Salvage Reirradiation Research Articles

Salvage Re-Irradiation Versus-Concurrent Chemoradiotherapy For Esophageal Squamous Cell Carcinoma Patients With Locally Relapse After Definitive Chemoradiotherapy

This retrospectively study aimed to investigate the effects of re-irradiation therapy (re-RT) and re-concurrent chemoradiotherapy (re-CCRT) with the precise radiation techniques for the patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy. From January 2008 to December 2016, 109 patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy were involved in the study. Of all, patients with time to recurrence (TTR) over 24 months and ≤24 months were 36 (33.0%) and 73(77.0%) cases. Seventy-five (68.8%) patients had a recurrence of the esophagus and 34 (31.2%) patients suffered from local relapse and regional lymph node metastasis. Re-irradiation dose ranged from 45Gy to 61.2Gy. There were 79 (72.5%) patients treated with re-RT and 30 (27.5%) patients underwent re-CCRT. The objective response rates (ORRs) of the re-RT group and re-CCRT group were 62.0% and 70.0% (χ2 = 0.602, p = 0.438), and improvement rates of dysphagia (DIR) of the two groups were 65.7% and 56.0% (χ2 = 0.731, P = 0.393), respectively. The median survival time (MST) and 1-, 2-, 3-, 5-years survival rates in all patients were 8.0 months and 32.1%,16.5%, 8.3%, 3.7%, respectively. MST and 1-, 2-, 3-years survival rates were 8.0 months and 30.4%, 13.9%, 5.7% for re-RT versus 7.0 months and 33.3%, 23.3%, 16.6% for re-CCRT (χ2 = 2.085, p = 0.149). The MST in re-irradiation dose of ≤50Gy, >50to≤54Gy, and >54Gy groups were 6.0, 10.0 and 8.0 months, respectively (χ2 = 6.385, P = 0.041). The 1-, 2- and 3-years survival rates were 41.7%, 22.2% and 11.1% for patients with TTR over 24 months, which is significantly longer than those of 26.0%, 13.7% and 7.8% for patients with TTR ≤24 months (χ2 = 6.172, P = 0.013). Multivariate analysis showed that TTR was the independent factor for overall survival (hazard ratio, 0.573; 95% confidence interval, 0.365-0.900; P = 0.016).There was no significant difference between re-RT and re-CCRT groups in pneumonitis of grade ≥2, radiation esophagitis of grade 2-3 and the esophageal fistula (χ2 = 0.248, p = 0.619; χ2 = 0.509, P = 0.808; and χ2 = 0.030, P = 0.862). The morbidity of grade ≥2 myelosuppression was much lower in re-RT group than in re-CCRT group (3.7% vs 36.7%; χ2 = 18.151, p<0.001). Salvage re-irradiation therapy could be a treatment choice for patients with local relapse of esophagus after definitive chemoradiotherapy owing to ORR and improving dysphagia. However, overall survival still remains poor. Re-CCRT shows a higher toxicity of myelosuppression than re-RT. Re-radiation dose of >50 to ≤54Gy may be suitable for locally relapse patients as salvage. Patient with TTP over 24 months is a favorable factor for dim survival.

Prospective Longitudinal Assessment of Quality of Life and Activities of Daily Living as Patient-Reported Outcome Measures in Recurrent/Progressive Glioma Treated with High-dose Salvage Re-irradiation

AimsTo evaluate quality of life (QOL) and activities of daily living (ADL) longitudinally in patients treated with salvage re-irradiation for recurrent/progressive glioma. Secondary end points included post-re-irradiation survival. Materials and methodsPatients with diffuse glioma, aged 18–70 years with preserved performance status and unequivocal evidence of recurrence/progression with a minimum 2-year time interval from index radiation therapy were eligible. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and brain cancer module (BN20). ADL was assessed using a modified Barthel's index. Assessments were carried out longitudinally, first before re-irradiation, at completion of re-irradiation and subsequently periodically on follow-up. Summary scores were calculated from raw scores as per the EORTC scoring manual; higher functional scores and lower symptom scores indicating better QOL. Summary mean scores for the modified Barthel's index were also calculated, with lower scores indicating higher disability. Differences between the summary scores at different time points were tested using the Friedman test. ResultsIn total, 225 assessments were carried out in 60 patients accrued on the study. A significant improvement in scores was noted for physical function (P < 0.001), emotional function (P = 0.002), cognitive function (P = 0.009) and social functioning (P = 0.047) over time. Role function scores (P = 0.182) and global health status scores (P = 0.074) remained stable. Among symptom scores, fatigue showed a statistically significant improvement over time (P = 0.01), whereas other symptom scores remained largely stable. There was a significant increase in the modified Barthel's index score over time (P = 0.001), suggesting greater functional independence. At a median follow-up of 12.9 months, the 1-year Kaplan–Meier estimates with 95% confidence intervals of post-re-irradiation progression-free survival and overall survival were 45.1% (31.5–58.7%) and 62.2% (49.2–75.2%), respectively. ConclusionsHigh-dose salvage re-irradiation in carefully selected patients with recurrent/progressive glioma is associated with stable QOL (preserved functional domains and reduced symptom burden) and improvement in ADL (greater functional independence) over time with encouraging survival outcomes.

