Re-irradiation for isolated neck recurrence in head and neck tumor: impact of rN category.

Unresectable, isolated lymph node recurrence after radiotherapy is rare but a candidate for re-irradiation. However, severe toxicity is anticipated. Therefore, this study aimed to explore the efficacy and toxicity of re-irradiation in isolated lymph node recurrence of head and neck lesions. We analyzed 46 patients who received re-irradiation for lymph node recurrence without local progression. The primary tumor sites included the oral cavity in 17 patients, the hypopharynx in 12, the oropharynx in seven, the larynx in three, the nasopharynx in two, and other sites. During a median follow-up time of 10 months, the median survival time was 10.6 months, and the 1-year overall survival rate was 45.5%. The 1-year local control and progression-free survival rates were 49.8% and 39.3%, respectively. According to univariate analysis, age (≥ 65 years), the interval between treatment (≥ 12 months), rN category (rN1), and gross tumor volume (GTV < 25 cm3) were predisposing factors for better survival. In the multivariate analysis, the rN category and interval were identified as statistically significant predictors. Late toxicity grade ≥ 3 occurred in four patients (8.6%). These were all Grade 5 carotid blowout syndrome, which associated with tumor invasion of the carotid artery and/ or high doses administration for the carotid artery. Small-volume rN1 tumor that recur after a longer interval is a feasible candidate for re-irradiation. However, strict patient selection and meticulous care for the carotid are required.

Brachytherapy is an effective and safe salvage option for re-irradiation in recurrent glioblastoma (rGBM): A systematic review.

PURPOSE: To evaluate the clinical efficacy and toxicity of brachytherapy as a salvage therapy for patients with recurrent glioblastoma (rGBM). METHODS AND MATERIALS: We searched the PubMed, Embase, and Cochrane libraries from its inception to June 2023, for eligible studies in which patients underwent brachytherapy for rGBM. Outcomes of interest were mOS, mPFS, OS, PFS, and adverse events (AEs). For individual clinical survival outcomes and common AEs, weighted-mean descriptive statistics were calculated as a summary measure using study sample size as the weight. The calculation formula is as follows: weighted-mean = Σwx/Σw (w is the sample size and x is the outcome). RESULTS: This review included 29 studies with a total of 1202 rGBM patients, including 22 retrospective and 7 prospective studies. The results showed that from the time of brachytherapy, the mOS and mPFS were 6.8 to 24.4 months and 3.7 to 11.7 months. The OS of 6 months, 1 year, 18 months, 2 years, and 3 years after brachytherapy were 58.3 % to 85.2 % (weighted-mean 76.2 %), 26 % to 66 % (weighted-mean 41.9 %), 20 % to 37 % (weighted-mean 27.6 %), 11 % to 23 % (weighted-mean 14.8 %), and 8 % to 15 % (weighted-mean 12.1 %), respectively. The PFS of 6 months and 1 year after brachytherapy were 26.7 % to 86 % (weighted-mean 53.4 %) and 14 % to 81 % (weighted-mean 24.1 %). Most patients with rGBM will experience treatment failure again during the follow-up period, mainly local (10.7 % to 79.4 %) or marginal(3.6 % to 22.2 %) recurrence, followed by distant failure (6.7 % to 57.7 %). Although therapeutic AEs had not been uniformly reported, the overall toxicity rate was considered to be low. The common AEs reported included progressive neurologic deterioration, seizures, CSF leak, brain necrosis, hemorrhage, and infection/meningitis, with a weighted-mean incidence of 1.9 %, 2.4 %, 4.1 %, 5.4 %, 2.1 %, and 3.8 %, respectively. CONCLUSIONS: The evidence summarized above, albeit mostly level III, suggests that brachytherapy has acceptable safety and good post-treatment clinical efficacy for selected patients with rGBM. Well-designed, high-quality, large-sample randomized controlled and prospective studies are needed to further validate these findings.

Stereotactic reirradiation in the treatment of head and neck cancers: A retrospective study on the long-term experience of the Oscar Lambret Center.

