Salvage Stereotactic Body Radiotherapy Research Articles

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

Local recurrences after radical prostatectomy (RP) and postoperative radiotherapy (RT) are challenging for salvage treatment. Retrospective analysis of own experiences with salvage re-irradiation was performed. The study included all consecutive patients treated with salvage stereotactic body radiotherapy (sSBRT) for prostate bed recurrence following RP and postoperative RT at asingle tertiary center between 2014 and 2021. Treatment toxicity defined as the occurrence of CTCAE grade ≥ 2 genito-urinary (GU) or gastro-intestinal (GI) adverse events (AEs) was assessed. APSA response, biochemical control (BC) and overall survival (OS) were also evaluated. The study group included 32patients with amedian age of 68years and amedian follow-up of 41months, treated with CyberKnife (53%) or Linac (47%) sSBRT. Total dose of 33.75-36.25 Gy in five fractions (72%) was applied in the majority of them. Approximately 19% patients reported grade ≥ 2 GU AEs both at baseline and at three months, and grade ≥ 2 GI toxicity increased from 0% at baseline to 6% at three months after sSBRT. There was some clinically relevant increase in late toxicity with 31% patients reporting late ≥ 2 GU, and 12.5% late ≥ 2 GI AEs. Two grade3 AEs were recorded: recto-urinary fistulas. The majority of patients showed aPSA response (91% at one year post-sSBRT). The 3‑year BC was 40% and 3‑year OS was 87%. Manageable toxicity profile and satisfactory biochemical response suggest that SBRT in patients with local recurrence following RP and postoperative RT might be asalvage option for selected patients.

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.

Safety and efficacy of stereotactic body radiotherapy (SBRT) to oligoresidual sites combine with osimertinib in stage IV EGFR mutant NSCLC patients: A prospective pilot study.

e21069 Background: Presently osimertinib is used as first-line therapy in stage IV EGFR mutation NSCLC patients. Unfortunately, acquired resistance gradually develops, resulting in disease progression in most patients after 1 to 2 years. A retrospective study demonstrates that similar to the first- and second-generation EGFR-TKIs, half of the patients experienced failure within the residual disease. Consolidative local therapy had been evaluated as a promising strategy to improve PFS and delayed the appearance of new metastatic lesions in the pre-osimertinib era. It is intriguing to hypothesize that new distant metastases may arise from drug-resistant tumor cells at the residual tumor lesions. Therefore, compared to the salvage SBRT, preemptive consolidative SBRT to all oligo-residual tumor sites could potentially prevent recurrence and improve survival. Of note, this proposal is challenging because both EGFR-TKI and thoracic radiation have a detrimental effect on pulmonary interstitial tissue. Two retrospective studies had reported severe pneumonitis with radiotherapy plus osimertinib. Therefore, the potential toxicity profile needs to evaluate prospectively. Therefore, we performed this preliminary trial (ChiCTR2100053807) to evaluate the safety of consolidation SBRT at maximal osimertinib response. Methods: Patients were enrolled if residual metastasis was limited to five sites. Consolidative SBRT was initiated to all residual sites with different doses (30–50Gy) and fractions (3-10) when maximal tumor shrinkage was achieved with osimertinib. The primary endpoint was an adverse reaction defined by the Common Terminology Criteria for Adverse Events, version 4.0. Results: 5 consecutive patients were enrolled between December 2021 and December 2022. 80% of their residual disease was located in the lungs and lymph nodes, which constituted targets for thoracic SBRT. The median time to maximal response was 3 months (range, 2-6). The median follow-up time from consolidative SBRT was 6 months（range,6-12）. The most common grade 1-2 adverse events included leukopenia (60%, n = 3), anorexia (40%, n = 2), lymphopenia (40%, n = 2), paronychia (40%, n = 2), rash (40%, n = 2), which were thought to be likely related to osimertinib. One patient suffered from grade 1 pulmonary fibrosis at 16 months after SBRT. There was no Grade 3/4 acute and late radiation toxicity. So far, no disease progression occur with a median follow-up time of 18 months（range, 13-19）. Conclusions: This pilot studydemonstrated concurrent treatment with osimertinib and SBRT for the oligo-residue disease at TKI maximum response was well tolerated. Future prospective, randomized studies are desirable to confirm these preliminary findings. Clinical trial information: ChiCTR2100053807 .

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.

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study

BackgroundManagement of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. ObjectiveTo assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. Design, setting, and participantsWe conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. Outcome measurements and statistical analysisProgression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. Results and limitationsThe median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6–33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08–1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38–8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10–26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61–8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12–3.16; p = 0.02, respectively). ConclusionsSalvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. Patient summaryWe found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer.