Savoir « passer la main » devant une situation complexe

Seeking a second medical advice as a medical practitioner is a frequent situation that should be facilitated to best suit patients’ expectations, while maintaining medical confidentiality. The patient and his relatives need to be involved with diagnostic and therapeutic procedures. The radiation oncologist should accept and help a patient who seeks a second advice, and patients will always appreciate when the physician helps them to seek such an advice. Examples that each practitioner should know include tertiary centers tumor boards, centers with access to innovation or clinical research, or with special teams to take care of specific populations such as adolescents and young adults. In some situations, no treatment can also be the best treatment, and it takes time to explain and discuss such watchful waiting strategies to patients. In case of recurrent disease after radiotherapy, salvage reirradiation must be discussed at a tertiary tumor board and weighed against other options, especially for rare and complex cases. Radiation oncology has gained multiple options with technological advances, such as proton therapy, brachytherapy, stereotactic body radiotherapy with respiratory tracking or contact therapy. Radiation oncologists must know the benefits associated with each option in terms of survival, local control or organ preservation in order to address patients to the best practitioner.

The Management of rNPC: Salvage Surgery vs. Re-irradiation.

Treatment failure, in the form of either persistence or local recurrence, occurs in 10 to 30% of nasopharyngeal carcinoma patients after initial radiotherapy (RT). Early detection of persistent or recurrent disease aids in the recognition of tumors that can be candidates for salvage nasophayngectomy or re-irradiation. There is no consensus till now on the indications or selection of the above two salvage treatment. In recent years, there has been a paradigm shift from open to endoscopic approach for nasopharyngectomy, which carries nearly no complications. For salvage re-irradiation, intensity-modulated radiotherapy (IMRT) is the most commonly indicated modality. Compared to IMRT, salvage endoscopic nasopharyngectomy may be more beneficial in terms of prolonging survival, improving quality of life, and minimizing treatment-related complications and medical costs in a selected subset of recurrent nasopharyngeal carcinoma (rNPC) patients. Salvage nasopharyngectomy should be the mainstay of treatment for rNPC.

Intra-operative radiation therapy as salvage treatment option for recurrent glioblastoma multiforme.

2535 Background: Glioblastoma multiforme (GBM) is an extremely aggressive cerebral tumor with poor prognosis. The majority of patients relapse after the initial surgery plus adjuvant radiation and chemotherapy. In case of recurrence there is no established standard therapy. The optimal techniques for salvage re-irradiation are unclear, so that procedure poses a challenge. In contrast to traditional external beam radiotherapy (EBRT) intra-operative radiotherapy (IORT) may improve patient’s outcome at the cost of minimal side effects and short treatment duration. Methods: A total of 30 patients were treated with recurrent GBM between August 2016 and June 2019. All patients underwent maximal safe resection; patients were divided into IORT and EBRT groups. 15 patients were included in each group with similar clinical characteristics. All patients in IORT group underwent maximal safe microsurgical resection with subsequent intraoperative balloon electronic brachytherapy (IBEB) and no further adjuvant treatment. IBEB was performed using Axxent electronic brachytherapy device (Xoft Electronic Brachytherapy (eBx) System, USA. Patients in EBRT group underwent same surgery followed by external beam radiotherapy. Contrast-enhanced brain MRI with perfusion was performed within 24 hours of surgery +/- brain PET-CT with 18-FDOPA and then every 3 months. Both groups were also assigned to subgroups (≤ 2.5cm3 and &gt; 2.5cm3) based on post-operative contrast-enhancing volume (POCEV). Median overall survival (OS) since diagnosis and local progression-free survival (locPFS) following the second surgery were analyzed. Possible toxicities and prognostic factors were also evaluated. Results: Median OS was 27 months in IORT group and 21 months in EBRT group. The locPFS range between 3.5 to 39 months in IORT group and only 2 to 10 months in group with EBRT. Kaplan-Meier OS curves in patients with POCEV ≤ 2.5cm3 showed more favorable outcomes for patients in the IORT group (p &lt; 0.05). In patients with POCEV &gt; 2.5cm3 the median OS was 17 months in IORT group and 13.5 months in EBRT group. Conclusions: IORT of recurrent GBM is feasible and provides encouraging local progression-free and overall survival; no high-grade radiation induced toxicities occur and further studies to establish this method are mandatory. The toxicity profile of additional IBEB was manageable. Maximal safe microsurgical resection is the most important prognostic factor and could determine the effectiveness of post-surgical IBEB.

