Evaluation of normal tissue complications in breast cancer re-irradiation: a meta-analysis study.

BACKGROUND: In recent years, evidence has accumulated that a second method of conserving the breast from cancer with re-irradiation as part of treatment may be feasible and safe. Many oncologists are skeptical of breast re-irradiation due to concerns about late complications, so access to quantitative data on the prevalence of breast re-irradiation complications is very important. In this meta-analysis, we determine the prevalence of complications in normal tissue after breast re-irradiation. MATERIALS AND METHODS: A search was done to recognize qualified studies using EMBASE, MEDLINE, PUBMED, Google Scholar, and Cochrane Collaboration Library electronic databases from 2000 to 2023. In total, ten primary studies were applied in this meta-analysis to estimate the prevalence of complications of disorders, skin fibrosis, and chest pain. Heterogeneity was investigated using the I2 index and the meta-regression to evaluate variables suspected of causing heterogeneity. Statistical analysis and synthesis were performed using Stata 17. RESULTS: The average dose received by patients who underwent radiation therapy in two stages was 100.32 Gy, and in these patients, the prevalence of skin fibrosis and disorders was 47% (95% CI 71-22%; I2 = 96.76%, P < 0.001) and the prevalence of chest pain was 35% (95% CI 68-8%; I2 = 98.13%, P < 0.001). CONCLUSIONS: There is little clinical information about the incidence of complications in breast re-irradiation therapy. This meta-analysis presents the prevalence of complications after breast re-irradiation to help radiation oncologists and physicists make better decisions.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Hemostatic palliative radiotherapy for gastric cancer: A literature review.

Background: Gastric cancer has a high prevalence in Asia and may only be diagnosed in advanced stages. Therefore, patients with gastric cancer may experience fatal symptoms, such as bleeding or stenosis at the time of consultation. In this review, we aimed to describe the effectiveness and toxicity of hemostatic radiotherapy (RT). Methods: A total of 17 retrospective and 3 prospective studies were analyzed. The prescription dose, biologically effective dose, equivalent dose in 2 Gy fractions, response rate, survival prognosis, and toxicities were also reported. Results: Using 20 studies, the following observations were made the hemostatic effect was âˆ¼ 80 %, the mean survival time after irradiation was about 3 months, and prescribed doses of 30 Gy/10 fractions and 20 Gy/5 fractions were considered suitable. Conclusion: In this review, studies on hemostatic irradiation have been summarized, and the most optimal treatment method has been proposed. 30 Gy/10 fractions and 20 Gy/5 fractions were ideal. However, because palliative RT is preferably completed within a short period of time, a randomized trial is needed to determine whether the 8 Gy/single fraction treatment is equivalent to fractionated RT. Therefore, more prospective studies are warranted to establish a standard of care for palliative RT in gastric cancer.

Interdisciplinary Approach Toward Reirradiation of Cancer Patients.

As systemic therapies, alongside radiation, for cancer treatment continue to evolve, the radiation oncology community is facing an increasing number of reirradiation (re-RT) of tumor sites subject to recurrences. There are multiple factors associated with choosing re-RT as a treatment option for a previously irradiated site. The factors include the site of previous radiotherapy (RT), the current extent of the disease, the nature of recurrence, the technique used for previous irradiation, and the previous RT details including dose and dose fractionation. There is a persistent heterogeneity in the workflow and decision-making in cancer care centers worldwide. The current review is an attempt to dive into the practices of decision-making for re-RT, interdisciplinary attention given to the re-RT patients, and acceptable doses to the organ at risk (OAR) deduced from the understanding of previous RT and radiobiology of the tumor and sites evidence of better techniques for effective execution.

Reirradiation in head and neck squamous cell carcinoma; prognostic indicators, oncologic and functional outcomes.

