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Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32-72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14-40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting.

Introduction: Anaplastic meningiomas, categorized as WHO grade 3 tumors, are rare and highly aggressive, accounting for 1-2% of all meningioma cases. Despite aggressive treatment, including surgery and Radiation, they exhibit a high recurrence rate and poor survival outcomes. The aggressive histopathological features emphasize the urgent need for effective management strategies. Methods: A retrospective multi-institutional analysis was conducted on patients with recurrent anaplastic meningioma who underwent re-irradiation between 2017 and 2023. Clinical, dosimetric, and outcome data were collected and analyzed, focusing on local control, progression free survival and treatment-related adverse events. Results: Thirty-four cases were analyzed, with a median follow-up 11 months after re-irradiation. Progression-free survival at 12 months was 61.9%, with higher doses correlating with better outcomes. Concomitant Bevacizumab improves progression-free survival and reduces the risk of radiation necrosis. CDKN2A homozygote deletion correlated with a higher risk of local failure. Symptomatic radiation necrosis occurred in 20.5% of cases, but its incidence was lower with concomitant Bevacizumab treatment. Conclusion: Re-irradiation presents a viable option for recurrent anaplastic meningioma despite the associated risk of radiation necrosis. Higher doses with concomitant Bevacizumab improve clinical outcomes and reduce toxicity. Individualized treatment approaches are necessary, emphasizing the importance of further research to refine management strategies for this challenging disease. [ABSTRACT FROM AUTHOR]

Purpose: Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. Methods: We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. Results: Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. Conclusion: Salvage re-irradiation is safe and effective and should be considered in patients with IRR. [ABSTRACT FROM AUTHOR]

Abstract Introduction Anaplastic meningiomas, categorized as WHO grade 3 tumors, are rare and highly aggressive, accounting for 1-2% of all meningioma cases. Despite aggressive treatment, including surgery and Radiation, they exhibit a high recurrence rate and poor survival outcomes. The aggressive histopathological features emphasize the urgent need for effective management strategies. Methods A retrospective multi-institutional analysis was conducted on patients with recurrent anaplastic meningioma who underwent re-irradiation between 2017 and 2023. Clinical, dosimetric, and outcome data were collected and analyzed, focusing on local control, progression free survival and treatment-related adverse events. Results Thirty-four cases were analyzed, with a median follow-up 11 months after re-irradiation. Progression-free survival at 12 months was 61.9%, with higher doses correlating with better outcomes. Concomitant Bevacizumab improves progression-free survival and reduces the risk of radiation necrosis. CDKN2A homozygote deletion correlated with a higher risk of local failure. Symptomatic radiation necrosis occurred in 20.5% of cases, but its incidence was lower with concomitant Bevacizumab treatment. Conclusion Re-irradiation presents a viable option for recurrent anaplastic meningioma despite the associated risk of radiation necrosis. Higher doses with concomitant Bevacizumab improve clinical outcomes and reduce toxicity. Individualized treatment approaches are necessary, emphasizing the importance of further research to refine management strategies for this challenging disease.

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. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of brain tumors in pregnant patients poses challenges, as the out‐of‐field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre‐treatment study that compared fetal dose exposure between intensity‐modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric‐modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment. Materials and methods: Pre‐treatment measurements of clinical plans, 3DCRT, VMAT, and IMPT, were conducted on a phantom. Measurements were performed using a device capable of neutron detections, closely following AAPM guidelines, TG158. For photon measurements, fetus shielding was utilized. On patient treatment days, which was determined to be proton treatment, shielding was used only during daily imaging for patient setup. Additionally, an in vivo measurement was conducted on the patient. Results: Measurements showed that IMPT delivered the lowest fetal dose, considering both photon and neutron out‐of‐field doses to the fetus, even when shielding was implemented for photon measurements. Additionally, the proton plans demonstrated superior treatment for the mother, a reirradiation case. Conclusion: The patient was treated with proton therapy, and the baby was subsequently delivered at full term with no complications. This case study supports previous clinical findings and advocates for the expanded use of proton therapy in this patient population. [ABSTRACT FROM AUTHOR]

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

We report the case of a 70‐year‐old woman with metastatic brain tumors who underwent surgical removal of the tumor and radiation necrosis. The patient had a history of colon cancer and had undergone surgical removal of a left occipital tumor. Histopathological evaluation revealed a metastatic brain tumor. The tumor recurred six months after surgical removal, followed by whole‐brain radiotherapy, and the patient underwent stereotactic radiosurgery. Six months later, the perifocal edema had increased, and the patient became symptomatic. The diagnosis was radiation necrosis and corticosteroids were initially effective. However, radiation necrosis became uncontrollable, and the patient underwent removal of necrotic tissue two years after stereotactic radiosurgery. Pathological findings predominantly showed necrotic tissue with some tumor cells. Since the vascular endothelial growth factor (VEGF) and hypoxia‐inducible factor‐1α (HIF‐1α) were expressed around the necrotic tissue, the main cause of the edema was determined as radiation necrosis. Differences in the expression levels and distribution of HIF‐1α and VEGF were observed between treatment‐naïve and recurrent tumor tissue and radiation necrosis. This difference suggests the possibility of different mechanisms for edema formation due to the tumor itself and radiation necrosis. Although distinguishing radiation necrosis from recurrent tumors using MRI remains challenging, the pathophysiological mechanism of perifocal edema might be crucial for differentiating radiation necrosis from recurrent tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment options for children with recurrent medulloblastoma are often limited due to extensive previously received treatments after initial diagnosis. Especially, repeated radiotherapy is associated with significant side-effects. In this study, we study the impact on survival of repeated radiotherapy at recurrence for patients with previous irradiation, as well as first irradiation at recurrence when no previous radiotherapy was applied. We find that repeated radiotherapy provides a short-time benefit in terms of survival, but survival ten years after recurrence is not significantly improved. At the same time, we find that applying radiotherapy at recurrence when patients received no previous irradiation did significantly improve survival, both short and long term. 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. [ABSTRACT FROM AUTHOR]