MP67-08 SALVAGE ROBOT ASSISTED RADICAL PROSTATECTOMY VS SALVAGE RE-IRRADIATION FOR PATIENT WITH RADIO-RECURRENT PROSTATE CANCER AFTER PRIMARY RADIOTHERAPY: ONCOLOGICAL OUTCOMES

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy III (MP67)1 Apr 2020MP67-08 SALVAGE ROBOT ASSISTED RADICAL PROSTATECTOMY VS SALVAGE RE-IRRADIATION FOR PATIENT WITH RADIO-RECURRENT PROSTATE CANCER AFTER PRIMARY RADIOTHERAPY: ONCOLOGICAL OUTCOMES Damiano Vizziello*, Ettore Di Trapani, Dario Zerini, Damaris Patricia Rojas, Francesco Alessandro Mistretta, Stefano Luzzago, Giulia Marvaso, Andrea Conti, Giulia Garelli, Giovanni Cordima, Giuseppe Petralia, Matteo Ferro, Victor Deliu Matei, Barbara Alicja Jereczek, Gennaro Musi, and Ottavio de Cobelli Damiano Vizziello*Damiano Vizziello* More articles by this author , Ettore Di TrapaniEttore Di Trapani More articles by this author , Dario ZeriniDario Zerini More articles by this author , Damaris Patricia RojasDamaris Patricia Rojas More articles by this author , Francesco Alessandro MistrettaFrancesco Alessandro Mistretta More articles by this author , Stefano LuzzagoStefano Luzzago More articles by this author , Giulia MarvasoGiulia Marvaso More articles by this author , Andrea ContiAndrea Conti More articles by this author , Giulia GarelliGiulia Garelli More articles by this author , Giovanni CordimaGiovanni Cordima More articles by this author , Giuseppe PetraliaGiuseppe Petralia More articles by this author , Matteo FerroMatteo Ferro More articles by this author , Victor Deliu MateiVictor Deliu Matei More articles by this author , Barbara Alicja JereczekBarbara Alicja Jereczek More articles by this author , Gennaro MusiGennaro Musi More articles by this author , and Ottavio de CobelliOttavio de Cobelli More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000947.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To compare oncological outcomes after salvage Robot Assisted Radical Prostatectomy (S-RARP) or salvage re-irradiation (S-RT) in patients with radiation-recurrent prostate cancer (rrPCa) after primary external beam radiation therapy (EBRT) or brachytherapy (BT). METHODS: We retrospective identified 74 patients with rrPCa (2010-2016). Of those, 54 (73 %) vs. 20 (27 %) were previously treated with EBRT vs. BT. All patients with rrPCa were diagnosed with PSA raising and choline PET (showing non-metastatic disease), or multiparametric MRI followed by prostate biopsy in both groups. Overall, 29 (40%) vs. 45 (60%) patients were treated with S-RARP vs. S-RT. All S-RARP were non Nerve Sparing with extended bilateral pelvic limph node dissection, while S-RT patients underwent intensity modulated or stereotactic radiation therapy on the prostate with a 25 to 30 Gy dose divided in 5 to 6 fractions. Kaplan-Meier plots depicted progression free (PFS), cancer-specific (CSS) and overall (OS) rates over time in S-RARP vs. S-RT patients. The cut off for Biochemical Relapse (BCR) after S-RT was assessed as PSA nadir after RT + 2 ng/ml, according to the Philadelphia criteria, while for S-RARP was 0,1 ng/ml. RESULTS: Compared to S-RARP, patients treated with S-RT were older (75.8 vs. 67 years; p=0.001). Overall, 16 (55%) vs. 23 (52%) and 13 (45%) vs. 22 (48%) patients treated with S-RARP vs. S-RT had a primary diagnosis of ISUP GG1 and ISUP GG 2 PCa before primary RT (p=0.7). Median time from primary RT to salvage treatment was, respectively, 65.5 (IQR 26.55 - 90.15) vs 102.6 (IQR 78.4 – 130.6) months for S-RARP vs S-RT (P= 0.001). Median time follow-up after salvage treatment was 41.5 months. Overall, 11 (39.3%) vs. 22 (56.4%) patients had biochemical recurrence after S-RARP vs. S-RT (p=0.1). Moreover, CSM and OCM rates were, respectively, 0(0 %) vs. 6 (13 %) (p=0,04) and 0 (0 %) vs. 6 (13 %) (p= 0,04) in patients treated with S-RARP vs. S-RT. CONCLUSIONS: S-RARP and S-RT appears to achieve the same rates of cancer control in patient swith radio-recurrent prostate cancer after primary RT. Despite this, randomized control trials are needed to confirm these results. Source of Funding: none. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1028-e1028 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Damiano Vizziello* More articles by this author Ettore Di Trapani More articles by this author Dario Zerini More articles by this author Damaris Patricia Rojas More articles by this author Francesco Alessandro Mistretta More articles by this author Stefano Luzzago More articles by this author Giulia Marvaso More articles by this author Andrea Conti More articles by this author Giulia Garelli More articles by this author Giovanni Cordima More articles by this author Giuseppe Petralia More articles by this author Matteo Ferro More articles by this author Victor Deliu Matei More articles by this author Barbara Alicja Jereczek More articles by this author Gennaro Musi More articles by this author Ottavio de Cobelli More articles by this author Expand All Advertisement PDF downloadLoading ...