BACKGROUND AND PURPOSE: Stereotactic radiotherapy potentially treats unresectable recurrences of previously irradiated head and neck (H&N) cancer. This study aimed to assess its efficacy and safety and evaluate prognostic factors. MATERIALS AND METHODS: We conducted a large retrospective series that included 110 patients who had undergone 36-Gy, six-fraction stereotactic reirradiation (CyberKnife®) for recurrent/secondary H&N cancer between 2007 and 2020 at the Oscar Lambret Center. Patient characteristics and toxicities were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. RESULTS: Median follow-up time was 106.3 months. The 2-year OS rate was 43.8 % (95 % confidence interval, 95 % CI, 34.3-52.9) and the median survival was 20.8 months (95 % CI, 16.5-26.3). The cumulative 2-year local-recurrence, regional-recurrence, and distant-metastasis rates were 52.2 % (95 % CI, 42.4-61.1 %), 12.8 % (95 % CI, 7.4-19.8 %), and 11 % (95 % CI, 6.0-17.6 %), respectively. 73 patients received concomitant cetuximab, and it was not significantly beneficial (HR = 1.34; 95 % CI, 0.80-2.26; p = 0.26). The cumulative incidences of grade ≥ 2 late toxicity was 42 % (CI95%: 33-51) at 24 months. Two grade 4 bleedings and no treatment-related deaths were reported. CONCLUSION: In a large retrospective series of SBRT reirradiation for recurrent or second primary H&N cancers, we observed a median OS of 20.8 months, with a cumulative incidence of grade ≥ 2 late toxicity of 42 % at 24 months. Such a treatment is feasible. However, local recurrence rates remain non-negligible, warranting further research. Radiosensitizer use is currently under study. Therefore, establishing a balance between therapeutic modifications and toxicity is essential.

Curative high-dose reirradiation for patients with recurrent head and neck adenoid cystic carcinomas: outcomes and analysis of patterns of failure.

BACKGROUND: To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for unresectable recurrent or second primary head and neck adenoid cystic carcinoma (HNACC). METHODS: Ten patients, mostly KPS 90%, were reirradiated (3/10 with IMRT and 7/10 with PT) at a median maximum dose to the CTV of 64.2 Gy from July 2011 to November 2021. Locations at the time of reRT were mainly the sinus (4/10) and the salivary glands (including the parotid and submandibular gland, 3/10). CTCAEv5 was used to assess acute and late toxicities. Follow-up was the time between the end of reRT and the date of last news. RESULTS: The median time between the two irradiations was 53.5 months (IQR: 18-84). After a median follow-up of 26 months (range, 12.5-51.8 months), six patients had developed a locoregional recurrence (LR), of which four occurred within the previously irradiated volume. Two and three-year locoregional failure-free survival (LFFS) and overall survival (OS) were 55.6% [95%CI: 31-99.7%], and 41% [18.5-94%] and 66.7% [42-100%] and 44.4% [21.4-92.3%], respectively. LFFS and OS were significantly better in the subgroup of sinus tumors (p = .013) and the subgroup of patients re-irradiated more than two years after the first course of irradiation (p = .01). Seven patients had impairments before the start of reRT, including hearing impairment (3/10) and facial nerve impairment (3/10). The most severe late toxicities were brain necrosis (2/10), osteoradionecrosis (1/10) and vision decreased (1/10). CONCLUSION: Curative reRT for HNACC is possible for selected cases, but the LR rate in the irradiated field and the risk of severe toxicity remain high. Improved selection criteria and more carefully defined target volumes may improve outcome in these patients. A further study including larger cohort of patients would be useful to confirm these results.

Stereotactic body radiotherapy (SBRT) re-irradiation for local failures following radical prostatectomy and post-operative radiotherapy.

