Distant Progression-free Survival Research Articles

MR-guided online adaptive stereotactic body radiotherapy (MRgSBRT) of primary lung tumors and lung oligometastases.

Stereotactic body radiotherapy is pivotal in the treatment of lung tumors, demonstrating effective local control. However, challenges persist with intra-fractional anatomical changes and organs at risk during delivery. Magnetic resonance-guided online adaptive stereotactic body radiotherapy (MRgSBRT) represents anovel technique promising to achieve safe delivery of ablative doses with improved outcomes for primary lung tumors or lung oligometastases. In this single-institution retrospective analysis, we evaluated 64patients (92lesions) with primary lung cancer or lung oligometastases treated with MRgSBRT. Using Kaplan-Meier method and log-rank test; we estimated local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS), and overall survival (OS). Atotal of 64patients (92lesions) treated with MRgSBRT were included comprising 14.1% primary lung cancer lesions and 85.9% lung oligometastases. Median total dose, fraction number, fraction dose and BED10 were 50 Gy (range, 21-70 Gy), 5(range, 1-10), 10 Gy (range, 6-34 Gy), 100 Gy (range, 48-180.0 Gy) respectively. Of the 420 fractions administered, 88.6% (n = 372) involved on-table adapted plans. Median LPFS was not reached and the 1‑ and 3‑year LPFS rates were 96.3% (95% CI 92.4-100.0%) and 86.4% (95% CI 76.9-95.9%), respectively. No local recurrences were observed post-treatment with atotal dose of > 50 Gy, BED10 > 100 Gy, fractional dose of > 10 Gy or aCCI > 0.96. Our study of MRgSBRT in 92lung lesions revealed a1-year and 3‑year LPFS rates of 96.3 and 86.4%, respectively without ≥ grade3 toxicity. Future prospective studies evaluating lung MRgSBRT are awaited.

Minimally Invasive Image-Guided Percutaneous Irreversible Electroporation of Adrenal Metastases.

A single-center retrospective study was performed to evaluate the safety and efficacy of minimally invasive irreversible electroporation (IRE) to treat metastatic adrenal tumors. This single-center study, approved by the Institutional Review Board, retrospectively analyzed six patients who underwent image-guided percutaneous IRE for adrenal metastases. Pre-procedural imaging included CT, MRI and/or 18F-FDG PET-CT scans. Primary outcomes measures included technical success, efficacy and safety, while secondary outcome measures were local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS). Follow-up scans were scheduled post-procedure, and data analysis employed Excel, SPSS and R. Patients had diverse primary tumor origins including renal cell carcinoma (2/6), colorectal carcinoma (1/6), non-small cell lung carcinoma (1/6), leiomyosarcoma (1/6) and urothelial carcinoma (1/6). Adverse events were minimal, with only one grade 1 complication reported. Tumor characteristics revealed tumors close to critical structures, with a median pre-ablation size of 23mm. Technical success was achieved in all procedures. At first follow-up, one patient had complete response, one patient had partial response of the right adrenal gland and complete response of the left adrenal gland, two patients had partial response and two patients had stable disease. Local tumor progression occurred in two out of seven tumors with a median LPFS of 10.9months, and distant progression was observed in four out of six patients. Percutaneous, minimally invasive IRE shows promise as a safe treatment option for unresectable metastatic adrenal tumors, demonstrating potential effectiveness. However, further studies with larger patient cohorts are needed to confirm its safety and efficacy.

Isolated Limb Infusion for Limb-Threatening Sarcomas.

Isolated limb infusion (ILI) treats unresectable extremity malignancies with high-dose regional chemotherapy limited to the limb. This study assessed long-term outcomes after ILI for limb-threatening sarcomas. A retrospective review analyzed patients with an extremity sarcoma who underwent ILI with melphalan and dactinomycin from 2008 to 2023 at a single institution. The study identified 61 patients (52.5% female; median age, 73 years; range, 20-94 years). Of these patients, 68.9% had lower-extremity disease. The median follow-up period was 6.9 years. The overall response rate was 48.3% (complete response [CR], 21.7%; partial response [PR], 26.7%), and the disease control rate (DCR: CR+PR+stable disease [SD]) was 65%. The median progression-free survival (PFS) for the patients with CR/PR/SD/progressive disease (PD) was respectively 16.8/9.6/4.8/2.4 months (P<0.0001). The responders (CR+PR) had significantly longer PFS than the non-responders (SD+PD) (hazard ratio [HR], 6.3; 95% confidence interval [CI], 3.1-12.9; P<0.001). The median in-field PFS times for CR/PR/SD/PD were respectively 16.8/12/4.8/2.4 months (P<0.001). The responders had a significantly longer risk of in-field PFS than the non-responders (HR, 5.9; 95% CI 2.9-12.0; P<0.001). The median distant relapse PFS for CR/PR/SD/PD was not reached (NR)/NR/44.4/40.8 months (P=0.02). The responders had a significantly longer distant relapse PFS than the non-responders (HR, 2.7; range, 1.1-6.8; P=0.04). The median overall survival (OS) was 8.6 years for the responders and 4.1 years for the non-responders (P=0.02). The disease-specific survival (DSS) rates were 87% at 1 year, 71% at 3 years, and 64% at 5 years. The median DSS was not reached for the responders and was 4.1 years for the non-responders (P=0.003). The limb salvage rates at 6 months were 85% at 1 year, 80% at 3 years, and 70% at 5 years. The patients with PD had a higher risk of requiring amputation than the patients with CR+PR+SD (HR, 3.0; 95% CI 1.0-8.7; P=0.04). The 5-year limb salvage rates after ILI are notably high, reaching 70%. After ILI, the responders had significantly better in-field and distant relapse PFS, OS, and DSS.