Extent of re-excision, sequence/timing of salvage re-irradiation, and disease-free interval impact upon clinical outcomes in recurrent/progressive ependymoma.

To report clinical outcomes of salvage re-irradiation (re-RT) in recurrent/progressive ependymoma. Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive ependymoma were analyzed retrospectively. The linear-quadratic model was used to provide estimates of biologically effective dose (BED) of irradiation using an α/β value of 2 for late CNS toxicity for each course of irradiation and summated to derive cumulative BED without correcting for the assumed recovery. A total of 55 patients (median age 10years at index diagnosis) treated with curative-intent re-RT between 2010 and 2018 were included. Median time to first recurrence was 29months with an inter-quartile range (IQR) of 16-64months. Majority (n = 46, 84%) of patients underwent surgical re-excision of recurrent disease. Median interval from first course of irradiation (RT1) to second course (RT2) was 35months (IQR = 26-66months) with a median re-RT dose of 54Gy in 30 fractions (range 40-60Gy), resulting in median cumulative equivalent dose in 2Gy fraction (EQD2) of 106.2Gy (range 92.4-117.6Gy). Volume of re-RT was based on location and pattern of relapse, comprising uni-focal (n = 49, 89%), multi-focal (n = 3, 5.5%), or craniospinal irradiation (CSI) in 3 (5.5%) patients respectively. Thirty-six (66%) patients received platinum-based salvage chemotherapy either before or after RT2. At a median follow up of 37months (range 6-80months), the Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) for the entire study cohort were 40% and 51% respectively. Gross total resection at recurrence; early salvage re-RT (prior to chemotherapy, if any); and longer (> 2years) disease-free interval (DFI) were associated with better survival outcomes. Salvage re-RT was generally well tolerated with only 3 (5.5%) patients developing symptomatic radiation necrosis necessitating corticosteroids. Extent of re-excision, sequence/timing of re-RT, and DFI impact upon outcomes in curative-intent, multi-modality salvage therapy for recurrent ependymoma.

Helical tomotherapy re-irradiation for patients affected by local radiorecurrent prostate cancer.

Salvage re-irradiation in patients affected by radiorecurrent prostate cancer might be a valid as well as challenging treatment option. The aim of this study was to evaluate feasibility and toxicity of salvage external beam radiotherapy (EBRT) re-treatment in patients affected by radiorecurrent prostate cancer within the prostate gland or the prostate bed. 15 patients underwent EBRT re-treatment using helical tomotherapy (HT), with daily Megavolt computed tomography image-guidance. We registered toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Biochemical relapse was defined as a PSA increase > 20% compared with the pre-EBRT re-treatment value. Survival curves were calculated using the Kaplan-Meier method. All patients received a total dose of 50Gy (25×2Gy), and 7 (46.6%) had concomitant androgen deprivation therapy (median duration of 12 months). With a median follow-up of 40.9 months, the 2-year and 4-year biochemical relapse-free survival were 55% and 35%, respectively. Acute and late genito-urinary (GU) toxicity ≥2 were recorded in 4 (26.6%) and 5 (33.3%) patients, respectively, and the 4-year late GU toxicity was 30%. Acute gastrointestinal toxicity ≥2 was recorded in 2 (13.3%) cases, whereas no patient experienced late toxicity. Despite the inherent bias of a retrospective analysis, our long-term results showed a low toxicity profile with a relatively low rate of biochemical control for HT re-treatment in patients affected by local radiorecurrent prostate cancer. Prospective trials are needed to investigate the role of EBRT in this setting.