PURPOSE: Local recurrences after radical prostatectomy (RP) and postoperative radiotherapy (RT) are challenging for salvage treatment. Retrospective analysis of own experiences with salvage re-irradiation was performed. METHODS: The study included all consecutive patients treated with salvage stereotactic body radiotherapy (sSBRT) for prostate bed recurrence following RP and postoperative RT at a single tertiary center between 2014 and 2021. Treatment toxicity defined as the occurrence of CTCAE grade ≥ 2 genito-urinary (GU) or gastro-intestinal (GI) adverse events (AEs) was assessed. A PSA response, biochemical control (BC) and overall survival (OS) were also evaluated. RESULTS: The study group included 32 patients with a median age of 68 years and a median follow-up of 41 months, treated with CyberKnife (53%) or Linac (47%) sSBRT. Total dose of 33.75-36.25 Gy in five fractions (72%) was applied in the majority of them. Approximately 19% patients reported grade ≥ 2 GU AEs both at baseline and at three months, and grade ≥ 2 GI toxicity increased from 0% at baseline to 6% at three months after sSBRT. There was some clinically relevant increase in late toxicity with 31% patients reporting late ≥ 2 GU, and 12.5% late ≥ 2 GI AEs. Two grade 3 AEs were recorded: recto-urinary fistulas. The majority of patients showed a PSA response (91% at one year post-sSBRT). The 3­year BC was 40% and 3­year OS was 87%. CONCLUSIONS: Manageable toxicity profile and satisfactory biochemical response suggest that SBRT in patients with local recurrence following RP and postoperative RT might be a salvage option for selected patients.

Outcomes and toxicity in re-irradiation of gynecologic cancer: Systematic review of the Italian association of radiation and clinical oncology (AIRO).

AIMS: The aim of this study was to provide a literature review on the efficacy and safety of reirradiation(re-I) of locoregional recurrences in gynecological malignancies. METHODS: A computerized literature search was performed in 4 electronic databases (1993-2020). Random-effects models and a tendency towards high heterogeneity (Cochran Q chi-square test and the I2 statistic) were used. A meta-analysis technique over single and multi-arm studies was performed to determine the pooled acute and late toxicity rate ≥ G3, locoregional control (LC), and overall survival (OS). RESULTS: Out of 178 articles, only 18 articles accounting for 820 patients (pts) met the inclusion criteria. Outcomes were evaluable for 522 patients. Subgroup analyses highlighted moderate to high heterogeneity among studies. BT (Brachytherapy) showed a 2y OS of 63% (95% CI, 55 to 71 p = 0,36) and 5y OS of 42% (95% CI, 35 to 50, p = 0,43) with 1y-2y-3y LC of 74 (95% CI, 62 to 75, p = 0.04)49% (95% CI, 40 to 58, p = 0.38) and 48% (95% CI, 39 to 58, p = 0,45) respectively. Chemotherapy does not improve SBRT outcomes: BT showed a G3- G4 toxicities rate was of26% (95% CI: 8-49%); studies on SBRT re-I showed a G3-G4 toxicity around of 20% if combined with CHT, and <10 when alone. CONCLUSION: A large heterogeneity among studies was revealed, but showing promising results in terms of safety and feasibility. BT resulted the best kind of radiation therapy delivery in terms of clinical outcome and comparable to the SBRT technique in terms of toxicities.

Delivery of re-irradiation and complex palliative radiotherapy using proton therapy in pediatric cancer patients.

BACKGROUND: The intent of this study is to characterize indications for pediatric palliative-intent proton radiation therapy (PIPRT). PROCEDURE: We retrospectively reviewed patients 21 years and younger who received PIPRT. We defined PIPRT as radiotherapy (RT) aimed to improve cancer-related symptoms/provide durable local control in the non-curative setting. Mixed proton/photon plans were included. Adjacent re-irradiation (reRT) was defined as a reRT volume within the incidental dose cloud of a prior RT target, whereas direct reRT was defined as in-field overlap with prior RT target. Acute toxicity during RT until first inspection visit was graded according to the Common Terminology Criteria for Adverse Events. The Kaplan-Meier method, measured from last PIPRT fraction, was used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: Eighteen patients underwent PIPRT between 2014 and 2020. Median age at treatment start was 10 years [2-21]. Median follow-up was 8.2 months [0-48]. Treatment sites included: brain/spine [10], abdomen/pelvis [3], thorax [3], and head/neck [2]. Indications for palliation included: durable tumor control [18], neurologic symptoms [4], pain [3], airway compromise [2], and great vessel compression [1]. Indications for protons included: reRT [15] (three adjacent, 12 direct), craniospinal irradiation [4], reduction of dose to normal tissues [3]. Sixteen experienced grade (G) 1-2 toxicity; two G3. There were no reports of radionecrosis. Median PFS was 5.3 months [95% confidence interval (CI): 2.7-16.3]. Median OS was 8.3 months [95% CI: 5.5-26.3]. CONCLUSIONS: The most common indication for PIPRT was reRT to provide durable tumor control. PIPRT appears to be safe, with no cases of high-grade toxicity.

