Local Toxicity Research Articles

Fractionated Stereotactic Radiotherapy vs. Stereotactic Radiosurgery for Vestibular Schwannoma: Local Control, Hearing Preservation, and Toxicities

The use of radiation therapy (RT) in vestibular schwannoma (VS) is well-established, but limited studies detail outcomes in patients treated with fractionated stereotactic radiotherapy (FSRT) versus stereotactic radiosurgery (SRS). In this study, we provide an outcome-based comparison of FSRT versus SRS in patients with VS with emphases on local control, hearing preservation, and toxicities. We hypothesize that FSRT and SRS will have similar rates of local control with FSRT having improved rates of hearing preservation. Patients treated at a single tertiary referral center between 2013 and 2018 for VS using FSRT (46.8 Gy in 26 fractions) or SRS (12 Gy in 1 fraction) were identified. Records from radiation oncology, neurosurgery, and otolaryngology were included. Endpoints included local control, defined as absence of tumor progression or need for salvage treatment, hearing preservation, quantified by Gardner-Robinson (GR) scoring and defined as maintaining GR1-2 hearing, and toxicities as per Common Terminology Criteria for Adverse Events (CTCAE), version 5. A total of 77 patients with VS were identified, of which 50 had FSRT and 27 had SRS. In the FSRT group, the median patient age was 58 years (range 23-81) and 50% were female, whereas the median patient age was 68 years (range 24-90) and 41% females were in the SRS group. 81% (n = 35) patients in the FSRT group and 24% (n = 6) in the SRS group had serviceable hearing prior to RT. Median follow-up was 51.2 months (range 4.3-103.2) in the FSRT group and 21.0 months (range 2.7-98.6) in the SRS group. The 2-year, 3-year, and 5-year local control rates in the FSRT and SRS groups were 100% and 100%, 97% and 76%, 94% and 76%, respectively. Of those with local progression, 33% (n = 1) in the FSRT group was salvaged with stereotactic body radiation therapy (SBRT) and 100% (n = 2) in the SRS group was salvaged with FSRT. For patients with serviceable hearing prior to RT, hearing preservations rates were 46% and 17% with a median time to hearing loss of 8.2 months (range 4.0-59.5) and 7.7 months (range 2.0-11.9) in the FSRT and SRS groups, respectively. Progression-free survival analyses showed superior hearing preservation in those treated with FSRT compared to SRS (p-value = 0.0064), especially those receiving FSRT who initially presented with GR1 vs GR2 hearing (p-value = 0.0095). There were 60 reported toxicities with 12% (n = 7) Grade 2+ in the FSRT group, whereas the SRS group had 5 toxicities with 40% (n = 2) Grade 2+. Both FSRT and SRS provide favorable local control for VS, with most progressions salvageable. Hearing preservation rate is higher in the FSRT group. This favors the use of FSRT in those with serviceable hearing, with patients with baseline GR1 hearing demonstrating additional benefit. Further prospective randomized studies are needed to better identify treatment outcomes and prognostic factors.

Predicting Dosimetry of Stereotactic Ablative Radiotherapy for the Treatment of Multiple Lung Lesions

Stereotactic ablative radiotherapy (SABR) has recently been used to treat increasing numbers of lung metastases, either synchronously or over multiple courses of treatment. Selecting the optimal dose and fractionation to balance risk of local failure and treatment toxicity is challenging. This project uses machine learning to provide rapid dosimetry predictions of SABR to multiple lung lesions, allowing exploration of different dose prescription options prior to the radiation (RT) planning process. A generative adversarial network (GAN) was trained to predict the dosimetry of multi-lesion thoracic SABR treatment from the planning CT scan, target and organ at risk contours, and the prescribed dose-fractionation without the need to carry out treatment planning. RT plans of patients who received at least one SABR treatment for ≥2 lung lesions between 2014-2020 at a single tertiary center were included in the analysis. All prescriptions were converted to their equivalent doses in two Gray fractions (EQD2). SABR treatments received at different timepoints were registered, and EQD2 doses were accumulated with no repair. Model performance was assessed using 5-fold cross validation. Plans were randomly divided into 5 folds, stratified by the number of lesions (no patients crossed folds). Each fold served as the testing set once, with the model trained on the other 4 folds. The model was evaluated on the difference in the volume of lung receiving above 20 Gray (V20) of the predicted dosimetry compared to the true dosimetry. Treatment plans (n = 103) were included from 81 patients with 280 lesions (62, 23, 8, and 10 plans had 2, 3, 4, and ≥5 lesions respectively). Fifty-five, 18, and 4 patients had a single, 2 and 3 courses of RT respectively. Fifty-two patients were treated for primary lung cancer, 28 patients treated for metastases from other sites, and 1 patient for both. Seven patients (8.6%) developed ≥ Grade 2 pneumonitis. Doses prescribed were 60/8 (n = 136), 55/5 (n = 49), 54/3 (n = 27), 24/1 (n = 21), 35/5 (n = 13), 30/5 (n = 9), and other (n = 25). The mean lung V20 for all patients was 11.3% [1.5%-29.6%]; the mean lung V20 was 9.3%, 12.2%, 13.5% and 20.4% for plans with 2, 3, 4, ≥ 5 lesions respectively. The mean absolute difference (MAD) in lung V20 between the predicted dosimetry and true dosimetry over all 5-folds was 1.9% [0.0%-13.4%]; the MAD in lung V20 between the predicted and actual dosimetry was 1.6%, 2.1%, 2.9% and 2.6% for plans with 2, 3, 4, ≥ 5 lesions respectively. The GAN-based model created in this study can predict the dosimetry of any number of lesions in the thorax treated with SABR. The model can be used to quickly determine the feasibility of SABR treatment for multiple synchronous lesions, or in the retreatment setting. The ability to explore the dosimetry of different prescription options for a given patient prior to RT planning may allow for personalized risk-adapted treatment if combined with local control and toxicity modelling.

