Dataset Information

Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-to-next systemic treatment.

ABSTRACT: PURPOSE:Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR). METHODS:Records of men with OPC who underwent consolidative SABR at our institution were reviewed. SABR was delivered in 1-5 fractions of 5-18 Gray. Kaplan-Meier estimates of local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir?+?2), distant progression-free survival (DPFS), and time-to-next intervention (TTNI) were calculated. RESULTS:In total, 66 OPC patients were identified with consolidative SABR delivered to 134 metastases: 89 bone, 40 nodal, and 5 viscera. The majority of men (49/66) had hormone-sensitive prostate cancer (HSPC). Crude grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no ??grade 3 toxicity. At 1 year, LPFS was 92% and bPFS and DPFS were 69%. Of the 18 men with HSPC who had deferred hormone therapy , 11 (56%) remain disease free following SABR (1-year ADT-FS was 78%). In 17 castration-resistant men, 11 had >?50% prostate-specific antigen (PSA) declines with 1-year TTNI of 30%. CONCLUSIONS:Consolidative SABR in OPC is feasible and well tolerated. The heterogeneity and small size of our series limit extrapolation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggest that this approach warrants continued prospective study.

SUBMITTER: Moyer CL

PROVIDER: S-EPMC6401357 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-to-next systemic treatment.

Moyer C Leigh CL Phillips Ryan R Deek Matthew P MP Radwan Noura N Ross Ashley E AE Antonarakis Emmanuel S ES Reyes Diane D Wright Jean J Terezakis Stephanie A SA Song Daniel Y DY DeVille Curtiland C Walsh Patrick C PC DeWeese Theodore L TL Carducci Michael M Schaeffer Edward M EM Pienta Kenneth J KJ Eisenberger Mario M Tran Phuoc T PT

World journal of urology 20180906 12

<h4>Purpose</h4>Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR).<h4>Methods</h4>Records of men with OPC who underwent consolidative S ...[more]

PMID: 30191396

Similar Datasets

Project description:PurposeStereotactic ablative radiotherapy (SAbR) is a promising alternative for selected patients with renal cell carcinoma (RCC) with oligometastasis. The objective of this study was to evaluate the potential of SAbR for longitudinal control in patients with persistently oligometastatic RCC. We report the impact of SAbR on tumor control rates as well as its tolerability in systemic therapy-naïve patients with oligometastatic disease (without brain metastases) and assess the effect of SAbR on subsequent first line systemic therapy by comparison to historical controls.Methods and materialsWe reviewed patients with metastatic RCC treated with front-line SAbR with a curative intent from 2007 to 2017 at UT Southwestern Kidney Cancer Program. We analyzed local control rates (LCR), toxicity, freedom from systemic therapy (FST), type and duration of first-line systemic therapy, and overall survival (OS). Cox regression and Kaplan-Meier analyses were used.ResultsWe identified 47 patients with oligometastatic RCC treated with SAbR to 88 metastases; 11 patients had more than 1 SAbR course. The local control rate was 91.5% at 2 years with no reported grade ≥3 toxicity. With a median follow-up of 30 months (interquartile range, 13.7-40.9), median FST from first SAbR was 15.2 months (95% confidence interval [CI], 8.8-40.1). The most common systemic therapies initiated after SAbR were pazopanib (60.7%) and sunitinib (14.3%). The duration of first line systemic therapy appeared unaffected by SAbR. Improved FST was observed in patients with metachronous disease (hazard ratio, 2.67; P = .02), solitary metastasis (HR, 2.26; P = .05), and non-bone metastasis (HR, 2.21; P = .04). One-year and 2-year OS after SAbR were 93.1% (95% CI, 80.1-97.7) and 84.8% (95% CI, 69.1-92.9), respectively. Median OS was not reached.ConclusionsSAbR is an effective and safe treatment for selected patients with oligometastatic RCC, can provide longitudinal disease control without systemic therapy for over a year, and does not appear to adversely affect the effectiveness of first-line systemic therapy once initiated. Prospective validation of these findings is being sought through a phase 2 trial.

Project description:BackgroundWe describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease.Methods/designPatients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory.DiscussionThe ORIOLE trial is the first randomized, non-blinded Phase II interventional study in the North America evaluating the safety and efficacy of SABR in oligometastatic hormone-sensitive prostate cancer. Leading-edge laboratory and imaging correlates will provide unique insight into the effects of SABR on the oligometastatic state.Trial registrationsClinicalTrials.gov Identifier: NCT02680587. URL of Registry: https://clinicaltrials.gov/show/NCT02680587 Date of Registration: 02/08/2016. Date of First Participant Enrollment: 05/23/2016.