OBJECTIVES: Patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) have a poor prognosis and limited therapeutic alternatives. While reirradiation is feasible, it is usually associated with high treatment toxicity and is not yet considered the standard of care. Based on current NCCN guidelines, in the context of very advanced head and neck cancer (recurrent and/or persistent disease), surgical intervention is explored initially with/without adjuvants while unresectable disease is approached with radiation and/or systemic therapies. Specific and reliable prognostic indicators for both -oncologic and functional outcomes- have yet to be defined for this population. METHODS: Retrospective chart review of 54 patients treated with reirradiation at a tertiary academic institution between January of 1998 and January of 2024. Only patients with non-metastatic recurrent, and second primary HNSCC were included in the series. Demographics, staging, radiation dose and technique, additional therapy, histopathologic variables, EORTC toxicity, pre- and post-treatment PEG/tracheotomy dependency and oncologic outcomes were retrieved. RESULTS: The study cohort consisted of 54 patients (37 males, 17 females) with HNSCC, averaging 62.7 years in age. Initial tumors were locally advanced in over 42 % of cases, with 58 % being node-negative. The head and cutaneous regions (24.5 %) and tongue (20.8 %) were the most common tumor sites. Primary surgical resection and adjuvant radiation were performed in 47.2 % of cases, and concurrent chemotherapy was used in 40.7 %. Reirradiation was mainly for local or regional recurrence (88.9 %), often following salvage surgery (68.5 %), with a mean dose of 5623 Gy over 52.5 fractions. Positive surgical margins were present in 29.4 % of cases, and extracapsular spread in 59.5 %. No significant differences were found between the salvage surgery and definitive reirradiation groups except for tumor site (P = 0.022). Median follow-up was 52.6 months, with 27 deaths reported. Lymphovascular invasion was significantly correlated with overall survival (P = 0.017), while initial tumor T-stage and neck disease involvement were linked to local-regional control (P = 0.030 and P = 0.033, respectively). Reirradiation increased tracheotomy and PEG-tube dependency by 20 % (P = 0.011) and 23 % (P = 0.003), respectively. CONCLUSIONS: Reirradiation is a feasible therapeutic alternative in recurrent head and neck SCC. Oncologic outcomes observed in this series compare favorably to most published reports. Complete response and perineural invasion were independent prognostic factors for survival and locoregional control. While no mortality directly associated with treatment was observed in this series, reirradiation had a significant impact in functional outcomes in terms of increased risk of tracheotomy and peg tube dependency. Further studies are required to define the role of this treatment in head and neck cancer.

Does a peer review group consensus process for MR-Linac patients affect clinical care? Evaluation of impact and feasibility.

Background and purpose: Peer review is an important component of quality assurance in radiotherapy. To our knowledge, there are no studies reporting on the feasibility and outcomes of the peer review process for magnetic resonance (MR) guided radiotherapy (MRgRT) on the MR linear accelerator (MR-Linac) despite the planning complexity involved and its evolving clinical indications. This study aimed to quantify the rate of change in treatment plans post-peer review and the time and resources required. Materials and methods: Fifty-five cases presented at weekly MR-Linac peer review meetings across two centres from 8 June to 21 September 2023 were prospectively collected. Cases were analysed to determine the rate and extent of plan changes based on the Peer Review Audit Tool for radiation oncology (PRAT) developed by the Royal Australian and New Zealand College of Radiologists (RANZCR). Results: Peer review resulted in changes to 36.4 % of treatment plans (n = 20), with 3.6 % (n = 2) having major changes requiring deferment of treatment. The most frequent changes were to organs at risk (OAR) volumes involving both delineation and increased OAR sparing (16.4 %, n = 9), total dose and fractionation (10.9 %, n = 6) and target volume dose coverage (5.5 %, n = 3). Patients with SBRT plans (39.1 % cf 22.2 %), oligometastatic/oligoprogressive sites (38.1 % cf 30.7 %) and reirradiation cases (41.2 % cf 34.2 %) had higher rates of change. Cases took a mean of 7 min (range 2-15 minutes) to discuss. Conclusion: The high rates of plan changes support the value of peer review in MRgRT. We recommend, where possible that all MRgRT cases, particularly those involving SBRT plans, oligometastatic/oligoprogressive sites, and/or reirradiation, be subject to peer review.