Salvage stereotactic ablative body radiotherapy after thermal ablation of primary kidney cancer.

To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA). This study was a multi-institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer-specific survival (CSS), overall survival (OS), treatment-related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan-Meier method was used to estimate freedom from local and distant failure, CSS and OS. Seventeen patients with 18 biopsy-confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6-68.7) years, a median (IQR) tumour size of 3.5 (1.9-4.1) cm and follow-up (reverse Kaplan-Meier method) of 3.36 (95% confidence interval [CI] 1.6-4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5-5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression-free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%-100%), 92.3% (95% CI 78.9%-100%) and 82.1% (95% CI 62.1%-100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40-71) mL/min, and at last follow-up, it was 48 (33-57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end-stage renal disease. The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA.

Irreversible Electroporation in Treating Colorectal Liver Metastases in Proximity to Critical Structures

PurposeTo evaluate the safety, effectiveness, and oncological outcomes of irreversible electroporation (IRE) of unresectable colorectal liver metastases (CRLMs) close to critical structures. Materials and MethodsThis is a single-center, institutional review board (IRB)–approved, retrospective analysis of patients who underwent percutaneous computed tomography (CT)–guided IRE of CRLM. Between August 2018 and October 2023, 26 patients had 46 tumors treated with percutaneous IRE in 30 ablation sessions. Primary end points were tumor response and local progression-free survival analyzed using Kaplan-Meier survival curves. Secondary end points were overall survival (OS), distant progression-free survival (DPFS) analyzed using Kaplan-Meier survival curves, adverse events rated according to the Common Terminology Criteria for Adverse Events (CTCAE), and length of hospital stay. ResultsAll tumors were close to critical structures, including the portal and hepatic veins, inferior vena cava, bile ducts, and gallbladder. All patients received preprocedural systemic therapy (median 10 cycles). Median length of hospital stay was 1 night. Adverse events occurred in 7 (23%) of 30 procedures, with four Grade 1 and two Grade 2 adverse events, including pleural effusions (n = 2), ileus (n = 1), small hematoma (n = 1), and pneumothorax (n = 2) requiring chest tube placements. Following IRE, the 1- and 2-year local tumor progression-free survival rates were 55.0% and 51.3%. The median DPFS was 3.5 months, with 1- and 2-year DPFS rates of 23.3% and 9.7%. Six patients (23.1%) died during follow-up, with a median OS of 40.4 months. The 1- and 2-year OS rates were 90.9% and 83.9%. ConclusionsIRE is a safe and viable option in the treatment of unresectable CRLMs in locations close to critical structures, but carries a risk of local recurrence.

Safety and Effectiveness of Irreversible Electroporation in Lymph Node Metastases

PurposeDemonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.Materials and MethodsAn IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS).ResultsNineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0–52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3–8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively.ConclusionIRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.Graphical

Surgery versus thermal ablation for small-size colorectal liver metastases (COLLISION): An international, multicenter, phase III randomized controlled trial.