Project description:ImportanceComplete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT).ObjectiveTo determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer.Design, setting, and participantsThe Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized.InterventionsPatients were randomized in a 2:1 ratio to receive SABR or observation.Main outcomes and measuresThe primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)-measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)-targeted positron emission tomography in the identification of metastatic disease.ResultsIn the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P = .005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P = .002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%; P = .006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P = .03).Conclusions and relevanceTreatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates.Trial registrationClinicalTrials.gov Identifier: NCT02680587.

Project description:To investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).Ten prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTV(Prostate) prescription, and PTV(DIL) prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively.When treating the prostate alone, the median PTV(DIL) prescription was 125% (range: 110%-140%) of the PTV(Prostate) prescription. Median PTV(DIL) D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTV(DIL) prescriptions and similar PTV(DIL) median doses were possible when including the proxSV within the prescription. TCP depended on prostate ?/? ratio and was highest with an ?/? ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm(3) of rectum (Dmax(0.5cc)), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions.Boosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax(0.5cc). If the ?/? ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting.

Project description:PurposePatients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clinical trial.Methods and materialsPatients with a pathologically proven diagnosis of oligometastatic colorectal cancer were enrolled as part of a prospective study. SABR dose and fractionation schedules were dependent on the lesion location and size. Patient follow-up occurred 6 weeks after completion of SABR and at 3-month intervals for the following 3 years. Patients received the Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up visit to assess PR-QoL. The total Functional Assessment of Cancer Therapy-General questionnaire scores were compared with those from baseline using the Wilcoxon signed rank test. Overall survival, local progression-free survival (PFS), and distant PFS were calculated using the Kaplan-Meier estimation to the date of the last follow-up visit/death or local/distant failure.ResultsA total of 31 patients with oligometastatic colorectal cancer with 1 (71.0%), 2 (16.1%), 3 (3.2%), 4 (3.2%), or 5 (6.5%) metastatic lesions were identified. After a median follow-up time of 50.1 months, the median OS from the time of completion of the SABR was 53.9 months (95% confidence interval, 23.2-84.6), and the 5-year OS, local PFS, and distant PFS were 45%, 83%, and 27%, respectively. Acute grade 2+ toxicity was 9.7% (pain, nausea, fatigue) and late grade 3+ toxicity (small bowel obstruction) was 3.2% with no significant change in PR-QoL in the year after SABR.ConclusionsThis subset analysis of a prospective phase 2 study demonstrates that SABR is a safe and effective treatment option for patients with unresectable oligometastic colorectal cancer. In addition, SABR of oligometastatic disease preserves PR-QoL.

Project description:PurposeDespite the strong interest in combining stereotactic ablative radiation therapy (SAR) with immunotherapy, limited data characterizing the systemic immune response after SAR are available. We hypothesized that the systemic immune response to SAR would differ by irradiated site owing to inherent differences in the microenvironment of various organs.Methods and materialsPatients receiving SAR to any organ underwent prospective blood banking before and 1 to 2 weeks after SAR. Peripheral blood mononuclear cells (PBMCs) and serum were isolated. PBMCs were stained with fluorophore-conjugated antibodies against T and natural killer (NK) cell markers. Cells were interrogated by flow cytometry, and the results were analyzed using FlowJo software. Serum cytokine and chemokine levels were measured using Luminex. We analyzed the changes from before to after therapy using paired t tests or 1-way analysis of variance (ANOVA) with Bonferroni's post-test.ResultsA total of 31 patients had evaluable PBMCs for flow cytometry and 37 had evaluable serum samples for Luminex analysis. The total number of NK cells and cytotoxic (CD56dimCD16+) NK cells decreased (P = .02) and T-cell immunoglobulin- and mucin domain-containing molecule-3-positive (TIM3+) NK cells increased (P = .04) after SAR to parenchymal sites (lung and liver) but not to bone or brain. The total memory CD4+ T cells, activated inducible co-stimulator-positive and CD25+CD4+ memory T cells, and activated CD25+CD8+ memory T cells increased after SAR to parenchymal sites but not bone or brain. The circulating levels of tumor necrosis factor-α (P = .04) and multiple chemokines, including RANTES (P = .04), decreased after SAR to parenchymal sites but not bone or brain.ConclusionsOur data suggest SAR to parenchymal sites induces systemic immune changes, including a decrease in total and cytotoxic NK cells, an increase in TIM3+ NK cells, and an increase in activated memory CD4+ and CD8+ T cells. SAR to nonparenchymal sites did not induce these changes. By comparing the immune response after radiation to different organs, our data suggest SAR induces systemic immunologic changes that are dependent on the irradiated site.

Dataset Information

Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-to-next systemic treatment.

Publications

Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-to-next systemic treatment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets