Salvage Stereotactic Body Radiation Therapy Research Articles

A Phase 1 Trial of Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer After Brachytherapy

NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response. This trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen-based positron emission tomography imaging-defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter. Between August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment. The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity.

Thoracic Reirradiation with Stereotactic Body Radiation Therapy (SBRT) for Recurrent Advanced Non-Small Cell Lung Cancer (NSCLC)

BackgroundNon-small cell lung cancer (NSCLC) local control remains suboptimal with rates around 75%. Stereotactic body radiation therapy (SBRT) is an option for isolated local recurrences of small volume recurrences. This study investigates the safety and efficacy of 60 Gy in eight fractions in large volume local recurrences. MethodsA retrospective chart review of patients treated with salvage SBRT for NSCLC lung parenchymal recurrence between July 2013 and February 2020. Reirradiation prescribed dose was 60 Gy in eight fractions utilizing SBRT technique. The primary endpoint was local control at most recent follow-up or death. Secondary endpoints included overall survival, disease-free interval, cancer-specific survival, and treatment related toxicities. ResultsSeven patients met criteria. Median follow up time was 38 months (18.1-72.4). Median age was 67 years (63-80). The median time to reirradiation was 18.2 months (7.3-28.6). Retreatment median ITV was 57.9cc (15.8-344.6) and PTV median was 113.6cc (38.3-506.9). Local control was maintained in four of seven patients (57.1%). Two of the seven patients (28.6%) remained alive. Median disease-free interval was 22.5 months (11-65). Three of seven patients (42.9%) had grade two toxicities. One patient (14.3%) had a grade 3 rib/chest wall toxicity with concurrent disease recurrence invading the chest wall. ConclusionThis study reports that SBRT of 60 Gy in eight fractions was delivered safely and effectively to large volume recurrent NSCLC previously treated with radiation therapy. The disease-free interval of nearly 2 years is meaningful for patients’ quality of life and duration of time off of systemic therapy.

The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand?

Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor whilst sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for the traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as an alternative to brachytherapy boost after external beam RT. It is also used as a primary treatment option for elderly or medically unfit patients. More recently, an SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications.

A Phase I Trial of Focal Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer.

Locally recurrent prostate cancer after radiotherapy (RT) is an increasingly recognized entity with no standard management. NCT03253744 was a phase I trial with a primary objective of identifying the maximally tolerated dose (MTD) of a course of image-guided, focal, salvage stereotactic body radiotherapy (SBRT) for patients with local recurrence after prior definitive RT. Additional objectives included biochemical control and imaging response on mpMRI and 18F-DCFPyL (PSMA) PET/CT. SBRT was prescribed to three dose levels (DLs): 40Gy (DL1), 42.5Gy (DL2), and 45Gy (DL3) in 5 fractions. The prescription dose was delivered to a PTV defined by mpMRI and PSMA imaging and biopsy confirmed tumor volume. Dose escalation followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities above baseline were scored using CTCAE v5.0 criteria for two years after completion of SBRT. Escalation was halted if 2 dose limiting toxicities (DLTs) were observed. DLTs were defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT, and any grade 3 GU or grade 4 GI toxicity thereafter. Imaging response was compared between baseline and 6-months by the Wilcoxon signed rank test. Between 08/2018 and 05/2022, 8 patients underwent salvage SBRT to 11 intraprostatic lesions with a median follow-up of 27 months. No DLTs were observed on DL1. Two patients were enrolled on DL2 and both experienced grade 3 GU toxicities, prompting de-escalation and expansion (n = 6) on DL1, the MTD. The most common toxicities were grade 2 GU toxicities: acute urinary urgency/frequency, acute weak urinary stream, and noninfective cystitis. One patient at DL1 had a self-limited episode of grade 2 GI toxicity (proctitis). No grade 3 GI toxicities were observed. All but two patients achieved an undetectable PSA nadir. Only one of these experienced biochemical failure (nadir + 2.0) at 33 months with suspicion of distant metastatic failure on restaging PET/CT. Imaging response was demonstrated by MRI in all lesions with heterogeneity in volumetric response (6% to 100%). A significant (p<0.01) response on PSMA PET/CT was observed for all measured parameters (SUVMax, SUVMean, GTVPSMA, Total Lesion PSMA [SUVMean × GTVPSMA]). Of the 11 lesions, 1 (9%) demonstrated a complete response (CR) by MRI and 9 (82%) by PSMA PET/CT. A single lesion increased in volume by 0.06 cc (16%) at 6-month PSMA PET/CT compared to baseline in the only patient who did not achieve an undetectable PSA nadir and did not have imaging suggestive of distant failure. On this phase I dose escalation study of salvage SBRT for isolated intraprostatic local failure after definitive RT, the MTD was 40Gy in 5 fractions. producing a 100% 24-month bPFS, with one late failure at 33 months occurring after the 24-month study period. The most frequent clinically significant toxicity was late grade 2 GU toxicity. Imaging response was demonstrated in all lesions on MRI and PSMA PET/CT with exception of a single lesion.

