Reirradiation In Patients Research Articles

Re-irradiation plus pembrolizumab: Phase II study for recurrent glioblastoma patients.

Radiation therapy may enhance anti-tumor immune responses by several mechanisms including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma. Sixty recurrent glioblastoma patients received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n=30) or with bevacizumab continuation (cohort B, n=30). Dual primary endpoints including overall response rate (ORR) and overall survival at either 12 (OS-12; cohort A) or six months (OS-6; cohort B) were assessed per cohort relative to historical benchmarks. Paired paraffin-embedded formalin-fixed tumor samples were assessed for immunologic biomarkers by immunohistochemistry using digital quantification and Co-Detection-by-InDEXing (CODEX). Study therapy was well tolerated with most toxicities being grade ≤ 3. For cohort B, the primary endpoint of OS-6 was achieved (57%), however survival was not improved for cohort A patients. The ORR was 3.3% and 6.7% for cohorts A and B, respectively. CODEX analysis of paired tumor samples from 5 patients revealed an increase of activated T cells in the tumor microenvironment after study therapy. Compared to historical controls, re-irradiation plus pembrolizumab appeared to improve survival among bevacizumab-refractory patients but not among bevacizumab-naïve patients. CODEX revealed evidence of intratumoral infiltration of activated immune effector cells. A randomized, properly controlled trial of PD-1 blockade plus re-irradiation is warranted to further evaluate this regimen for bevacizumab refractory patients, but alternative approaches are needed for bevacizumab-naïve patients.

REMIT: Reirradiation of diffuse midline glioma patients – a NOPHO feasibility study

Diffuse midline glioma (DMG) continues to be an aggressive brain stem cancer among children and young adults. It has a dismal prognosis with less than 10% of patients alive two years after diagnosis. Radiotherapy has been demonstrated to be effectful, albeit transient. Hence, radiotherapy is considered a cornerstone in the treatment. Reirradiation has, in retrospective studies, shown promising overall survival and palliative effect but no pan-European consensus for reirradiation exists. The REMIT (Reirradiation of diffuse Midline glioma paTients) protocol evaluates safety and the palliative efficacy of reirradiation of patients with DMG (clinicaltrials.gov NCT06093165). Patients included in the protocol will be followed with 1) performance status (Karnofsky or Lansky), 2) toxicity monitored with NCI Common Terminology Criteria for Adverse Events (CTCAE), 3) motor and functioning skill with PEDI-CAT (The Paediatric Evaluation of Disability Inventory) and 4) quantification of corticosteroid use. Furthermore, the impact on quality of life and well-being will be assessed qualitatively with interviews as well as with the Pediatric Quality of Life Inventory (PedsQl) Cancer Module questionnaire. The protocol also includes dose accumulation and contouring studies to assess standardization as well as a pre-screening log to address selection bias of patients. The safety and palliative efficacy of reirradiation in DMG will be prospectively evaluated, including qualitative patient reported outcomes, through the REMIT protocol. REMIT is planned to open for inclusion in 2024.

Pulsed Reduced Dose Rate Re-Irradiation for Patients with Recurrent Grade 2 Gliomas

Abstract BACKGROUND Patients with grade 2 glioma exhibit highly variable survival. Re-irradiation for recurrent disease has limited mature clinical data. We report treatment results of pulsed reduced dose rate (PRDR) radiation for patients with recurrent grade 2 glioma. METHODS A retrospective analysis of 58 patients treated with PRDR from 2000-2021 was performed. Radiation was delivered in 0.2 Gy pulses every three minutes encompassing tumor plus margin. Survival outcomes and prognostic factors on outcome were Kaplan Meier and Cox regression analyses. RESULTS The median survival from date of initial surgery was 8.6 years (95% CI 5.5-11.8 yrs). 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% CI 8.3-17.0 mo) and progression free survival was 6.2 months (95% CI 3.8-8.6 mo). Overall response rate based on post PRDR MRI was 36%. In patients who maintained grade 2 histology at recurrence, overall survival from PRDR was 22.0 months with five patients remaining disease free, the longest at 8.2 and 11.4 years. PRDR was generally well tolerated. CONCLUSIONS To our knowledge, this is the largest reported series of patients with recurrent grade 2 gliomas treated with PRDR radiation for disease recurrence. We demonstrate promising survival and acceptable toxicity profiles following re-irradiation. In the cohort of patients who maintain grade 2 disease, prolonged survival (>5 years) is observed in selected patients. For the entire cohort, 1p19q co-deletion, KPS, and longer time from initial diagnosis to PRDR were associated with improved survival.