Feasibility and Safety of Single-Isocenter/Multi-Lesion (SIML) HyperArc Brain SRT: Clinical Implementation and Early Outcomes

Patients with multiple brain metastases may not tolerate relatively longer treatment times for traditional stereotactic radiation therapy (SRT) with individual isocenter plans for each lesion due to discomfort or co-morbidities. SRT using a single-isocenter/multi-lesion (SIML) HyperArc volumetric modulated arc therapy (VMAT) plan with flattening filter free (FFF) beam could significantly shorten overall treatment time, and improve patient comfort, compliance, and clinic efficiency. We report early clinical results of treating multiple brain metastases with SIML HyperArc SRT. Twenty-three patients with multiple brain metastatic tumors (range, 2-9 lesions; total treated lesions, n = 96) were simulated using Encompass support and Q-fix mask, and treated with a highly-conformal SIML VMAT SRT plans via non-coplanar HyperArc geometry. Mean tumor distance to isocenter was 5.3 cm, maximum up to 7 cm. Common prescriptions were 25-30 Gy/5 fractions, 24-27 Gy/3 fractions, and 20 Gy/1 fraction prescribed to each planning target volume (PTV) using 2 mm margin around standard gross tumor volume (GTV) delineated on contrasted enhanced MP-RAGE MRI fusion. Acuros dose calculation for 6MV-FFF beam was used for tissue heterogeneity corrections. Alliance A071801 criteria was used for dose constraints to organs at risk (OAR) and target conformality. Treatment was delivered every other day with CBCT-guidance, adjustments made with 6DOF couch corrections on a medical linear accelerator, and treatment delivery time within 15 minutes. Local control rates were reported, and toxicity profile rated based on CTCAE v5.0 for brain radionecrosis, optic neuropathy, and brainstem dysfunction. All plans met Alliance A071801 requirements for each tumor coverage, dose to OAR including optic apparatus, brainstem, and spinal cord. Mean GTV and PTV volume were 9.4 cc (range, 0.3-54.8 cc) and 16.13 cc (range, 1.0-80.2 cc). Patient-specific quality assurance results were 98.3% for gamma passing criteria of 2%/2mm. Independent in-house Monte Carlo physics second check agreed with HyperArc plans by ±3.0%. Mean follow up was 6 months (range, 0.0-18.6 months). Of the 23 patients treated, 17 (74%) had post-treatment MRI imaging to assess local control and toxicity. Local control was achieved in 69/73 (95%) of treated and followed lesions. CTCAE grade 2 radionecrosis occurred in 2 patients and were managed with dexamethasone. No CTCAE grade 3+ events of radionecrosis, optic pathway dysfunction, or brainstem toxicity were observed. SIML HyperArc Brain SRT for multiple brain metastases has excellent local control and low toxicity profile in our patients. It can significantly reduce treatment delivery time as compared to traditional multiple-isocenter brain SRT or chronologically separate treatment courses and thus, help to improve patient comfort, compliance, ease of care, and clinic workflow. Longer median follow up of SIML brain SRT on larger patient cohort is warranted.

Clinical Outcomes of Synchronous Lung Stereotactic Body Radiation Therapy Lesions via Single-Isocenter/Multi-Lesion Treatments

Lung cancer patients with synchronous primary or oligometastatic (< 5 lesions) with associated co-morbidities may not retain their treatment position for the extended stereotactic body radiotherapy (SBRT) treatment times with individual isocenter plans for each lesion due to discomfort or shortness of breath. SBRT using a single-isocenter/multi-lesion (SIML) volumetric arc therapy (VMAT) plan with flattening filter free (FFF) beam could significantly shorten overall treatment time, improve patient comfort and compliance and clinic efficiency. We report clinical results of treating multiple lung metastases or synchronous primary lung cancers with SIML lung SBRT. Eighty patients with synchronous primary lung cancers or oligometastatic lung tumors (two, n = 61; three, n = 10; four, n = 4; five n = 5; total treated lesions, n = 193) were simulated with abdominal compression and/or 4D-CT MIP images and treated with a highly-conformal SIML VMAT lung SBRT plans via 3-4 non-coplanar arcs. Common prescriptions were 50-55 Gy/5 fractions and 54 Gy/3 fractions prescribed 70-80% isodose line to the each PTV. Acuros dose calculation for 6MV-FFF beam was used for tissue heterogeneity corrections. RTOG-0618/0813 criteria were used to dose constraints to organs at risk (OAR) and target conformality. Treatment was delivered every other day or twice weekly with CBCT-guidance, adjustments made with 6DOF couch corrections on a medical linear accelerator, and treatment delivery time within 15 minutes. Local control rates and toxicity profile was evaluated using CTCAE v. 5.0 grading for pneumonitis, rib fracture and chest wall pain. All plans met RTOG-0618/0813 requirements for each tumor coverage, dose to OAR including normal lung and ribs. Mean follow up after last fraction of treatment was 16.9 months (range, 1.0-54.2 months). PTV volume ranged from 2.17 to 167.8 cc with mean volume of 16.1 cc. Of the 80 patients treated, 71 had adequate post-treatment thoracic CT imaging to assess local control. Local control was achieved in 167/175 (95.4%) of treated and followed lesions. CTCAE grade 1 asymptomatic pneumonitis was noted on thoracic CT scans in 42/71 (59.2%) of patients and occurred, on average 4.8 months after SBRT. Symptomatic pneumonitis and rib fracture did not occur in any patient. CTCAE grade 2 chest wall pain occurred in 4/80 (5.0%) treated patients and was managed conservatively with over-the-counter NSAIDS or acetaminophen. SIML lung SBRT for synchronous primary lung cancers or multiple lung metastases can be used as a variant to traditional multiple isocenter SBRT or chronologically separate treatment courses, and has excellent local control rates and low toxicity profile in our patient population. It can help improve comfort and compliance of the patients who have difficulty lying still for an extended treatment course, and significantly reduces treatment time via isocenter shifts/repeated CBCTs for image guidance, thus improving clinic efficiency.

MRI Guided Adaptive Radiotherapy (MRgART) in Primary and Metastatic Liver Lesions

The role of stereotactic body radiotherapy (SBRT) in the management of primary hepatic and metastatic tumors has increased significantly over the past few years. MR-Linac is rapidly gaining evidence in the delivery of ablative doses using MR guided adaptive radiotherapy (MRgART) with improved accuracy and dose coverage to the lesions. We report local control and toxicity of patients with primary and metastatic liver lesions treated with MR guided adaptive SBRT. All patients were treated with MRgART on the Unity 1.5T MR Linacs at two institutions and consented to the ADAPT-MRL study (1). A 4DCT and MRI with abdominal compression were obtained at simulation and the primary MRI sequence used for online treatment included a T2 3D navigated scan. A balanced turbo field echo (btFFE) 2D cine motion scan was also acquired at every fraction to determine movement of the tumor to aid in internal target volume margin. All plans were treated with SBRT prescribed to 3-5 alternate daily fractions. Acute toxicity was reported according to Common Terminology Criteria for Adverse Events version 5 (CTCAE) v.5. Patient demographics, prescribed dose fractionation, acute toxicity and clinical response at 6 months were analyzed. Clinical response to treatment was measured according to RECIST criteria 1.1. Between February 2021 to January 2023 a total of 30 patients were treated with 149 fractions to the liver. Patients were majority male (70%) with a median age of 66 (range 36-83). 16 patients were treated for primary hepatocellular carcinoma (HCC) of the liver and 14 patients for metastatic liver lesions. The median prescribed dose was 48 Gy (range 30-50Gy) in median 5 fractions (range (3-5 fractions). All patients completed treatment with no interruptions. The mean time from 'patient setup' to 'beam-off' was 52.6 minutes (range 37-73 minutes). Data on acute toxicity at 3 month follow up was available for 28 patients. Of these patients 7/28 (25%) had grade 1 or 2 toxicity and no >/ = grade 3 toxicity was reported. Clinical response at 6 months was available for 18 patients and showed complete response in 44% (8/18), partial response in 22% (4/18), stable disease in 22% (4/18) and progressive disease in 11.1% (2/18). Our experience on MRgART to the liver has shown good local control and minimal acute toxicity in the treatment of primary and metastatic liver lesions. We continue to collect data on patient reported outcomes, clinical response and toxicity to determine the feasibility and safety of this system.