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.

Risk of radiculopathy caused by second course of spine stereotactic body radiotherapy.

Stereotactic body radiotherapy is used to treat spinal metastases; however, 10% of patients experience local failure. We aimed to clarify the outcomes of the second course of stereotactic body radiotherapy for spinal metastases with a uniform fractionation schedule at our institution. Data of patients treated with a second salvage stereotactic body radiotherapy course at the same spinal level or adjacent level from July 2018 to December 2020 were retrospectively reviewed. The initial prescribed dose was 24Gy in two fractions, and the second dose 30 or 35Gy in five fractions. The spinal cord dose constraint at the second course was 15.5Gy at the maximum point dose. The endpoints were local failure and adverse effects. Local failure was defined as tumor progression using imaging. We assessed 19 lesions in 17 patients, with radioresistant lesions in 14 (74%) cases, the second stereotactic body radiotherapy to the same/adjacent spinal level in 13/6 cases, the median interval between stereotactic body radiotherapy of 23 (range, 6-52) months, and lesions compressing the cord in 5 (26%) cases. The median follow-up period was 19months. The 12- and 18-month local failure rates were 0% and 8%, respectively. Radiation-induced myelopathy, radiculopathy and vertebral compression fractures were observed in 0 (0%), 4 (21%) and 2 (11%) lesions, respectively. Three patients with radiculopathy experienced almost complete upper or lower limb paralysis. The second course of salvage stereotactic body radiotherapy for spinal metastases achieved good local control with a reduced risk of myelopathy. However, a high occurrence rate of radiation-induced radiculopathy has been confirmed.

Clinical Outcomes and Prognostic Factors of Salvage Stereotactic Body Radiotherapy for Post-Surgical Thoracic Oligo-Recurrence/Metastasis of Non-Small-Cell Lung Cancer.

PurposeThe study aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) using CyberKnife (CK) in patients with postoperative thoracic oligo-recurrence/metastasis of non-small-cell lung cancer (NLCLC), and to analyze the prognostic factors affecting overall survival after SBRT.Patients and MethodsA total of 44 patients with postoperative thoracic oligo-recurrence/metastatic of NLCLC treated with SBRT were reviewed. Thoracic oligo-recurrence/was defined as 1–3 loco-regional confined to lung lobe, hilar/mediastinal lymph nodes, bronchial stump, or chest wall. Primary endpoints included local control (LC), overall survival (OS), progression-free survival (PFS) and toxicity. Prognostic factors that affected these patients were analyzed by the univariate and multivariate analysis by Kaplan–Meier methods and Cox regression models, respectively.ResultsThe median follow-up time after salvage SBRT was 48.5 months. Measuring from the date of salvage SBRT, the median OS of the 44 patients was 52.60 (95% CI: 29.59–75.60) months. 1-,3-and 5-year OS rates were 97.7%, 65.3% and 47.7%, respectively. The 1-,3-year and 5-year LC rates were 97.7%, 85.1% and 80.1%, respectively. At 1, 3 and 5 years, the PFS rates were 77.1%, 28.8% and 5.3%, respectively. Multivariate analysis demonstrated that pre-SBRT neutrophil-to-lymphocyte ratio (NLR) and Charlson comorbidity index (CCI) were independent prognostic factors (p < 0.05). The treatment-related side-effects were well tolerated. No patients developed grade 3 or greater pulmonary toxicity.ConclusionSBRT is a promising salvage therapeutic option for postoperative thoracic oligo-recurrence/metastasis of non-small-cell lung cancer with acceptable toxicity. Low pre-SBRT neutrophil-to-lymphocyte ratio (NLR) and low Charlson comorbidity index (CCI) were associated with a better prognosis and longer survival and might be considered as reliable and independent prognostic factors in these patients treated with SBRT.