Intensity-modulated ventricular irradiation for intracranial germ-cell tumors: Survival analysis and impact of salvage re-irradiation.

Background and purposeThe roles of surgery, chemotherapy, and parameters of radiation therapy for treating very rare central nervous system germ cell tumors (CNS-GCT) are still under discussion. We aimed to evaluate the survival and recurrence patterns of patients with CNS-GCT treated with chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy.Materials and methodsWe reviewed the clinical outcomes of 20 consecutive patients with CNS-GCT treated with chemotherapy and intensity-modulated radiation therapy from 2004 to 2014 in two partner institutions.ResultsTwenty children with a median age of 12 years were included (16 males). Sixteen tumors were pure germinomas, and 4 were non-germinomatous germ cell tumors (NGGCT). All patients were treated with intensity-modulated radiation therapy guided by daily images, and 70% with volumetric intensity-modulated arc radiotherapy additionally. The median dose for the whole-ventricle was 25.2 Gy (range: 18–30.6 Gy) and 36 Gy (range: 30–54 Gy) for the tumor bed boost. The median post-radiation therapy follow-up was 57.5 months. There were 3 recurrences (2 NGGCT and 1 germinoma that recurred as a NGGCT), with 1 death from the disease and the other 2 cases each successfully rescued with chemotherapy and craniospinal irradiation. The overall survival at 5 years was 95% and disease-free survival was 85%.ConclusionsThe results of this study suggest that the combined use of chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy is effective for CNS-GCTs, especially pure germinomas. Even being rescued with craniospinal irradiation, the NGGCT cases have markedly worse prognoses and should be more rigorously selected for localized treatment.

Rare entities in head-and-neck cancer: salvage re-irradiation with carbon ions

BackgroundThe objective of this investigation is to evaluate the outcomes and toxicity of carbon-ion re-irradiation (CIR) in patients with rare head and neck cancers (HNC). There is a paucity of data regarding treatment approaches in this patient cohort, which we aim to address in this work.MethodsThirty-two (n = 32) consecutive patients with uncommon HNC treated between 2010 and 2017 were retrospectively analyzed in terms of clinical outcomes, patterns of failure, and toxicity.ResultsMucoepidermoid carcinoma (MEC) was the most common histology (22%). Patients received a median cumulative dose equivalent in 2 Gy fractions (EQD2) after CIR of 128.6 Gy (range, 105.8–146.5 Gy). The local and distant control rates 1 year after CIR were 66 and 72%. No serious acute or late toxicity (≥ grade 3) after CIR was observed.ConclusionsCIR may represent an effective and safe treatment alternative to palliative systemic therapies in these rare indications.

Efficacy and Feasibility of Salvage Re-Irradiation with CyberKnife for In-Field Neck Lymph Node Recurrence: A Retrospective Study.

Neck lymph node (LN) recurrence in the irradiated field represents an important aspect of treatment failure after primary radiotherapy owing to the lack of a standard treatment. The aim of this study is to investigate the efficacy and safety of CyberKnife treatment for neck LN recurrence after radiotherapy. Between 2008 and 2016, 55 neck LN recurrences after radiotherapy in 16 patients were treated with CyberKnife. The median follow-up period was 17 months (range, 2–53 months). The median previous radiotherapy dose was 68 Gy (range, 50–70 Gy). The median marginal dose as equivalent dose delivered in 2-Gy fractions (α/β = 10) was 50 Gy (range, 40–58 Gy). The one-year local control (LC) and overall survival rates were 81% and 71%, respectively. The one-year LC was higher with a target volume ≤1.0 cm3 than that with a target volume >1.0 cm3 (p = 0.006). Fatal bleeding was observed in one patient who had large (91 cm3) and widespread tumor with invasion to the carotid artery before CyberKnife treatment. CyberKnife treatment for neck LN recurrence is safe and feasible in most cases. Indication for the treatment should be carefully considered for large and widespread tumors.