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

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Purpose: We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. Materials and methods: Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. Results: The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50–105 Gy2, 60–70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose). Conclusion: Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities. [ABSTRACT FROM AUTHOR]

Purpose of Review: Management of breast cancer is multidisciplinary, balancing local and systemic control between treatment modalities. Surgical, radiation, and medical therapies are combined to give the best prognosis. The goal of this review is to examine the advancements in radiotherapy in the treatment of breast cancer. Recent Findings: Published data supports the shortening of radiation schedules through ultrahypofractionation and utilizing new energy sources through proton beam radiation. Emerging techniques have minimized radiation dosage to organs at risk and skin when compared to traditional radiation sources and plans. Traditionally an ipsilateral breast tumor recurrence after breast conservation therapy necessitated mastectomy. Re-irradiation is now an alternative option with comparable outcomes. Summary: Advances in radiotherapy have contributed to more patients choosing breast-conserving surgery over mastectomy. This has prompted the investigation of alternative technologies and techniques to decrease toxicities, while maintaining oncologic efficacy [ABSTRACT FROM AUTHOR]

IntroductionHemangiopericytoma (HPC) in the central nervous system (CNS) is rare. Our report aims to present an HPC case with multiple surgeries at the lumbar spine, and demonstrates an effective treatment as salvage.Case reportIn this report, we present the case of a young girl with recurrent meningeal invasion of lumbar spinal HPC. The patient underwent multiple surgeries to remove the tumors, and adjuvant radiotherapy was administered after the initial resection. And it presented a pathological anaplastic transformation with subsequent accelerated recurrence. A combination therapy approach involving triple chemotherapy and sequential re-irradiation was found to be effective as salvage treatment at the third recurrence.ConclusionsSurgical resection remains the primary treatment modality for HPC in the spine, despite its high tendency for local recurrence and the risk of metastasis. For unresectable recurrent HPC, combining chemotherapy and sequential re-irradiation might be a highly effective, and safe reference regimen as the salvage treatment for the refractory case.

Objectives We present the case of a 37-year-old female who underwent partial resection in 2018 for a diffuse fibrillary astrocytoma (WHO II) that invaded almost the entire right cerebral hemisphere. The patient followed conventional radiotherapy and chemotherapy. She presents after 6 years of regularly follow-ups with left hemiparesis, intracranial hypertension syndrome and tumor recurrence on MRI. The patient underwent another surgical intervention and the new histopathological diagnosis was diffuse astrocytoma grade IV. Therapeutic options for these patients are limited considering the fact that a gross total resection or a conventional re-irradiation could impact the quality of life. Therefore, exploring new therapeutic methods, such as targeted molecular therapy like EGFR antagonists or proteasome inhibitors, or proton therapy, should be considered. Material and Methods We conducted extensive research in two public medical databases for information related to the molecular pathways and management of primary and recurrent malignant astrocytoma and relevant articles were selected. Subsequently, we correlated this information with our direct experience in our case and discussed the observed results. Results Treatment modalities for these patients include reintervention, re-irradiation and second line chemotherapeutics. In relapsing cases the goal of reintervention is both to alleviate symptoms and obtain tumoral tissue for immunohistochemical analysis for identification of the new mutations. Conventional re-irradiation for large lesions carries high risks of producing both short-term and long-term side effects, impacting the quality of life. Alternatively, proton therapy minimizes the risk of adverse events due to Bragg peak reducing the irradiation of the surrounding tissue. Conclusions Genetic characterization of these lesions can facilitate targeted molecular therapy and help in establishing the prognosis. Re-irradiation of malignant astrocytomas with proton therapy is an effective treatment measure allowing for comparable tumor control to conventional radiotherapy.

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.

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.

Abstract Background To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment. Methods We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors. Results The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group. Conclusions For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Introduction: Diffuse intrinsic pontine glioma (DIPG) is the most common malignant brainstem tumour in children. Despite advances in understanding its biology, current treatments have shown minimal impact on overall survival in this fatal disease. Focal radiotherapy (RT) is the only treatment proven to improve symptoms and extend progression-free survival. Albeit palliative, re-irradiation (rRT) has emerged as the best alternative for progressive disease. This study presents the Spanish experience with re-irradiation in DIPG. Results: Between April 2015 and December 2023, 44 paediatric patients with progressive DIPG underwent rRT in 16 Spanish institutions. Median time from diagnosis to progression was 9.9 months (range, 4.2–24.3 months). Median dose of rRT was 20 Gy (range, 18–40 Gy) in 2 Gy fractions (range, 1.3–4 Gy). Twenty-two patients (50 %) received other treatments besides RT. Clinical improvement was seen in 77.3 %, and radiological improvement in 60 %. Treatment was well tolerated (1 case toxicity >grade 2 related to rRT). Median overall survival was 15.5 months (range, 8.2–63.2 months), with a median time from rRT to death of 4.2 months (range, 0.6–10.3 months). Longer time between diagnosis and rRT (>10 months) and dose of rRT >20 Gy were statistically significantly correlated with better overall survival. There was no survival benefit in patients receiving additional treatments. Conclusions: Re-irradiation is safe and effective in progressive DIPG patients, not only improving symptoms but also prolonging survival. However, the ideal candidates for rRT remain undefined, as well as the best irradiation scheme. Prospective studies are needed.