Local control by salvage stereotactic body radiotherapy for recurrent/residual hepatocellular carcinoma after other local therapies

Background: To clarify local control by salvage stereotactic body radiotherapy (SBRT) for recurrent/residual hepatocellular carcinoma (HCC) compared with initial definitive SBRT for local treatment-naïve HCC.Material and methods: We retrospectively investigated HCC patients that received SBRT between July 2005 and December 2017. We classified HCC tumors as the initial definitive SBRT group (Arm-1; initial definitive SBRT, Arm-2; initial definitive planned SBRT following transarterial chemoembolization (TACE)) and salvage SBRT group (Arm-3; salvage SBRT for recurrent/residual tumors after TACE, Arm-4; salvage SBRT for recurrent/residual tumors after radiofrequency ablation (RFA), Arm-5; salvage SBRT for recurrent/residual other than Arm-3 or Arm-4). Local control was evaluated by mRECIST.Results: We reviewed 389 HCC tumors of 323 patients treated by 35–40 Gy/5 fr. The median follow-up time for local recurrence of tumors was 34.8 months (range, 6.5–99.2). The cumulative local recurrence rates at 3 years of Arm-1–5 were 1.4% (95% CI, 0.3–4.4%), 5.0% (95% CI, 1.6–11.5%), 12.4% (95% CI, 5.7–21.9%), 14.8% (95% CI, 3.3–34.3%) and 7.3% (95% CI, 1.9–18.0%), respectively. The cumulative local recurrence rates at 3 years of initial definitive treatment and salvage treatment groups were 2.8% (95% CI, 1.1–5.6%) and 11.1% (95% CI, 6.3–17.3%), respectively (p=.004). On multivariate analysis, salvage treatment and the tumor diameter were significant risk factors of local recurrence (p = .02, p < .001 respectively). Estimated overall survival at 3 years for all patients in initial definitive treatment and salvage treatment groups were 71.5% (95% CI, 63.4–78.1%) and 66.1% (95% CI, 56.4–74.2%), respectively (p = .20). No treatment-related death caused by SBRT was observed.Conclusions: This analysis showed local control of salvage SBRT for recurrent/residual HCC was significantly worse than that of initial definitive SBRT for local treatment-naïve HCC. However, local control of salvage SBRT was relatively good, and salvage SBRT is one of the favorable treatment options for recurrent/residual HCC.

Salvage stereotactic body radiotherapy for post-operative oligo-recurrence of non-small cell lung cancer: A single-institution analysis of 59 patients.

A standard treatment for patients with early-stage non-small cell lung cancer (NSCLC) who undergo surgery, and subsequently develop local failure or intrathoracic oligo-recurrence, has not yet been established. The present study aimed to assess the feasibility of stereotactic body radiotherapy (SBRT) for this subgroup of patients. Consequently, a retrospective analysis was conducted of patients with NSCLC recurrence who were treated with SBRT, and previously underwent curative surgical resection between October 2011 and October 2016. Post-SBRT survival [overall survival (OS); progression-free survival (PFS); and local control (LC)] and toxicity were analyzed. Prognostic factors for OS were identified using univariate and multivariate analysis. A total of 52 patients and 59 tumors were analyzed. The median follow-up time was 25 months (35 months for surviving patients), and median OS following salvage SBRT was 32 months. The 1- and 3-year OS rates were 84.4 and 67.8%, respectively. 1- and 3-year PFS rates were 80.8 and 58.7%, respectively. Only 4 patients (7.7%) developed local failure. Median LC was 71 months and 1- and 3-year LC rate were 97.9 and 94.9%, respectively. A total of 4 patients experienced grade 3 or higher adverse events (AEs) and two experienced grade 5 AEs (pneumonitis and hemoptysis). Central tumor location and the possibility of re-operation were independent prognostic factors for OS. The present study indicated that post-operative salvage SBRT is a promising therapeutic option for patients with NSCLC with locoregional or intrathoracic oligo-recurrence. We regard toxicity was also acceptable. However, further research is required on the appropriate selection of subjects, and stratification of the analysis by certain risk factors would increase the accuracy of the conclusions.

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.

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes.

The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD.

PUB057 Re-Irradiation of Non-Small Cell Lung Cell Cancer Recurrences with Stereotactic Body Radiotherapy