Proton beam reirradiation for locally recurrent rectal cancer patients with prior pelvic irradiation.

The aim of the present study was to report the feasibility of proton beam reirradiation for patients with locally recurrent rectal cancer (LRRC) with prior pelvic irradiation. The study population included patients who were treated with proton beam therapy (PBT) for LRRC between 2008 and December 2019 in our institution. Those who had a history of distant metastases of LRRC, with or without treatment, before reirradiation, were excluded. Overall survival (OS), progression-free survival (PFS) and local control (LC) were estimated using the Kaplan-Meier method. Ten patients were included in the present study. The median follow-up period was 28.7months, and the median total dose of prior radiotherapy (RT) was 50Gy (range, 30Gy-74.8Gy). The median time from prior RT to reirradiation was 31.5months (range, 8.1-96.6months), and the median reirradiation dose was 72Gy (relative biological effectiveness) (range, 56-77Gy). The 1-year/2-year OS, PFS and LC rates were 100%/60.0%, 20.0%/10.0% and 70.0%/58.3%, respectively, with a median survival time of 26.0months. Seven patients developed a Grade 1 acute radiation dermatitis, and no Grade≥2 acute toxicity was recorded. Grade≥3 late toxicity was recorded in only one patient, who had developed a colostomy due to radiation-related intestinal bleeding. Reirradiation using PBT for LRRC patients who had previously undergone pelvic irradiation was feasible. However, the indications for PBT reirradiation for LRRC patients need to be considered carefully due to the risk of severe late GI toxicity.

Re-Irradiation in Squamous Cell Carcinoma of the Head and Neck

Abstract Background Re-irradiation as a therapeutic option for locoregional recurrence in patients with recurrent, persistent tumour or second primary malignant neoplasm has great advantages for locally advanced unresectable tumours. Methods We intended to characterise the patient pool that underwent re-irradiation and to perform a comparative analysis between previously known data related to prognostic factors with an impact on 2 years OS of these patients, and evaluate the therapeutic impact of re-irradiation in patients with recurrent, persistent tumour or second primary malignant neoplasm in the head and neck region, treated at the Radiotherapy Department in Portuguese Institute of Oncology in Coimbra (IPOC), from the year 2016 to 2020. Results A total of 39 patients were included in this study. All patients were submitted to both primary radiotherapy and re-irradiation with a median time interval between treatment of 20 months (minimum: 8 – maximum: 190). Only the time between irradiations was associated with a decrease in the risk of mortality (HR=0.828; CI 95% 0.731–0.939; p=.03). There were no significant differences in terms of toxicity severity between irradiations. Conclusion Re-irradiation is an important therapeutic alternative in the treatment of patients with malignant tumours in the head and neck region.

The role of FDG uptake to predict the need for re-irradiation in patients treated with 8 Gy (X-ray) single fraction palliative radiotherapy for bone metastases

The role of FDG uptake to predict the need for re-irradiation in patients treated with 8 Gy (X-ray) single fraction palliative radiotherapy for bone metastases

The Lyman Normal Tissue Complication Probability Model and Risk Prediction for Temporal Lobe Injury after Re-Irradiation in Patients with Recurrent Nasopharyngeal Carcinoma

The risk of temporal lobe injury (TLI) in recurrent nasopharyngeal carcinoma (rNPC) patients with intensity-modulated radiation therapy (IMRT) is high. We aimed to construct the normal tissue complication probability (NTCP) model for TLI of rNPC and establish a risk predictive model. We retrospectively analyzed 103 patients with rNPC who had received two courses of IMRT in our institution. The 206 temporal lobes (TLs) of these patients were randomly divided into a training (n = 144) and validation group (n = 62). We determined the mean value of the following parameters to construct the Lyman NTCP model: TD50(1) (the dose with a 50% probability of complications to an organ when all volumes are irradiated), m [steepness of the dose-response at TD50(1)], and n (the parameter related to volume effect). The most predictive dosimetric parameter and clinical variables were integrated in Cox proportional hazards models. A nomogram was developed for predicting risk of TLs. The parameters of the fitted NTCP model were TD50(1) = 107.84 Gy (95% confidence interval (CI), [97.15, 118.54]), m = 0.16 (95% CI, [0.14, 0.19]), and n = 0.04 (95% CI, [0.01, 0.06]). The cumulative dose delivered to 0.1 cm3 of temporal lobe volume (D0.1cc-c) was the most predictive dosimetric parameter for TLI. The Kaplan-Meier curves showed a significant difference in 2-year TLI-free survival among different risk groups according to the total score of nomograms. The TD50(1) of TLI in patients with rNPC is 107.84 Gy in Lyman NTCP model. The nomogram model can accurately predict the risk of TLI for individual.