Background: The optimal management strategy for recurrent glioblastoma (rGBM) remains uncertain, and the impact of re-irradiation (Re-RT) on overall survival (OS) is still a matter of debate. This study included patients who achieved gross total resection (GTR) after a second surgery after recurrence, following the GlioCave criteria. Methods: Inclusion criteria include being 18 years or older, having histologically confirmed locally recurrent IDHwt or IDH unknown GBM, achieving MRI-proven GTR after the second surgery, having a Karnofsky performance status of at least 60% after the second surgery, having a minimum interval of 6 months between the first radiotherapy and the second surgery, and a maximum of 8 weeks from second surgery to the start of Re-RT. Results: A total of 44 patients have met the inclusion criteria. The median OS after the second surgery was 14 months. All patients underwent standard treatment after initial diagnosis, including maximum safe resection, adjuvant radiochemotherapy and adjuvant chemotherapy. Re-RT did not significantly impact OS. However, MGMT promoter methylation status and a longer interval (> 12 months) between treatments were associated with better OS. Multivariate analysis revealed the MGMT status as the only significant predictor of OS. Conclusion: Factors such as MGMT promoter methylation status and treatment interval play crucial roles in determining patient outcomes after second surgery. Personalized treatment strategies should consider these factors to optimize the management of rGBM. Prospective research is needed to define the value of re-RT after second surgery and to inform decision making in this situation. [ABSTRACT FROM AUTHOR]

Background: Recurrence in glioblastoma lacks a standardized treatment, prompting an exploration of re-irradiation's efficacy. Methods: A comprehensive systematic review from January 2005 to May 2023 assessed the role of MRI sequences in recurrent glioblastoma re-irradiation. The search criteria, employing MeSH terms, targeted English-language, peer-reviewed articles. The inclusion criteria comprised both retrospective and prospective studies, excluding certain types and populations for specificity. The PICO methodology guided data extraction, and the statistical analysis employed Chi-squared tests via MedCalc v22.009. Results: Out of the 355 identified studies, 81 met the criteria, involving 3280 patients across 65 retrospective and 16 prospective studies. The key findings indicate diverse treatment modalities, with linac-based photons predominating. The median age at re-irradiation was 54 years, and the median time interval between radiation courses was 15.5 months. Contrast-enhanced T1-weighted sequences were favored for target delineation, with PET-imaging used in fewer studies. Re-irradiation was generally well tolerated (median G3 adverse events: 3.5%). The clinical outcomes varied, with a median 1-year local control rate of 61% and a median overall survival of 11 months. No significant differences were noted in the G3 toxicity and clinical outcomes based on the MRI sequence preference or PET-based delineation. Conclusions: In the setting of recurrent glioblastoma, contrast-enhanced T1-weighted sequences were preferred for target delineation, allowing clinicians to deliver a safe and effective therapeutic option; amino acid PET imaging may represent a useful device to discriminate radionecrosis from recurrent disease. Future investigations, including the ongoing GLIAA, NOA-10, ARO 2013/1 trial, will aim to refine approaches and standardize methodologies for improved outcomes in recurrent glioblastoma re-irradiation. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurately predicting survival in patients with cancer receiving palliative radiotherapy is important for clinical decision making in cancer care management and delivery. This remains a challenge due to the heterogeneity of cancer diagnoses and a wide variety of prognostic factors. This study aims to review the literature to identify prognostic factors for clinical use as well as prognostic tools available to clinicians treating this population of patients. Based on the literature, we formulated evidence-based recommendations for clinicians to implement into practice with the intention of improving prognostic accuracy and overall patient care. (1) Background: Prognostication in patients with cancer receiving palliative radiotherapy remains a challenge. To improve the process, we aim to identify prognostic factors in this population from the literature and offer evidence-based recommendations on prognostication in patients undergoing palliative radiotherapy for non-curable or advanced cancers. (2) Methods: A systematic review was performed on the medical literature from 2005 to 2023 to extract papers on the prognosis of palliative radiotherapy patients with advanced cancer. The initial selection was performed by at least two authors to determine study relevance to the target area. Studies were then classified based on type and evidence quality to determine final recommendations. (3) Results: The literature search returned 57 papers to be evaluated. Clinical and biological prognostic factors were identified from these papers to improve clinical decision making or construct prognostic models. Twenty prognostic models were identified for clinical use. There is moderate evidence supporting (i) evidence-based factors (patient, clinical, disease, and lab) in guiding decision making around palliative radiation; (ii) that certain biological factors are of importance; (iii) prognostication models in patients with advanced cancer; and that (iv) SBRT or re-irradiation use can be guided by predictions of survival by prognostic scores or clinicians. Patients with more favorable prognoses are generally better suited to SBRT or re-irradiation, and the use of prognostic models can aid in this decision making. (4) Conclusions: This evaluation has identified several factors or tools to aid in prognosis and clinical decision making. Future studies should aim to further validate these tools and factors in a clinical setting, including the leveraging of electronic medical records for data availability. To increase our understanding of how causal factors interact with palliative radiotherapy, future studies should also examine and include prediction of response to radiation as an outcome. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is globally the leading cancer in women, and despite the high 5-year survival rate the most frequent cause of cancer related deaths. Surgery, systemic therapy and radiotherapy are the three pillars of curative breast cancer treatment. However, locoregional recurrences frequently occur after initial treatment and are often challenging to treat, amongst others due to high doses of previous radiotherapy treatments. Radiotherapy can be combined with local hyperthermia to sensitize tumor cells to radiation and thereby significantly reduce the required radiation dose. Therefore, the combination treatment of mild local hyperthermia, i.e. locally heating of the tissue to 39-43°C, and reirradiation with a reduced total dose is a relevant treatment option for previously irradiated patients. The mechanisms of this effect in the course of the therapy are to date not well understood and will be investigated in the HISTOTHERM study. Methods and analyses: Patients with local or (loco)regional recurrent breast cancer with macroscopic tumors are included in the study. Local tumor control is evaluated clinically and histologically during the course of a combination treatment of 60 minutes mild superficial hyperthermia (39 - 43°C) using water- filtered infrared A (wIRA) irradiation, immediately followed by hypofractionated re-irradiation with a total dose of 20-24 Gy, administered in weekly doses of 4 Gy. Tumor and tumor stroma biopsies as well as blood samples will be collected prior to treatment, during therapy (at a dose of 12 Gy) and in the follow-up to monitor therapy response. The treatment represents the standard operating procedure for hyperthermia plus re-irradiation. Various tissue and blood-based markers are analyzed. We aim at pinpointing key mechanisms and markers for therapy response which may help guiding treatment decisions in future. In addition, quality of life in the course of treatment will be assessed and survival data will be evaluated. [ABSTRACT FROM AUTHOR]