Decision of salvage therapy for lung cancer recurrences is a major problem because of poor results with re-treatments having greater risk of side-effects. Stereotactic body radiotherapy (SBRT) is a promising technique in re-irradiation of lung cancer recurrences. In this study, we intent to present our results, including the toxicity and outcome of our patients treated with SBRT after radiotherapy failure. 403 patients were treated with SBRT for lung cancer at our department between June 2010 and August 2015. Among these, we identified 16 patients who were re-irradiated using SBRT. PET-CT was used in staging in all patients. All patients had recurrent disease only within the previous radiotherapy treatment volume. The median previous EBRT dose was 66 Gy (range, 46 - 66 Gy). Tumor responses were evaluated with PET-CT 3 months after SBRT and with computerized tomography (CT) every 3 months interval. Outcomes analyzed were > grade 3 radiation pneumonitis, overall survival (OS), local control (LC), progression free survival (PFS) and distant metastasis. The median follow-up time was 30 months from salvage SBRT. The locations of recurrent tumors were central in 12 and peripheral in 4 patients. The median largest tumor size was 4.35 cm (range; 1.4 and 6.6 cm) and planning target volume was median 47.3 cm3 (range; 5.4 and 153.4 cm3). The median SBRT dose was 38 Gy (range; 30 – 60Gy). Total biological equivalent dose (BED) was 63 Gy10 (range, 48 - 115 Gy10) and SBRT was applied after a median time of 12 months (range; 3-36 months) from prior radiation. Complete response was in 13, partial response was in 2, stable or progressive disease was observed in 1 patient. The 1 year, 2 year and 3 year LC rate was 93.8%, 85.2% and 85.2% respectively. The 1 year, 2 year and 3 year OS rate was 87.5% - 67.3% and 40.4% respectively. One and 3-year PFS rates were 49.2% and 28.1% respectively. At the last follow-up 5 patients were alive with no evidence of disease and one patient was alive with systemic metastases. The rate of symptomatic > grade 3 pneumonitis was 12.5 % and one patient developed fatal pneumonitis. Symptomatic > grade 3 chest wall pain or esophagitis was not observed. Salvage therapy with re-irradiation with SBRT technique for in-field recurrent lung tumors appears to be a effective and well-tolerated option for cautiously selected patients even centrally located. Our results suggest that, lower BED doses could still provide excellent LC for recurrent lung tumors in the previous RT field with an acceptable complication rate.

Stereotactic Body Radiation Therapy as Salvage for Intrathoracic Recurrence in Patients With Previously Irradiated Locally Advanced Non–Small Cell Lung Cancer

The purpose of this study is to provide data on the outcomes of using stereotactic body radiotherapy (SBRT) as a means of salvage for non-small cell lung cancer (NSCLC) relapses previously treated with radiation. The records of 128 consecutive patients treated with thoracic SBRT from 2009 through 2012 were retrospectively reviewed. Twenty-seven patients (29 lesions) treated with prior thoracic radiation for stage IIB-IIIB NSCLC with subsequent recurrences and retreated with SBRT were identified. The median prior radiation dose was 64.8 Gy (range, 45 to 74 Gy) with a median retreatment dose of 50 Gy (range, 30 to 54 Gy), corresponding to a biological equivalent dose of 100 Gy (range, 48 to 151 Gy), at a median time of 13.4 months from prior radiation. The mean follow-up after salvage SBRT was 22 months. Local failure following salvage was 11%, nodal failure was 37%, and distant failure was 30%. The local recurrence-free survival at 2 years was 72%. Out-of-field failure was predictive for worse local control (hazard ratio, 47.38; 95% confidence interval, 5.795-64.899). Progression-free survival at 1 year was 55% and 38% at 2 years. Overall survival at 2 years from SBRT salvage was 79%. Salvage biological equivalent dose ≥100 Gy was predictive of improved progression-free survival (48% vs. 18%, P=0.021) and overall survival (91% vs. 52%, P=0.004) at 2 years. The rate of symptomatic pneumonitis was 63% and chest wall pain reported was 26%. We observed improved outcomes following SBRT as a means of salvage for locally advanced recurrent NSCLC over traditional radiation therapy options. The toxicities were greater than expected from naive lung irradiation, but the adverse effects remained controlled with medications.

(18)F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: preliminary results.

BackgroundA new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [18F]Choline ([18F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa).MethodsTwenty-nine pts with oligometastatic PCa (≤3 synchronous active lesions detected with [18F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [18F]FMCHPET/CT.ResultsA total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3–40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20–62.14 months). No grade 3 or 4 toxicity was recorded.ConclusionsRepeated salvage [18F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa.

Salvage Stereotactic Body Radiotherapy (SBRT) Following In-Field Failure of Initial SBRT for Spinal Metastases

We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (P<.01). No radiation-induced vertebral compression fractures or cases of myelopathy were observed. A second course of spine SBRT, most often with 30 Gy in 4 fractions, for spinal metastases that failed initial SBRT is a feasible and efficacious salvage treatment option.

Salvage stereotactic body radiotherapy for locally recurrent non-small cell lung cancer after sublobar resection and i(125) vicryl mesh brachytherapy.