A Phase 1 Trial of Focal Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer

NCT03253744 was a phase 1 trial to identify the maximum tolerated dose (MTD) of image-guided, focal, salvage stereotactic body radiation therapy (SBRT) for patients with locally radiorecurrent prostate cancer. Additional objectives included biochemical control and imaging response. The trial design included 3 dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions delivered ≥48 hours apart. The prescription dose was delivered to the magnetic resonance- and prostate-specific membrane antigen imaging-defined tumor volume. Dose escalation followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until 2 years after completion of SBRT using Common Terminology Criteria for Adverse Events, version 5.0, criteria. Escalation was halted if 2 dose-limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT and any grade 3 genitourinary (GU) or grade 4 gastrointestinal (GI) toxicity thereafter. Between August 2018 and May 2022, 8 patients underwent salvage focal SBRT, with a median follow-up of 35 months. No dose-limiting toxic effects were observed on DL1. Two patients were enrolled in DL2 and experienced grade 3 GU toxicities, prompting de-escalation and expansion (n=6) at the MTD (DL1). The most common toxicities observed were grade ≥2 GU toxicities, with only a single grade 2 GI toxicity and no grade ≥3 GI toxicities. One patient experienced biochemical failure (prostate-specific antigen nadir+2.0) at 33 months. The MTD for focal salvage SBRT for isolated intraprostatic radiorecurrence was 40 Gy in 5 fractions, producing a 100% 24-month biochemical progression free survival, with 1 poststudy failure at 33 months. The most frequent clinically significant toxicity was late grade ≥2 GU toxicity.

Early Safety and Efficacy Profile of Homogeneously Dosed Salvage Stereotactic Body Radiotherapy (SBRT) for Intraprostatic Recurrences After Low Dose Rate (LDR) Brachytherapy.

We set out to evaluate the safety and efficacy of homogeneously dosed salvage stereotactic body radiation therapy (SBRT) for intraprostatic recurrences following low dose rate (LDR) brachytherapy. An institutional prostate SBRT database was interrogated for patients treated between January 2018 and December 2021 with salvage SBRT for intraprostatic recurrences who were previously treated with LDR brachytherapy. Patients received 30 to 34 Gy in 5 fractions to the prostate with a simultaneous integrated boost of 34 to 37.5 Gy to gross disease. The maximum urethral dose allowed was 34 Gy. Toxicities were graded using Common Terminology Criteria for Adverse Events, version 5.0. Eleven patients met our study's inclusion criteria with a median follow-up time of 37.9 months (range, 24.3-51.8 months). Median time between LDR brachytherapy and salvage SBRT was 7 years (range, 2-11 years) with a median PSA of 3.15 ng/mL (range, 0.90-9.83) at the time of salvage radiation. All 11 patients were alive at the time of last follow-up. Our 3-year Kaplan-Meier progression-free survival rate was 70.1%. Median time to recurrence was 24.1 months (range, 18.7-29.7 months). Late (≥3 months) grade 1, 2, and 3 urinary toxicity rates were 27.3%, 36.4%, and 9.1%, respectively. Late (≥3 months) grade 1, 2, and 3 gastrointestinal toxicity rates were 18.2%, 0%, and 9.1%, respectively. Homogeneous salvage SBRT to the prostate with urethral dose minimization has a favorable safety and efficacy profile for treating intra-prostatic recurrences following LDR brachytherapy. This may represent an ideal form of salvage SBRT for re-irradiation.

Stereotactic reirradiation for local prostate cancer recurrence: Mono-institutional experience of 108 patients.

365 Background: The aim of this study was to report the efficacy and toxicity of salvage stereotactic body radiation therapy (SBRT) for local prostate cancer recurrence after radiotherapy. Methods: We retrospectively reviewed a total of 108 medical records of patients treated with salvage SBRT for prostate cancer recurrence, between July 2015 and February 2021 in our institution. Patients who had initial radical prostatectomy were excluded. The median time interval between the two radiation treatments was 9 years (range, 3-20 years). All the patients had biochemical recurrence, with a PSA of 3.5 ng/mL (range, 1.8-43 ng/mL). Local recurrence was to be proven by biopsies, without distant lymph node or metastasis. The local recurrence was visible in 82% and 99% of patients on mpMRI and choline/PSMA PET/CT, respectively. The salvage treatment consisted in SBRT at a total dose of 36 Gy in six fractions delivered every other day, associated with androgen deprivation therapy in 44% of patients. We reported efficacy and toxicity (according to CTCAE v 4.03 classification) after salvage SBRT. Results: Median follow-up was 19.6 months (range, 2.3-67 months). Two year biochemical recurrence-free survival and lymph node/metastases free survival rates were 76% (95% CI: 66-87%) and 88% (95% CI: 80-96%), respectively. Regarding acute toxicity, rates of grade 2 and 3 GU toxicities were 27% and 2%, respectively. Rate of grade 2 GI toxicity was 2%, without grade ≥3. Regarding late toxicity, 2 year rates of grade 2 and 3 GU toxicities were 50% (95% CI: 44-56%) and 8% (95% CI: 2-14%), respectively. One patient experimented a grade 4 GU toxicity (bladder necrosis requiring a cystectomy) 8 months after SBRT. Two year rate of grade 2 GI toxicity was 2 (95% CI: 0-5%), without grade ≥3. Conclusions: The main toxicity of prostate salvage SBRT is GU. With a short follow-up, a subset of patients may be controlled by the salvage treatment.

The Safety and Efficacy of Salvage Stereotactic Radiation Therapy in Patients with Intraprostatic Tumor Recurrence After Previous External Radiation Therapy: Phase 1 Results from the GETUG-AFU 31 Study

BackgroundThere is no consensus on the best local salvage treatment for prostate cancer recurrence after primary external beam radiotherapy. Prospective data on stereotactic body radiation therapy (SBRT) are very scarce. ObjectiveTo determine the optimal dose regimen for salvage SBRT. Design, setting, and participantsThe present report concerns the phase 1 part of the GETUG-AFU 31 multicenter open-label study. The main inclusion criteria were histologically proven biochemical recurrence, clinical stage T1-T2 upon relapse, multiparametric magnetic resonance imaging data, prostate-specific antigen (PSA) level ≤10 ng/ml prior to salvage SBRT, PSA doubling time >10 mo, and an International Prostate Symptom Score of ≤12. InterventionFive or six fractions of 6 Gy were delivered using focal SBRT. Outcome measurements and statistical analysisDose-limiting toxicity (DLT) was defined as grade ≥3 gastrointestinal or genitourinary tract toxicity, or any grade 4 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) occurring in the first 18 wk following treatment initiation. A time-to-event continual reassessment method was used to select the dose regimen. Results and limitationsTwenty-one patients were treated (median [interquartile range] age: 76.8 yr [72.2–80.8]), including 12 at 6 × 6 dose level. No DLT was observed. The acute grade 2 genitourinary tract toxicity rate was 19%. With a median follow-up of 12.3 mo, the estimated cumulative incidence of late grade 2 genitourinary toxicity was 41.2% (95% confidence interval: 18.1–63.1%). No grade >2 genitourinary toxicity and no grade ≥2 gastrointestinal toxicity were reported. All treated patients were alive and relapse free at the last follow-up. ConclusionsA 6 × 6 Gy dose regimen was selected for our phase 2 study of salvage SBRT. With a short follow-up period, the level of toxicity appears to be acceptable. Patient summaryThere is no consensus on the best local treatment for patients with local relapse after radiotherapy for prostate cancer. Prospective data are very scarce. Our early phase trial allowed us to recommend six fractions of 6 Gy using high-precision radiotherapy for further studies.