Background: To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment. Methods: We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors. Results: The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group. Conclusions: For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) plays a fundamental role in the definitive treatment of carcinoma of the head and neck cancer, but loco regional relapse happens up to 40% of the patients despite optimal initial multidisciplinary treatment, as well as second neoplasmstumors. Management of these scenarios is challenging, as re-treating an already irradiated field has a narrow balance between disease control benefit and toxicity risk. We aimed to provide data of outcomes in terms of disease control, survival and toxicity of re-irradiated patients, to facilitate selection and stratification of those who could benefit more. Retrospective analysis of patients with loco-regional relapse or second primary head and neck carcinomastumor who were re-irradiated between 2009 and-2023 in a previously irradiated field (≥50 Gy) using 3D or IMRT/VMAT, and conventional fractionation. Data about event-free survival (EFS), overall survival (OS), acute and chronic toxicity according to CTCAEv54 wereas collected from clinical reports. Sixty patients were re-irradiated. Most of them (78%) were male and 98% were ECOG 1-0. Mean age at diagnosis was 60 years (median 59y, range 51-67y). First diagnosis tumor histology was SCC in 94% of the patients, and was alsowas the most frequent histology (98%) for the second primary alsotumor. Most common site for both, first and second tumortumor was oral cavity (49% and 38%, respectively). Time between two RT treatments was at least 2 years in 63% of the patients, with no patients treated with less than 6 month6-month period (mean time to second RT 40.4 months, median 30.5 months, range range 19.5-54.5 months). Most of the patient retreated underwent adjuvant RT (n=32, 58%), reaching a mean dose of 59.95Gy (70.00-48.40) in addition to concomitant chemotherapy (67%). Re-irradiation was more mostly used in an adjuvant context (55%). Systemic concomitant treatment was 65%, with preference for triweekly regimens (34%). After second treatment, 58% of the patients had complete response, 40% had a partial response or stable disease, and only one patient progressedhad progression. Mean total dose for re-irradiation was 60 Gy (median 60 Gy, range 54-70 Gy). Only 22 of the re-irradiation treatment volumes included cervical areas. IMRT/VMAT was the preferred treatment technique (76%). All treatments were normo-fractionated treatments. Mean follow up is was 2.7 years from the end of RT. All patients had at least a 6-months follow up. Acute toxicity after re- irradiation was very common (95%), occurring in 70% of the patients presented mucositis and 67% epithelitis. Long- term toxicity consisted of dysphagia (45 patients74), osteonecrosis (6 patients), fistula (5 patients), trismus (5 patients G3-4). Carotid rupture happened in one patient. Mean time to progression was 20.4 months. Kaplan Kaplan-Meier analysis for event- free survival (EFS) shows better outcomes in patients who received re-irradiation at least 2 years after the first irradiation, with a median time to event of 9.59 6 months (95%CI 4.14-9.92m) compared with 4.94 months in patients who had earlier re-irradiation (95%CI 6.14-22.11m), with no statistically significant differences (Figure 1). No statistically significant differences in time to event according to total dose of re-irradiation were seen, as well as between patients with adjuvant or radical intention. Median overall survival (OS) was 18.2 months (95%CI 14.061-40.1m) (Figure 2). At 51 months, 15 patients are still alive. OS is better in patients receiving RT more than 2 years after the first treatment (22.67 months vs 18.23 months), with differences maintained over the follow up. Patients who were treated with more than 50 Gy seem to have better median OS (19.7m vs 13.37m4m) without statistically significant differences. [Display omitted] Our analysis shows that patients with head and neck cancer with good performance status who undergo a re-irradiation treatment with curative intent present prolonged survival and disease control after the treatment, which seems benefited when second irradiation happens later than 2 years after the first course of RT, for both adjuvant and radical RT strategies. [ABSTRACT FROM AUTHOR]

