered with partial breast irradiation and 33% (n=17/52) with whole breast radiotherapy (median dose of 25Gy in 5 fractions) ± simultaneous integrated boost to the primary tumour. Most primary tumours (65%, n=34/52) and target lymph nodes (61%, n=17/28) were treated with a dose of 35 Gy in 5 fractions. Most treatments (52%) were delivered with intensity-modulated radiotherapy (IMRT). Radiotherapy was delivered daily (20%), every other day (18%), twice weekly (36%) or weekly (26%). The 2-year cumulative incidence of LF was 11.4% and grade≥3 toxicity was 15.1%. The grade ≥3 toxicity was 6.5% for IMRT treatments, versus 7.7% for non-IMRT treatments targeting partial breast and/or lymph nodes (HR 1.13, P=0.92), versus 38.9% for non-IMRT treatments targeting the entire breast (HR 6.91, P=0.023). All grade ≥3 toxicity cases were radiation dermatitis. No cases of brachial plexopathy were observed. 35-40 Gy in 5 fractions is a safe and effective breast stereotactic body radiotherapy regimen and may be an attractive option for patients who are not surgical candidates. Highly conformal techniques (i.e. IMRT or partial breast irradiation) were associated with a reduced risk of toxicity and should be the preferred treatment approaches.

Image-guided high-dose-rate brachytherapy as the method of choice in medically inoperable early-stage endometrial cancer patients

PurposeAbout 3–9% of patients with endometrial cancer are unable to undergo surgery due to medical comorbidities, including morbid obesity, or age-related frailty syndrome. An alternative curative option is irradiation. The aim of this prospective study was to evaluate clinical outcomes of high-dose-rate intracavitary brachytherapy (HDR-ICBT) treatment in such patients. Materials and methodsSeventy-eight patients with FIGO stage I-II endometrial cancer disqualified from surgery were treated with HDR-ICBT with 45–52,5 Gy prescribed to high-risk clinical target volume (HR-CTV) in 5–9 fractions given once a week. All fractions were planned using computed tomography (CT) scans. ResultsThe median follow-up time was 67 months. Median age was 79 years (range: 42–93 years). Median body mass index (BMI) was 39,1 kg/m2 (range: 24,2–68 kg/m2). We observed no statistically significant impact of BMI ≥ 40 on overall survival (OS) or prgression free survival (PFS). The 3- and 5-year OS for the whole population were 69% and 55%, respectively. The impact of high risk features (FIGO II, grade 3 or type 2 cancer) on OS was significant (p = 0,049). The 5-year cumulative incidence of local failure, distant metastases and non-cancer death were 12,9% [95% CI: 5,4%–20,5%], 6,4% [95% CI: 0,9%–11,9%], 33,1% [95% CI: 22,3%–43,9%], respectively. The 5-year risk of cancer and non-cancer death were 9% (95% CI: 3%–16%) and 36% (95% CI: 25%–47%), respectively. We observed G1 vaginal apex stenosis only. ConclusionsCT-guided HDR-ICBT is a feasible and safe management of FIGO stage I endometrial cancer in obese and elderly patients. The survival outcome of the treated group is influenced more by associated comorbidities than by the progression of endometrial cancer.

RADT-21. LINEAR ACCELERATOR BASED RADIOSURGERY WITH DYNAMIC CONFORMAL ARCS FOR PATIENTS WITH MULTIPLE BRAIN METASTASES: A PROSPECTIVE COHORT STUDY

Abstract PURPOSE Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is gaining popularity as an alternative due to its high delivery efficiency and improved accessibility. This study focuses on the radiosurgery protocol of a single institution, utilizing single-isocenter multi-target SRS treatment with an inverse-optimized dynamic conformal arc technique. Materials &amp; METHODS A prospective cohort study was conducted from August 2020. The study protocol was approved by the Research Ethics Committee. Patients with brain tumors referred for SRS were treated based on the indications. Prescription doses were determined by target size and radiation oncologists. The protocol included a 1-2 mm expansion of tumors for the planning target volume (PTV), with a requirement of at least 85% PTV coverage. At least three non-coplanar arcs are needed. Competing risk survival analysis was used to assess the cumulative incidence of failure. RESULTS A total of 57 patients with 190 brain tumors underwent SRS in this study. 12 patients (21.1%) received at least 2 radiation courses for recurrent lesions. Tumor sizes ranged from 0.45 to 8.0 cm (median 1.41 cm). The maximal dose relation ranged between 71.5% and 91.4% (median 81.6). The conformal index ranged from 1.08 to 2.19 (median 1.19), and the dose gradient index ranged from 2.19 to 6.95 (median 3.59). The 1-year cumulative incidence of local failure and intracranial distant failure rates were 10.8% and 35.6%, respectively. CONCLUSION LINAC-based SRS using dynamic conformal arcs achieves optimal tumor coverage and a high dose gradient with ease. It demonstrates a low rate of local failure, effectively protects normal brain tissue, and allows for the postponement of whole brain radiotherapy, enabling patients to maintain a normal quality of life. In conclusion, LINAC-based SRS with dynamic conformal arcs may be a beneficial treatment option for brain metastases, even with a high lesion count, particularly in institutions equipped with LINAC.