Combined Modality Stereotactic Body Radiotherapy vs. Salvage Stereotactic Body Radiotherapy in the Management of Patients with Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> The management of hepatocellular carcinoma (HCC) is complex and requires careful consideration of the patient's tumor characteristics and underlying liver function. Local therapies including stereotactic body radiation therapy (SBRT), trans-arterial chemoembolization, trans-arterial radioembolization, trans-arterial embolization, and microwave ablation have been shown to be safe and effective. Limited data exist characterizing the outcomes of combined modality therapy (CMT), defined as thermal ablative or transarterial liver directed therapy followed by consolidative SBRT. We hypothesized that upfront CMT would result in better outcomes compared to local therapy followed by SBRT for local salvage. <h3>Materials/Methods</h3> Patients with HCC who were treated with SBRT were prospectively enrolled into an institutional database from 2012-2021. Patients treated with upfront CMT or local therapy followed by salvage SBRT were identified. Overall survival (OS) and local control (LC) were evaluated using the Kaplan-Meier method. Local control was evaluated using both radiographic and pathologic data when available. <h3>Results</h3> 67 patients with a total of 77 tumors were included in our analysis with a median follow up of 31.8 months. Median tumor size was 3.3 cm. Median dose delivered was 45 Gy in a median of 5 fractions. 27 (40%) patients received CMT and 40 (60%) patients received salvage SBRT. The groups were comparable in terms of baseline characteristics including age, Child Pugh score, Milan eligibility, and radiation dose. There was a significantly greater proportion of CMT patients who were listed for transplant (60% 16/27 versus 30% 12/40 in the salvage SBRT group, <i>p</i> = .01). The estimated 1-year LC rate were similar between the two cohorts with 100% LC in the CMT group and 94.3% LC in the salvage SBRT group (<i>p</i> =0.62). OS was also similar between cohorts with an estimated 1-year OS of 92.59% in the CMT group and 89.5% in the salvage SBRT group (<i>p</i> =0.3). Radiographic response rates between the CMT and salvage SBRT cohorts were comparable with a radiographic complete response (rCR) of 73% (19/26) in the CMT group and 67% (29/43) in the salvage SBRT group. Of the tumors that were pathologically analyzed either at explant or autopsy, pathologic complete response rates (pCR) were similar with 50% (7/14) of CMT patients and 67% (8/12) of salvage SBRT patients achieving a pCR. Toxicity rates were low with only 3 patients (11.1%) in the CMT cohort and 3 patients (7.5%) in the salvage SBRT cohort who had grade 3+ adverse events. Regardless of treatment type, 56% had stable or improved CPT scores by 6 months post SBRT. <h3>Conclusion</h3> Both upfront CMT and salvage SBRT following local failure provide excellent local control, are associated with similar overall survival, and have acceptable rates of toxicity. Further studies are needed to evaluate the role of CMT with SBRT in patients with HCC to avoid over treatment and maximize cost efficiency.

SBRT as Salvage Re-Irradiation for Isolated In-Field Regional Relapse After Bilateral Breast Cancer – a Case Report

"Stereotactic body radiation therapy (SBRT) is a type of radiotherapy which uses a high radiation dose delivered in a single or a few fractions and is employed with local curative intent for early-stage cancer, relapsed cancer or in the oligometastatic setting. The aim of this case report is to illustrate the potential of this technique in the salvage re-irradiation of a late isolated in field regional relapse after bilateral breast cancer. This is the case of a 65-years-old woman with a metachronous bilateral breast cancer (left side-1998, stage IIB, Luminal type; right side-2010, stage IIA, Her2 positive) who received both chemo- and endocrine systemic therapy, underwent surgery and was irradiated on both sides, with a late solitary recurrence in her left internal mammary node chain (2018) treated by SBRT re-irradiation (40 Gy in 5 fractions). Three years after salvage SBRT, under Palbociclib+Letrozole and thorough follow-up protocol, she is still in clinical complete remission, with a normal CA 15-3 and metabolically inactive residual mass on PET-CT, negative on a recent biopsy. SBRT is becoming a hallmark of oligometastatic disease management and can be invaluable in patients subjected to prior radiotherapy."

Salvage Prostate Stereotactic Body Radiation Therapy After Definitive Cryoablation

PurposeWhole gland cryoablation is a guideline-approved definitive treatment for localized prostate cancer, and is being explored for partial gland ablation. However, there is limited data regarding management of cryoablation failures. Stereotactic body radiation therapy (SBRT) is a well-established method of primary treatment for prostate cancer. Here we review salvage SBRT after cryoablation failures. Methods and MaterialsA large database of patients treated with definitive SBRT was interrogated to identify those who underwent primary cryoablation. All patients were determined to have progressive disease based on a rising prostate specific antigen and/or postcryoablation biopsy. All patients were treated with SBRT over 5 treatment fractions using a robotic radiosurgical platform. Baseline cryoablation characteristics and pre- and posttreatment Expanded Prostate Cancer Index Composite questionnaires were analyzed. Acute and late toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Cancer outcomes after salvage SBRT were stratified by disease and treatment characteristics. ResultsA total of 51 patients were identified who underwent cryoablation followed by salvage SBRT. The majority (47%) were found to have intermediate-risk disease at the time of SBRT salvage and most commonly were treated with 3500 cGy in 5 fractions to the prostate and seminal vesicles. Only 1 grade 3+ toxicity was identified. Patient-reported quality of life metrics after SBRT salvage followed prior patterns observed in the de novo SBRT setting. With a median follow-up of 40 months, 76% of the cohort demonstrated disease control. Median time to prostate cancer recurrence was 57.5 months, and recurrence was predominantly seen in patients with underlying high-risk disease. ConclusionsThis is the largest cohort of patients treated with any radiation therapy salvage after cryoablation and the first institution to report SBRT as a modality of salvage. Salvage SBRT after cryoablation results in low rates of high-grade toxicity, acceptable changes in patient-reported quality of life, and durable rates of long-term oncologic control.

Salvage re-irradiation using stereotactic body radiation therapy for locally recurrent prostate cancer: the impact of castration sensitivity on treatment outcomes

BackgroundAdvances in imaging, biomaterials and precision radiotherapy provide new opportunities to salvage locally recurrent prostate cancer (PC). This study evaluates the efficacy and safety of re-irradiation using stereotactic body radiation therapy (SBRT). We hypothesized that patients with castrate-resistant PC (CRPC) would benefit less from local salvage.MethodsA prospective clinical database was reviewed to extract 30 consecutive patients treated with prostate re-irradiation. Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography was performed following prostate-specific antigen failure in all patients and biopsy was obtained in 18 patients (60%). Re-irradiation was either focal (n = 13) or whole-gland (n = 17). Endo-rectal balloons were used in twenty-two patients and hydrogel spacers in eight patients. The median prescription dose was 5 fractions of 6.5 (range: 6–8) Gray (Gy).ResultsMedian follow-up was 28 months. Failure occurred in 10 (out of 11) CRPC patients versus 6 (out of 19) castrate-sensitive patients (91% vs. 32%, p = 0.008) after a median of 13 and 23 months, respectively. Metastases occurred in 64% (n = 7) of CRPC patients versus 16% (n = 3) of castrate-sensitive patients (p = 0.007). Two patients experienced local in-field recurrence, thus local control was 93%. The 2 and 3-year recurrence-free survival were 84% and 79% for castrate-sensitive patients versus 18% and 9% for CRPC patients (p < 0.001), and 3-year metastasis-free survival was 90% versus 27% (p < 0.01) for castrate-sensitive and CRPC patients, respectively. Acute grade II and III genitourinary (GU) toxicity occurred in 27% and 3%, and late GU toxicity in 30% and 3%, respectively. No ≥ grade II acute gastrointestinal (GI) toxicity occurred, and only one patient (3%) developed late grade II toxicity.ConclusionsEarly delivery of salvage SBRT for local recurrence is associated with excellent 3-year disease control and acceptable toxicity in the castrate-sensitive phenotype. PSMA imaging for detection of local recurrence and the use of precision radiotherapy with rectal protective devices should be further investigated as a novel salvage strategy for radio-recurrent PC.

Toxicity and Outcomes of Re-Irradiation for Intra-Thoracic Recurrence Using Stereotactic Body Radiation Therapy (SBRT)