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.

Anti-PD-1 immunotherapy with dose-adjusted ultra-hypofractionated re-irradiation in patients with locoregionally recurrent head and neck cancer

IntroductionPatients with recurrent inoperable squamous-cell head-neck cancer (HNSCC) after chemo-radiotherapy have an ominous prognosis. Re-irradiation can be applied with some efficacy and high toxicity rates. Anti-PD-1 immunotherapy is effective in 25% of patients. Immunogenic death produced by large radiotherapy (RT) fractions may enhance immune response.Materials and methodsWe evaluated the efficacy and tolerance of ultra-hypofractionated immuno-radiotherapy (uhypo-IRT) in 17 patients with recurrent HNSCC and 1 with melanoma. Four of HNSCC patients also had oligometastatic disease. Using a dose/time/toxicity-based algorithm, 7, 7 and 4 patients received 1, 2 and 3 fractions of 8 Gy to the tumor, respectively. Nivolumab anti-PD-1 immunotherapy was administered concurrently with RT and continued for 24 cycles, or until disease progression or manifestation of immune-related adverse events (irAEs).ResultsEarly and late RT toxicities were minimal. Three patients developed irAEs (16%). After the 12th cycle, 7/17 (41.2%) and 5/17 (29.4%) patients with HNSCC showed complete (CR) and partial response (PR), respectively. CR was also achieved in the melanoma patient. The objective response rates in HNSCC patients were 57%, 86% and 66%, after 1, 2 and 3 fractions, respectively (overall response rate 70.6%). Most responders experienced an increase in peripheral lymphocyte counts. The median time to progression was 10 months. The 3-year projected locoregional progression-free survival was 35%, while the 3-year disease-specific overall survival was 50%.ConclusionsAnti-PD1 uhypo-IRT is safe and effective in patients with recurrent HNSCC. The high objective response rates and the long survival without evidence of disease support further trials on uhypo-IRT.

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

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. 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. 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. 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.

Reirradiation for local recurrence of oral, pharyngeal, and laryngeal cancers: a multi-institutional study

This study aimed to examine the efficacy and toxicity of reirradiation in patients with locally recurrent oral, pharyngeal, and laryngeal cancers. We conducted a retrospective, multi-institutional analysis of 129 patients with previously irradiated cancer. The most frequent primary sites were the nasopharynx (43.4%), oral cavity (24.8%), and oropharynx (18.6%). With a median follow-up duration of 10.6 months, the median overall survival was 14.4 months and the 2-year overall survival rate was 40.6%. For each primary site, the 2-year overall survival rates were 32.1%, 34.6%, 30%, 60.8%, and 5.7% for the hypopharynx, oral cavity, larynx, nasopharynx, and oropharynx, respectively. Prognostic factors for overall survival were primary site (nasopharynx versus other sites) and gross tumor volume (GTV) (≤ 25 cm3 versus > 25 cm3). The 2-year local control rate was 41.2%. Twenty-four patients (18.6%) presented with grade ≥ 3 toxicities, including nine with hemorrhages that led to grade 5 toxicities in seven patients. All nine tumors that caused hemorrhage showed tumor encasement of the carotid ≥ 180 degrees and eight of nine tumors had larger GTV > 25 cm3. Reirradiation is a feasible treatment option for small local recurrence of oral, pharyngeal, and laryngeal cancers, with the requirement of a strict eligibility assessment for large tumors with carotid encasement.

