STRILL: Phase I Trial Evaluating Stereotactic Body Radiotherapy (SBRT) Dose Escalation for Re-Irradiation of Inoperable Peripheral Lung Lesions.

Few data are available on the role of SBRT re-irradiation for isolated recurrences. We designed a prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation, for peripheral lung lesions. RT was delivered with a dose escalation design from 30 Gy in five fractions up to 50 Gy in five fractions. The primary end point was the definition of the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation. The dose-limiting toxicity was pneumonia ≥G3. Fifteen patients were enrolled. No cases of pneumonia ≥G3 occurred in any of our cohorts. Only one patient developed pneumonia G1 during treatment. Three patients developed acute toxicities that included dyspnea G1, cardiac failure G3, and chest wall pain. One patient developed G3 late toxicity with acute coronary syndrome. After a median follow-up of 21 months (range 3.6-29.1 months), six patients (40%) had a local relapse. Distant relapse occurred in five patients (33.3%). At the last follow-up, six patients died, all but two due to progressive disease. SBRT dose escalation for thoracic re-irradiation is an effective and well-tolerated option for patients with inoperable lung lesions after a first thoracic RT with acceptable acute and late toxicities.

Re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after initial definitive radiotherapy - A systematic review and meta-analysis of recent trials.

Background: There is increasing data on re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after definitive radiotherapy for prostate cancer, with increasing evidence on prostate re-irradiation using a C-arm LINAC or an MR LINAC in recent years. We therefore conducted this systematic review and meta-analysis on prostate re-irradiation including studies published from 2020 to 2023, to serve as an update on existing meta-analysis. Methods: We searched the PubMed and Embase databases in October 2023 with queries including combinations of "repeat", "radiotherapy", "prostate", "re-irradiation", "reirradiation", "re treatment", "SBRT", "retreatment". Publication date was set to be from 2020 to 2023. There was no limitation regarding language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. After data extraction, heterogeneity testing was done by calculating the I2. A random effects model with a restricted maximum likelihood estimator was used to estimate the combined effect. Funnel plot asymmetry was assessed visually and using Egger's test to estimate the presence of publication and/or small study bias. Results: 14 publications were included in the systematic review. The rates of acute ≥ grade 2 (G2) genitourinary (GU) and gastrointestinal (GI) toxicities reported in the included studies ranged from 0.0-30.0 % and 0.0-25.0 % respectively. For late ≥ G2 GU and GI toxicity, the ranges are 4.0-51.8 % and 0.0-25.0 %. The pooled rate of acute GU and GI toxicity ≥ G2 were 13 % (95 % CI: 7-18 %) and 2 % (95 % CI: 0-4 %). For late GU and GI toxicity ≥ G2 the pooled rates were 25 % (95 % CI: 14-35 %) and 5 % (95 % CI: 1-9 %). The pooled 2-year biochemical recurrence-free survival was 72 % (95 % CI: 64-92 %). Conclusions: SBRT in the re-irradiation of radiorecurrent prostate cancer is safe and effective. Further prospective data are warranted.

Efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of recurrent cervical cancer: a prospective cohort.

OBJECTIVE: This study aimed to investigate the efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted computed tomography (CT)-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of pelvic recurrent cervical carcinoma after external beam radiotherapy. METHODS: From January 2019 to August 2023, 45 eligible patients were enrolled in this prospective cohort. All patients underwent 3D-PNCT-assisted CT-guided HDR-ISBT with a prescribed dose of 4-7 Gy/fraction to the high-risk clinical target volume (HR-CTV) over 3-8 fractions, either for curative or palliative purposes. The primary endpoints were local progression-free survival (LPFS) and tumor response rate (TRR). The secondary outcome measures included overall survival (OS), toxicities, and symptom resolution. RESULTS: Forty-five patients received 261 fractions of 3D-PNCT-assisted HDR-ISBT. Twenty-nine patients had isolated pelvic recurrence, and 16 patients had simultaneous extra-pelvic or distant recurrences. The TRR was 66.7%. The 2- and 5-year LPFS rates were 30.0% and 25.7%, respectively. The median OS was 23.2 months, and 2- and 5-year OS rates were 49.5% and 34.0%, respectively. The multivariate analysis indicated that squamous cell carcinoma, radical surgery, recurrence-free interval≥12 months, tumor diameter, pelvic recurrence type, and HR-CTV D90≥45 Gy were independent factors influencing LPFS (all p<0.05). D100≥21 Gy, V100≥83%, and V150≥45% were associated with better LPFS (all p<0.05). Tumor diameter and metastasis were independent predictive factors for OS (all p<0.05). The pain relief rate was 66.7% (10/15). Grade 3-4 toxicities occurred in 20.0% of patients. CONCLUSION: 3D-PNCT-assisted HDR-ISBT for reirradiation of recurrent cervical cancer proved to be an effective and safe alternative to radical surgery.