Salvage re-irradiation in non-melanoma skin cancers: A multicenter analysis.

BACKGROUND AND PURPOSE: We conducted a multicentre real-world study to assess the outcomes of radical salvage re-irradiation for non-melanoma skin cancer (nMSC) recurrences following definitive or postoperative radiotherapy. MATERIALS AND METHODS: Data on patients treated between 2006 and 2022 with re-irradiation for nMSCs were retrospectively collected from five high-volume brachytherapy centers. The primary endpoint was local control (LC). Secondary endpoints included overall survival, progression-free survival, and adverse events (AEs). The Kaplan-Meier estimator and Cox Proportional-Hazards Model were utilised in the analysis. RESULTS: A total of 58 patients with a median age of 78.4 years with recurrences of previously irradiated nMSC in the head and neck region were included in the analysis. The majority had cutaneous basal cell carcinoma (BCC; 91.4%), and were irradiated with high-dose-rate brachytherapy (HDR-BT; 91.4%). The most common locations included the nasal region (36.2%) and external ear (18.9%). The 1-year LC was 73.1% and decreased to 41.7% at three years. The size of the re-irradiated lesion was the single independent prognostic factor in Cox analysis (per mm; HR 1.07; 95% CI 1.04-1.11; p < 0.001). Grade 3 or worse AEs were reported in 7 cases (12.1%). CONCLUSION: Re-irradiation for nMSCs, predominantly administered with brachytherapy for radiorecurrent BCC, is associated with high recurrence rates, and the risk of failure significantly increases with the size of the treated lesion. Re-irradiation could be an option for selected elderly patients with small, localised, inoperable recurrences after RT to achieve local control or defer systemic treatment; however, prospective trials are necessary to confirm its safety and efficacy.

Stereotactic reirradiation with CyberknifeR for locally recurrent prostate cancer, long-term toxicity and clinical outcomes from a monocentric cohort.

PURPOSE: Up to 47% of patients with localized prostate cancer (PCa) treated with radiotherapy (EBRT) eventually develop local recurrence. To date, no clear consensus exists on optimal management. A growing body of interest supports the use of stereotaxic re-irradiation (rSBRT), with promising oncological outcomes and low toxicity profile. We collected a single-center case series of locally recurrent PCa who underwent re-irradiation after a previous course of postoperative or definitive radiotherapy. METHODS AND MATERIALS: Data from 101 patients treated at our institution for locally recurrent PCa from June 2012 to June 2021 were retrospectively collected. Patients underwent rSBRT with CyberKnife system (Accuray Inc., Sunnyvale, CA, USA), delivered to intraprostatic or macroscopic recurrences within the prostate bed, for a total dose of 30 Gy in 5 fractions. RESULTS: All patients received prior EBRT. The median EQD2 total dose was 75.0 Gy (range, 60-80 Gy). Thirty-two (32%) patients were receiving androgen deprivation therapy (ADT) after prior biochemical recurrence. After a median follow-up of 57.8 months, BR occurred in 55 patients (54.5%), with a median BR-free survival (BRFS) of 40.4 months (95% C.I. 34.3-58.3). Thirty-two patients (31.7%) developed metastatic disease, with a median metastasis-free survival (MFS) not reached. PSA ≥ 2.5 ng/ml and ADT were associated with worst BRFS (26.06 vs. 39.3 months, p = 0.03 and 22.7 vs. 27 months, p = 0.01, respectively). Castration-resistant status and ADT were found to be predictive of worst MFS (34.1 vs. 50.5 months, p = 0.02 and 33.5 vs. 53.1 months, p = 0.002, respectively). Concomitant ADT was confirmed as an independent factor for MFS (HR 4.8, 95% CI 1.5-10.6, p = 0.007). No grade > /2 adverse were recorded. CONCLUSIONS: After almost 5 years of follow-up, with a median BRFS of 40.4 months and no grade ≥ 2 AEs, CyberknifeR rSBRT proved effective and safe in a cohort of 101 patients affected by locally recurrent PCa.