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.

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.

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.

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.

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.

Comparison between Reirradiation by Stereotactic Body Radiation Therapy and Moderately Hypofractionated Radiotherapy in Combination with Temozolomide for Treatment of Recurrent High Grade Glioma.

OBJECTIVE: High grade glioma (HGG) is considered a lethal disease with a high recurrence rate. There is no standard of care in recurrent HGG. Many treatment options are present, such as resurgery, systemic therapy, and re-irradiation. Re-irradiation seems to be a promising option. In this study, we aimed at comparing the efficacy and toxicity of two re-irradiation protocols. METHODS: Forty patients with recurrent HGG were randomized equally into two arms. Arm A received 30 Gy/10f/2w, and arm B received stereotactic body radiotherapy (SBRT) 30 Gy/5f/1w. Concurrent temozolamide (TMZ) was given in both arms. Median progression free survival (PFS) and overall survival (OS) were calculated, and brain MRI was done after 2 months of radiotherapy and then every 2 months, with documented toxicity using the Common Terminology of Adverse Events version 5 (CTCAE). RESULTS: The median follow-up time after the re-irradiation course was 11 months (range 8-15 months). The median PFS after recurrence was 6.4 months (95% CI 5.3-7.4), the median OS after recurrence was 8.6 months (95% CI 7.5-8.7), and the median total OS form date of diagnosis was 18.5 months (95% CI 17.3-19.8) among the included patients. There was a statistically significant difference in PFS favoring arm B, with a median PFS of 7.3 versus 6.2 months in arm A, with p values of 0.004. There was no statistically significant difference in in median OS (9.3 months in arm B versus 8.4 months in arm A) with p values of 0.088. All patients tolerated their treatment well, and acute and subacute G1-G2 toxicity, consisting of headache, malaise, and nausea, were recorded during and shortly after the end of the re-irradiation course. CONCLUSION: Re-irradiation in recurrent HGG by both protocols is safe and effective, with a significant improvement in PFS in SBRT arm but no significant improvement in OS.

Hypofractionated partial breast re-irradiation in the conservative retreatment of breast cancer local recurrence.

AIM: to evaluate the outcome of partial breast re-irradiation (re-PBI) with intensity modulated RT (IMRT), using a hypofractionated scheme for breast cancer (BC) local recurrence (LR) operated on with repeat breast-conserving surgery (re-BCS). METHODS: IMRT-based re-PBI was performed using either helical or step-and-shoot modality to deliver 37.05 Gy in 13 fractions in 2.5 weeks. Cumulative incidence (CumI) of 2ndLR, toxicity, disease-free (DFS), BC specific (BCSS), and overall (OS) survival were evaluated. RESULTS: Between 5/2012 and 5/2021, 70 patients had re-PBI. Median follow-up (FU) was 6.3 years (Q1-Q3, 4.0-8.1.). Median age at 1stLR was 62. The median primary BC-1stLR interval was 12.4 years (range: 1.6-26.7). Luminal A-like 1stLR accounted for 41% of the cases and median size was 0.8 cm. During FU, 18 (26%) patients showed a subsequent event: three 2snLRs (corresponding to 8-y Cumulative rate of 4%), 3 regional nodal recurrences, 7 distant metastases, and 5 other primary tumors. At 8 years, DFS, BCSS and OS were 76%, 90%, and 90%, respectively. At multivariate analysis, Grade 3 and extensive intraductal component were independent predictors for DFS. For 51 and 46 patients, chronic toxicity and cosmesis were evaluated, respectively: 4% had grade 3 fibrosis and cosmesis was deemed good/excellent in just over 60% of the cases. CONCLUSION: Re-PBI after re-BCS represents a feasible alternative to mastectomy with regard to local control, showing an acceptable toxicity profile. A long-term FU is crucial to better understand the pattern of relapse and consolidate the position of re-PBI in clinical practice.

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.

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-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 follow-up are needed to refine treatment strategies and ensure safe and efficacious care delivery in this complex clinical scenario.

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.

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.

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.