LBA3501 Background: The standard of care for local treatment of patients (pts) with colorectal liver metastases (CRLM) is surgical resection. However, growing evidence suggests thermal ablation to be associated with a superior safety profile, lower costs, and shorter hospital stay, while rivaling surgical resection in terms of local control and overall survival (OS). This study aimed to explore the potential non-inferiority of thermal ablation compared to surgical resection for pts with small-size (≤3cm) resectable CRLM. Methods: In this multicenter, phase 3 Dutch Colorectal Cancer Group trial, pts aged 18 years and older with previously untreated CRLM were recruited from 14 centers in the Netherlands, Belgium and Italy. Pts with ≤10 CRLM, no extrahepatic metastases and ECOG 0-2 were stratified into low, intermediate and high disease burden subgroups and randomly assigned (1:1) to undergo surgical resection or thermal ablation. Though approach was left at the discretion of the operator, laparoscopic (+/- robot) resections and percutaneous ablations were favored over open procedures. To avoid drop-outs patients undergoing open procedures were randomized intra-operatively. The primary outcome was overall survival (OS) (log-rank; power 80%, 5% type I error rate; 1-sided). Secondary outcomes include distant and local tumor progression-free survival (PFS), local control, safety, length of hospital stay, quality of life and cost-effectiveness. Results: A total of 341 patients were enrolled; 299 were randomly assigned: 147 assigned to thermal ablation, 148 to surgical resection; 4 were excluded after randomization for not having the disease assessed. The trial was stopped at halftime for having met predefined stopping rules. After a median follow-up time of 28.8 months there was no difference regarding OS (HR 1.042; 95% CI, 0.689-1.576; p = 0.846) with a conditional probability of &gt;90% to prove the hypothesis of non-inferiority. Procedure related mortality was 2.1% (n=3) for resection vs. 0% (n=0) for thermal ablation. The total number of adverse events (p = &lt;0.001), the length of hospital stay (median 4 days [range 1-36] vs 1 day [range 1-44], p = &lt;0.001) and local control also favored thermal ablation (HR 0.184; 95% CI, 0.040-0.838; p = 0.029). No differences were found regarding local (HR 0.833; 95% CI, 0.473-1.469; p = 0.528) and distant PFS (HR 0.982; 95% CI, 0.739-1.303; p = 0898). Conclusions: In conclusion, transitioning from surgical resection to thermal ablation as standard of care for patients with small-size (≤3 cm) CRLM would reduce complications, shorten hospital stay and improve local control, without compromising disease-free and overall survival. COLLISION is funded by a Medtronic-Covidien Investigator Sponsored Research grant. Clinical trial information: NCT03088150 .

Survival outcomes for women with a solitary extracranial metastasis from breast cancer

BackgroundAggressive metastasis directed treatment of extracranial oligometastatic breast cancer with the aim of increasing disease-free survival has emerged as a new potential treatment paradigm, however there is currently a lack of data to assist in identifying the subset of patients who will potentially benefit most. This single-institute retrospective cohort study aimed to evaluate survival outcomes for patients with a solitary extracranial metastasis from breast cancer and to assess for significant prognostic factors. Methods and materialsMedical records of 70 female breast cancer patients with a solitary extracranial metastasis actively managed at the Peter MacCallum Cancer Centre (PMCC) Melbourne Campus between 2000 and 2019 were reviewed. Kaplan-Meier curves were used to estimate overall survival (OS), local progression free survival (LPFS) and distant progression free survival (DPFS). ResultsMedian follow-up period was 9.4 years. The study included 40 hormone receptor positive/HER2 negative (HR+HER2-), 14 hormone receptor positive/HER2 positive (HR+HER2+), 3 hormone receptor negative/HER2 positive (HR-HER2+), 9 triple negative (TNBC) and 4 unclassified breast cancer patients. 5-year OS rate for all patients was 46%, LPFS rate was 56% and DPFS was 20%. Tumour receptor group had a statistically significant association with OS and DPFS rates. TNBC patients had significantly poorer OS and DPFS rates in comparison to HR+HER2-patients. ConclusionAmong patients with a solitary extracranial metastasis from breast cancer, TNBC was associated with the poorest OS and DPFS rates. Identification of other significant prognostic factors for oligometastatic breast cancer patients may inform guidelines for metastasis directed treatments.

Abstract 7656: Clinicogenomic anlaysis reveals a role for TP53 mutations in distant progression of high-grade glioma

Abstract Purpose: High-grade glioma (HGG), the most common form of primary brain tumor, is highly lethal and treatment options remain limited. Despite advances in genomic technologies, there are few molecular biomarkers to guide precision medicine for HGG. Here, we aimed to identify the clinicogenomic features associated with HGG prognosis and recurrence patterns. Methods: Our single-institution retrospective analysis included 220 patients initially diagnosed with adult HGG (grade 3 or 4) who underwent next-generation sequencing targeting 82 brain tumor-relevant genes. The patients were categorized according to the 2021 WHO classification and their clinical status, survival, genomic profile, and recurrence patterns were analyzed. Results: At a median follow-up of 23 months (ranges, 2-59 months), 180 patients (82%) showed either progression or recurrence. A total of 15% of patients were reclassified under the 2021 WHO classification, revealing a clear separation of progression-free survival (PFS) and overall survival (OS) curves between grades 3 and 4 gliomas. We found that TP53 mutations were significantly associated with the occurrence of distant progression, especially in grade 4 gliomas. Additionally, TP53 mutations were more common in patients with higher Ki67 index and subependymal/leptomeningeal seeding, indicating an increased risk of distant progression in TP53-mutated grade 4 glioma patients. Following multivariate Cox regression analysis, TP53 mutations were independent predictors of OS (hazard ratio [HR]=1.47, P=0.039) and distant PFS (HR=1.71, P=0.005). Conclusion: Considering the elevated risk of distant progression in grade 4 gliomas with TP53 mutations, our results underscore the necessity for additional research into the most effective treatment approaches for these patients. Keywords: high-grade glioma, TP53, pattern of failure, distant progression, next-generation sequencing Citation Format: Byung-Hee Kang, Seungbok Lee, Joo Ho Lee. Clinicogenomic anlaysis reveals a role for TP53 mutations in distant progression of high-grade glioma [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 7656.

Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology)

Background and purposeStereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. Materials and methodsThis is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. ResultsFrom 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. ConclusionSABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Updated evidence of primary tumor resection in stage IV breast cancer: a systematic review and meta-analysis

Background: In stage IV breast cancer, surgical resection of the primary tumor was traditionally performed solely to palliate symptoms such as bleeding, infection, or pain. The ongoing discussion has shown that there are many research gaps in the current literature and differences in clinical practice. Thus, this systematic review and meta-analysis was designed to evaluate how primary tumor resection (PTR) affects the overall survival (OS) of patients with stage IV breast cancer. Method: A thorough literature search was completed using different databases (PubMed, Google Scholar, Scopus, ScienceDirect, and Cochrane Library) to find papers contrasting PTR with no PTR. The quality of research articles was evaluated using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale (NOS). Review Manager 5.4 was used to determine how much demographic and clinical factors contribute to heterogeneity through subgroup and meta-regression analysis. Results: Data derived from 44 observational studies (OS) and four randomized controlled trials (RCTs) including 227,889 patients were analyzed. Of all cases, 150,239 patients were included in the non-PTR group, and 70,795 patients in the PTR group (37 observational studies and 4 randomized control trials). The pooled outcomes of four RCT studies (Hazard Ratio (HR) = 1.03, 95%CI: 0.67-1.58; I 2 = 88%; P &lt; 0.0001; chi-square 24.57) favor non-PTR. While pooled outcomes of 43 observational studies showed PTR significantly improved OS (HR = 0.66, 95%CI: 0.61-0.71; I 2 = 87%; P &lt; 0.00001; chi-square 359.12). Additionally, subgroup analysis that compared PTR with non-PTR in patients with stage IV breast cancer for progression free-survival (HR = 0.89, 95%CI: 0.62-1.28; P = 0.03; I 2 = 71%) and locoregional progression-free survival (LPFS) (HR = 0.33, 95%CI: 0.14-0.74; P = 0.0004; I 2 = 87%) was found to be significant favoring the PTR group. Distant progression-free survival (DPFS) had a non-significant relationship (HR = 0.42, 95%CI: 0.29-0.60; P = 0.12; I 2 = 53%), while overall, there was a significant relationship (HR = 0.49, 95%CI: 0.32-0.75; P &lt; 0.00001; I 2 = 90%). Subgroup analysis revealed that PTR is beneficial in patients with bone metastasis (HR = 0.83, 95%CI: 0.68-1.01; P = 0.01; I 2 = 56%), with one metastatic site (HR = 0.75, 95%CI: 0.63-0.59; P = 0.006; I 2 = 62%), but not in patients with positive margins (HR = 0.84, 95%CI: 0.67-1.06; P = 0.07; I 2 = 61%), negative margins (HR = 0.61, 95%CI: 0.59-0.63, P = 1.00; I 2 = 0%). Most of the patients in PTR and non-PTR groups belonged to white compared to other ethnic groups. Overall, observational studies were of high quality, while RCTs were of low quality. Conclusion: The current research suggests that PTR may be discussed as a possible option.

Recurrent Colorectal Liver Metastases: Upfront Local Treatment versus Neoadjuvant Systemic Therapy Followed by Local Treatment (COLLISION RELAPSE): Study Protocol of a Phase III Prospective Randomized Controlled Trial

PurposeThe objective of the COLLISION RELAPSE trial is to prove or disprove superiority of neoadjuvant systemic therapy followed by repeat local treatment (either thermal ablation and/or surgical resection), compared to repeat local treatment alone, in patients with at least one recurrent locally treatable CRLM within one year and no extrahepatic disease.MethodsA total of 360 patients will be included in this phase III, multicentre randomized controlled trial. The primary endpoint is overall survival. Secondary endpoints are distant progression-free survival, local tumour progression-free survival analysed per patient and per tumour, systemic therapy-related toxicity, procedural morbidity and mortality, length of hospital stay, pain assessment and quality of life, cost-effectiveness ratio and quality-adjusted life years.DiscussionIf the addition of neoadjuvant systemic therapy to repeat local treatment of CRLM proves to be superior compared to repeat local treatment alone, this may lead to a prolonged life expectancy and increased disease-free survival at the cost of possible systemic therapy-related side effects.Level of EvidenceLevel 1, phase III randomized controlled trial.Trial RegistrationNCT05861505. May 17, 2023.Graphical