Evaluation of Proton Therapy Reirradiation for Patients With Recurrent Head and Neck Squamous Cell Carcinoma

Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret. To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma. This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects. Proton therapy reirradiation. Follow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS. A total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10-pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P < .001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects. The findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Single Photon Emission Computed Tomography (SPECT) Functional Liver Imaging to Facilitate Reirradiation for Liver Malignancies: A Phase 1 Trial

<h3>Purpose/Objective(s)</h3> Functional imaging, such as Tc-99m- sulfur colloid single photon emission computed tomography (SPECT), may allow preferential sparing of functional liver volume and facilitate safe reirradiation. The primary objective of this study is to evaluate the safety of hypofractionated reirradiation for patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC) or liver metastases (LM) who received prior radiation with either external beam radiotherapy (EBRT) or yttrium-90 radioembolization (Y90 RE) when using SPECT functional liver imaging for planning. <h3>Materials/Methods</h3> This is a Phase I trial with a 3+3 design used to test three levels of dose constraints for safety. Eligible patients had a diagnosis of HCC, IHC or LM and received EBRT >/=12 months prior or Y90 RE >/=6 months prior. After giving informed consent, patients underwent simulation and subsequent SPECT scan in the treatment position. Functional liver was estimated based on 40% maximum intensity as threshold. The prescription dose was 45Gy-67.5Gy in 15 fractions. Composite constraints were bowel/duodenum/stomach Dmax <45Gy, esophagus Dmax <50Gy, common bile duct Dmax <60Gy, and V45Gy <10% for the heart. The mean functional liver dose constraint was <20Gy or 18Gy for patients treated with EBRT and Y90 RE, respectively. The volumetric dose constraint for functional liver volume receiving <22Gy depended on the dose level of trial enrollment: level 0 was ≥400cc, level -1 was 500cc and level +1 was 300cc. Dose limiting toxicities (DLTs), including grade 3 hypoalbuminemia, increase in INR, increase in bilirubin, ascites or hepatic failure as well as any grade 4 toxicity related to reirradiation, were assessed within 2 months after re-radiation. Any liver decompensation qualifying as a DLT was attributed to radiation therapy. The maximal dose constraint (MDC) is defined as the highest constraint level at which no more than one patient has experienced DLT in six patients treated at that dose constraint. <h3>Results</h3> A total of thirteen patients were enrolled between May 2018 and April 2021. The median [IQR] reirradiation GTV volume was 57cc [32-287cc]. The median [IQR] liver-minus-GTV and functional liver volumes were 1402cc [1141-1481cc] and 869 [784-1077], respectively. All plans spared >/=500ccs of functional liver from receiving ≥22Gy (median [IQR] 726 [637-783]). The median [IQR] mean function liver volume dose was 14.9Gy [10.4-18.6Gy]. The first 3 patients in dose level 0 and the next 3 patients treated in dose level +1 experienced no DLTs. Of the next seven patients treated using dose level +1 constraints, one developed a DLT possibly attributable to radiation. <h3>Conclusion</h3> SPECT functional imaging facilitates safe reirradiation for primary and metastatic liver tumors. Due to the ability to spare >/=500ccs of functional liver from >22Gy for all patients with only 1 of 13 patients experiencing DLT, we conclude this to be a reasonable constraint for reirradiation.

Safety and Efficacy of MR-Guided Re-Irradiation in Patients with GI Malignancies

<h3>Purpose/Objective(s)</h3> This study aimed to assess the safety of administering re-irradiation in the abdomen or pelvis with MR-guided radiation therapy to patients with primary gastrointestinal (GI) malignancies. <h3>Materials/Methods</h3> A retrospective analysis was performed on a total of 9 patients that received MR-guided re-irradiation from March 2018 to February 2022 at a single institution. Patients were re-irradiated with 5 fractions using a dose constraint to re-irradiated mucosal structures of V 20 Gy <1cc. Treatment and clinical parameters including staging, histology, prescription radiation dose, and time interval between radiation treatments were collected. Patients were monitored for acute and late toxicity. <h3>Results</h3> Majority of the patients had pancreatic adenocarcinoma (n=6; 66%) and localized disease (n=6; 66%). The median age at the time of re-irradiation was 58 years (range 36-84 years) and median follow-up was 16 months (range 0.4- 39 months). 8 patients had surgery following the first dose of radiation. The median time between radiation treatments was 11.6 months (range 6.8 -87.9 months). The mean prescription was slightly higher at the time of re-irradiation compared to the initial prescription dose). The mean total prescription was 158.0 Gy EQD2 equivalent dose (range 99.4 Gy – 200 Gy). Majority of the patients experienced no acute toxicity or grade 1 toxicity, including fatigue and abdominal pain. One patient experienced grade 2 abdominal cramping. Dose constraints were met in all patients. No patients had recurrence in the re-irradiated field. Two patients experienced additional recurrences in their initially radiated fields after re-irradiation. No patients experienced late toxicity. <h3>Conclusion</h3> MR-guided re-irradiation in patients with GI malignancies may be a safe alternative in select patients. Further studies are needed to optimize patient selection and safe dose constraints.