Although re-irradiation as a therapeutic procedure has already been explored over a few decades, it still remains a field of various uncertainties, and the majority of retrospective clinical studies contain quite a lot of "blank points". The critical point of this therapy is the severity of the radiation response of the normal organs at risk, which limits the planned and delivered dose. Re-irradiation is often considered a palliative treatment, although the results of the stereotactic hypofractionation (SHRT) strongly suggest that it can easily be used with radical intent. While tolerance doses (TD) were more or less arbitrarily established (not estimated) many years ago, they have not been verified during the passing time, but at least accounted for the 3/3 or 1/3 volume of the organ at risk. Regarding the so-called "remembered dose", it becomes crucial when the primary and re-irradiated volume of normal organs overlap. Knowledge of that parameter contains many loopholes. Such "doses" have mainly been approximately deduced from experimental and some clinical studies, and for a few organs at risk only. Present review the selected studies including 8,427 recurrences reported in a small number of the retrospective studies providing complete factors and parameters of the primary and re- -irradiation procedures. The review's results are presented and discussed. In 2022, the ESTRO/EORTC experts council defined re-irradiation procedures including three therapeutic scenarios, which are presently discussed. That consensus provides at least the detailed basics to optimize and improve quantitative knowledge on re-irradiation, which is the major aim of this paper. [ABSTRACT FROM AUTHOR]

Objective: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. Results: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ ∑ D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ ∑ D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. Conclusions: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re‑irradiation with IMRT and we propose a EQD2_ ∑ D80 threshold of 137.035 Gy for the nasopharynx. [ABSTRACT FROM AUTHOR]

Purpose: Retrospective audit of recurrent glioma patients treated by different fractionation schedules and to validate the modified Combs prognostic score in Indian patient cohort. Materials and Methods: Between Jan 2009 and June 2022, 66 recurrent gliomas patients treated with standard adjuvant treatment--radiation (RT) ± temozolomide (chemotherapy)--and re-treated with RT (± chemotherapy) were categorized as per modified Combs prognostic criteria and outcomes were compared. Results: Sixty-six patients with recurrent gliomas who received reirradiation (re-RT) were audited--53% males; 61% Karnofsky performance status (KPS) =80 at time of re-RT; median age 41.5 years (range, 6 to 70 years); 67% <50 years; primary histology low-grade glioma in 33%; grade III 27%, grade IV 40%; initial median dose of 60 Gy equivalent dose in 2 Gy fractions (EQD2); maximum safe resection at recurrence 41%; mean and median follow-up 78 ± 51 months and 66 months. Mean time interval between RT was 46.4 ± 39 months. Mean planning target volume (PTV) volume in conventional RT (Conv-RT), hypofractionated RT (Hypo-RT), and ultra-hypofractionated RT (UF-RT) was 226.1 ± 140.7 mL, 162.8 ± 123.3 mL, and 143.3 ± 145.8 mL. Mean dose for Conv-RT, Hypo-RT, and UF-RT was 50 Gy (range, 40 to 60), 31 Gy (range, 20 to 40), and 20 Gy (range, 10 to 30). Mean overall survival (OS) in Conv-RT, Hypo-RT, and UF-RT cohort was 18.8 months (range, 2.4 to 76.8); 6.6 months (range, 2 to 17.4), and 13.9 months (range, 3 to 131.9). Median OS as per Combs criteria were 16.6 months (Group a), 24.6 months (Group b), 4.6 months (Group c), and 3 months (Group d). Significant survival benefit was with good KPS score (KPS >80 vs. <80; 20.46 vs. 5.25 months; p < 0.001), patients receiving salvage chemotherapy (20.46 vs. 6.96 months; p = 0.001), and patients received re-RT biological equivalent dose (BED3) >80 Gy (16.62 vs. 5.48 months; p = 0.03). Median overall survival (OS) in our patient cohort and Combs cohort in Group a was 16.6 and 19.5 months; Group b was 24.6 and 11.3 months; Group c was 4.7 and 8.1 months, and Group d was 2 and 5.5 months, respectively. Six months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 100%, 92%, 34%, 17% and 94%, 79%, 70%, 41%, respectively. Twelve months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 88%, 74%, 22%, 0% and 88%, 47%, 22%, 7%, respectively. Conclusion: Modified Combs prognostic factors predicts OS and is applicable in Indian subcontinent patient population. [ABSTRACT FROM AUTHOR]

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low a/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options. [ABSTRACT FROM AUTHOR]

Purpose: The Re-irradiation and the Breast Cancer Working Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey to provide an overview of the policies for breast cancer (BC) re-irradiation (re-RT) among the Italian radiotherapy (RT) centers. Methods: In October 2021, 183 RT centers were invited to answer a survey: after an initial section about general aspects, the questionnaire focused on radiation oncologists' (ROs) attitude toward re-RT in three different scenarios: ipsilateral breast tumor recurrence (IBTR) treated with second conservative surgery, IBTR treated with mastectomy and inoperable IBTR. Surveyed ROs were also asked to express their interest in being involved in a prospective trials. Results: Seventy-seven/183 (42.0%) centers answered the Survey, only one RO per center was requested to answer. In particular, 86.5% ROs declared to have performed "curative" re-RT for IBTR during the previous two years (2019–2020): 76.7% respondents administered re-RT after second BCS, 50.9% after mastectomy, and 48.1% for inoperable IBTR. Re-RT practice varied widely among centers in terms of treatment volumes, dose and fractionation schedules, techniques and dose-volume constraints for organs at risks (OARs). Forty-six participants (59.7%) expressed their interest in participating in a prospective study investigating BC re-RT. Conclusions: About one out of three RT centers in Italy delivered re-RT for IBTR. Nevertheless, practice of re-RT varied widely among centers highlighting the needs for prospective studies to improve knowledge in this field. [ABSTRACT FROM AUTHOR]

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

Abstract 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

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. [ABSTRACT FROM AUTHOR]

Background: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high‐dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F‐SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. Study Design: The F‐SHARP is a multi‐institutional two‐stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. Endpoints: The primary endpoint is the acute radiation‐related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease‐specific and overall survival, and health‐related quality of life, as measured by the International Prostate Symptom Score and 26‐item Expanded Prostate Cancer Index Composite instruments. Patients and Methods: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1–3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long‐term toxicity profile, quality of life, and compare single‐ vs multi‐fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers. [ABSTRACT FROM AUTHOR]