Improved survival outcome with not-delayed radiotherapy and immediate PD-1/PD-L1 inhibitor for non-small-cell lung cancer patients with brain metastases

PurposeTo investigate the impact of radiotherapy (RT) and immune checkpoint inhibitor (ICI) sequence on the survival outcome in NSCLC patients with brain metastasis, and decide the best time to initiate RT.MethodsPatients were managed with delayed RT (ICI delivered over 2 weeks prior to RT), concurrent RT (ICI delivered within 2 weeks prior to or after RT), or upfront RT (RT delivered over 2 weeks prior to ICI). Overall survival (OS), intracranial local progression-free survival (iLPFS), and intracranial distant progression-free survival (iDPFS) were assessed. A meta-analysis was performed to analyze the association between survival outcome and RT/ICI sequence.ResultsA total of 73 NSCLC patients were identified with a median follow-up of 13.9 months. Patients who receive delayed RT demonstrated shorter iLPFS (P = 0.0029), iDPFS (P = 0.016), and OS (P < 0.001). A meta-analysis was conducted and a total of 4 studies, 254 patients were included. The HR was 0.44 for iDPFS (P = 0.03), 0.41 for OS (P < 0.01) when compared concurrent with delayed RT, 0.21 for iDPFS (P < 0.01), 0.32 for OS (P < 0.01) when compared upfront with delayed RT, consistent with our conclusion that delayed RT brought with worst iDPFS and OS. More importantly, the best overall response rate (BOR) decreased in cases with longer RT and ICI intervals. Patients who receive intervals of RT and ICI within 7 days achieve the best median BOR of − 53%.ConclusionsDelayed RT brought poor survival outcomes including iLPFS, iDPFS, and OS in NSCLC patients. The shorter interval of RT and ICI is associated with better BOR.

Clinical Outcomes with Thoracic Radiotherapy for Extensive-Stage Small-Cell Lung Cancer in the Era of Immunotherapy: A Retrospective Analysis

Chemo-immunotherapy has shown significant benefits for extensive-stage small-cell lung cancer (ES-SCLC), which prolonged overall survival (OS) of nearly 2-4.5 months compared with platinum-based chemotherapy alone. However, thoracic radiotherapy (TRT), was not allowed to be used in previous trials. This retrospective study aimed to evaluate the safety and efficiency of TRT for ES-SCLC patients in the era of Immunotherapy. We retrospectively reviewed ES-SCLC patients treated with chemo-immunotherapy between 2017 and 2021 in our center. Patients who accepted consolidative or salvage TRT were included. The overall survival, progression-free survival (PFS), local progression-free survival (LPFS), and distant progression free-survival (DPFS) were calculated using the Kaplan-Meier method. Toxicity was recorded based on CTCAE 5.0 scale. We finally enrolled 30 patients in our study. The median follow-up time was 26.0 months (95% confidence interval, 18.2-33.8 months). 26(86.7%) patients have undergone first-line chemotherapy and immunotherapy, while 4(13.3%) have undergone immunotherapy as a second-line agent. 23(76.6%) patients achieved CR/PR/SD to initial systematic therapy. All patients were treated with TRT with a median dose of 51 Gy (24-60.2 Gy). The median interval between TRT and immunotherapy was 35 days. Median OS was 26 months (95% confidence interval, 17.8-34.2 months) and median PFS was 8 months (95% confidence interval, 5.3-10.7 months). 2-year OS, PFS, and DPFS were 51.4%, 21.4%, and 27.4%, respectively. 18 months LPFS was 59.6%. There was no ≥ G3 radiation-related adverse event except 2(6.7%) G3 esophagitis. G1-2 pneumonitis was reported in 8(26.7%) patients. TRT is well-tolerated and effective for selected ES-SCLC patients in the modern era of immunotherapy. Prospective trials are still needed to further evaluate the combination of TRT and immunotherapy for patients with ES-SCLC.