Patients treated for a thoracic malignancy carry a significant risk of developing other lung lesions. Locoregional control of intrathoracic recurrences is challenging due to the impact of prior therapies on normal tissues. We examined the safety and efficacy of thoracic re-irradiation using high-precision image-guided stereotactic body radiation therapy (SBRT). Records of 24 patients with prior intra-thoracic radiation therapy (RT) who underwent SBRT for a subsequent primary, recurrent or metastatic lung tumor from April/2013 to December/2018 were retrospectively reviewed. Survival duration was calculated from the date of start of re-irradiation. Overall survival (OS) rates and local progression-free survival (LPFS) rates were estimated using the Kaplan-Meier method. Acute and late toxicities were grated per CTCAE ver4. Toxicity rates were compared using univariate Cox proportional hazard models adjusted for age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), primary site (legion and characteristics), biologically effective prescription dose (α/β = 10) (BED10), interval time between prior RT and re-irradiation, tumor size, planning target volume (PTV), the volume of normal lung receiving ≥20 Gy (V20), and the mean lung dose (MLD). The median patient age was 75 years (range 44-92 years). 16 patients received prior RT for a primary lung cancer, 7 for metastases from other histologies, and 1 for a pleural tumor. Median dose of prior RT was 60 Gy (range 45–70 Gy). Median BED10 of SBRT was 102.5 Gy (range 48-180 Gy). With a median follow-up of 20.5 months among survivors, median OS time were 29 months. 2-year OS rates and LPFS rates were 77.9% and 58.8%, respectively. Grade 2 and 3 pulmonary toxicity, including dyspnea, cough, pleural effusion, pneumonitis and pneumothorax were observed in 25% and 8.3% of patients, respectively. No grade 5 events and pulmonary hemorrhage occurred. Univariate analysis demonstrated that PTV of re-irradiation was found to be associated with Grade2 radiation pneumonitis (P = 0.02). V20 and MLD of lung at re-irradiation were not significantly associated. Salvage SBRT for intrathoracic recurrences after initial RT appears safe, with low treatment related toxicity and encouraging rates of tumor control.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Locoregional Recurrences After Prior Chemoradiation for Advanced Esophageal Carcinoma.

Purpose: This study aimed to investigate the feasibility of stereotactic body radiation therapy (SBRT) as salvage therapy for locally recurrent esophageal cancer. We hypothesized that SBRT would provide durable treated tumor control with minimal associated toxicity in patients with progressive disease after definitive radiation, chemotherapy, and surgical resection.Methods: This single-institution retrospective study assessed outcomes in patients who received SBRT for locoregional failure of esophageal cancer after initial curative-intent treatment. Only patients who had received neoadjuvant chemoradiation (≥41.4 Gy) for esophageal cancer were selected. Subsequent surgical resection was optional but institutional follow-up by an oncologist was required. The primary endpoints of this study were gastrointestinal and constitutional toxicity, scored with the Common Terminology Criteria for Adverse Events v5.0. A secondary outcome, treated-tumor control, was assessed with RECIST v1.1.Results: Nine patients (11 locoregional recurrences) treated with SBRT were reviewed, with a median follow-up time of 10.5 months. Most patients initially presented with T3 (88.9%), N1 (55.6%), moderately differentiated (66.7%) adenocarcinoma (88.9%), and had received a median 50.4 Gy delivered over 28 fractions with concurrent carboplatin/paclitaxel chemotherapy followed by surgical resection. Median time to recurrence was 16.3 months. Median total dose delivered by SBRT was 27.5 Gy (delivered in five fractions). Two patients experienced acute grade 1 fatigue and vomiting. No patient experienced grade 3 or higher toxicity. One patient experienced failure in the SBRT treatment field at 5.8 months after treatment and six patients developed distant failure. The median progression-free survival time for SBRT-treated tumors was 5.0 months, and median overall survival time was 12.9 months.Conclusions: This single-institution study demonstrated the feasibility of SBRT for locoregional recurrence of esophageal cancer with minimal treatment-related toxicity and high rates of treated tumor control. Prospective studies identifying ideal salvage SBRT candidates for locoregional failure as well as validating its safety are needed.

Dosimetric comparison between RapidArc and HyperArc techniques in salvage stereotactic body radiation therapy for recurrent nasopharyngeal carcinoma

BackgroundTo evaluate dosimetric differences of salvage irradiations using two commercially available volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) techniques: RapidArc (RA) and HyperArc (HA), for recurrent nasopharyngeal carcinoma (NPC) after initial radiation therapy.MethodsTen patients with recurrent NPC status previously treated with radiation therapy were considered suitable candidates for salvage SBRT using VMAT approach. Two separate treatment plans were created with HA and RA techniques for each case, with dosimetric outcomes compared with respect to tumor target coverage and organs-at-risk (OARs) sparing. Furthermore, the cumulative radiobiological effects to the relevant OARs from the original radiotherapy to the respective salvage SBRT plans were analyzed in terms of biologically effective dose (BED).ResultsTreatment with HA exhibited similar target dose coverage as with RA, while delivering a higher mean dose to the targets. Using RA technique, the mean maximal doses to optic apparatus and the mean brain dose were reduced by 1 to 1.5 Gy, comparing to HA technique. The conformity index, gradient radius, and intermediate dose spillage in HA plans were significantly better than those in RA. With HA technique, the volume of brain receiving 12 Gy or more was reduced by 44%, comparing to RA technique. The cumulative BEDs to spinal cord and optic apparatus with RA technique were 1 to 2 Gy3 less than those with HA. HA technique significantly reduced the volume within body that received more than 100 Gy.ConclusionsWith better dose distribution than RA while maintaining sufficient target dose coverage, HA represents an attractive salvage SBRT technique for recurrent NPC.