International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

PURPOSE: Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. While postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. METHODS AND MATERIALS: A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. RESULTS: The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60Gy, and hyperfractionation has shown promise in reducing toxicity. CONCLUSION: These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for the clinical experts involved in the treatment of locally recurrent NPC. SUMMARY: This article provides international recommendations on postoperative management for potentially resectable locally recurrent nasopharyngeal carcinoma (NPC), with a special focus on postoperative re-irradiation (re-RT). The consensus guidelines highlight the importance of achieving clear surgical margins, suggest considering re-RT for patients with positive or close margins, recommend an optimal re-RT dose of around 60Gy, and propose the use of hyperfractionation to reduce toxicity. The aim is to improve patient outcomes in the management of resectable locally recurrent NPC.

Re-irradiation treatment regimens for patients with recurrent glioma - Evaluation of the optimal dose and best concurrent therapy.

PURPOSE: Re-irradiation (reRT) is an effective treatment modality for patients with recurrent glioma. Data on dose escalation, the use of simulated integrated boost and concomitant therapy to reRT are still scarce. In this monocentric cohort of n = 223 patients we investigated the influence of reRT dose escalation as well as the concomitant use of bevacizumab (BEV) with regard to post-recurrence survival (PRS) and risk of radionecrosis (RN). PATIENTS AND METHODS: Patients with recurrent glioma treated between July 2008 and August 2022 with reRT with BEV, reRT with temozolomide (TMZ) and reRT without concomitant systemic therapy were retrospectively analyzed. PRS and RN-free survival (RNFS) were calculated for all patients using the Kaplan-Meier estimator. Univariable and multivariable cox regression was performed for PRS and for RNFS. The reRT Risk Score (RRRS) was calculated for all patients. RESULTS: Good, intermediate and poor risk of the RRRS translated into 11 months, 9 months and 7 months of median PRS (univariable: p = 0.008, multivariable: p = 0.013). ReRT was applied with a dose of ≤36 Gy (n = 140) or >36 Gy (n = 83). Concomitant bevacizumab (BEV) therapy was performed in n = 122 and concomitant temozolomide (TMZ) therapy in n = 32 patients. Median PRS was 10 months in patients treated with >36 Gy and 8 months in patients treated with ≤36 Gy (univariable: p = 0.032, multivariable: p = 0.576). Regarding concomitant TMZ therapy, median PRS was 14 months vs. 9 months for patients treated with or without TMZ (univariable: p = 0.041, multivariable: p = 0.019). No statistically significant influence on PRS was seen for concomitant BEV therapy in this series. RN was less frequent for reRT with concomitant BEV, (17/122; 13.9 %) than for reRT without BEV (30/101; 29.7 %). Regarding RNFS, the hazard ratio for reRT with BEV was 0.436 (univariable; p = 0.006) and 0.479 (multivariable; p = 0.023), respectively. ReRT dose did not show statistical significance in regards to RN (univariable: p = 0.073, multivariable: p = 0.404). RNFS was longer for patients receiving concomitant BEV to reRT than for patients treated with reRT only (mean 31.7 vs. 30.9 months, p = 0.004). CONCLUSION: In this cohort, in patients treated with concomitant BEV therapy RN was less frequently detected and in patients treated with concomitant TMZ longer PRS was observed. Based on these results, the best concomitant therapy and the optimal dose should be decided on a patient-by-patient basis.