66 Salvage Reirradiation Using External Beam Radiotherapy for Local Failure in Prostate Cancer: A Systematic Review

66 Salvage Reirradiation Using External Beam Radiotherapy for Local Failure in Prostate Cancer: A Systematic Review

Clinical Outcomes of Proton Beam Re-Irradiation for Recurrent Gliomas

Despite improved molecular subtyping, overall prognosis of recurrent gliomas remains poor. Salvage re-irradiation (reRT) for recurrence can result in significant local control and proton beam radiotherapy (PBRT) offers a potential advantage due to lower integral dose to previously irradiated tissue. There is limited data on PBRT reRT outcomes. Twenty-two consecutive patients (median age 49, range 24-73) who received PBRT reRT for recurrent glioma between 2013 and 2018 were analyzed. The majority underwent PBRT reRT for recurrent Grade IV glioma (50%, 41% for WHO Grade III, and 9% for WHO Grade II). Prior to PBRT reRT, patients had a median of 1 surgery (range 1-4) and 2 systemic therapy regimens (range 1-5); 82% and 18% had 1 and 2 prior courses of RT, respectively, with a median duration of 27 months (range 7-232) prior to PBRT. Median total prior RT dose was 60 Gy (range 50.4-119.4). PBRT reRT was delivered using 3D conformal (50%), pencil beam (45%) scanning or a mix (5%). Planned reRT dose was a hypofractionated regimen in 45% of patients with doses of 30-40 Gy (RBE) in 10-15 fractions while the remaining 55% had doses of 45-60 Gy (RBE) in 25-33 fractions. Kaplan-Meier was used to determine local failure (LF), intracranial distant failure (DF), and overall survival (OS) from start of PBRT. Proportional hazards modeling was used to assess clinical predictors of these outcomes. The median OS post PBRT reRT was 11 months (6 months for Grade IV, 11 months for Grade III). Grade IV tumors had significantly poorer local control with a median time to LF after reRT of 6 months (p=0.02). Median time to DF was 7 months with no significant differences by WHO grade. Tumors with 1p19q codeletion (HR=0.1, p=0.02) and increased duration from prior RT (HR=0.98, p=0.04) were associated with improved OS post PBRT reRT while IDH1 mutant status trended toward better OS (HR=0.3, p=0.06). No molecular tumor markers were found to be associated with LF or DF, including MGMT methylation status. The number of prior lines of systemic therapy was also not associated with OS, LF, or DF. Patients had large reRT volumes with median PTV of 190 cc (range 3-676). PTV size was not prognostic of LC but hypofractioned courses trended towards poorer LC (HR 4.2, p=0.08) with no difference in DF (p=0.97) or OS (p=0.12). Two patients (10%) terminated PBRT early, one due to a mechanical fall and subsequent subdural hematoma; the other progressed during PBRT and required urgent debulking surgery. Three patients (14%) developed symptomatic radiation necrosis at 2, 2, and 12 months post reRT that were treated with bevacizumab and high dose steroids. PBRT reRT was generally well tolerated with low rate of radiation necrosis and promising local disease control for recurrent glioma. While tumor grade and 1p19q codeletion status were predictive of OS, local control after reRT was associated with tumor grade and not tumor molecular markers. Further study is needed to elucidate which patients would most benefit from proton reRT.

Salvage Reirradiation using External Beam Radiotherapy for Local Failure in Prostate Cancer: A Systematic Review

Salvage Reirradiation using External Beam Radiotherapy for Local Failure in Prostate Cancer: A Systematic Review

Efficacy and Toxicity Following Salvage High-Dose-Rate Brachytherapy for Locally Recurrent Prostate Cancer after Radiotherapy: A Single Center Retrospective Analysis