Salvage Stereotactic Body Radiation Therapy for Isolated Local Recurrence After Primary Surgical Resection of Non–small-cell Lung Cancer

IntroductionWe sought to evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) as salvage treatment for local recurrence after prior surgical resection for non–small-cell lung cancer (NSCLC). Materials and MethodsWe surveyed our prospective lung SBRT registry for patients who received salvage SBRT (sSBRT) for local recurrence after previous resection of a primary NSCLC. Following sSBRT, local control, distant metastases, overall survival, and treatment-related toxicity were evaluated. ResultsFrom 2004 to 2017, 48 patients met inclusion criteria. At initial surgery, 44 (83%) patients had stage I to II disease, and surgical approaches were 47.9% wedge resection, 4.2% segmentectomy, 43.8% lobectomy, and 4.2% bilobectomy. The median time to local recurrence after surgery was 26.4 months, and 36 (75%) recurrences were biopsy-proven. Surgical salvage was not possible owing to un-resectability or underlying comorbidities in 45 (93.8%) patients. Most (68.8%) patients received 50 Gy in 5 fractions. The median follow-up after sSBRT was 22.6 months (range, 3.8-108.8 months). Eight (16.7%) patients experienced local or lobar failure, and 9 (19.1%) patients had nodal failure at a median of 12.5 months (range, 2-66.1 months). Nineteen (39.6%) patients failed distantly at a median of 11.4 months. The median overall survival after sSBRT was 29.3 months. A total of 72.9% of patients experienced no toxicity after sSBRT. Three (6.3%) patients developed grade III toxicity (cough, atelectasis, or soft tissue necrosis) following sSBRT. ConclusionsSimilar to SBRT for primary early stage NSCLC, sSBRT for local relapse following surgical resection of NSCLC offers high rates of local control with limited toxicity. Distant failure remains the primary pattern of failure.

Repeat stereotactic body radiation therapy (SBRT) for salvage of isolated local recurrence after definitive lung SBRT

PurposeOptimal management of isolated local recurrences after stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) is unknown and literature describing repeat SBRT for in-field recurrences after initial SBRT are sparse. We investigate the safety and efficacy of salvage SBRT for isolated local failures after initial SBRT for NSCLC. Methods/MaterialsPatients receiving SBRT for isolated local recurrence after initial SBRT for early NSCLC were identified using a prospective registry. Both courses were 3–5 fractions with a biologically effective dose (BED10) of ≥100 Gy. Local failure was defined as within 1 cm of the initial planning target volume (PTV) or an overlap of the ≥25% isodose lines of the first and second treatments. Failures >1 cm beyond the PTV and without ≥25% overlap, or with additional recurrence sites were excluded. Kaplan-Meier analysis was used to estimate survival. ResultsA total 21 patients receiving salvage SBRT from 2008 to 2017 were identified. Median interval from initial SBRT to salvage SBRT was 23 months (7–52). Six patients (29%) had central tumors. Median follow-up time from salvage SBRT was 24 months (3–60). Median overall survival after salvage was 39 months. After reirradiation, two-year primary tumor control was 81%, regional nodal control was 89%, distant control was 75% and overall survival was 68%. Grade 2 pneumonitis occurred in 2 patients (10%) and grade 2 chest wall toxicity in 4 patients (19%). No grade 3+ toxicity was observed. ConclusionsSalvage SBRT for isolated local failures after initial SBRT appears safe, with low treatment-related toxicity and encouraging rates of tumor control.

Salvage Stereotactic Body Radiation Therapy for Local Prostate Cancer Recurrence After Radiation Therapy: A Retrospective Multicenter Study of the GETUG