Dosimetric Parameters Predictive of Treatment-Related Toxicity in High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

High dose-rate (HDR) brachytherapy as monotherapy is an effective treatment for patients with low- and intermediate-risk prostate cancer and is increasingly being offered as a 2-fraction protocol. There is a lack of consensus on the optimal dosimetric planning parameters to use, or whether there is any benefit summating dosimetric parameters from more than one implant. Our goal is to determine planning parameters associated with disease control, toxicity and health-related quality of life (HRQOL). Data were collected on 83 patients with low- and intermediate-risk prostate cancer who received 2 fractions of 13.5 Gy HDR brachytherapy without androgen-deprivation therapy as part of a randomized phase II clinical trial. An in-house deformable, registration algorithm was used to co-register and dose-summate the plans from both implants for each patient. Acute and late GU and GI toxicities were measured using CTCAE 4.0 and HRQOL was measured in urinary, bowel, sexual and hormonal domains using the EPIC scores. Treatment efficacy was assessed through PSA measurement and imaging with or without biopsy where indicated. Covariates included baseline clinical factors, disease characteristics and treatment dosimetric parameters. Cox proportional hazards was performed to evaluate covariates impact on treatment toxicity and efficacy, and logistic regression analysis evaluated covariates impact on HRQOL. Among the 83 patients, median prostate volume was 46.7cm3. Median summated planning target volume receiving 100% prescription dose (PTV V100%) was 97.4%, median PTV V150% 42.4% and median PTV V200% 15.5%. Median highest dose to the 1cm3 rectum (D1cc) was 66.9% of the prescription dose and median rectum V80% was 0.008cm3. Median urethral D1cc was 99.0% of the prescription dose, median urethral Dmax 121.7% and median urethral D10% 116.2%. Grade ≥2 GI toxicity was uncommon (3.7% acute and 8.5% late), but grade ≥2 GU toxicity was reported in 73.2% (acute) and 46.3% (late) patients. Rectum D1cc and V80% were found to be significantly associated with grade 2 or higher acute GI toxicity, while use of a-blocker at baseline was associated with grade ≥2 acute GU toxicity. Similarly, use of a-blocker was associated with late grade ≥2 GU toxicity, but with no dosimetric associations. No other variables were associated with treatment-related toxicities. Only rectum D1cc was significantly associated with changes in bowel EPIC scores. Estimated 5-year biochemical disease-free survival was 93.9% and 5-year cumulative incidence of local failure was 3.8%. HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.

Assessment of Minimum Dose as a Strong Predictor of Local Failure after Spine SBRT

Stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). Even so, a wide range of dose-fractionation schemes are used in clinical practice. We seek to assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. From a large institutional database, spine SBRT treatments with subsequent imaging follow-up to assess local control were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, generally delivering 20-24 Gy in 1 fraction to the high dose volume and 16 Gy to the low dose volume (or 30-36 Gy and 24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. Statistical analyses included Cox proportional hazards analyses and the robust log-rank statistic for cut-point analysis. The cumulative incidence of local failure with death as a competing risk was considered as the primary endpoint. A total of 522 eligible spine SBRT treatments (68% single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95% confidence interval: 34.3-54.4). The cumulative incidence of local failure was 19.3% (15.3-23.2) at 1 year and 25.6% (21.1-29.9) at 2 years. Univariate analysis identified that the minimum dose (normalized for the prescription dose) was a strong predictor of local failure (p = 0.0093). Among patients treated with a single fraction, statistical significance was maintained (p = 0.024). No other dosimetric factors were predictive of local failure. In a cut point analysis, the log-rank statistic was maximized at 15.8 Gy minimum dose for single-fraction treatment (HR = 0.51, 95% CI: 0.34 - 0.75, p = 0.0009). Cumulative incidence of local failure was 15.1% (9.8-20.2) vs. 24.7% (17.2-31.5) at 1 year using this cut-off. Comparable local control was demonstrated with a minimum dose of 14 Gy (HR = 0.57, 95%: 0.37 - 0.87, p = 0.009), with reduced local control with lower minimum doses. Among a range of clinical factors assessed, only epidural and soft tissue involvement were predictive of local failure (HR = 1.80 and 1.98, respectively). Multivariable analyses incorporating soft tissue involvement, epidural extension, and multilevel disease confirmed the 15.8 Gy cutoff for single fraction cases (HR = 0.58, 95% CI: 0.38-0.88, p = 0.011). Spine SBRT offers favorable local control using a range of dose-fractionation schemes; however, minimum dose has a strong association with local control, unlike any other dosimetric factors tested. Furthermore, statistical significance was maintained even when considering epidural extension and potential limitations from dose to the spinal cord. Our data suggests that the minimum dose should be prioritized during treatment planning, ideally to at least 14 - 15.8 Gy for single fraction.

Association between Radiation Dose and Local Failure in Recurrent High-Risk Neuroblastoma

Historically, standard-of-care (SoC) for high-risk neuroblastoma recurrences is irradiation to 2160 cGy for gross or microscopic disease. Boosting gross disease to 3000-3600 cGy remains controversial. Prior reports have demonstrated worse local control with gross disease irradiated to <3000 cGy. We sought to evaluate whether higher radiation doses delivered to sites of recurrence affected local control. We identified seventy-five high-risk neuroblastoma patients aged 6 months to 26 years that completed definitive treatment between 2007 and 2021 at two large academic centers. Only patients with distant recurrences treated with radiotherapy were included for analysis. Treatments were stratified into 1800-2160 cGy or 3000-3600 cGy dose levels. Local failure after irradiation was defined as progression within the radiation field after salvage RT. The Fine-Gray competing risk model was used to identify cumulative incidence of local failure (CILF) after irradiation with competing risk of death. Thirteen patients experienced recurrence after completion of definitive treatment, representing 30 metastatic lesions. Thirteen lesions received 1800-2160 cGy and seventeen received 3000-3600 cGy. With a median follow-up of 42.0 months (IQR 30.8-60.8), local failure after irradiation occurred in 10% (3/30) of metastatic lesions. Median time to failure was 7 months. All three failures had been treated to 2160 cGy; two in the calvarium and one in the femur. There were no local failures among patients treated to 3000-3600 cGy. The 1-year and 2-year CILF for the low- versus high-dose levels were 15% versus 0% (p<0.01) and 25% versus 0% (p<0.01), respectively. Four of the 13 patients (31%) died at a median time of 12.5 months after first recurrence; all four had distant recurrences. Dose-escalated irradiation ≥3000 cGy was associated with improved local control in recurrent high-risk neuroblastoma; prospective study and validation is warranted.

Safety and Efficacy of Stereotactic Body Radiotherapy for Ultra-Central Thoracic Tumors

Stereotactic body radiotherapy (SBRT) is increasingly utilized in the management of ultra-central thoracic tumors, although concerns regarding significant toxicity remain. We sought to evaluate the toxicity and efficacy of SBRT to these tumors at our institution. Patients with ultra-central lung tumors or nodes treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. Ultra-central was defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus. All SBRT plans were generated with homogenous dose distributions using target coverage objectives of ITV V100% >99%, PTV V95% >99%, and an ideal PTV Dmax <105% (strict <120%). All plans were reviewed in quality assurance rounds by a team of dosimetrists, physicists, and radiation oncologists. The primary endpoint was incidence of severe toxicity (ST), defined as SBRT-related grade ≥3 toxicities, graded using the Common Terminology Criteria for Adverse Events V5.0. Secondary endpoints included local failure (LF), progression-free survival (PFS) and overall survival (OS). Competing risk analysis was used to estimate incidence and predictors of ST and LF, with death as a competing risk. Kaplan-Meier method was used to estimate PFS and OS. A total of 154 patients who received 162 ultra-central courses of SBRT were included, with a median follow-up of 21.5 months. Treatment intent was most commonly for oligoprogression (46%), oligometastasis (30%), followed by curative (20%). The most frequent tumor histologies were NSCLC (41%) and RCC (26%). SBRT prescription doses ranged from 30-55 Gy in 5 fractions (BED10 range 48-115 Gy). The most common prescription was 50 Gy in 5 fractions (42%). The cumulative incidence of ST was 8.9% at 3-years. The most common ST was pneumonitis (n = 4). Notable toxicities included bronchopleural fistula (n = 2, grade 3 and 4), bronchial stricture (n = 1, grade 3), and esophagitis leading to bleeding (n = 1, grade 4). There were no esophageal strictures or perforations, and no bronchial bleeds. There was 1 possible treatment related death from pneumonitis/pneumonia. Predictors of any ST included increased lung V5 Gy, decreased PTV V95%, and not having prior radiation therapy to the chest. The cumulative incidence of LF was 4.8%, 11% and 14% at 1-, 2-, and 3-years respectively. Predictors of LF included younger age, and greater volume of overlap between the PTV and esophagus. Median PFS was 8.4 months, while median OS was 3.7 years. In one of the largest case series of ultra-central thoracic SBRT reported to date, homogenously prescribed SBRT plans were associated with relatively low rates of ST and LF across a variety of treatment indications. Predictors of ST should be interpreted recognizing the heterogeneity in toxicities observed. Identified predictors of both ST and LF can contribute to future work to optimize the therapeutic ratio in treatment of ultra-central thoracic tumors.