Outcomes of MR-Guided Stereotactic Body Radiotherapy (MRgSBRT) for Adrenal Metastases: A Multi-Institutional Pooled Analysis

Stereotactic body radiotherapy (SBRT) is an effective treatment for adrenal metastases, but it is technically challenging and there are concerns about toxicity due to the proximity of organs at risk. We hypothesized that MR-guided SBRT (MRgSBRT) using a 0.35 T MR-Linac for adrenal metastases can achieve durable local control (LC) with a low probability of toxicity. In an ethics-approved study, we analyzed clinical and dosimetric data of patients treated with MRgSBRT at 10 institutions between 2016-2022. LC, local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS) were estimated using Kaplan-Meier method and log-rank test. Responses were evaluated using RECIST criteria. Toxicity was graded according to CTCAE (v4.0). OS and DPFS were calculated on a per-patient basis, while LC and LPFS were calculated on a per-lesion basis. A total of 249 patients (260 adrenal lesions) were included; median age was 65 years (range 28-91), 65.5% were male, 83.9% had ECOG PS 0-1. The most common primary tumor was lung cancer (69.1%). Adrenal metastases were synchronous, metachronous, oligoprogressive or oligopersistent in 20%, 41.5%, 35.8% and 2.7% of patients, respectively. Metastatic pattern was solitary in 26.9%, oligometastatic in 57.3% and polymetastatic in 15.8% of patients. Right-sided metastases comprised 40%, left-sided 51.5% and lesions were bilateral in 8.5%. Chemotherapy and immunotherapy were administered in 67.1% and 60.6% of patients, respectively. Median gross tumor volume was 21.8 cc (range 1.1-383.2) and median planning target volume was 36.9 cc (range 3.6-516.9). Median total dose was 45 Gy (range 16-60), median fraction number was 5 (range 1-8) and median fraction dose used was 10 Gy (range 5-24). Median BED10 was 100 Gy (range 37.5-132); 87.8% of fractions used adapted plans. At a median follow-up was 17.7 months (IQR 5.5-21.7), local responses were scored as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) in 36.9%, 28.2%, 25.7%, and 9.1%, respectively. Median OS was 30.4 months, with 1- and 2- year OS rates of 75.3% and 57.1%, respectively. On multivariate analysis, significantly higher OS rates were seen in patients achieving a CR (p = 0.007, HR 0.50) and with ECOG scores of 0-1 (p = 0.001, HR 0.43). One- and 2- year LPFS rates were 94.5% and 88.8%, respectively. No local recurrences were observed after treatment to a BED10>100 or with single fraction (range 16-24 Gy). Only 2 patients (0.8%) had ≥grade 3 chronic toxicity. This multi-institutional study of MRgSBRT outcomes for adrenal metastases revealed a 2-year LPFS of 89%, with a <1% risk of ≥grade 3 toxicity. Daily adaptation was performed in 90% of plans, indicating a beneficial role for MR guidance.

Preoperative Radiotherapy of Soft Tissue Sarcoma with Simultaneous Integrated Boost: A Phase II Study

Neoadjuvant radiotherapy to 50 Gy in 25 fractions is delivered in operable Soft Tissue Sarcoma (STS) patients to downstage the tumor and improve resectability, although at the expense of increased risk of wound dehiscence. Nonetheless, clear margin resection (R0) may not be achieved in tumors located in proximity of critical structures such as the neurovascular bundle (NVB), resulting in impaired local control. The aim of this study is to increase R0 rate through addition of an IMRT boost to the potential sites of suboptimal resection in STS patients receiving neoadjuvant RT. We report hereby the dosimetric results and safety results from the first 5 patients enrolled in this trial. We designed a prospective monocentric interventional single-arm Phase II study enrolling locally advanced STS eligible for surgery. RT is administered in 25 daily fractions to include the MRI-based Gross Tumor Volume (GTV) and peritumoral tissue at risk of microscopic spread (CTV1) to a dose of 50 Gy (2Gy/fraction), with SIB (Simultaneous Integrated Boost) intensification to the tumor/dissection plane interface (CTV2) to a dose of 60 Gy (2.4 Gy/fraction). CTV2 delineation is approved by both a Radiation Oncologist and Surgeon. A margin of 0.5 cm is applied to both CTV to obtain PTV1 and PTV2. Concurrent anthracyclines-based chemotherapy (ChT) is allowed up to 3 cycles. Primary endpoint is R0 resection rate. Secondary endpoints include pathologic complete response rate, objective response rate, overall survival, local and distant progression-free survival, acute and chronic toxicity rate. To assess an increase in R0 rate from 81% to 97% assuming β = 80% e α = 0.05, 33 patients will be included. Dose constraints are summarized in Table1. At least 95% of the PTV1 and PTV2 should be covered by 95% the prescription dose up to a maximum allowed dose of 107%. Five patients were included. Tumor was located in the limbs and in the trunk in respectively 4 and 1 patient. Mean age was 47 years (range: 19-67). Concurrent chemotherapy was performed in 2 patients. Mean GTV size was 228.6 cm3 (range: 59.8-314.5). Mean PTV coverage by the 95% of the dose prescription was 98% (95-100) and 97% (95-100) in PTV1 and PTV2, respectively. Mean PTV1 and PTV2 Dmax were 61.6 Gy (range: 59-63) and 64.1 Gy (range:63-66), in both cases below the 107% threshold. Mean Bone Dmax was 55 Gy (56.6-61.8 Gy). Dmax to the skin corridor exceeded 20 Gy in 1 patient (range 12.5-58.1). While the NVB was overlapping the PTV2 in all cases, Dmax was below 66 Gy. At the time of this report, no Grade ≥3 acute skin toxicity was observed. Two patients underwent surgery with a radiological partial response (RECIST) and pathological complete response. No major wound complication was reported. Planning goals of the first 5 enrolled patients are achieved in most cases. Preliminary results show a benign safety profile and promising tumor response rate.