Reirradiation versus systemic therapy versus combination therapy for recurrent high-grade glioma: a systematic review and meta-analysis of survival and toxicity.

PURPOSE: This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free survival (PFS), adverse effects (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG). METHODS: A search was performed on PubMed, Scopus, Embase and CENTRAL. Studies reporting OS, PFS, AEs and/or QoL and encompassing the following groups were included; reirradiation vs systemic therapy, combination therapy vs systemic therapy, combination therapy vs reRT, and bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy. Meta-analyses were performed utilising a random effects model. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-one studies (three randomised, twenty-eight non-randomised) comprising 2084 participants were included. In the combination therapy vs systemic therapy group, combination therapy improved PFS (HR 0.57 (95% CI 0.41-0.79); low certainty) and OS (HR 0.73 (95% CI 0.56-0.95); low certainty) and there was no difference in grade 3 + AEs (RR 1.03 (95% CI 0.57-1.86); very low certainty). In the combination therapy vs reRT group, combination therapy improved PFS (HR 0.52 (95% CI 0.38-0.72); low certainty) and OS (HR 0.69 (95% CI 0.52-0.93); low certainty). In the bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy group, adding bevacizumab improved PFS (HR 0.46 (95% CI 0.27-0.77); low certainty) and OS (HR 0.42 (95% CI 0.24-0.72; low certainty) and reduced radionecrosis (RR 0.17 (95% CI 0.06-0.48); low certainty). CONCLUSIONS: Combination therapy may improve OS and PFS with acceptable toxicities in patients with rHGG compared to reRT or systemic therapy alone. Particularly, combining bevacizumab with reRT prophylactically reduces radionecrosis. REGISTRATION: CRD42022291741.

Stereotactic Body Reirradiation in Gynaecological Cancer: Outcomes and Toxicities from a Single Institution Experience.

AIMS: To report toxicity profile, outcomes and quality of life (QoL) data in patients with recurrent gynaecological cancer who underwent stereotactic body radiotherapy (SBRT) retreatment. MATERIALS AND METHODS: Data from patients' folders were retrospectively extracted, focusing on the primary neoplasm, previous systemic therapies and previous radiotherapy. Concerning SBRT, the total dose (five daily fractions) was delivered with a linear accelerator using intensity-modulated radiotherapy techniques. Acute and late toxicities were assessed by the CTCAE 4.03 scale. QoL was evaluated according to the Cancer Linear Analogue Scale [CLAS1 (fatigue), CLAS2 (energy level), CLAS3 (daily activities)]. RESULTS: Between December 2005 and August 2021, 23 patients (median age 71 years, range 48-80) with 27 lesions were treated. Most patients had endometrial (34.8%), ovarian (26.1%) and cervical cancer (26.1%) as the primary tumour. The most common SBRT schedules in five fractions were 30 Gy (33.3%), 35 Gy (29.6%) and 40 Gy (29.6%). The median follow-up was 32 months (range 3-128). There were no patients reporting acute or late toxicities higher than grade 2, except for a bone fracture. One- and 2-year local control was 77.9% and 70.8%, respectively. One- and 2-year overall survival was 82.6% and 75.1%, respectively. The overall response rate was 96.0%. Regarding QoL, no statistically significant difference was identified between the baseline and follow-up values: the median CLAS1, CLAS2 and CLAS3 scores for each category were 6 (range 4-10) at baseline and 6 (range 3-10) 1 month after SBRT. CONCLUSIONS: This preliminary experience suggests that SBRT retreatment for recurrent gynaecological cancer is a highly feasible and safe treatment with limited side-effects and no short-term QoL impairment.

Reirradiation with stereotactic body radiotherapy for primary or secondary lung malignancies: Tumor control probability and safety analyses.