Background: Although re‐irradiation is increasingly used in clinical practice, almost no dedicated planning software exists. Purpose: Standard dose‐based optimization functions were adjusted for re‐irradiation planning using accumulated equivalent dose in 2‐Gy fractions (EQD2) with rigid or deformable dose mapping, tissue‐specific α/β, treatment‐specific recovery coefficients, and voxelwise adjusted EQD2 penalization levels based on the estimated previously delivered EQD2 (EQD2deliv). Methods: To demonstrate proof‐of‐concept, 35 Gy in 5 fractions was planned to a fictitious spherical relapse planning target volume (PTV) in three separate locations following previous prostate treatment on a virtual human phantom. The PTV locations represented one repeated irradiation scenario and two re‐irradiation scenarios. For each scenario, three re‐planning strategies with identical PTV dose‐functions but various organ at risk (OAR) EQD2‐functions was used: 1)reRTregular: Regular functions with fixed EQD2 penalization levels larger than EQD2deliv for all OAR voxels.2)reRTreduce: As reRTregular, but with lower fixed EQD2 penalization levels aiming to reduce OAR EQD2.3)reRTvoxelwise: As reRTregular and reRTreduce, but with voxelwise adjusted EQD2 penalization levels based on EQD2deliv. PTV near‐minimum and near‐maximum dose (D98%/D2%), homogeneity index (HI), conformity index (CI) and accumulated OAR EQD2 (α/β = 3 Gy) were evaluated. Results: For the repeated irradiation scenario, all strategies resulted in similar dose distributions. For the re‐irradiation scenarios, reRTreduce and reRTvoxelwise reduced accumulated average and near‐maximum EQD2 by ˜1–10 Gy for all relevant OARs compared to reRTregular. The reduced OAR doses for reRTreduce came at the cost of distorted dose distributions with D98% = 92.3%, HI = 12.0%, CI = 73.7% and normal tissue hot spots ≥150% for the most complex scenario, while reRTregular (D98% = 98.1%, HI = 3.2%, CI = 94.2%) and reRTvoxelwise (D98% = 96.9%, HI = 6.1%, CI = 93.7%) fulfilled PTV coverage without hot spots. Conclusions: The proposed re‐irradiation‐specific EQD2‐based optimization functions introduce novel planning possibilities with flexible options to guide the trade‐off between target coverage and OAR sparing with voxelwise adapted penalization levels based on EQD2deliv. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic MR-guided on-table adaptive radiotherapy (SMART) allows the precise delivery of high-dose radiation to tumors in great proximity to radiation-sensitive organs. The aim of this study is to evaluate the toxicity and clinical outcome in locally advanced or recurrent pancreatic tumors, with or without prior irradiation, treated with SMART. Methods: Patients were treated for pancreatic cancer (PC) using SMART technology to a prescribed dose of 50 Gy (BED10, 100 Gy) in five fractions, with daily on-table adaptation of treatment plan. Endpoints were acute and late toxicities, local control, local disease-free period, and overall survival. Results: A total of 54 PC patients were treated between August 2019 and September 2022, with a median follow-up of 8.9 months from SMART. The median age was 70.4 (45.2--86.9) years. A total of 40 patients had upfront inoperable PC (55% were locally advanced and 45% metastatic), and 14 had local recurrence following prior pancreatectomy (six patients also had prior adjuvant RT). Of the patients, 87% received at least one chemotherapy regimen (Oxaliplatin based, 72.2%), and 25.9% received ≥2 regimens. Except from lower CA 19-9 serum level at the time of diagnosis and 6 weeks prior to SMART in previously operated patients, there were no significant differences in baseline parameters between prior pancreatectomy and the inoperable group. On-table adaptive replanning was performed for 100% of the fractions. No patient reported grade ≥2 acute GI toxicity. All previously irradiated patients reported only low-grade toxicities during RT. A total of 48 patients (88.9%) were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for a median of 9 months (2.8--28.8); three had later local progression. Eight patients had regional or marginal recurrence. Six- and 12-month OS were 75.0% and 52.1%, respectively. Apart from mild diarrhea 1--3 months after SMART and general fatigue, there were no significant differences in toxicity and outcomes between post-pancreatectomy and inoperable groups. Conclusion: SMART allows safe delivery of an ablative dose of radiotherapy, with minimal treatment-related toxicity, even in previously resected or irradiated patients. In this real-world cohort, local control with complete response was achieved by 20% of the patients. Further studies are needed to evaluate longterm outcome and late toxicity. [ABSTRACT FROM AUTHOR]

Aim: To analyze the demographic profile, treatment outcome, and factors affecting them in multiple primary head and neck squamous cell cancer (MPHNSCC) patients. Materials and Methods: Hospital case records of patients with histopathology proven MPHNSCC registered in the radiation oncology department from January 2008 to December 2020 were retrospectively studied. Modified Warren–Gates criteria were used to define MPHNSCC. Demographic and clinical details were recorded and analyzed. Results: Twenty-seven patients had histopathology proven MPHNSCC. The median age at diagnosis of an index case was 50 years (minimum 26, maximum 70) with a male to female sex ratio of 22:5. Seventeen (62.96%) patients were tobacco users; either smoked or smokeless. The oral cavity was the commonest sub-site for both an index and second primary malignancy (22 patients; 81.48%) and the majority presented in a locally advanced stage of disease (10; 37.03% and 16; 62.95% for an index and second primary, respectively). The presentation was simultaneous, synchronous, and metachronous in 1 (3.7%), 2 (7.4%), and 24 (88.89%) patients, respectively. Two patients had three sites of MPHNSCC. The average duration of chronicity was 54.37 months (min. 8 and max. 156). MPHNSCC were ipsilateral in 10 (37.04%) patients and re-irradiation was planned for 22 (81.48%) patients with 50% treatment compliance. At the time of the last hospital visit, 18 (66.66%) patients were alive with disease, 7 (25.92%) patients were alive without disease, and 2 (7.40%) patients died of disease. Conclusion: A higher percentage of MPHNSCC originated from the oral cavity and the majority presented in the locally advanced stage of disease; despite the site being accessible to self-oral examination. Patient education and physician's awareness regarding the MPHNSCC are needed. [ABSTRACT FROM AUTHOR]

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.