Long-Term Survival in Patients with Brain-Only Metastatic Lung Cancer Undergoing Upfront Intracranial Stereotactic Radiosurgery and Definitive Treatment to the Thoracic Primary Site

To evaluate modern clinical outcomes for patients with brain-only metastatic lung cancer treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site. Patients with new diagnosis of lung cancer and synchronous brain-only metastatic disease treated with intracranial SRS were identified in a prospectively maintained, single institution database. Patients were stratified based on whether they did (Group A) or did not receive (Group B) definitive primary site treatment, defined by surgical resection or radiation therapy (RT) to a dose > 40 Gy. Patient demographics and treatment details were recorded. Intrathoracic, distant body, and intracranial progression, as well as overall survival (OS) and cancer-specific survival (CSS) were recorded, with 2- and 5-y rates estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analysis (MVA) were performed to determine predictors of OS. From 2008-2022, 107 patients were identified. 57 patients received definitive primary site treatment, of whom forty received upfront and seventeen received consolidative treatment at a median 9 months after diagnosis. 45 patients underwent fractionated RT to a median dose of 60 Gy (range 45-74 Gy), 9 underwent SBRT to a median dose of 50 Gy in 5 fractions (range 40-60 Gy), and 3 had lobectomy. Median follow-up was 2.7 y (A) and 1.2 y (B) (p<0.01). Median number of brain metastases was 1 (range 1-17; 82% 1-3 and 18% ≥ 4). There were no significant differences in patient age, sex, race, smoking status, histology, targetable mutations, AJCC T- or N-stage, receipt of systemic therapy, number or volume of brain metastases, neurologic deficits, or resected brain metastases between the groups. 82% (A) and 72% (B) of patients were T1-4N1-3, while 16% (A) and 24% (B) were T1-3N0. 32 (56%) patients in Group A received immunotherapy (ICI) versus 19 (38%) in Group B (p = 0.048). There were no differences in intracranial progression-free survival (PFS) (p = 0.17) or CNS-related death (p = 0.30) between groups. 2- and 5-y estimates for OS were 61.4% and 38.5% (A) versus 28.3% and 0% (B) (p = 0.002). 2- and 5-y CSS were 83.8% and 64.2% (A) versus 48.6% and 0% (B) (p = 0.002). 2- and 5-year intrathoracic PFS were 90% and 75% (A) versus 55% and 55% in (B) (p<0.01). 2- and 5-y distant body PFS were 49.3% and 32% (A) versus 17.3% and 0% (B) (p = 0.001). On UVA, definitive primary site treatment, receipt of immunotherapy, and young age were significant predictors of OS, and each of these remained significant on MVA. Definitive treatment to the thoracic primary site in patients with brain-only metastatic lung cancer after intracranial radiosurgery was associated with not only reduced rates of intrathoracic progression but also lower rates of distant systemic progression and improved overall and cancer-specific survival.

PSMA-Positive Extracellular Vesicles Predict Disease Recurrence in Oligometastatic Castration-Sensitive Prostate Cancer Treated with Stereotactic Ablative Radiotherapy: Analysis of the ORIOLE trial

