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A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis.

ABSTRACT: Purpose:Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. Methods and Materials:A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ?grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. Results:Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (?/? = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ?grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. Conclusions:Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

SUBMITTER: Corkum MT

PROVIDER: S-EPMC7557139 | biostudies-literature | 2020 Sep-Oct

REPOSITORIES: biostudies-literature

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A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis.

Corkum Mark T MT Mendez Lucas C LC Chin Joseph J D'Souza David D Boldt R Gabriel RG Bauman Glenn S GS

Advances in radiation oncology 20200512 5

<h4>Purpose</h4>Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT.<h4>Methods and materials</h4>A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for ...[more]

PMID: 33083660

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Project description:PurposeTo evaluate the efficacy and toxicity of external beam reirradiation using a pulsed low-dose-rate (PLDR) technique.Methods and materialsWe evaluated patients treated with PLDR reirradiation from 2009 to 2016 at a single institution. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0, and local control was assessed using the Response Evaluation Criteria In Solid Tumors, version 1.1. On univariate analysis (UVA), the χ2 and Fisher exact tests were used to assess the toxicity outcomes. Competing risk analysis using cumulative incidence function estimates were used to assess local progression.ResultsA total of 39 patients were treated to 41 disease sites with PLDR reirradiation. These patients had a median follow-up time of 8.8 months (range 0.5-64.7). The targets were the thorax, abdomen, and pelvis, including 36 symptomatic sites. The median interval from the first radiation course and reirradiation was 26.2 months; the median dose of the first and second course of radiation was 50.4 Gy and 50 Gy, respectively. Five patients (13%) received concurrent systemic therapy. Of the 39 patients, 9 (23%) developed grade ≥2 acute toxicity, most commonly radiation dermatitis (5 of 9). None developed grade ≥4 acute or subacute toxicity. The only grade ≥2 late toxicity was late skin toxicity in 1 patient. On UVA, toxicity was not significantly associated with the dose of the first course of radiation or reirradiation, the interval to reirradiation, or the reirradiation site. Of the 41 disease sites treated with PLDR reirradiation, 32 had pre- and post-PLDR scans to evaluate for local control. The local progression rate was 16.5% at 6 months and 23.8% at 12 months and was not associated with the dose of reirradiation, the reirradiation site, or concurrent systemic therapy on UVA. Of the 36 symptomatic disease sites, 25 sites (69%) achieved a symptomatic response after PLDR, including 6 (17%) with complete symptomatic relief.ConclusionReirradiation with PLDR is effective and well-tolerated. The risk of late toxicity and the durability of local control were limited by the relatively short follow-up duration in the present cohort.

Project description:BackgroundReirradiation using brachytherapy (BT) and external beam radiation therapy (EBRT) are salvage strategies with locally radiorecurrent prostate cancer. This systematic review describes the oncologic and toxicity outcomes for salvage BT and EBRT [including Stereotactic Body Radiation Therapy (SBRT)].MethodsAn International Prospective Register of Systematic Reviews (PROSPERO) registered (#211875) study was conducted using Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. EMBASE and MEDLINE databases were searched from inception to December 2020. For BT, both low dose rate (LDR) and high dose rate (HDR) BT techniques were included. Two authors independently assessed study quality using the 18-item Modified Delphi technique.ResultsA total of 39 eligible studies comprising 1967 patients were included (28 BT and 11 SBRT). In 35 studies (90%), the design was single centre and/or retrospective and no randomised prospective studies were found. Twelve BT studies used LDR only, 11 HDR only, 4 LDR or HDR and 1 pulsed-dose rate only. All EBRT studies used SBRT exclusively, four with Cyberknife alone and 7 using both Cyberknife and conventional linear accelerator treatments. Median (range) modified Delphi quality score was 15 (6-18). Median (range) follow-up was 47.5 months (13-108) (BT) and 25.4 months (21-44) (SBRT). For the LDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 71% (48-89.5) and 52.5% (20-79). For the HDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 74% (63-89) and 51% (45-65). For the SBRT studies, the median (range) 2-year bRFS for the SBRT group was 54.9% (40-80). Mean (range) acute and late grade≥3 GU toxicity rates for LDR-BT/HDR-BT/SBRT were 7.4%(0-14)/2%(0-14)/2.7%(0-8.7) and 13.6%(0-30)/7.9%(0-21.3%)/2.7%(0-8%). Mean (range) acute and late grade≥3 GI toxicity rates for LDR-BT/HDR-BT/SBRT were 6.5%(0-19)/0%/0.5%(0-4%) and 6.4%(0-20)/0.1%(0-0.9)/0.2%(0-1.5). One third of studies included Patient Reported Outcome Measures (PROMs).ConclusionsSalvage reirradiation of radiorecurrent prostate cancer using HDR-BT or SBRT provides similar biochemical control and acceptable late toxicity. Salvage LDR-BT is associated with higher late GU/GI toxicity. Challenges exist in comparing BT and SBRT from inconsistencies in reporting with missing data, and prospective randomised trials are needed.

Project description:We assessed survival after radical prostatectomy, intensity modulated radiation therapy or conformal radiation therapy vs no local therapy for metastatic prostate cancer adjusting for patient comorbidity, androgen deprivation therapy and other factors.We identified men 66 years old or older with metastatic prostate cancer treated with radical prostatectomy, intensity modulated radiation therapy, conformal radiation therapy or no local therapy in the SEER-Medicare linked database from 2004 to 2009. Multivariable Cox proportional hazards models before and after inverse propensity score weighting were used to assess all cause and prostate cancer specific mortality. Competing risk regression analysis was done to assess prostate cancer specific mortality.Of 4,069 men with metastatic prostate cancer radical prostatectomy in 47, intensity modulated radiation therapy in 88 and conformal radiation therapy in 107 were selected as local therapy vs no local therapy in 3,827. Radical prostatectomy was associated with a 52% decrease (HR 0.48, 95% CI 0.27-0.85) in the risk of prostate cancer specific mortality after adjusting for sociodemographics, primary tumor characteristics, comorbidity, androgen deprivation therapy and bone radiation within 6 months of diagnosis. Intensity modulated radiation therapy was associated with a 62% decrease (HR 0.38, 95% CI 0.24-0.61) in the risk of prostate specific cancer specific mortality. Conformal radiation therapy was not associated with improved survival compared to no local therapy. Propensity score weighting yielded comparable results. Competing risk analysis revealed a 42% and 57% decrease (SHR 0.58, 95% CI 0.35-0.95 and SHR 0.43, 95% CI 0.27-0.68, respectively) in the risk of prostate cancer specific mortality for radical prostatectomy and intensity modulated radiation therapy.Local therapy with radical prostatectomy and intensity modulated radiation therapy but not with conformal radiation therapy was associated with a survival benefit in men with metastatic prostate cancer. This finding warrants prospective evaluation in clinical trials.

Project description:PurposeNCT03253744 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.Methods and materialsThis 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.ResultsBetween 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.ConclusionsThe 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.

Dataset Information

A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis.

Publications

A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis.

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