Locally recurrent non-small cell lung cancer (LR-NSCLC) remains challenging to treat, particularly in patients having received prior radiotherapy. Heterogeneous populations and varied treatment intent in existing literature result in significant limitations in evaluating efficacy of lung re-irradiation. In order to better establish the impact of re-irradiation in patients with LR-NSCLC following high-dose radiotherapy, we report outcomes for patients treated with prior sublobar resection and brachytherapy that subsequently underwent stereotactic body radiotherapy (SBRT). A retrospective review of patients initially treated with sublobar resection and I(125) vicryl mesh brachytherapy, who later developed LR-NSCLC along the suture line, was performed. Patients received salvage SBRT with curative intent. Dose and fractionation were based on tumor location and size, with a median prescription dose of 48 Gy in 4 fractions (range 20-60 Gy in 1-4 fractions). Thirteen consecutive patients were identified with median follow-up of 2.1 years (range 0.7-5.6 years). Two in-field local failures occurred at 7.5 and 11.1 months, resulting in 2-year local control of 83.9% (95% CI, 63.5-100.0%). Two-year disease-free survival and overall survival estimates were 38.5% (95% CI, 0.0-65.0%) and 65.8% (95% CI, 38.2-93.4%). Four patients (31%) remained disease-free at last follow-up. All but one patient who experienced disease recurrence developed isolated or synchronous distant metastases. Only one patient (7.7%) developed grade ≥3 toxicity, consisting of grade 3 esophageal stricture following a centrally located recurrence previously treated with radiofrequency ablation. Despite high-local radiation doses delivered to lung parenchyma previously with I(125) brachytherapy, re-irradiation with SBRT for LR-NSCLC results in excellent local control with limited morbidity, allowing for potential disease cure in a subset of patients.

Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication.

To determine the feasibility of stereotactic body radiotherapy (SBRT) in patients with pelvic sidewall recurrence of uterine cervical cancer after radical hysterectomy or definitive radiotherapy. We retrospectively reviewed 23 patients with locally recurrent uterine cervical cancer limited to the pelvic sidewall who were treated with SBRT at our institution between January 2003 and May 2010. The SBRT dose ranged from 27 to 45 Gy (median, 39 Gy) in three fractions, and the fractional SBRT dose ranged from 9 to 15 Gy (median, 13 Gy). The 2-year overall survival, local progression-free survival and disease progression-free survival rates were 43%, 65% and 52%, respectively. Patients with small tumors (gross tumor volume <30 cm(3) ) had a significantly longer 2-year overall survival rate and 2-year local progression-free survival rate than did patients with large tumors (overall survival rate: 89% vs 12%; P = 0.0001 and local progression-free survival: 85% vs 0%; P = 0.0199). There were three cases (13%) of severe toxicities (rectovaginal fistula). Pelvic pain relief was achieved in all patients. In particular, 10 of 14 patients (71%) achieved analgesic (nonsteroidal anti-inflammatory drug or narcotic) reduction of 50% or more from baseline. SBRT is a feasible treatment option for women with pelvic sidewall tumors from recurrent uterine cervical cancer, especially for small recurrent tumors. However, SBRT should be used carefully in the treatment of large tumors, as the incidence of severe late toxicity increases with the size of the tumor.

O12 Salvage stereotactic body radiotherapy for patients with limited prostate cancer metastases: Deferring androgen deprivation therapy

Patients with metastatic prostate cancer are uniformly treated with castration (surgically or medically), which is associated with numerous side effects such as sexual dysfunction, fatigue, osteoporosis, metabolic syndrome, and others. This single-arm study including 24 patients with limited bone or lymph node prostate cancer (PCa) metastases shows that repeated salvage stereotactic body radiotherapy is well tolerated and defers the necessity to start castration treatment. Background: We investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases. Patients and Methods: Patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. Results: We treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression-free survival was 100% and 42%, respectively. Eleven and 3 patients, respectively, required a second and third salvage treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed. Conclusion: Repeated salvage SBRT is feasible, well tolerated and defers palliative ADT with a median of 38 months in patients with limited bone or lymph node PCa metastases.

Salvage Stereotactic Body Radiotherapy for Patients With Limited Prostate Cancer Metastases: Deferring Androgen Deprivation Therapy

BackgroundWe investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases. Patients and MethodsPatients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. ResultsWe treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression-free survival was 100% and 42%, respectively. Eleven and 3 patients, respectively, required a second and third salvage treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed. ConclusionRepeated salvage SBRT is feasible, well tolerated and defers palliative ADT with a median of 38 months in patients with limited bone or lymph node PCa metastases.