Implementation of a Special Medical Physics Consult Process for Re-Irradiation in Patients with Brain Tumors: Planning and Toxicity Outcomes

<h3>Purpose/Objective(s)</h3> We hypothesized that implementation of a systematic approach to re-irradiation (ReRT) using a special medical physics consult (SMPC) process would lead to acceptably low rates of high-grade toxicity associated with planning parameters impacting clinical management. <h3>Materials/Methods</h3> Consecutive patients treated using the ReRT-SMPC process during the first 18 months of its implementation were included. Accuracy of data set registration in the region of treatment was assessed by physics and verified by physician to generate cumulative physical and biologically corrected dose maps (equivalent dose in 2 Gy fractions EQD₂, alpha/beta 2.5 for normal tissue). Standardized dose discounts based on time interval from prior treatment and consistent guidelines for acceptable EQD₂ dose-limits per organ-at-risk (OAR) were used in all cases to provide allowable dose constraints prior to planning. Post-planning physics evaluation highlighted exceeded limits to assist clinical management. Comparison of planning parameters among patients with and without high-grade toxicity (grade 3 or higher) per CTCAE v5.0 was performed using 2-sided t-test and significance level 0.05. <h3>Results</h3> From April 2017 to September 2018, 261 consecutive patients underwent ReRT using this workflow, of whom 55 (21%) had brain tumors. ReRT with conventional fractionation (CFRT) was given to 47% primarily for gliomas (median EQD₂ 47 Gy (IQR, 41-56)), and with single or multi-fraction stereotactic radiosurgery in 53% primarily for brain metastases (median EQD₂ 100 Gy (IQR 57-120)). Median follow-up after ReRT among patients alive at time of analysis was 6.9 months (IQR, 5.3-10.8). No high-grade toxicity was observed in any delineated OAR including brainstem or optic structures. No specific normal brain constraint was employed in the SMPC process, and 5 (9%) patients experienced high-grade toxicity both early (cerebral edema, n=3) and late (necrosis, n=2). Cumulative EQD₂ was lower among patients with vs without toxicity (D0.03cc 87 vs 155 Gy, p=0.047), as 80% of patients with toxicity underwent ReRT with CFRT to larger volumes (39 vs 14 cc). While no constraints were applied for normal brain, recovery factors based on interval from index treatment were applied for all patients. However, no association with time interval was observed in patients with vs without toxicity (p=0.4). In two instances, the ReRT-SMPC analysis resulted in physician decision not to treat due to potential toxicity concerns. <h3>Conclusion</h3> Re-irradiation of primary and metastatic brain tumors using a standardized SMPC process yields low rates of high-grade CNS toxicity and meaningfully impacts physician decision-making. Future planning parameters including normal brain dose will be refined using this systematic process to improve the therapeutic ratio among patients undergoing re-irradiation.

Curative high-dose reirradiation for patients with recurrent head and neck squamous cell carcinoma using IMRT or proton therapy: Outcomes and analysis of patterns of failure.

To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. After a median follow-up of 41.3months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p=0.031). Main late grade ≥2 toxicities were dysphagia and trismus. Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.

DIPG-24. Neurological symptom improvement after re-irradiation in patients with diffuse intrinsic pontine glioma (DIPG): A retrospective analysis of the SIOP-E-HGG/DIPG project.

Abstract PURPOSE: To investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression. METHODS: Re-analysis of the SIOP-E retrospective DIPG cohort by investigating clinical benefits after re-RT with focus on the neurological triad. Patients were divided as "responding" or "non-responding" to re-RT. To assess the interdependence between patients’ characteristics and clinical benefits we used a Chi-Square or Fisher’s Exact test. Survival according to clinical response to re-RT was calculated by the Kaplan-Meier method. RESULTS: As earlier reported, 77% (n = 24/31) of patients had any clinical benefit after re-RT. Among 25/31 well documented patients, 44% (n=11/25) had improvement in cranial nerve palsies, 40% (n=10/25) in long-tract signs, 44% (11/25) in cerebellar signs. Clinical benefits were observed in at least 1, 2 or 3 out of 3 symptoms of the DIPG triad, in 64%, 40% and 24% respectively. Patients irradiated with a dose ≥ 20 Gy versus &amp;lt; 20 Gy may improve slightly better with regards of ataxia (67% versus 23%; P-value = 0.028). The survival from the start of re-RT to death was not different between responding and non-responding DIPG patients (P-value = 0.871). CONCLUSION: A median re-irradiation dose of 20 Gy provides a neurological benefit in two-third of patients with an improvement of at least one symptom of the triad. DIPG patients receiving ≥20 Gy appear to improve slightly better with regards of ataxia, however we need more data to determine whether dose escalation up to 30 Gy provides additional benefit.