A multi-centre retrospective study of long-term outcomes of spinal re-irradiation with SABR.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is a highly conformal technique utilising a high dose per fraction commonly employed in the re-treatment of spinal metastases. This study sought to determine the safety and efficacy of re-irradiation with SABR to previously treated spinal metastases. METHODS: This was a retrospective analysis of patients at three Australian centres who have undergone spinal SABR after previous spinal radiotherapy to the same or immediately adjacent vertebral level. Efficacy was determined in terms of rates of local control, while safety was characterised by rates of serious complications. RESULTS: Thirty-three spinal segments were evaluated from 32 patients. Median follow-up for all patients was 2.6 years, and median overall survival was 4.3 years. Eleven of 33 (33.3%) treated spinal segments had local progression, with a local control rate at 12 months of 71.4% (95% C.I. 55.2%-92.4%). Four patients (16.7%) went on to develop cauda equina or spinal cord compression. Thirteen out of 32 patients (40.6%) experienced acute toxicity, of which 12 were grade 2 or less. Five out of 30 spinal (16.7%) segments with follow-up imaging had a radiation-induced vertebral compression fracture. There was one case of radiation myelitis which occurred in a patient who had mediastinal radiotherapy with a treatment field which overlapped their prior spinal radiation. CONCLUSION: The patients in this study experienced long median survival, durable tumour control and high rates of freedom from long-term sequelae of treatment. These results support the use of SABR in patients who progress in the spine despite previous radiotherapy.

Re-re-irradiation for palliation: knowns, unknowns, and next steps.

: With improving rates of survival among patients with metastatic malignancies, the request for palliative re-irradiation and re-re-irradiation continues to grow despite an absence of standardized guidelines. With only limited data regarding extra-cranial third-course palliative radiation, many radiation oncologists may feel uncomfortable proceeding with third-course irradiation of the same site. The review explores the available modern data regarding re-re-irradiation. A literature review identified four modern peer-reviewed studies investigating palliative, extra-cranial third-course irradiation with external beam radiation. These studies were retrospective, small, and heterogenous. While they reported comparable rates of pain palliation to first course irradiation and low rates of acute toxicity, interpretation is complicated by heterogeneous treatment parameters and insufficient reporting of cumulative dose equivalents and time intervals. With limited data available, it is critical to prioritize patient safety and quality of life in palliative radiotherapy. Patient selection should be meticulous, considering factors such as initial treatment response and predicted life expectancy. Conformal radiation techniques, strict immobilization, and daily image guidance should be employed to minimize toxicity to organs at risk (OARs). Long-term follow-up is essential for identifying and managing late toxicities effectively. Despite the scarcity of data, retrospective series suggest that extra-cranial third course irradiation can provide effective pain palliation comparable to first-course irradiation with tolerable rates of toxicity. However, careful consideration of patient prognosis and adherence to established principles of palliative radiotherapy are essential in decision-making. Further research and long-term followup are needed to refine treatment strategies and ensure safe and efficacious care delivery in this complex clinical scenario.

Feasibility and flexibility of a novel multi-dose level avoidance reirradiation technical methodology in recurrent head and neck cancer.

Reirradiation in recurrent head and neck cancer presents a considerable clinical challenge in radiation oncology. Though technically feasible due to advanced treatment delivery and planning techniques, confidence in delivering such treatments is not universal and patient selection is critical. Radiotherapy planning in reirradiation cases presents a complex technical challenge owing to the often-considerable overlap of dose from a patient's first treatment plan. This technical note describes three clinical case studies of recurrent head and neck cancer and the technical details of how their multidose level reirradiation was planned. Each patient had confirmed recurrence of squamous cell carcinoma and was referred for reirradiation to a previously irradiated area. The clinical details for each patient are provided before a detailed description of the treatment planning methodology is presented, which specifies how to approach such complex overlapping treatment volumes. The patient outcomes are described and a discussion is presented outlining the clinical challenges associated with these cases and the variables that must be accounted for when considering patients for potential reirradiation.