Traditionally, external beam radiation therapy has a dogma pronouncing that re-irradiation of a region previously exposed to radical dose radiotherapy is contraindicated due to unacceptable risk to surrounding tissues. This edict is often zealously maintained to the detriment of certain, carefully selected patients that may benefit from re-irradiation. Liposarcoma is a high-grade malignancy with a poor prognosis and high rates of recurrence. A case is described of multiply recurrent liposarcoma that we treated with re-irradiation of an extended field encompassing the gross recurrent tumor mass and including the previously irradiated region. The patient had a very good cosmetic outcome and remained disease-free after 3 years of follow-up. The case demonstrates the potential to significantly improve patient care if established dogmas are challenged related to the re-irradiation of recurrent high-grade tumors. We propose that with careful patient selection, re-irradiation can be delivered safely to patients with recurrent tumors and contribute to improved clinical outcomes.

More than 1/3rd of head and neck cancer patients eventually fail loco-regionally or appear as second primary, despite ever-improving treatment options.1,2 Recommended potentially curative treatment options include salvage surgery if the disease is amenable to surgery, or reirradiation.2 Reirradiation of head and neck cancers presents a dilemma in terms of achieving adequate doses to the target, maintaining the organ-at-risks (OAR) dose constraints within limits, and managing toxicities emerging during and after the treatment.3–5 Intensity-modulated radiotherapy (IMRT) has slowly evolved to be the modality of choice for re-irradiation owing to its ability to improve disease control and reduce treatment-related toxicity.6 We present the data of re-irradiated head and neck cancer patients treated at our centre with IMRT. This was a retrospective single-arm observational analysis. Details of head and neck cancer patients treated at our hospital with re-irradiation were retrieved. After reviewing all the treatment records, the follow-up details were assembled. All the cases were treated with IMRT with or without concurrent chemotherapy. All the patients received radiation and re-irradiation with a dose-per-fraction of 1.8 to 2Gray with adjuvant or definitive intent, for five days a week for six weeks or above. The dose prescribed was preferably 60 – 66Gy in 30-33 fractions. Dose constraints used for OARs were: Spinal cord Dmax <=45Gy, and brainstem and optic apparatus Dmax <=54Gy.3,5 Special care was also taken to limit the cumulative dose of carotid arteries to <120Gy.7 The mean dose of parotid was limited at 23Gy, although target volume coverage was given priority, whenever the two were in proximity. Patients were immobilised using a 5-clamp head and neck thermoplastic mask. 3 mm slice thickness contrast-enhanced computed tomography (CT) images were obtained from vertex to 2 cm below the carina using Siemens Emotion 6 (Somatom, Germany). The treatment planning was done on MONACO (Version 5.11). The target volumes for definitive treatment were contoured as per ICRU 62.8 The decision to include nodes depended on certain factors: previous history of nodal positivity, nature of irradiation in the first radiotherapy schedule, nature and location of primary during second irradiation, definitive/adjuvant intent of re-irradiation, surgical resection of nodes, duration between the irradiation treatments, dose volumes used and dosimetric parameters achieved for OARs in the first radiotherapy. Patients were treated by using linear accelerator (Elekta Compact and Synergy; Elekta, Crawley, UK). All patients were followed up on a regular basis. Response assessment scans were done after 3 months of treatment completion. Overall Survival (OS) was defined time from start date of re-irradiation to the date of death or date of last clinical follow-up. Progression-free survival (PFS) was defined as interval from the start date of RT to any documented recurrence. Analysis was performed with the SPSS statistical (version 23.0; IBM, Armonk, NY, USA). All potential prognostic factors were analysed. the patients were divided into three prognostic subgroups using Multi-Institution Re-irradiation (MIRI) recursive partitioning analysis (RPA).9 Seventy-three cases were included in the final analysis. During the re-irradiation schedule, 34/73 cases were treated with definitive irradiation, whereas 39 cases were treated with postoperative adjuvant radiotherapy. Median interval between both the RT schedules was 55 months (range: 13-197). Median follow-up duration after re-irradiation was 23 months (range: 4-74). Median initial RT dose was 60 Gy (range: 58-66) and median re-irradiation dose was 60Gy (range: 54-66). The median initial RT and re-irradiation dose was 2Gy (range: 1.8-2). There were 41 events in PFS. The 2-year and 4-year PFS rates were 55.8% and 29.2%. The estimated 4-year DFS definitive re-irradiation versus adjuvant radiotherapy were 28.7 vs 29.3% (p-0.786). There was no statistically significant difference for 3-year OS of de novo versus post-operative cases (54.7 vs 56.3%, p-0.559). No significant differences in DFS or OS were elucidated for duration of re-irradiation for a 2-year period (48.6 vs 39.7, p-0.648) and 3-year period (3yr DFS – 48 vs 57.5%, p-0.091). Patients recurring within 2 years of primary radiation had poorer OS than those recurring after 2 years. (57.14 vs 49.25%, p-0.039). Patients with more than 3 high-risk factors during adjuvant reirradiation post-surgery had poor OS. (38.46 vs 31.5%, p-0.043). The number of cases in RPA Class I, II, and III were 16, 49 and 8, respectively. The 2-year DFS for Class I, II and III, were 62.5%, 59.7% and 12.5% (p<0.0001). Re-irradiation in head and neck cancers is tolerable and toxicities are acceptable. A larger cohort and a longer duration of study will help in discerning the factors that will help in reducing the toxicities and improving outcomes further. [ABSTRACT FROM AUTHOR]