Assessment of therapeutic outcome and role of reirradiation in patients with radiation-induced glioma

BackgroundWe sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and 2 mutation status in patients with radiation-induced glioma (RIG).MethodsWe retrospectively reviewed the clinical characteristics and treatment outcomes of 11 patients with high-grade glioma who satisfied Cahan’s criteria for RIG in our database during 2001–2021. IDH 1/2 mutations were analyzed by Sanger sequencing and/or pyrosequencing.ResultsThe RIGs included glioblastoma with IDH 1/2 wild-type (n = 7), glioblastoma not otherwise specified (n = 2), anaplastic astrocytoma with IDH1/2 wild-type (n = 1), and anaplastic astrocytoma not otherwise specified (n = 1). The median period from primary disease and RIG diagnosis was 17 years (range: 9–30 years). All patients underwent tumor removal or biopsy, 5 patients postoperatively received reirradiation combined with chemotherapy, and 6 patients were treated with chemotherapy alone. The median progression-free and survival times were 11.3 and 28.3 months. The median progression-free survival time of patients treated with reirradiation and chemotherapy (n = 5) tended to be longer than that of patients that received chemotherapy alone (n = 6) (17.0 vs 8.1 months). However, the median survival time was similar (29.6 vs 27.4 months). Local recurrence was observed in 5 patients treated with chemotherapy alone, whereas in 2 patients among 4 patients treated with reirradiation and chemotherapy. None of the patients developed radiation necrosis. In one case, the primary tumor was diffuse astrocytoma with IDH2 mutant, and the secondary tumor was glioblastoma with IDH 1/2 wild-type. Based on the difference of IDH2 mutation status, the secondary tumor with IDH 1/2 wild-type was diagnosed as a de novo tumor that was related to the previous radiation therapy.ConclusionsRIG can occur beyond 20 years after successfully treating the primary disease using radiotherapy; thus, cancer survivors should be informed of the long-term risk of developing RIG and the need for timely neuroimaging evaluation. Reirradiation combined with chemotherapy appears to be feasible and has favorable outcomes. Determining the IDH1/2 mutational status is useful to establish RIG diagnosis when the primary tumor is glioma.

Clinical outcomes of dose-escalated re-irradiation in patients with recurrent high-grade glioma.

Re-irradiation for recurrent gliomas is a controversial treatment option with no clear standard dose or concurrent systemic therapy. This series represents a single-institution retrospective review of patients treated with re-irradiation for recurrent high-grade glioma. After 2012, patients were commonly offered concurrent bevacizumab as a cytoprotective agent against radiation necrosis. Kaplan-Meier method was used to estimate overall survival and progression-free survival. Cox proportional hazards regression was used to identify factors associated with overall survival and progression-free survival. Between 2001 and 2021, 52 patients underwent re-irradiation for a diagnosis of recurrent high-grade glioma. 36 patients (69.2%) had a histologic diagnosis of glioblastoma at the time of re-irradiation. The median BED10 (biological equivalent dose 10 Gy) of re-irradiation was 53.1 Gy. Twenty-one patients (40.4%) received concurrent bevacizumab with re-irradiation. Median survival for the entire cohort and for glioblastoma at the time of recurrence patients was 6.7 months and 6.0 months, respectively. For patients with glioblastoma at the time of recurrence, completing re-irradiation (HR 0.03, P < .001), use of concurrent bevacizumab (HR 0.3, P = .009), and the BED10 (HR 0.9, P = .005) were predictive of overall survival. Nine patients developed grade 3-5 toxicity; of these, 2 received concurrent bevacizumab and 7 did not (P = .15). High dose re-irradiation with concurrent bevacizumab is feasible in patients with recurrent gliomas. Concurrent bevacizumab and increasing radiation dose may improve survival in patients with recurrent glioblastoma.

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer

PurposeAccelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation. Methods and MaterialsThis was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period. ResultsFrom 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience. ConclusionsAPBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.