Stereotactic Body Radiation Therapy (SBRT) for Head and Neck Cancer Re-Irradiation: Should >180˚ Carotid Encasement or Dermal Involvement Remain an Exclusion Criteria?

Patients with recurrent head and neck cancer (HNC) who present with carotid encasement (CE) >180˚ and skin involvement/abutment (SI/A) are often not considered for SBRT re-irradiation and are excluded from RTOG 3507. We reviewed our institutional experience of SBRT re-irradiation in such cases. From an IRB approved registry, we identified previously irradiated HNC patients treated by SBRT with CE >180˚, SI/A, or use of bolus from 2013-2022. Toxicity as per CTCAEv4.0 and recurrence patterns were analyzed. The cumulative incidence of local progression was estimated with death as a competing risk. Survival analysis was performed with the Kaplan-Meier method. Thirty-five patients were treated with SBRT to 37 sites with median follow up of 5.7 months (mo) (IQR 2.7-10.6). A total of 20 cases exhibited CE >180˚, 20 cases had SI/A, and 3 cases had both. The median time from prior radiation was 12.7 mo (range 1.9-144.1). Histology was squamous cell carcinoma in 89%. The site of SBRT was most commonly the neck (65%), 24% mucosa, 8% skull base, and 3% scalp. SBRT was delivered in 5 fractions every other day (62%) or 2 fractions per week (38%). 78% (N = 29) received ≥40 Gy while 22% (N = 8) received a lower dose. The cumulative incidence of local failure at 3 and 6 mo was 12.4% (95% CI 0.8-24.0) and 31.3% (95% CI 14.9-47.8), respectively. The median time of local and regional recurrence free survival was 7.0 and 4.9 mo. Median OS was 8.3 mo. Of the 20 cases with true SI, 40% (N = 8) completely resolved, 35% (N = 7) improved or had residual ulceration attributed to disease, and 25% (N = 5) had ulceration related to toxicity. There were no carotid bleeding events (CBE) related to SBRT, however 10% (N = 2) experienced fatal CBE related to progressive disease at 2.3 mo and 6.7 mo from SBRT. The rate of grade ≥2 treatment related skin toxicity was 19% (N = 7) and only occurred in those with pre-SBRT SI/A. These included a grade 2 neck wound and tracheostomy infection, a grade 3 infection, and two grade 3 soft tissue necrosis. One patient had cellulitis/meningitis related to scalp radiation, and one had an untreated SBRT wound as they transitioned to hospice. Dysphagia requiring PEG occurred in 5% (N = 2), one of which was related to CNX palsy. Six patients (17%) had post-SBRT nerve impairment including one each of grade 2 facial nerve paralysis, grade 2 brachial plexopathy, grade 3 CNVIII dysfunction, grade 3 CNX impairment, and two patients with grade 2 CNXII impairment. SBRT for locally recurrent previously radiated HNC can provide effective local control in a patient population at high risk of morbidity and mortality from local disease progression. In patients who have >180˚ CE or SI/A, we observed non-trivial toxicity, but disease progression may have been more morbid. For appropriately counseled patients with limited treatment options, CE or SI/A may not be an absolute contraindication to SBRT re-irradiation.