To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy. Between April 2010 and January 2017, 100 patients were included in 7 centers. Disease extension was assessed by pelvic multiparametric magnetic resonance imaging and choline positron emission tomography in 87% and 94% of patients, respectively. The median time interval between the 2 treatments was 7.5 years (range, 2-18). Median prostate-specific antigen at recurrence was 4.3 ng/mL (range, 2-38). Median SBRT dose was 36 Gy (range, 25-36.25) in 6 fractions (range, 5-6), every other day. Thirty-four percent of patients were treated by androgen deprivation therapy for a median duration of 12 months. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03. Median follow-up was 29.3 months (range, 4-91). Second biochemical recurrence-free survival rate at 3 years was 55% (95% confidence interval [CI], 42%-66%). The initial D'Amico group, time interval after first radiation therapy, and SBRT dose were prognostic factors of biochemical recurrence-free survival in multivariate analysis (P = .09, P = .025, P = .018, respectively). No patient developed acute gastrointestinal toxicity of grade >1; rates of acute genitourinary toxicity of grade 2 and 3 were 8% and 1%, respectively. The actuarial 3-year grade ≥2 genitourinary and gastrointestinal toxicity was 20.8% (95% CI, 13%-29%) and 1% (95% CI, 0.1%-5.1%), respectively. One patient presented with neuritis of grade3. With a short follow-up, this study shows that salvage SBRT allows for encouraging control and acceptable toxicity. Further prospective studies are necessary to confirm these preliminary results and to determine late toxicity.

Stereotactic prostate focal reirradiation therapy for local recurrence: preliminary results of Hartmann Oncology Radiotherapy Group.

Objective:Our objective was to report our experience and to evaluate the feasibility and toxicity of focal salvage stereotactic body radiation therapy (SBRT) in patients with post-radiation local recurrence of prostate cancer.Methods:We retrospectively reviewed medical records of patients treated with Cyberknife ® between October 2014 and April 2017 at our institution for a focal reirradiation delivered to the prostate/prostatic bed for local recurrence after radical or adjuvant radiotherapy. All patients underwent prostate biopsies at recurrence at the time of fiducial markers placement, had choline PET/CT and pelvic MRI. The treatment consisted in 36 Gy in six fractions delivered every other day. Post reirradiation toxicities were assessed according to the CTCAE v4 (Common Terminology Criteria for Adverse Events).Results:42 patients were treated with followed with a median follow-up of 21 months (range 3 – 31). 34 patients had biopsy proven recurrence. The initial treatment was radical prostatectomy and radiation therapy for 9 patients and radiation therapy alone for 33 patients. 23 patients from the group of prostate reirradiation had placement of rectal spacers. No Grade 4 or 5 toxicity were observed. 27 acute urinary events were recorded: 18 patients experienced Grade 1, 9 patients experienced Grade 2 toxicity and 1 patient experienced Grade 3 urinary toxicity, namely cystitis and/or dysuria. No Grade 2 or more digestive toxicity was observed. Rectal doses were significantly lower with rectal spacers.Conclusion:Salvage focal Cyberknife ® seems feasible and show promising results.Advances in knowledge:SBRT for local prostate cancer recurrence after initial radiotherapy is well tolerated with short follow-up.

Reirradiation for isolated local recurrence of prostate cancer: Mono-institutional series of 64 patients treated with salvage stereotactic body radiotherapy (SBRT).

To evaluate high-precision external beam reirradiation (re-EBRT) for local relapse of prostate cancer (PCa) after radiotherapy. This retrospective study included patients with biochemical failure and evidence of isolated local recurrence of PCa after radical/salvage EBRT or brachytherapy that received salvage stereotactic body radiation therapy (SBRT, re-EBRT). Biopsy was not mandatory if all diagnostic elements were univocal (prostate specific antigen evolution, choline-positron emission tomography or magnetic resonance imaging). Salvage SBRT (re-EBRT) was delivered with image-guided radiation therapy (RapidArc®, VERO® and CyberKnife®). Data of 64 patients were included, median age at salvage SBRT was 73.2 years, median pre-salvage SBRT prostate specific antigen was 3.89 ng ml-1 . Median total dose was 30 Gy in five fractions, biologically effective dose (BED) of 150 Gy. One acute G3 genitourinary event and one late G3 genitourinary event were observed. No G ≥ 3 bowel toxicity was registered. At the median follow-up of 26.1 months, tumor progression was observed in 41 patients (64%). 18 patients (28%) experienced local relapse. 2-year local control, biochemical and clinical relapse free survival rates were 75, 40 and 53%, respectively. With BED ≥130 Gy 1-year biochemical and clinical progression-free survival rate were 85 and 90%, respectively. Salvage SBRT (re-EBRT) for isolated local PCa recurrence is a safe, feasible and noninvasive salvage treatment. Further investigation is warranted to define the optimal patient selection, dose and volume parameters. Salvage SBRT reirradiation for the locally recurrent PCa offer a satisfactory tumor control and excellent toxicity profile, if BED ≥130 Gy is administered.