Salvage low-dose-rate brachytherapy for locally recurrent prostate cancer after definitive irradiation.

Purpose: The optimal management of locally recurrent prostate cancer after definitive irradiation is still unclear but local salvage treatments are gaining interest. A retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity after salvage I-125 low-dose-rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer was conducted in a Comprehensive Cancer Center. Patients and methods: A total of 94 patients treated with salvage LDR-BT between 2006 and 2021 were included. The target volume was either the whole-gland +/- a boost on the GTV, the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 34 months. Initial radiotherapy was external beam radiotherapy in 73 patients (78 %) with a median dose of 76 Gy and I-125 BT in 21 patients (22 %) with a prescribed dose of 145 Gy. Median PSA at salvage was 3.75 ng/ml with a median interval between first and salvage irradiation of 9.4 years. Salvage brachytherapy was associated with androgen deprivation therapy for 32 % of the patients. Only 4 % of the patients were castrate-resistant. Failure free survival was 82 % at 2 years and 66 % at 3 years. The only factors associated with failure-free survival on multivariate analysis were hormonosensitivity at relapse and European Association of Urology (EAU) prognostic group. Late grade 3 urinary and rectal toxicities occurred in 12 % and 1 % of the patients respectively.No significant difference in toxicity or efficacy was observed between the three implant volume groups. Conclusion: The efficacy and toxicity results are consistent with those in the LDR group of the MASTER meta-analysis. Salvage BT confirms to be an effective and safe option for locally recurrent prostate cancer. A focal approach could be interesting to reduce late severe toxicities, especially urinary.

Salvage breast conserving surgery and re-irradiation with intraoperative electrons for recurrent breast cancer: a multicentric study on behalf of AIRO (Italian Association of Radiotherapy and clinical Oncology).

AIM: Intraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. MATERIALS AND METHODS: A database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) RESULTS: From 2002 to 2015, 109 patients underwent the conservative retreatment. The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. CONCLUSION: 2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.

Reirradiation after osteocutaneous free flap reconstruction for locally recurrent head and neck cancer.

PURPOSE: Recurrent head and neck cancer poses difficult management. Even after salvage surgery, many patients are considered high-risk for further recurrence and benefit from reirradiation, despite the sequelae such as chronic wounds, tissue necrosis, osteoradionecrosis and vascular damage associated with re-irradiation. Free flaps not only enable the reconstruction following salvage surgery, but there has been limited studies suggesting that free flap reconstruction may reduce the amount of reirradiation complications. However, there are no studies to date specifically examining the effects of osteocutaneous free flap reconstruction upon reirradiation outcomes. MATERIALS AND METHODS: In this retrospective study, patients with recurrent head and neck cancer that had a history of prior head and neck radiation who underwent salvage surgery with osteocutaneous free flaps followed by reirradiation were identified. Descriptive statistics were performed to assess outcomes. RESULTS: Five patients met criteria. Complications included chronic wound infection in one patient, fistula in one patient, plate exposure in two patients and plate removal in one patient. No patients had osteoradionecrosis or carotid rupture after reirradiation. There was an association between complications and further local disease recurrence. All patients were tube feed dependent at their most recent follow-up and two patients were tracheostomy dependent 12 months post-irradiation. Two patients had disease recurrence. Median overall survival was 16 months after reirradiation. CONCLUSIONS: Osteocutaneous free flap surgery with reirradiation may result in high rates of complications and low functional status with an equivocal improvement in survival. Larger studies are needed to substantiate these findings and assess the risk-benefit analysis.

Preliminary outcomes of boron neutron capture therapy for head and neck cancers as a treatment covered by public health insurance system in Japan: Real-world experiences over a 2-year period.