As radiotherapy (RT) is fundamental for definitive treatment of head and neck carcinomas and novel modulated techniques permit more selected patients to be re-irradiated, we aimed to collect data about chronic and acute toxicity after second irradiation and evaluate correlation with dosimetric parameters, for future specification of organ at risk constraints. Retrospective analysis of 60 patients treated at our institution for loco-regional relapse or second primary head and neck tumor, re-irradiated between 2009 and 2023 to a previously irradiated location (>50Gy) using 3D or IMRT with a total dose of 60Gy (mean 60Gy, range 54-70Gy) at 2-2.1Gy/Fx. Data about acute and chronic toxicity was collected from clinical reports, according to CTCAEv5. We were able to evaluate dosimetric data about 59 patients. For data extraction, rigid registration was made with TPS Eclipse. Sum plan of both treatments was created (dose distribution were not converted to EQD2 because of TPS limitations) on the most recent CT scan. Dosimetric data were extracted using homemade script from API Eclipse. Planning and calculation system: Eclipse (v10-v15.6). Calculation algorithm: AAA for IMRT plans, Acuros XB for VMAT plans. Acute toxicity after re-irradiation was very common (95%). 70% presented mucositis (28 out of 32 were G1-2) and 67% epithelitis (35 out of 40 were G1-2). Chronic toxicity after second RT consisted of dysphagia (74,5% of the patients, with 23 patients requiring use of nasogastric tube (NGT) or Percutaneous Endoscopic Gastrostomy (PEG), of which 16 were attributed to RT toxicity and not to prior treatment sequelae), osteonecrosis (6 patients), fistula (5 patients), trismus (24% G1-2, 3.3% G3-4). Carotid rupture happened in one patient. Of 6 patients presenting osteonecrosis, 3 were grade 3, with no patients with grade 4 toxicity. Looking at the plan sum, these all three patients had received a total D0.035 > 100Gy to the mandible bone, and received a higher mean dose (113.7Gy vs 100.8Gy) to the mandible compared with patients who presented milder or no toxicity (Figure 1). For dysphagia, we analysed mean dose to pharynx constrictor muscles. We can see that those needing PEG/NGT (G3 toxicity) receive a higher mean dose (61Gy vs 53Gy) than those who don't need it. Of the 16 patients who required these interventions due to RT toxicity (not because of surgery sequelae or similar), the received dose is still higher (60.4Gy) than the mean dose received in patients without PEG or NGT (Figure 2). Univariate model showed that those who required NGT or PEG after re-irradiation because of RT toxicity present higher risk of events, with HR of 3.05 (1.57-5.92, p<0.001). No statistically significant differences were seen for treatment technique (IMRT vs 3D) or other variables, also for the multivariable analysis. [Display omitted] Toxicity after re-irradiation in head and neck càncer patients is not negligible. Despite acute effects are the most frequent ones, regarding long term toxicity, dysphagia is the most frequent and the one with more impact in the quality of life of the patient, but this, as well as the other toxicities are rare to have a severe presentation (G3 or more). Our data seems to show a correlation between dose to the mandible bone and G3 osteonecrosis, but interpretation must be cautious, as the limitations of this analysis include the rigid dose registration instead of deformable, no EQD2 dose summation and the relevance of anatomic variations due to surgeries and tumor growth. Further investigations regarding these issues could help to improve the management of re-irradiation dosimetry evaluation. [ABSTRACT FROM AUTHOR]

Abstract Purpose Local primary-recurrence of esophageal squamous cell carcinoma (ESCC) after definitive treatment has the potential for increasing overall survival with re-irradiation (Re-RT), especially with advanced technique. This study aimed to evaluate the efficacy and toxicities of Re-RT using intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) for local primary-recurrence of ESCC. Materials and methods A total of 130 ESCC patients with local primary-recurrence from Xijing hospital between 2008 and 2021 were enrolled and 30 patients underwent IMRT/VMAT based salvage Re-RT. Cox regression analysis was used to analyze the prognostic factors for overall survival (OS) and after recurrence survival (ARS). The toxicities of 30 patients receiving Re-RT were also assessed. Results The median OS and ARS of the 130 recurrent patients were 21 months (1−164 months) and 6 months (1−142 months). The 1-, 2-, and 3-year OS rates were 81.5%, 39.2%, and 23.8%, respectively. Besides, the 1-, 2-, and 3-year ARS rates were 30.0%, 10%, and 6.2%. Multivariate analysis showed that Re-RT ± chemotherapy (p = 0.043) and chemotherapy alone (p 12 months) and initial radiation dose (> 60 Gy) were significantly associated with improved OS. Radiation esophagitis (Grade 1–2) occurred in 16 patients and myelosuppression (Grade1−2) occurred in 10 patients. Grade 3 toxicities (radiation esophagitis and myelosuppression) were only 13.3%. There were no grade 4 toxicities. Conclusion Our results demonstrated that IMRT/VMAT-based Re-RT was an effective therapeutic option for ESCC patients with local primary-recurrence compared with chemotherapy alone or without any treatment. Re-RT had improved OS but unfavorable ARS.