According to the NCCN guidelines, Salvage Brachytherapy is a treatment option for pathologically confirmed local recurrence after EBRT or brachytherapy. We retrospectively evaluated the feasibility and the toxicity of high dose rate (HDR) brachytherapy at our institution. Between November 2013 and February 2018, 30 consecutive patients with biopsy proven intraprostatic recurrence of cancer after definitive radiation therapy underwent a salvage re-irradiation using HDR brachytherapy. Treatment regimen was 24 Gy delivered to the whole gland in 2 implants of 12 Gy performed 2-4 weeks apart. All patients had had no severe side effect of the previous radiotherapy course and underwent a rectoscopy to ascertain the absence of radiation proctitis prior to salvage procedure. Biochemical control was assessed according to the Phoenix definition. Secondary outcomes included survival and toxicities. Median age at the salvage brachytherapy was 68.5 years (range 61.3-83.2). The median interval between salvage HDR brachytherapy and the first radiotherapy course was 9.1 years (range 0.8-22.4). The median PSA at salvage brachytherapy was 4.9 ng/mL (range 1.3-40) and 6 pts (20%) were castration-resistant. After a median follow-up of 1.7 years, a total of 19 pts (63%) presented a biochemical relapse with a median time of 1.3 years (range 0.2 – 3.9) and 16 a clinical relapse (4 local only, 2 local and regional, 5 regional and metastatic and 5 metastatic only). Local relapses occurred after a median time of 2.7 y (range 0.9-4.7). Overall toxicity profile was good, with no severe grade 3 or higher acute or late gastrointestinal or genitourinary toxicity recorded. Salvage HDR brachytherapy for locally recurrent prostate cancer after radiotherapy is feasible and associated with an acceptable toxicity profile. The high rate of clinical relapse warrants further investigation to define the subgroup of patients who will benefit from salvage local therapy.

Salvage Reirradiation for Spinal Metastases Following Local Failure after Stereotactic Radiosurgery

The management of recurrences following spine stereotactic radiosurgery (SSRS) poses a challenge due to concerns for toxicity associated with reirradiation (re-RT) and a paucity of data on treating SSRS failures. We report our institutional experience on salvage re-RT for spinal tumors using conventional radiotherapy (RT) and SSRS techniques following an ablative SSRS regimen. We retrospectively identified 33 metastatic spinal segments in 30 patients who received salvage conventional re-RT or SSRS following imaging-confirmed local progression at a site which previously received SSRS between 2003 and 2013 at our institution. Clinicopathologic features were abstracted from the medical record. Overall survival (OS) for each patient and local control (LC) for each treated segment were calculated from the date of initial SSRS and estimated using the Kaplan-Meier method. Median follow-up was 26 months (range, 2-168). The 1- and 2-year OS was 77% and 50%, respectively, with a median OS of 27 months (range, 3-168). Male patients and renal clear cell carcinoma tumors comprised 57% (17/30) and 33% (11/33) of the cohort, respectively. Eight spinal segments among 7 patients were irradiated with conventional RT prior to SSRS and then a second course of conventional RT: 5 spine directed-treatments, 2 from thoracic-directed RT, and 1 from pelvic-directed RT. The median initial SSRS dose and number of fractions was 27 Gy in 3 fractions (range, 16-30 Gy in 1-5 fractions). Treatment sites included the C-spine (21%), T-spine (45%), L-spine (30%), and sacrum (3%). The median duration to local failure after the initial SSRS course was 9 months (range, 1-67) with a median time from initial SSRS to salvage RT of 13 months (interquartile range, 7-34). For salvage, a total of 25 spinal segments were treated with RT without surgery: 16 segments in 14 patients were treated with conventional RT (20-36 Gy /5-14 fractions) whereas 9 segments in separate patients were salvaged with a second course of SSRS (18-27 Gy/1-3 fractions). Additionally, 8 segments received surgery followed by postoperative RT (n=5, conventional RT – 30 Gy /10-20 fractions; n=3 SSRS 20-27 Gy/1-3 fractions). Following salvage re-RT, the crude LC rate was 76% (25/33 lesions), with a median LC of 19 months (range, 2-23). No local failures were observed in the 8 spinal segments treated salvage surgery and postoperative RT. No grade ≥3 neurological toxicities or vertebral compression fractures were observed after re-RT. We observed favorable LC rates following salvage re-RT with low toxicity in patients who locally recurred following previous SSRS. We recommend ideally at least a 6 month window between initial SSRS and salvage re-RT. Prospective clinical studies are needed to determine the optimal salvage dose and fractionation.

Salvage reirradiation for local prostate cancer recurrence after radiation therapy. For who? When? How?

PurposeLiterature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. Materials and methodsA total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47months for low-dose-rate brachytherapy, 36months for high-dose-rate brachytherapy and 21months for stereotactic body radiotherapy. ResultsLate genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified. ConclusionDespite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.