BACKGROUND: Reirradiation with stereotactic body radiotherapy (SBRT) for patients with primary or secondary lung malignancies represents an appealing definitive approach, but its feasibility and safety are not well defined. The purpose of this study was to investigate the tumor control probability (TCP) and toxicity for patients receiving reirradiation with SBRT. PATIENTS AND METHODS: Eligible patients with recurrence of primary or secondary lung malignancies from our hospital were subjected to reirradiation with SBRT, and PubMed- and Embase-indexed articles were reviewed. The patient characteristics, pertinent SBRT dosimetric details, local tumor control, and toxicities were extracted. The logistic dose-response models were compared for TCP and overall survival (OS) in terms of the physical dose and three-, four-, and five-fraction equivalent doses. RESULTS: The data of 17 patients from our hospital and 195 patients extracted from 12 articles were summarized. Reirradiation with SBRT yielded 2-year estimates of 80% TCP for doses of 50.10 Gy, 55.85 Gy, and 60.54 Gy in three, four, and five fractions, respectively. The estimated TCP with common fractionation schemes were 50%, 60%, and 70% for 42.04 Gy, 47.44 Gy, and 53.32 Gy in five fractions, respectively. Similarly, the 2-year estimated OS was 50%, 60%, and 70% for 41.62 Gy, 46.88 Gy, and 52.55 Gy in five fractions, respectively. Central tumor localization may be associated with severe toxicity. CONCLUSIONS: Reirradiation with SBRT doses of 50-60 Gy in 3-5 fractions is feasible for appropriately selected patients with recurrence of peripheral primary or secondary lung malignancies, but should be carefully considered for centrally-located tumors due to potentially severe toxicity. Further studies are warranted for optimal dose/fractionation schedules and more accurate selection of patients suitable for reirradiation with SBRT.

Re-Irradiation with Intensity-Modulated Radiation Therapy for the Treatment of Recurrent Cervical Cancer in the Pelvis: An Analysis of Outcomes and Toxicity.

Background and Objectives: Treatment options for most patients with recurrent cervical cancer within the previously irradiated field are limited. This study aimed to investigate the feasibility and safety of re-irradiation using intensity-modulated radiation therapy (IMRT) for patients with cervical cancer who experienced intrapelvic recurrence. Materials and Methods: We retrospectively analyzed 22 patients with recurrent cervical cancer who were treated with re-irradiation for intrapelvic recurrence using IMRT between July 2006 and July 2020. The irradiation dose and volume were determined based on the range considered safe for the tumor size, location, and previous irradiation dose. Results: The median follow-up period was 15 months (range: 3-120) and the overall response rate was 63.6%. Of the symptomatic patients, 90% experienced symptom relief after treatment. The 1- and 2-year local progression-free survival (LPFS) rates were 36.8% and 30.7%, respectively, whereas the 1- and 2-year overall survival (OS) rates were 68.2% and 25.0%, respectively. Multivariate analysis revealed that the interval between irradiations and gross tumor volume (GTV) were significant prognostic factors for LPFS. The response to re-irradiation showed borderline statistical significance for LPFS. The GTV and response to re-irradiation were also independent prognostic factors for OS. Grade 3 late toxicities were observed in 4 (18.2%) of the 22 patients. Recto- or vesico-vaginal fistula occurred in four patients. The irradiation dose was associated with fistula formation with borderline significance. Conclusions: Re-irradiation using IMRT is a safe and effective treatment strategy for patients with recurrent cervical cancer who previously received RT. Interval between irradiations, tumor size, response to re-irradiation, and radiation dose were the main factors affecting efficacy and safety.

Spinal Reirradiation-Mediated Myelopathy: A Systematic Review and Meta-Analysis.

Reirradiation of the spine is carried out in 42% of patients who do not respond to treatment or have recurrent pain. However, there are few studies and data on the effect of reirradiation of the spine and the occurrence of acute and chronic side-effects caused by reirradiation, such as myelopathy, in these patients. This meta-analysis aimed to determine the safe dose in terms of biological effective dose (BED), cumulative dose and dose interval between BED1 and BED2 to decrease or prevent myelopathy and pain control in patients undergoing radiation therapy in the spinal cord. A search was carried out using EMBASE, MEDLINE, PUBMED, Google Scholar, Cochrane Collaboration library electronic databases, Magiran, and SID from 2000 to 2022 to recognise qualified studies. In total, 17 primary studies were applied to estimate the pooled effect size. The random effects model showed that the pooled BED in the first stage, the BED in the second stage and the cumulative BED1 and BED2 were estimated at 77.63, 58.35 and 115.34 Gy, respectively. Studies reported on dose interval. The results of a random effects model showed that the pooled interval was estimated at 13.86 months. The meta-analysis revealed that using appropriate BED1 and/or BED2 in a safe interval between the first and second phases of treatment can have an influential role in preventing or reducing the effects of myelopathy and regional control pain in spinal reirradiation.

Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity.

BACKGROUND: Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity. MATERIAL AND METHODS: Between 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. RESULTS: Twenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53-1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89-1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%). CONCLUSION: Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

Magnetic resonance guided SBRT reirradiation in locally recurrent prostate cancer: a multicentric retrospective analysis.

AIMS: Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit. METHODS: Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up. RESULTS: Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/ß of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%). CONCLUSION: The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs).

Phase 1 Dose Escalation of Stereotactic Body Radiation Therapy and Concurrent Cisplatin for Reirradiation of Unresectable, Recurrent Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Patients with locoregional recurrence of squamous cell carcinoma of the head and neck (SCCHN) have relatively poor outcomes; therefore, stereotactic body radiation therapy (SBRT) has been investigated for this patient population. We performed a phase 1 clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin in previously irradiated locoregional SCCHN. METHODS AND MATERIALS: Patients with recurrent SCCHN who had previously undergone radiation therapy to doses ≥45 Gy to the area of recurrence ≥6 months before enrollment and who were not surgical candidates or refused surgery were eligible. SBRT was delivered every other day for 5 fractions. Starting dose level was 6 Gy × 5 fractions, followed by 7 Gy × 5 fractions and 8 Gy × 5 fractions. Chemotherapy consisted of cisplatin given before every SBRT fraction at a dose of 15 mg/m2. Patients were monitored for dose-limiting toxicities (DLT) that occurred within 3 months from the start of SBRT. Secondary endpoints included locoregional failure, distant metastasis, and overall survival. RESULTS: Twenty patients were enrolled, with 18 patients evaluable for endpoints. One patient at dose level 1 (30 Gy) died of unknown causes 2 weeks following completion of treatment. Therefore, an additional 3 patients were accrued to the 30-Gy dose level, with no further DLTs observed. Three patients were then accrued at dose level 2 (35 Gy) and 9 patients at dose level 3 (40 Gy) without DLTs. At a median follow-up of 9.5 months, cumulative incidence of locoregional failure at 2 years was 61% (95% confidence interval [CI], 12%-66%), cumulative incidence of distant metastasis was 11% (95% CI, 74%-100%) at 2 years, and overall survival was 22% (95% CI, 9%-53%) at 2 years. CONCLUSIONS: Concurrent cisplatin and reirradiation with an SBRT dose of ≤40 Gy was safe and feasible in patients with locoregionally recurrent or second primary SCCHN.

Salvage stereotactic reirradiation for intraprostatic cancer recurrence: A large retrospective study.

INTRODUCTION: Prostate cancer is the most common cancer in men. Thirty to forty-seven percent of patients treated with exclusive radiotherapy for prostate cancer will experience intraprostate recurrence. The use of radiotherapy in stereotactic conditions allows millimetric accuracy in irradiation to the target zone that minimizes the dose to organs at risk. In this study, we evaluated the clinical outcome of prostatic reirradiation with stereotactic body radiation therapy (SBRT) in patients with intraprostatic recurrence initially treated by radiotherapy. METHOD: This single-center retrospective study included 41 patients diagnosed with exclusive local recurrence of prostate cancer after radiotherapy and treatedby stereotactic Cyberknife irradiation. The objective of this study was to assess the efficacy and the safety of stereotactic reirradiation for patients with intraprostatic recurrence initially treated with radiotherapy. RESULTS: Median follow-up was 35 months. The 2-year biochemical relapse-free survival was 72.89%, the 2-year local recurrence free survival was 93.59%, the 2-year local regional recurrence-free survival was 85.24%, and the 2-year metastasis-free survival was to 91.49%. The analysis of toxicities showed a good tolerance of stereotactic irradiation. Urinary and gastro-intestinal adverse events was mostly of grades 1-2 (CTCAEv4). Grade 3 toxicity occurred in one to two patients. CONCLUSION: Stereotactic reirradiation appears effective and well-tolerated for local recurrence of prostate cancer and might allow to delay the introduction of hormonal therapy and its side effects.