Stereotactic ablative radiation therapy (SABR) can prolong progression free survival in oligometastatic prostate cancer (omPC) patients. However, predictive tools to identify those who will benefit from SABR are necessary. Our group was the first to demonstrate that plasma levels of prostate cancer-derived extracellular vesicles (ProstEVs) correlate with tumor burden and predict disease progression in omPC after SABR. Herein, we conducted a blinded validation study using plasma samples from the ORIOLE randomized phase 2 clinical trial in castration-sensitive patients. Plasma samples from 46 omPC patients from the Baltimore ORIOLE trial: a 2:1 ratio randomization to SABR vs observation (NCT02680587). Baseline PSMA+ ProstEV levels were measured by standardized and calibrated nanoscale flow cytometry using fluorescent PSMA antibodies. Median ProstEV levels was used as cut-off for low and high levels. Kaplan-Meier curves and Cox regression models were used to determine the association of ProstEV levels with clinical outcomes [PSA progression-free survival (psaPFS) and radiographic distant progression free survival (rPFS)]. No association was observed between number of metastatic lesions or baseline PSA and plasma ProstEV levels. The rPFS for patients treated with SABR was 29.6 months. The rPFS for patients treated with SABR with high and low ProstEV levels were 11.1 months and 36 months, respectively (Hazard Ratio: 2.85; 95% CI, 1.01-7.48; P = 0.02). The psaPFS for patients treated with SABR was 11.9 months. The psaPFS for patients with high and low ProstEV levels were 5.9 months and 24.3 months, respectively (HR: 2.44; 95% CI, 1.00-5.94; P = 0.03). ProstEVs is the first blood biomarker of tumor burden that can prognosticate the risk of disease recurrence in omPC patients treated with SABR. While biomarker-guided trials are warranted, our validation study strengthens the clinical value of ProstEVs for personalized radiation therapy.

Stereotactic Body Radiotherapy for Spine Oligometastases: A Multicentre Retrospective Study From the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

AimTo evaluate the efficacy of stereotactic body radiotherapy (SBRT) for spine oligometastases. Materials and methodsThis was a multicentre retrospective study of a series of patients who received SBRT for spine oligometastases. The efficacy of SBRT was evaluated in terms of local control as the primary endpoint. Survival outcomes were also analysed to identify predictive factors for clinical outcomes. Toxicity was assessed according to CTCAE v4.0. ResultsBetween March 2018 and July 2022, 183 lesions in 177 patients were analysed. In most patients, SBRT was delivered to a single spine metastasis (82%) for a median total dose of 21 Gy (14–35 Gy) in three fractions (one to five fractions) and a median BED10 = 119 Gy (57.7–152 Gy). Local control rates were 90.3% at 1 year, 84.3% at 2 years and 84.3% at 3 years. Distant progression-free survival rates were 33.1%, 18.5% and 12.4% at 1, 2 and 3 years, with prostate histology (P = 0.023), oligorecurrent disease (P = 0.04) and BED10 > 100 Gy (P = 0.04) found to be predictive on univariate analysis. A further oligometastatic progression was observed in 33 patients (18.6%) treated with a second course of SBRT, reporting at univariate analysis improved overall survival rates (P = 0.01). Polymetastases-free survival rates were 57.8%, 43.4% and 32.4%; concurrent therapy was related to improved outcomes at multivariate analysis (P = 0.009). Overall survival rates were 91.8%, 79.6% and 65.9%, with prostate histology and non-cervical metastases related to better overall survival at multivariate analysis. Pain-flare after SBRT was recorded in 3.3%; five patients underwent surgical decompression after SBRT; there were no grade ≥3 adverse events. ConclusionsIn our experience of only oligometastatic patients, spine SBRT gave excellent results in terms of safety and efficacy. Prostate histology and oligorecurrent disease were predictive factors for improved clinical outcomes; also, patients who experienced a further oligoprogression after SBRT maintained a survival advantage compared with polymetastatic progression. No severe adverse events were reported.

Can STEreotactic Body Radiation Therapy (SBRT) Improve the Prognosis of Unresectable Locally Advanced Pancreatic Cancer? Long-Term Clinical Outcomes, Toxicity and Prognostic Factors on 142 Patients (STEP Study).

The gold standard of care for pancreatic adenocarcinoma is the integrated treatment of surgery and chemotherapy (ChT), but about 50% of patients present with unresectable disease. Our study evaluated the efficacy in terms of local control, survival and safety of stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). A retrospective study (STEP study) analyzed patients with LAPC treated with a dose of 45 Gy in 6 fractions. Local control (LC), distant progression free survival (DPFS), overall survival (OS) and toxicity were analyzed according to the Kaplan-Meier method. A total of 142 patients were evaluated. Seventy-six patients (53.5%) received induction ChT before SBRT. The median follow-up was 11 months. One-, 2- and 3-year LC rate was 81.9%, 69.1% and 58.5%. Median DPFS was 6.03 months; 1- and 2-year DPFS rate was 19.9% and 4.5%. Median OS was 11.6 months and 1-, 2- and 3-year OS rates were 45.4%, 16.1%, and 9.8%. At univariate analysis, performed by the log-rank test, age < 70 years (p = 0.037), pre-SBRT ChT (p = 0.004) and post-SBRT ChT (p = 0.019) were associated with better OS. No patients experienced G3 toxicity. SBRT represents an effective and safe therapeutic option in the multimodal treatment of patients with LAPC in terms of increased LC. When SBRT was sequentially integrated with ChT, the treatment proved to be promising in terms of OS as well.