Salvage Re-irradiation With Single-modality Interstitial Brachytherapy for the Treatment of Recurrent Gynaecological Tumours in the Pelvis: A Multi-institutional Study

AimsRecurrent gynaecological tumours can cause significant morbidity with limited salvage options. This study investigates the strategy of salvage single-modality interstitial brachytherapy (SM-ISBT) for recurrent gynaecological pelvic cancer at two specialised ISBT centres. Materials and methodsPatients who had received salvage SM-ISBT for pelvic recurrence of gynaecological cancers from September 2008 to January 2017 were included. None had distant metastasis at the time of recurrence. Local control, progression-free and overall survival and long-term toxicities were evaluated. ResultsTwenty-six patients with a median follow-up of 24 months (range 2.5–106.3 months) after SM-ISBT were included. Primary cancer sites were endometrium (20), cervix (4), vulva (1) and vagina (1). All patients had prior whole-pelvic external beam irradiation and 16 had prior brachytherapy. The median disease-free survival prior to SM-ISBT was 20.3 months (interquartile range 9.9–30.5). SM-ISBT was delivered with high dose rate technique over three to six fractions. The median high-risk clinical target volume was 34.6 cm3, with a median D90 of 29.1 Gy (range 16.1–64.6). The median bladder, rectum and sigmoid D2cm3 were 15.5, 18.7 and 3.7 Gy, respectively. After SM-ISBT, complete and partial responses were achieved in 17 (64%) and 5 (19%) patients, respectively. Two (7.4%) patients had grade 3 toxicities (both vaginal stenosis), with no grade 4 complications. Eighteen patients (69%) recurred, including local, regional and metastatic in 14 (54%), 8 (30%) and 5 (19%) patients, respectively. Two-year local control, progression-free survival and overall survival were 50, 38 and 78%, respectively. In follow-up, 12 patients (46%) remained in local control. ConclusionsSalvage SM-ISBT re-irradiation for pelvic recurrence of gynaecological malignancies was feasible and safe. With limited salvage options, the local control obtained in more than a quarter of patients seems reasonable. Further efforts are needed to establish a consensus about the optimal patient selection, dose fractionation, implant technique and combination with systemic therapies.

Outcomes of salvage re-irradiation in recurrent medulloblastoma correlate with age at initial diagnosis, primary risk-stratification, and molecular subgrouping.

To report outcomes of salvage re-irradiation (re-RT) in recurrent/progressive medulloblastoma (MB). Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive MB between 2008 and 2018 were analyzed retrospectively. A total of 28 patients (median age 18years at index diagnosis) were included. Molecular subgrouping was done using real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on the differential expression of select set of 12 protein coding genes and 9 microRNAs. Fifteen of 17 (88%) patients with sonic hedgehog (SHH)-MB developed isolated local recurrence within the index tumor-bed, while 5 of 7 (72%) patients with Group 4MB developed localized relapse outside the posterior fossa. Diffuse neuraxial dissemination was seen in 2 patients with SHH-MB, and one each of Group 4 and wingless (WNT)-MB. Molecular subgrouping was not known in 3 patients. The dose and volume of re-RT was based on site and patterns of relapse, comprising unifocal in 18 (64%), multi-focal in 3 (11%), and repeat craniospinal irradiation (re-CSI) in 7 (25%) patients. Median interval from primary irradiation to re-RT was 49.5months (range 24-98months) with median cumulative biologically effective dose of 117Gy (range 78-132Gy). All patients received platinum-based salvage chemotherapy either before or after re-RT. One patient developed symptomatic radiation necrosis following re-CSI. At a median follow-up of 24months (range 6-84months), 2-year post-re-RT progression-free survival (PFS) and overall survival (OS) was 46% and 51% respectively. Younger age (< 18years) at index diagnosis, primary risk stratification (standard-risk) and molecular subgrouping (Group 4) were associated with significantly better post-re-RT outcomes. Salvage re-RT provides good local control and encouraging survival outcomes with acceptable toxicity in selected patients with recurrent/progressive MB.

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife.

To evaluate the toxicity and efficacy of re-irradiation with salvage stereotactic radiotherapy (SRT) for recurrent glioma using CyberKnife. This study retrospectively investigated 35 patients with 48 recurrent grade 2-4 gliomas who received SRT between 1998 and 2011. Six patients (17.1%) had grade 2 gliomas, nine (25.7%) had grade 3 gliomas, and 20 (57.1%) had glioblastomas; all initially underwent surgery and conventional radiotherapy. The median initial and subsequent radiotherapy doses were 60 and 26 Gy, respectively. After a median follow-up period of 9.0 months, the only toxicity of grade 2 or more was radiation-induced brain necrosis in four patients (11.4%). The median overall and progression-free survival periods following re-irradiation were 9.0 and 3.0 months, respectively. Univariate analysis revealed that performance status at salvage re-irradiation was a significant predictor of progression-free survival. Salvage re-irradiation using CyberKnife is feasible, with an acceptable toxicity profile, for patients with recurrent glioma.