Concurrent immunotherapy and re-irradiation utilizing stereotactic body radiotherapy for recurrent high-grade gliomas.

BACKGROUND: Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high-grade gliomas (rHGG) report 7%-20% 6-month progression-free survival (PFS), while re-irradiation demonstrates 28%-39% 6-month PFS. AIMS: We evaluate outcomes of patients treated with ICI and concurrent re-irradiation utilizing stereotactic body radiotherapy/fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy. METHODS AND RESULTS: Patients ≥18-years-old with rHGG (WHO grade III and IV) receiving ICI + SBRT or ICI monotherapy between January 1, 2016 and January 1, 2019 were included. Adverse events, 6-month PFS and overall survival (OS) were assessed. Log-rank tests were used to evaluate PFS and OS. Histogram analyses of apparent diffusion coefficient maps and dynamic contrast-enhanced magnetic resonance perfusion metrics were performed. Twenty-one patients with rHGG (ICI + SBRT: 16; ICI: 5) were included. The ICI + SBRT and ICI groups received a mean 7.25 and 6.2 ICI cycles, respectively. There were five grade 1, one grade 2 and no grade 3-5 AEs in the ICI + SBRT group, and four grade 1 and no grade 2-5 AEs in the ICI group. Median PFS was 2.85 and 1 month for the ICI + SBRT and ICI groups; median OS was 7 and 6 months among ICI + SBRT and ICI groups, respectively. There were significant differences in pre and posttreatment tumor volume in the cohort (12.35 vs. 20.51; p = .03), but not between treatment groups. CONCLUSIONS: In this heavily pretreated cohort, ICI with re-irradiation utilizing SBRT was well tolerated. Prospective studies are warranted to evaluate potential therapeutic benefits to re-irradiation with ICI + SBRT in rHGG.

Pain Response Rates After Conventional Radiation Therapy for Bone Metastases Assessed Using International Consensus Pain Response Endpoints: A Systematic Review and Meta-Analysis of Initial Radiation Therapy and Reirradiation.

Previous meta-analysis of conventional radiation therapy for painful bone metastases showed overall response (OR) rates of 72% to 75% (evaluable patients), 61% to 62% (intent-to-treat patients) for initial radiation therapy, and 68% for reirradiation (evaluable patients). However, the definition of pain response differed among the studies included. Hence, we conducted a systematic review and meta-analysis to determine the pain response rates assessed by the International Consensus Pain Response Endpoints (ICPRE) for both initial radiation therapy and reirradiation. The PubMed and Scopus databases were searched for articles published between 2002 and 2021. The inclusion criteria were (1) prospective studies or studies based on prospectively collected data and (2) studies in which pain response was assessed using ICPRE. Our primary outcomes of interest were the OR rates (sum of the complete and partial response rates) for both initial radiation therapy and reirradiation. Of the 6470 articles identified in our database search, 32 and 3 met the inclusion criteria for the analysis of initial radiation therapy and reirradiation, respectively. The OR rates of initial radiation therapy in evaluable patients (n = 4775) and intent-to-treat patients (n = 6775) were 60.4% (95% confidence interval [CI], 55.2-65.4) and 45.4% (95% CI, 38.7-52.4), respectively. The OR rates of reirradiation in evaluable patients (n = 733) and intent-to-treat patients (n = 1085) were 70.8% (95% CI, 15.7-96.9) and 62.2% (95% CI, 5.3-98.0), respectively. Subgroup analyses of initial radiation therapy including the comparison of randomized and nonrandomized studies showed no significant differences in any comparison, indicating similar response rates across different study designs. For initial radiation therapy, we determined the ICPRE-assessed response rates, which were lower than previously reported. The OR and complete response rates should be benchmarks for future randomized and nonrandomized studies. For reirradiation, the wide CIs demonstrate that the response rates based on ICPRE require further investigation.