Oncologic Outcomes and Safety after Spinal Re-Irradiation with Stereotactic Body Radiation Therapy

Management of spinal metastases that fail radiation therapy is a challenge, presenting a fine balance between the risk of pain and neurologic deficits if the tumor is not controlled and the increased risks associated with exceeding the tolerance of the spinal cord and other adjacent critical structures. Data regarding SBRT in the re-irradiation setting is limited. The purpose of this study was to report oncologic outcomes and toxicities for patients that received re-irradiation using SBRT. Patients treated with spine SBRT for re-irradiation at a target which overlapped or abutted a previous conventional RT or SBRT field at a single institution between 2010 and 2021 were retrospectively reviewed. The cumulative constraint to the neural avoidance structures were a BED3 ≤75 Gy (above the conus) or ≤106 Gy (below the conus) accounting for 25% repair at 6 months and 50% repair at 1 year following the first course of RT. Radiographic local recurrence was defined as progressive disease on CT and/or MRI in the treatment volume or at the margin of the treatment field compared with imaging studies before SBRT. Cumulative incidence of local recurrence was reported with death as a competing event, and overall survival was estimated with Kaplan-Meier. Toxicity grades were determined according to NCI CTCAE version 4.0. Ninety patients (225 vertebrae) with a median age of 56.5 years (range: 27-84 years) were included in the analyses. The most common histologies were NSCLC (17.7%), kidney (15.6%), prostate (14.4%), and breast (7.8%). The majority (51.1%) of metastases were in the T-spine, while 31.1% were in the L-spine and 13.3% in the C-spine. The median prescription dose was 27 Gy (range: 14-40 Gy) in a median of 3 fractions (range: 1-5). The median prescription isodose line was 59% (range: 48%-97%). The median time to re-irradiation with SBRT was 14 months (range: 1-89 months), and the most common prior spinal radiation dose was 30 Gy (range: 8-50 Gy) in a median of 5 fractions (range: 1-15). The median maximal BED3 of the spinal cord from prior radiation and re-irradiation were 52.6 Gy and 31.8 Gy, respectively. The median follow-up was 8.7 months (range: 0.4-43.9 months). The 6-month, 1-year, and 2-year local control rates were 88.9%, 83.4%, and 78.9%, respectively. Only 6.7% of patients underwent salvage surgery, at a median of 9 months after SBRT. The median overall survival was 14.0 months, and overall survival was 54.4% at 1 year and 27.8% at 2 years post-SBRT. All toxicities were grade < 2 and no patients developed spinal cord myelopathy. These data suggest excellent local control and low toxicity following SBRT for re-irradiation of spinal metastases. Future prospective and multi-institutional studies are needed to explore the optimal dose fractionation regimen and cumulative normal tissue constraints to maximize local control and minimize toxicity.

Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer

Local consolidative radiotherapy (LCT) for oligometastatic disease is a promising paradigm improving outcomes for various malignancies but has been underexplored for metastatic thyroid cancer. We hypothesize that LCT to distant sites with definitive RT doses can yield favorable outcomes and defer systemic therapy escalation for these patients. We reviewed 96 thyroid cancer patients who received 175 LCT courses from 2010-2022 to 228 metastatic sites, including: thorax (45%), bone (40%), brain (6%), head/neck (5%), and abdomen (3%). Common prescriptions were 50-55Gy/4-5fxs or 56-70Gy/8-10fxs for lung; 52.5-60Gy/15fxs for mediastinum; and 18-24Gy/1fx or 27-30Gy/3fxs for bone. RECIST v1.1 and CTCAE v5.0 were used to define progression and toxicities, respectively. Outcomes were evaluated via Kaplan-Meier and associations examined via Cox proportional hazards modeling. Median age was 63 years (range: 26-92), with 62 oligometastatic cases (total 1-5 sites) and 34 oligoprogressive (with 1-5 growing sites). Primary disease was controlled in all patients, with 39% receiving post-op RT and 66% prior RAI. Histologies included papillary (40%), anaplastic (25%), follicular (12%), medullary (9%), Hurthle (7%), and poorly-differentiated (7%). Median time from initial diagnosis to LCT was 3 yrs (IQR 1-8), and median follow-up from 1st LCT was 21 mos (IQR 9-51). Patients received an average 2 LCT courses (range 1-8) treating 1-4 sites. Median survival (OS) from 1st LCT was 9 yrs (95% CI = 5-14). On multivariable analysis (MVA), worse OS was associated with anaplastic histology (HR 4.6, p<.01), but longer OS was associated with prior RAI (HR 0.33, p = .02) and oligometastatic disease (HR 0.3, p = .01). For anaplastic histology, median OS was 1.2 years vs. 9.3 years for non-anaplastic; 3-yr OS was 36% vs. 88% (log-rank, p<.01). Five-year OS for oligometastatic cases was 75% vs 53% for oligoprogressive (log-rank, p = .04). Median progression free survival (PFS) from 1st LCT was 15.5 mos (95% C I = 11-20). On MVA for all LCT courses, time to any progression (TTP) was negatively associated with anaplastic histology (HR 1.7, p = .02) and 2nd or higher LCT course (HR 1.45, p = .05), but favorably associated with thoracic site (HR 0.49, p<.01). Following later LCT courses, median TTP was 11 mos vs 17 mos for initial LCT course (log-rank, p = .03). After LCT to lung/chest, TTP was 18.6 mos vs 9.5 mos for non-thoracic sites (log-rank, p<.01). Only 6% of failures occurred at previously treated lesions. Most LCT courses (67%) were without ongoing chemotherapy, while 25% entailed continuing the same regimen and 9% had planned treatment post-RT. There were 2 Grade 3 toxicities (pneumonitis and esophagitis) and no Grade 4-5 events. With high local control rates and minimal toxicity, LCT can be a feasible strategy to defer systemic therapy escalation for oligometastatic and oligoprogressive thyroid cancer.

A Phase 2 Trial of Efficacy and Safety of Intraoperative Radiation Therapy for Locally Advanced Laryngocarcinoma

For locally advanced laryngeal cancer (LAL), the local recurrence rate remains 19-40% after radical surgery with postoperative radiotherapy alone or with concurrent chemoradiotherapy in patients with unfavorable prognostic factors. We evaluate local control and acute toxicity of intraoperative radiation therapy (IORT) as a tumor bed boost for locally advanced laryngeal cancer in this prospective phase 2 trial. This phase II clinical study in which a total of 63 LAL patients (T2N1-3/T3N0-3/T4N0-3) were selected and received IORT (T2: 8-10Gy, T3,4:12-15 Gy) as a tumor bed boost during radical surgery, then received external-beam radiation therapy (EBRT) at a total dose of 54-60Gy within 6 weeks after surgery, 5 times per week, 1.8-2Gy per time, 30 times in total. The median follow-up time was 20 months (7 -39 months). The primary outcome was the local control (LC) and 2 - year survival rate determined using the Kaplan-Meier method. This study is registered with ClinicalTrials.gov, NCT04278638. A total of 63 patients consented to participate in the study; 59 males and 4 females, median age was 61 years (40-81 years), 14 patients had supraglottic LAL, 44 patients had glottic LAL and 5 patients had subglottic LAL. 10 patients showed high differentiation and 44 patients showed moderate differentiation and 9 patients showed low differentiation with laryngeal squamous cell carcinoma. 3 patients were in T2N1-2 stage, 40 patients in T3N0-2 stage, and 20 patients in T4N0-2 stage, 48 patients received total laryngectomy and 15 patients received hemilaryngectomy; 16 patients were lymph node-positive and 1 patient developed vascular tumor thrombus after surgery. After surgery combined with IORT and EBRT, the 1- and 2- year LC rates were 98.2% and 93.1 %, respectively, 2-year overall survival rate was 97.4%. Pharyngeal fistula was observed in 1 patient (1. 6 %) and wound infection in 3 patients (4.8%). Radiation Therapy Oncology Group (RTOG) grade 3 pain and RTOG grade 4 dyspnea were noted in one patient (1.6%) and 2 patients (3.2 %), respectively. In summary, our prospective phase II trial proved that the addition of intraoperative radiotherapy as a tumor bed boost to postoperative radiotherapy provided local therapeutic benefit to patients with locally advanced laryngeal cancer. Our data support the safety of this combined therapy. Additional investigation is warranted to determine the role of intraoperative radiotherapy in the local treatment of locally advanced laryngeal cancer.

Proton Beam Therapy for HCC Exceeding up-to-Seven Criteria

Whilst standard treatment for intermediate-stage hepatocellular carcinoma (HCC) is transcatheter arterial chemoembolization (TACE), those exceeding "up-to-seven" criteria don't respond as such as those within, and systemic therapy is suggested to be more beneficial. This is sought to be both because of the limited efficacy of TACE and its hepatic toxicity. Proton beam therapy (PBT) offers high local control and low toxicity rates, and we hypothesize that the same can be said in this patient group also. We here present the outcome of PBT for primary HCC exceeding "up-to-seven" criteria. Primary HCC treated with PBT between 2010 and 2018 were extracted from an all-in treatment database and retrospectively reviewed. (Maximum diameter of the largest tumor in centimeters) + (tumor count) > 7 was considered as exceeding "up-to-seven" criteria. Local recurrence was defined as tumor re-enlargement or the appearance of arterial phase hyperenhancement. Adverse events were evaluated by CTCAE v5.0. Overall survival and recurrence-free survival were determined by the Kaplan-Meier method, and local recurrence was analyzed as cumulative incidence with death as a competing risk. All statistical analyses were done using R. Out of 202 primary cases, 79 exceeded the "up-to-seven" criteria. The median tumor diameter was 8.0 cm (range 3.1 - 20 cm) and macroscopic vascular invasion (MVI) was observed in 26 cases. For tumor count, 36 were solitary, 28 were between 2 - 3, and 15 had 4 or more. According to the modified ALBI grade, 38 were grade 1, 18 were grade 2a and 23 were 2b. The prescribed dose was 66 Gy / 10 Fr for 6, 72.6 Gy / 22 Fr for 60, 74 Gy / 37 Fr for 12 and 60 Gy / 15 Fr for one case after relative biological effect weighting of 1.1. With a median follow-up period of 33 months (IQR 15 - 57 months), 2-year overall survival was 62% (95% C.I. 50 - 72%) and median survival time was 37 months (95% C.I. 30 - 52 months). 2-year recurrence-free survival and local recurrence rate were 42% (95% C.I. 30 - 53%) and 8% (95% C.I. 3 - 15%) respectively. Cox regression analysis revealed modified ALBI grade as the only significant risk factor for survival (hazard ratio 1.80, 95% C.I. 1.27 - 2.55, p = 0.0010) among age, sex, alpha-fetoprotein level, MVI, tumor count, and size. Other than one case of early death (2 weeks after treatment) with an unknown causal relationship, there were no adverse events of grade 4 or higher observed. PBT for primary HCC exceeding "up-to-seven" criteria appears to be safe and effective. Local control of intrahepatic lesions may be beneficial even in intermediate-stage cases, while results of this study suggests that suppression of out-of-field recurrence is required for further survival prolongment.

Clinical Efficacy and Safety of Once-Weekly Fractionation in Stereotactic Body Radiotherapy for Pulmonary Oligometastatic Lesions