PURPOSE: Since June 2020, boron neutron capture therapy (BNCT) has been a health care service covered by health insurance in Japan to treat locally advanced or recurrent unresectable head and neck cancers. Therefore, we aimed to assess the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers. MATERIALS AND METHODS: We retrospectively analyzed data from patients who were treated using BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. We assessed objective response rates based on the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events based on the Common Terminology Criteria for Adverse Events, version 5.0. Additionally, we conducted a survival analysis and explored the factors that contributed to the treatment results. RESULTS: Sixty-nine patients (72 treatments) were included in the study, with a median observation period of 15 months. The objective response rate was 80.5%, and the 1-year locoregional control, progression-free survival, and overall survival rates were 57.1% (95% confidence interval [CI]: 43.9%-68.3%), 42.2% (95% CI: 30.1%-53.8%), and 75.4% (95% CI: 62.5%-84.5%), respectively. Locoregional control was significantly longer in patients with earlier TNM staging and no history of chemotherapy. CONCLUSIONS: BNCT may be an effective treatment option for locally advanced or recurrent unresectable head and neck cancers with no other definitive therapies. If definitive surgery or radiation therapy are not feasible, BNCT should be considered at early disease stages.

Re-treatment of locally recurrent uveal melanoma with repeat eye plaque I-125 brachytherapy: A single institution experience.

PURPOSE: Eye plaque brachytherapy (EPBT) is the most common treatment for uveal melanoma with high local control rates of 95-100%. When local recurrences occur following EPBT, salvage options include enucleation, transpupillary thermotherapy (TTT), external beam radiation, or re-irradiation with EPBT. The purpose of this study is to report our institution's experience with EPBT re-irradiation for locally recurrent uveal melanoma. METHODS AND MATERIALS: Patients were included if they were previously treated for uveal melanoma with EPBT, experienced local recurrence, and were subsequently treated at our institution with EPBT from 2016- 2020. RESULTS: A total of 5 patients with median age 68 years were included. All patients were initially treated at an outside institution (OSI) with Iodine-125 or Ruthenium-106 EPBT. Mean time between EPBT at the OSI and EPBT at our facility was 130 months (range 28-231 months). Patients were re-irradiated with Iodine-125 EPBT prescribed to 85 Gy over 168 hours. Median follow up after re-treatment at our center was 24 months. Local control among this cohort was 100%. Metastasis occurred in two patients after re-treatment, at 8 months and 7 months. At last follow up, all treated lesions were decreased in size. Four patients experienced worsening visual acuity. Four patients developed cataracts, while two patients developed radiation retinopathy with cystoid macular edema requiring anti-VEGF injections. One patient developed radiation retinopathy but did not require injections. No patients required enucleation. CONCLUSIONS: Re-treatment of locally recurrent uveal melanomas with EPBT is a feasible alternative to enucleation with a high local control rate. Ocular toxicities have not been significant enough to require enucleation.

Normal tissue complication probability model of temporal lobe injury following re-irradiation of IMRT for local recurrent nasopharyngeal carcinoma.

Purpose: We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two courses of intensity modulated radiotherapy (IMRT) to provide more reliable dose-volume data reference to set the temporal lobe tolerance dose for recurrent NPC patients in the future. Methods and materials: Recurrent NPC patients were randomly divided into training data set and validation data set in a ratio of 2:1, All the temporal lobes (TLs) were re-contoured as R/L structures and named separately in the MIM system. The dose distribution of the initial IMRT plan was deformed into the second course planning CT via MIM software to get the deformed dose. Equivalent dose of TLs in 2Gy fractions was calculated via linear quadratic model, using an α/ß=3 for temporal lobes. NTCP model that correlated the irradiated volume of the temporal lobe and? the clinical variables were evaluated in a multivariate prediction model using AUC analysis. Results: From Jan. 2010 to Dec. 2020, 78 patients were enrolled into our study. Among which 26 (33.3%) developed TLI. The most important factors affecting TLI was the sum-dose d1.5cc of TL, while the possible clinical factors did not reach statistically significant differences in multivariate analysis. According to NTCP model, the TD5 and TD50 EQD2 dose of sum-dose d1.5cc were 65.26Gy (46.72-80.69Gy) and 125.25Gy (89.51-152.18Gy), respectively. For the accumulated EQD2 dose, the area under ROC shadow was 0.8702 (0.7577-0.9828) in model validation, p<0.001. Conclusion: In this study, a NTCP model of temporal lobe injury after a second course of IMRT for recurrent nasopharyngeal carcinoma was established. TD5 and TD50 doses of temporal lobe injury after re-RT were obtained according to the model, and the model was verified by validation set data.

Stereotactic Body Radiotherapy in Recurrent and Oligometastatic Head and Neck Tumours.

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.

Radiotherapy for Recurrent Medulloblastoma in Children and Adolescents: Survival after Re-Irradiation and First-Time Irradiation.

BACKGROUND: Radiotherapy (RT) involving craniospinal irradiation (CSI) is important in the initial treatment of medulloblastoma. At recurrence, the re-irradiation options are limited and associated with severe side-effects. METHODS: For pre-irradiated patients, patients with re-irradiation (RT2) were matched by sex, histology, time to recurrence, disease status and treatment at recurrence to patients without RT2. RESULTS: A total of 42 pre-irradiated patients with RT2 were matched to 42 pre-irradiated controls without RT2. RT2 improved the median PFS [21.0 (CI: 15.7-28.7) vs. 12.0 (CI: 8.1-21.0) months] and OS [31.5 (CI: 27.6-64.8) vs. 20.0 (CI: 14.0-36.7) months]. Concerning long-term survival after ten years, RT2 only lead to small improvements in OS [8% (CI: 1.4-45.3) vs. 0%]. RT2 improved survival most without (re)-resection [PFS: 17.5 (CI: 9.7-41.5) vs. 8.0 (CI: 6.6-12.2)/OS: 31.5 (CI: 27.6-NA) vs. 13.3 (CI: 8.1-20.1) months]. In the RT-naïve patients, CSI at recurrence improved their median PFS [25.0 (CI: 16.8-60.6) vs. 6.6 (CI: 1.5-NA) months] and OS [40.2 (CI: 18.7-NA) vs. 12.4 (CI: 4.4-NA) months]. CONCLUSIONS: RT2 could improve the median survival in a matched cohort but offered little benefit regarding long-term survival. In RT-naïve patients, CSI greatly improved their median and long-term survival.

Survival and toxicity after breast-conserving surgery and external beam reirradiation for localized ipsilateral breast tumour recurrence: A population-based study.

PURPOSE: Breast-conserving surgery followed by reirradiation for a localized ipsilateral breast tumour relapse may increase the radiation dose delivered to the heart and result in a greater risk of cardiac adverse events. This study aimed to compare the incidence of cardiac mortality in patients treated for a localized ipsilateral breast tumour relapse, either with breast-conserving surgery followed by reirradiation or with total mastectomy between 2000 and 2020. MATERIALS AND METHODS: All patients treated for a primary non-metastatic breast cancer with breast-conserving surgery and adjuvant radiotherapy were identified in the Surveillance, Epidemiology, and End Results (SEER) program database, and those who subsequently experienced a localized ipsilateral breast tumour relapse treated with breast-conserving surgery and reirradiation ("BCS+ReRT" group, n=239) or with total mastectomy ("TM" group, n=3127) were included. The primary objective was to compare the cardiac mortality rate between the patients who underwent breast-conserving surgery followed by reirradiation and total mastectomy. Secondary endpoints were overall survival and cancer specific survival. RESULTS: Cardiac mortality was significantly higher in patients treated with breast-conserving surgery followed by reirradiation (hazard ratio [HR]: 2.40, 95% confidence interval [95% CI]: 1.19-4.86, P=0.006) in univariate analysis; non-statistically significant differences were observed after adjusting for age, laterality and chemotherapy on multivariate analysis (HR: 1.96, 95% CI: 0.96-3.94, P=0.067), age being the only confounding factor. A non-statistically significant difference towards lower overall survival was observed in patients who had breast-conserving surgery followed by reirradiation compared with those who underwent total mastectomy (HR: 1.37, 95% CI: 0.98-1.90, P=0.066), and no differences were observed in terms of cancer specific survival (HR: 1.01, 95% CI: 0.56-1.82, P=0.965). CONCLUSION: In this study, the incidence of cardiac mortality was low, and breast-conserving surgery followed by reirradiation did not independently increased the risk of cardiac mortality for a localized ipsilateral breast tumour relapse.

Lomustine with or without reirradiation for first progression of glioblastoma, LEGATO, EORTC-2227-BTG: study protocol for a randomized phase III study.

BACKGROUND: Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known. METHODS: EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0-2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union's Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028. DISCUSSION: EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023.

Re-treatment of bone metastases for pain control: 2023 ASTRO education panel.

Bone metastases are a common and debilitating consequence of advanced cancer, often necessitating palliative radiation therapy (RT) for pain relief. Reirradiation (reRT) of bone metastases is often considered after lack of pain relief following an initial course of RT, after a partial but unsatisfying pain response to an initial course of radiotherapy, or after pain recurrence following a complete or partial pain response to an initial course of RT. The NCIC CTG SC.20 trial, a landmark multicenter, randomized, non-blinded, controlled non-inferiority trial, addressed the critical question of optimal dose fractionation for reRT in this patient population. This trial compared the efficacy and toxicity of a single 8 Gy fraction to multiple fractions totaling 20 Gy in 850 patients with painful bone metastases requiring reRT. The primary endpoint was overall pain response at 2 months, with secondary endpoints of quality of life (QoL) measures, functional interference, and toxicity profiles assessed using patient-reported questionnaires and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. The intention-to-treat analysis revealed no significant difference in pain response between the two arms, meeting the pre-specified non-inferiority criteria. The per-protocol analysis suggested a potential benefit for a subset of patients receiving multiple fractions, although this was not statistically robust. Acute toxicities were more prevalent in the multiple fractions arm, with implications for patient comfort and healthcare utilization. Importantly, responders to reRT reported significant improvements in functional interference and QoL. The trial's findings support the use of a patient-centric approach to palliative RT, highlighting the viability of a single 8 Gy fraction as a less toxic and more convenient treatment option, albeit with consideration for individual patient circumstances. These results have significant implications for clinical practice, potentially reducing healthcare burdens while optimizing patient convenience during palliative care for painful bone metastases.

Stereotactic Body Radiotherapy Reirradiation Is Safe in Patients With Lung Cancer With In-Field Enlarged Tumor Recurrence.

Introduction: Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for reirradiation. Materials and Methods: Fifteen patients with recurrent stage III lung cancer treated with stereotactic body radiotherapy (SABR) between October 2013 and December 2017 were retrospectively evaluated for local control as a first endpoint; overall survival, disease-free survival, and treatment-related toxicity were secondary endpoints. Results: The median age was 68 (IQR: 50-71) years, and the median tumor size was 3.3 cm (IQR: 3.0-4.5). The radiation field was all within the previous radiation (previous 80%-90% isodose line), and the median dose was 66 Gy/(2 Gy × 33 standard fractionation). For SABR, the median biologically effective dose at an α/ß ratio of 10 (BED10) was 60.0 Gy (IQR: 39.38-85.0) and given in 3 to 5 fractions. Three patients experienced grade 3 or 4 toxicity but none experienced grade 5. The median follow-up period was 14 (IQR: 10-23) months. The local control rate was found as 86.7% in the first year, 80% in the second year, and 80% in the third year. The median disease-free survival was 8 (IQR: 6-20) months and the median overall survival was 14 (IQR: 10-23) months. The rate of overall survival was 66.6% for the first year and 33.3% for the second and third years. The disease-free survival rate was 46.6% for the first year and 40% for the second and third years. Nine patients who received doses of BED10 ≥ 50 Gy developed no local recurrence (P = .044). Discussion: In local local-regional recurrence of lung cancer, radiosurgery as reirradiation can be used at doses of BED10 ≥ 50 Gy and above to provide local control for radical or palliative purposes. SABR is an important and relatively safe treatment option in such recurrences.