As the oligometastatic disease paradigm has become more widely accepted, further investigation is needed to risk-stratify patients within this spectrum of disease and define optimal treatment methods. Stereotactic Body Radiotherapy (SBRT) has emerged as an efficacious and safe modality to control individual lesions and improve clinical outcomes in the setting of oligometastatic disease. There is scant literature describing ideal SBRT inter-fraction time intervals or their impact on clinical outcomes, especially for treating pulmonary oligometastases. Most institutions appear to offer treatments on consecutive days or every other day. In this abstract, we sought to evaluate the efficacy and safety of delivering SBRT treatments in a once-weekly fractionation scheme. The study was undertaken via retrospective review at a single institution. We included patients with pulmonary metastatic lesions treated with SBRT at our institution between 2015 and 2019. Patients with oligometastatic disease were included, defined as patients with 5 or fewer total metastatic lesions. Treatments were delivered between 3 and 5 fractions and using at least 5 Gy per fraction. Per institutional protocol, all treatments were delivered 7 days apart. From a single institution, 204 lesions from 111 patients were included. Median follow-up was 16.5 months [IQR 7 - 36.3]. Median dose was 40 Gy [IQR 30 - 50], median BED was 80 Gy [IQR 60-100], median dose per fraction was 10 Gy [IQR 8-11]. Median internal target volume (ITV) was 18.5 cc [IQR 9.3 - 45.8]. The most common tumor histologies were lung adenocarcinoma (38.2%), colorectal adenocarcinoma (15.6%), lung squamous cell carcinoma (12.7%), renal cell carcinoma (5.9%), breast invasive ductal carcinoma (5.4%), small cell lung cancer (3.9%), and melanoma (2.9%). 2-year local control (LC) rate was 85.7% and 5-year LC rate was 84.3%. 2-year regional control (RC) rate was 53.9% and 5-year RC was 49%. Median overall survival (OS) was 20 months [IQR 9 - 37.3]. Cox regression analysis revealed biologically effective dose (BED) (HR 0.99 [0.98 - 0.99] p = 0.001) as well as dose per fraction (HR 0.92 [0.86 - 0.97] p = 0.003) were both associated with improved OS. Longest tumor dimension was associated with worse OS independent of BED and dose per fraction (HR 1.26 [1.1 - 1.4] p = 0.001). Total toxicity incidence was 7.3%, which consisted only of G1-G2 cough, dyspnea, and fatigue. Treatment of pulmonary oligometastatic lesions with SBRT delivered via once-weekly fractionation is associated with excellent local control and minimal toxicity. Larger studies are warranted to directly compare clinical outcomes of weekly SBRT fractionation to other conventional SBRT treatment schedules.

Impact of Dosimetric Parameters on Local Control and Toxicity of Head and Neck SBRT

SBRT is potentially useful as a local therapy for head and neck cancer patients who require re-irradiation, as well as those who may not be candidates for surgical resection or a lengthy course of conventionally fractionated radiation therapy. The objective of this study was to assess rates of local control with SBRT, as well as the impact of mucosal dosimetric parameters on rates of grade 3 or higher toxicity in patients treated with head and neck SBRT. We retrospectively reviewed patients within our institution who underwent SBRT for cancers of the oral cavity and oropharynx between 2013 and 2022. Primary endpoints were local control (LC) and grade 3 or higher toxicity potentially attributable to SBRT, based on CTCAE 5.0. We analyzed the following endpoints as potential predictors of toxicity: 1) ratio of total oral mucosal volume/oral mucosal volume outside of PTV, 2) mean dose to oral mucosa, and 3) maximum dose to oral mucosa. We conducted regression analysis to determine predictors of local failure and severe toxicity. We estimated local control using Kaplan-Meier analysis. We treated 66 tumors in 60 patients with a median age of 71 years. 41 patients (68.3%) had oral cavity cancer and 19 (31.6%) had oropharynx cancer. 64 tumors (97.0%) were squamous cell carcinomas. 32 tumors (48.5%) were previously irradiated. Mean PTV volume was 55 cc (range: 39.4-74.1 ccs). Median prescribed radiation dose was 40 Gy given in 5 biweekly fractions. A total of 51 patients received systemic therapy (platinum-based chemotherapy in 52%, Cetuximab in 38%). 10 patients (16.7%) additionally received immunotherapy, constituting 56% of 18 patients treated from 2019-2022. Median pain score at presentation was 3/10. Oral pain non-significantly increased between 3 weeks and 3 months after starting treatment and subsequently returned to baseline after SBRT (P = 0.227). Local control was 68.5%, at a median follow up of 9.8 months. In oral cavity tumors, 1- and 2-year local control rates were 78.7% and 43.1% respectively. 1- and 2-year rates of LC were 78.9% and 50.2% in oropharynx tumors. Grade 3 or higher toxicities were present in 18 patients (30.0%), including osteonecrosis in 6 (10.0%) and ulceration or extensive tissue necrosis in 12 (20.0%). No significant relationship was present between mucosal surface radiation doses and acute oral mucosa toxicity. On regression analysis for both local control and grade 3 or higher toxicity, we did not find any significant association with prior radiation, disease site, age, or PTV volume. SBRT provided comparable local control for tumors of the oropharynx and oral cavity, with slightly higher 2-year local control in tumors of the oropharynx, and comparable rates of toxicity. We appreciated increased use of immunotherapy in our study population from 2019 onwards. We did not find any relationships between dosimetric parameters and rates of grade 3 or higher toxicity, or local control, though our analysis is limited by a small sample size.

Image-Guided High-Dose-Rate Brachytherapy for Definitive Management of Primary Vaginal Cancer: A Single Institutional Experience

To assess the safety and efficacy of image-guided high-dose-rate brachytherapy (IGBT) alone or in combination with external beam radiation therapy (EBRT) for the treatment of vaginal cancers. The study analyzed patients diagnosed with primary vaginal cancers from 2004 to 2021 who received definitive radiotherapy at a single institution. Interstitial implants were performed using a freehand technique and transvaginal or transrectal-ultrasound for imaging guidance. IGBT was planned using inverse planning simulated annealing (IPSA) software. Data collected and analyzed included patient and tumor characteristics, dose and fractionation, and treatment outcomes. Complications were assessed using CTCAEv4 scores, and descriptive and survival analyses were performed using R-studio. Sixty-six patients met inclusion criteria. Patients were staged as I (14), II (23), III (19), and IV (10) based on revised FIGO 2018 staging. 47 (72%) had squamous cell carcinoma histology, and median age was 65 years. The most common regimen was 45 Gy in 25 fractions of EBRT followed by IGBT boost of 18 Gy in 3 fractions with 1 implant (n = 40). For melanoma, an IGBT boost of 19 Gy in 2 fractions with a single implant was used (n = 7). For IGBT monotherapy, the most common regimen was 36 Gy in 6 fractions delivered over 2 implants (n = 3). 41 (66%) of the patients received systemic therapy. Local failures occurred in 8 (12%) patients, while 8 (12%) developed distant metastases. Median overall survival was 64.7 months. Overall survival was 64.3% (95% CI 51.9-79.7%) at 3 years, and 50.9% (95% CI 35.7-72.5%) at 5 years. Grade 3 or 4 toxicities were reported in 4 (6%) patients including vaginal fistula (n = 3) and urethral stricture (n = 1). The results suggest that utilizing IGBT for freehand interstitial implants in combination with EBRT is a safe and effective primary treatment for vaginal cancer, with durable local control and low toxicity. Further research is needed to establish multi-institutional practice patterns and recommendations.

Effectiveness and Toxicity of Five Fraction Prone Accelerated Partial Breast Irradiation

Accelerated partial breast irradiation (APBI) after breast conserving therapy (BCT) is increasingly used to treat women with early stage breast cancer. Our institution was an early adopter of 5-fraction ABPI and delivers APBI primarily to patients in the prone position. This study reports long term oncologic and cosmetic outcome in a large cohort of women treated with 5-fraction external beam APBI. We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Late toxicities and clinician and patient rated cosmesis were evaluated for patients with > 6 month follow up. Univariate and multivariate logistic regression models were used to identify clinical and dosimetric factors associated with development of acute and late toxicities, clinician and patient rated cosmesis. All statistical tests were two-sided, and the null hypothesis was rejected for p<0.05. Kaplan Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS) and locoregional recurrence-free survival (LR-RFS). Four hundred and forty-two patients received APBI either daily (56%) or every other day (44%). Most of the patients (92%) were treated in the prone position. Average mean heart dose was 23 cGy for left-sided and 11 cGy for right-sided breast cancers. Ipsilateral lung V30% ≤ 30%. At a median follow up of 48 months (range: 5.96 - 155 months), 12 (2.7%) patients developed a local recurrence, 14 (3.2%) patients developed a contralateral breast primary, 10 patients (2.3%) developed a distant metastasis and one patient (0.2%) developed a local recurrence followed by a distant metastasis 1 month later. Out of 258 patients with > 6 month follow up, rates of late grade 1-2 telangiectasia, fibrosis, edema, atrophy and hyperpigmentation were 4%, 18%, 1%, 19% and 7% respectively. There was only one late grade 3 event in a patient who developed significant breast atrophy. The rate of good-excellent physician and patient rated cosmesis was 95% and 89% respectively (N = 256 at median follow up of 80 months). On multivariate logistic regression, patients who did not receive any adjuvant endocrine or chemotherapy were at increased risk of developing a local recurrence. Patients with PR negative disease were at increased risk of distant metastasis. Patient who experienced any grade of acute dermatitis during treatment were at increased risk of any high grade (grade ≥ 2) late adverse event and worse physician rated cosmesis. Daily or every other day treatment did not correlate with worse toxicity or clinical outcomes. Plastic surgery involvement, LVI, EIC, lobular histology, and ER negativity did not correlate with an increased risk of recurrence. Five-year LR-RFS, DFS and OS were 98%, 92.5% and 98.6% respectively. Five- fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity and excellent cosmetic scores at long term follow up.

Stereotactic Body Radiotherapy in Latin America: Real-World Evidence of Health Outcomes

Stereotactic body radiotherapy (SBRT) is an ultrafractionated radiotherapy modality approach to treat oligometastatic disease. Randomized trials have shown significant benefit on overall survival and disease-free survival. In the last decade multiple studies have support efficacy and safety of this new technique. However, data from Latin America and Mexico are limited. In Mexico only 5% of facilities develop SBRT in daily practice. Therefore, the aim of this study was to investigate the real-world outcomes of applying SBRT for oligometastatic in a Mexico institution. This study investigated a consecutive cohort of patients treated with SBRT. at Centro medico ABC in Mexico City (Mexico). Oligometastatic disease have been treated using different schedules from 30-60Gy/5-8 fractions (fx.). All p. were treated on LINAC (Novalis Tx), IGRT with ConeBeam CT and Exactrack. The study primary outcome was local control rates per lesion. Secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity profile (CTCAE 3.0). Between February 2015 and October 2022, 51 patients (p.) have been treated with SBRT in 71 lesions. The median follow-up was 17 months (2-60). Mean age was 59 years old (8-99), 1:1 sex ratio. primary tumor 21p. GI tumors, 10p. GU tumors, 6 p. sarcomas, 6 p. lung cancer, 6p., 5p. breast ca. and others 7p. locations treated were 21p. lung lesions, 16p. bone, 10p. liver, 6p. nodes and others (9p.). The average number of fractions and total dose prescribed was 5 (1-8)/38 Gy (18-60 Gy). Local response rates were complete response 24p. (33%), partial response 16p. (22%), stable 8p. (11%), progression 13p. (18%). Overall survival rate was 55 months. Acute toxicity grade 3 was observed in 2p. gastric ulcer surgically treated, 1p. liver disfunction (prior Child B). Late toxicity was observed in 2 p. painful lung fibrosis surgically resected. Our results indicate that SBRT is effective (high local control and acceptable toxicity) for treating oligometastatic in a real-world scenario in Mexico.

Escalating SBRT Dose to Hypoxic Centers of Large Pulmonary Tumors via Simultaneous Integrated Boost Confers Effective Local Control with Minimal Toxicity

Hypoxia confers radio-resistance to tumor cells and drives malignant disease progression. SBRT treatment of large (>5.0 cm) pulmonary tumors pose significant dosimetric challenges in minimizing dose to adjacent organs at risk (OARs). Here, we detail the use of SBRT with simultaneous integrated boost (SIB) to the hypoxic centers of large pulmonary masses with effective local control and minimal normal tissue toxicity. Highly conformal treatment plans utilized 3-4 non-coplanar VMAT arcs with 6MV-FFF (1400 MU/min) and 4D-CT on TrueBeam to deliver 50 Gy in 5 fractions to the planning target volume (PTV). SIB dose of 60 Gy was delivered to a 1-cm internal margin from the gross tumor volume (GTV). Dose was calculated using Acuros-based engine. Pre-treatment Conebeam CT imaging was used for patient setup and verification. Treatments were delivered in < 15 minutes. Patients underwent post-treatment clinical evaluation and CT imaging in 3-month intervals to assess changes in tumor size and post-radiation sequelae. Clinical outcomes reported include treatment response and toxicity. Twenty-six patients with large, centrally (n = 13) or peripherally (n = 13) located tumors were evaluated; this included 16 NSCLC patients with T2-T3N0 disease and 5 with pulmonary metastases from distant sites. One patient had declined surgery, while 25/26 (96.1%) were deemed medically inoperable. All plans met RTOG-0813 requirements for target coverage and dose to OARs. Median follow-up interval was 11 months (0 to 23 months). Twenty-one of 26 (80.7%) patients received post-treatment CT imaging within 6 months of SBRT. Local control was achieved in 20/21 (95.2%) patients; one patient with a peripherally located tumor progressed outside the treatment field. Acute toxicity profile amongst the 25 patients assessed included grade 1 fatigue (n = 2), grade 1 rib pain (n = 1), and grade 2 pulmonary fibrosis (n = 1). Otherwise, 22/25 (88%) patients reported no radiation induced toxicities. Subgroup analysis was performed on patients with centrally located tumors, defined as located <2 cm from the hilum, heart, or bronchial trees. One of 13 (7.6%) patients with central tumors reported grade 1 rib pain; otherwise, no radiation induced adverse effects were observed. All patients with centrally located lung tumors experienced local control on surveillance imaging. SBRT with SIB to the hypoxic centers of large pulmonary masses is a safe, efficacious treatment that confers improved local control while maintaining dose to adjacent OARs. This study demonstrates the feasibility of delivering doses up to 60 Gy to the hypoxic centers of large lung tumors, while decreasing local tumor burden, minimizing treatment mobility, and improving clinic workflow. SBRT with SIB shortens treatment course to 5 fractions (in contrast to the traditional daily 30 fractions), thus improving patient comfort and compliance.

Intraoperative Radiation Therapy for Pediatric Patients: A 25 Year Experience

To assess outcomes after intra-operative radiation therapy (IORT) in pediatric patients, including local control, overall survival, and toxicity. Single institution retrospective study of 184 pediatric patients treated with IORT from 1995-2022. Each IORT application was considered a separate event for a total of 213 sites treated. Local failure was calculated using the cumulative incidence function and survival by Kaplan-Meier method from the day of surgery. Median follow up for all patients was 14 months while median follow up for surviving patients was 3 years. Median patient age was 6 years (range 9 months to 21 years) and half were male. Patients were generally high risk with 76% having relapsed or refractory disease. Tumor types included neuroblastoma (n = 88), soft tissue sarcoma (n = 69), Wilms tumor (n = 11), and other solid tumors (n = 24). The majority (97%) of patients had prior chemotherapy, 69% had at least one prior attempt at resection, and 65% had prior external beam radiation to the site of IORT. Location of IORT included the retroperitoneum (n = 99), anterior abdominal wall (n = 14), pelvic region (n = 49), chest and thorax (n = 36), head (n = 5), neck (n = 7), and axilla/shoulder (n = 3), with a median dose of 12 Gy (range 4 to 18 Gy). Overall survival was 47% and 32% at 2 and 5 years respectively. Rates of local failure were 20% and 26% at 2 and 5 years. Local failure had a significant impact on overall survival (p = 0.009). Analyzing specific tumor types at 2 years, the rate of local failure and overall survival were 22% and 57% for soft tissue sarcomas, 23% and 39% for neuroblastoma, and 10% and 60% for Wilms tumor. Direct toxicity from IORT was rare, however there were several cases of surgical complications where a potential contribution from IORT could not be ruled out. The most common complications included abscesses in the surgical field, fistula or stricture development, and hydronephrosis. There were no post-operative mortalities related to IORT. Our study represents the largest scale analysis of efficacy and safety of IORT in patients with pediatric solid tumors. Less than one third of patients failed locally at 5 years. Achieving local control impacted overall survival, emphasizing the importance of local control in these patients. Minimal radiation related toxicities were observed. Overall, IORT is an effective technique to achieve local control in children with high-risk solid tumors.

Cesium-131 Low-Dose Rate Interstitial Brachytherapy as a Salvage Re-Irradiation Technique in Treating Cervical and Uterine Cancer Pelvic Recurrence with Prior History of Pelvic Radiation

Pelvic recurrence among cervical and uterine cancer patients with prior history of pelvic radiation is a poor prognostic factor and remains challenging. The standard of care is pelvic exenteration, which is a highly morbid surgical procedure. The purpose of this study is to report local control rate and toxicity profile of Cesium-131 low-dose rate interstitial brachytherapy (LDR) as a salvage re-irradiation technique in managing pelvic relapse. We reviewed procedures and outcomes from patients with previously irradiated uterine corpus or cervix neoplasms, who subsequently relapsed and then underwent cesium-131 LDR implants between January 2016 and December 2022. Patient demographics, treatment planning variables, and disease response were reviewed. Acute toxicities, late toxicities, and local control rate were compiled for this study. A total of 12 eligible patients (6 cervical and 6 uterine cancer) with 16 cesium-131 LDR implants were included in this study. The majority (75%) of pelvic relapses occurred at the exocervix (cervix-intact) or vaginal cuff (post-hysterectomy). Median time from disease relapse to cesium implant was 32 days. The average area of implementation was 9 cm2 and average number of seeds implanted was 16. The mean prescription dose was 50 Gy. Six patients also received high-dose rate vaginal intracavitary brachytherapy in addition to cesium-131 LDR. Median follow up was 12 months. 81% of cesium implants achieved complete response at first post-treatment follow-up, while the remaining 19% demonstrated partial response. The 6-months local control rate was 79%. After cesium implant, 25% patients had local recurrence and 33% with distal metastasis. The most reported acute toxicities included vaginal mucositis (63%), dysuria (50%) and pain (19%). All patients had various degrees of vaginal stenosis and strictures long-term. Only 1 (8%) out of 12 patients, with 4 repeated cesium-131 LDR implants, developed a rectovaginal fistula and chronic pain. Cesium-131 LDR interstitial brachytherapy is a safe and feasible salvage re-irradiation technique in treating pelvic relapse among uterine corpus or cervix cancer patients with prior history of pelvic radiation. Local control rate at 6-months was acceptable with minimum toxicity. Long-term follow up is warranted to validate the efficacy of cesium-131 LDR. We conclude that cesium-131 LDR interstitial brachytherapy is a promising alternative to pelvic exenteration in selective patient population. Future prospective study is warranted.

Outcomes with Five Fraction Image-Guided Partial Breast Irradiation to Reduced Target Volumes

The use of 5-fraction partial breast irradiation has been shown in a randomized trial to provide comparable rates of local control and reduced toxicities as compared to standard fractionation whole breast irradiation. The initial technique utilized a 2 cm expansion on the lumpectomy cavity (1 cm for clinical target volume [CTV], and 1 cm planning target volume [PTV]) without consistent image guidance (ex. cone beam computed tomography [CBCT]) or motion management recommendations. We present clinical outcomes using a 5-fraction image guided PBI technique (IG-PBI) to reduced target volumes for patients with early-stage breast cancer. A retrospective review of an IRB approved institutional registry was performed to identify patients treated with IG-PBI. A total of 258 patients with early-stage breast cancer (Stage 0-IIA) receiving IG-PBI were identified. Patients received a dose of 30 Gy in 5 fractions delivered daily or every other day. An expansion of 1 cm on the lumpectomy cavity was used for those patients using deep inspiration breath hold (DIBH) while an expansion of 1.5 cm was utilized for those not using DIBH. All patients received daily CBCT. Plans were delivered using intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique; while the prescription isodose line covered the PTV, the 26 Gy line was allowed to expand beyond the PTV. Kaplan-Meier analyses were used to assess rates of local control and survival. Patient demographics, stage, hormone therapy use, recurrence, mortality, and toxicity data were collected. Survival was analyzed with Kaplan-Meier curve. Median age at diagnosis was 67 years (range 40-87) with a median follow-up of 29 months (IQR 22-40). Forty-six (18%) patients had in situ disease, 200 (78%) patients T1 tumors, and 12 (5%) patients had T2 tumors. Two hundred thirty-four (91%) patients were White, 15 (6%) were Black, and 9 (4%) were other races. One hundred ninety-six (76%) patients received endocrine therapy, and 16 (6%) patients received chemotherapy. Thirty-two (12%) patients developed grade 1 dermatitis and no grade 2 events were observed. One (0.4%) patient had a cardiac event (aortic stenosis) 19 months after breast radiotherapy. At last follow-up, one (0.4%) patient had a local recurrence and one (0.4%) developed a distant metastasis, with no regional nodal failures. Overall, 4 (1.5%) patients had died, all due to other causes. At 3 years, locoregional control was 99.4%. Outcomes with IG-PBI demonstrate low rates of local recurrence and limited toxicity. The use of reduced target volumes is not associated with increased rates of local recurrence.

30 Gy vs. 45 Gy Consolidative Thoracic Radiation (cTRT) for Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Multicenter, Randomized, Phase 3 Trial

Consolidative thoracic radiotherapy (cTRT) showed potential benefit to extensive stage small cell lung cancer (ES-SCLC). However, the optimum dose of cTRT is unknown. The purpose of this randomized trial was to compare the effect of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC. This phase III, randomized trial was conducted in 12 public hospitals in China. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions or 45 Gy in 15 fractions cTRT. The primary outcome was 2-year overall survival (OS). Secondary outcomes included 2-year progression-free survival (PFS), 2-year local control (LC) and radiation treatment related toxicity. The primary objective was to detect an OS improvement in 45 Gy cTRT group at 2 years from 13% to 26% assuming a two-sided a = 0.05 and power of 85%, with a planned sample size of 186 patients. This trial was registered with Clinical Trials.gov, number NCT02675088. Between January 15, 2016, and September 20, 2022, 90 patients were randomly assigned either 30 Gy in 10 fractions (n = 50) or 45 Gy in 15 fractions (n = 40) cTRT group. Recruitment to the trial closed early due to slow accrual since first-line chemoimmunotherapy has become the new standard of care for ES-SCLC. The median age of patients was 58 years, 87.8% were male, 76.7% had a smoking history, 95.6% received IMRT, and 58.9% received prophylactic cranial irradiation. At a median follow-up of 39.9 months (IQR 27.2-59.2), there was no significant difference in the 2-year OS between the 45 Gy group and the 30 Gy group, at 43.4% (95% CI 29.3%-64.3%) and 40.0% (95% CI 27.9%-59.1%), respectively (log-rank p = 0.62; HR 1.13 [95% CI 0.69-1.84]). The 2-year PFS was 12.1% (95% CI 4.3%-33.8%) in the 45 Gy group and 9.0% (95% CI 3.2%-25.2%) in the 30 Gy group (log-rank p = 0.25, HR 0.76(95% CI [0.478-1.22]). There were also no significant differences in locoregional recurrence free survival (log-rank p = 0.75; HR 0.888 [95% CI 0.423-1.863]) and distant metastasis free survival (log-rank p = 0.95; HR 1.015 [95% CI 0.624-1.651]) between two groups. No grade 5 toxicity was observed in both groups. Patients treated with higher cTRT dose presented with increased incidence of grade 3+ radiation pneumonitis (10% vs 2%) and hematological toxicity (20% vs 12.5%). This randomized trial did not find a higher probability of survival improvement in patients with ES-SCLC receiving cTRT of 45 Gy in 15 fractions compared with 30 Gy in 10 fractions. In contrast, there was an increase in toxicity, especially radiation pneumonitis. Additional randomized studies investigating the role of cTRT in ES-SCLC after a response to chemoimmunotherapy are warranted.

Stereotactic Body Radiation Therapy for Large Volume Solid Tumor Spinal Metastases Involving Three or More Contiguous Vertebral Levels

Data for treating 3 or more contiguous vertebral bodies with SBRT is limited. The purpose of this study was to explore oncologic outcomes and toxicity of spine SBRT delivered to large volume solid tumor metastases involving 3 or more contiguous vertebral levels. Patients treated with spine SBRT for vertebral metastases involving 3 or more contiguous levels between 2009 and 2021 were retrospectively reviewed. Data on demographics, dosimetry, toxicity, and outcomes were collected. Radiographic local failure was defined as progressive disease on CT and/or MRI in the treatment volume compared to the pre-SBRT baseline. Local control (LC) and overall survival (OS) were calculated from end of SBRT using the Kaplan-Meier and log-rank test. A total of 141 patients were included with a median follow-up of 9.7 months. The majority of patients had either 3 (74%) or 4 (16%) involved contiguous vertebral levels. Twenty-two percent, 57%, 14%, and 7% of treated lesion began in the cervical, thoracic, lumbar, and sacral vertebral levels, respectively. The most common primary sites were NSCLC (15.6%), kidney (14.9%), and breast (13.5%). Thirty-two percent of patients had prior external beam radiation to the same vertebral level, 63% had prior surgery, and 43% had prior vertebral fracture. Paraspinal extension was identified in 26% at time of SBRT. Median pre-SBRT Bilsky grade was 2 (range 0-3). The median total prescription dose was 27 Gy (range: 12-43 Gy) with the most common dose (Gy)/fractionation schedules of 27/5 (32%), 30/5 (25%), and 25/5 (18%). The median Dmax was 4727 cGy (range 2070-7857) with a median prescription isodose of 58% (range 48-97). The median OS was 12.4 months (95% CI 9.6-15.3). 1- and 2- year OS were 51% and 35%, respectively. Local progression occurred across all histologies, most commonly in colon and NSCLC (16.7%). 1- and 2-year LC were 70% and 57%, respectively. In the radiation-naïve cohort, 1- and 2-year LC were 75% and 63%, respectively and 52% and 34% in the prior radiation group with no statistically significant difference in time to local progression (p = 0.075). There was no statistically significant difference in LC when comparing 3 versus 4 or more contiguous lesions (p = 0.66). Forty percent of patients that progressed underwent salvage treatment (58% surgery, 33% SBRT, 8% systemic therapy). Post-SBRT vertebral compression fracture rate was 11.6%. We present the largest series to date of patients treated with SBRT for large volume spinal metastases involving 3 or more contiguous levels. These data suggest reasonable local control and low toxicity with SBRT; therefore, SBRT should be considered a practical modality to offer this cohort.