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Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases.

ABSTRACT: Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases.We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC and toxicity after SAbR were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Predictors of local failure were analyzed with ?2, Kaplan-Meier, and log-rank tests.In most cases (74%), SAbR was delivered with total doses of 40 to 60 Gy, 30 to 54 Gy, and 20 to 40 Gy in 5 fractions, 3 fractions, and a single fraction, respectively. The median biologically effective dose (BED) using the universal survival model was 134.5 Gy. The 1-year LC rate after SAbR was 91.2% (95% confidence interval, 84.9%-95.0%; median follow-up, 16.7 months). Local failures were associated with prior radiation therapy (hazard ratio [HR], 10.49; P<.0001), palliative-intent radiation therapy (HR, 4.63; P=.0189), spinal location (HR, 5.36; P=.0041), previous systemic therapy status (0-1 vs >1; HR, 3.52; P=.0217), and BED <115 Gy (HR, 3.45; P=.0254). Dose received by 99% of the target volume was the strongest dosimetric predictor for LC. Upon multivariate analysis, dose received by 99% of the target volume greater than BED of 98.7 Gy and systemic therapy status remained significant (HR, 0.12 and 3.64, with P=.0014 and P=.0472, respectively). Acute and late grade 3 toxicities attributed to SAbR were observed in 3 patients (1.7%) and 5 patients (2.9%), respectively.SAbR demonstrated excellent LC of metastatic renal cell carcinoma with a favorable safety profile when an adequate dose and coverage were applied. Multimodality treatment with surgery should be considered for reirradiation or vertebral metastasis. A higher radiation dose may be required in patients who received previous systemic therapies.

SUBMITTER: Wang CJ

PROVIDER: S-EPMC5555369 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases.

Wang Chiachien Jake CJ Christie Alana A Lin Mu-Han MH Jung Matthew M Weix Derek D Huelsmann Lorel L Kuhn Kristin K Meyer Jeffrey J Desai Neil N Kim D W Nathan DWN Pedrosa Ivan I Margulis Vitaly V Cadeddu Jeffrey J Sagalowsky Arthur A Gahan Jeffrey J Laine Aaron A Xie Xian-Jin XJ Choy Hak H Brugarolas James J Timmerman Robert R Hannan Raquibul R

International journal of radiation oncology, biology, physics 20170501 1

<h4>Purpose</h4>Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases.<h4>Methods and materials</h4>We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC an ...[more]

PMID: 28587057

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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: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:Abstract Background Background: It is estimated that a significant number of patients presenting with metastatic RCC are either ineligible, not recommended for, or refuse surgery. There remains no well-established method for addressing the primary tumor in such patients. Stereotactic ablative radiotherapy (SABR) is a highly effective modality for the treatment of the primary tumor in RCC. Our study seeks to evaluate SABR as an alternative approach to treat the primary tumor in patients with metastatic RCC receiving immunotherapy, who are not recommended for surgery, or who decline surgery. The primary objective of the study is to determine whether the addition of SABR to the primary tumor in combination with immunotherapy improves outcomes compared to immunotherapy alone in patients with metastatic, unresected, renal cell carcinoma (RCC). The primary endpoint is nephrectomy and radiographic progression-free survival (nrPFS) with progression determined as per iRECIST criteria. Patients are eligible if they are not recommended for upfront surgery, have a primary tumor treatable with SABR, and are candidates for immunotherapy. Immunotherapy is physician’s choice and will include either two different immunotherapy regimens (IO-IO) or immunotherapy in combination with a VEGF inhibitor (IO-VEGF). Methods 240 patients will be randomized in a 2:1 ratio favoring SABR plus immunotherapy (n=160) as compared to standard of care immunotherapy alone (n=80). The sample size will provide 90% power at a one-sided alpha level of 0.05 to detect a hazard ratio for nrPFS of 0.61, i.e., a 40% reduction in the rate of events. One-year PFS in the nivolumab plus ipilmumab arm was 50% (n=550, intermediate/poor risk population). Checkmate 9ER (Choueiri 2021) showed a one-year PFS rate in patients receiving nivolumab plus Cabozantinib (n=323) of 45-58% (intermediate/poor risk population). We have therefore estimated a one-year nrPFS rate of 50% in the control (immunotherapy alone) arm for SAMURAI. We expect nephrectomies to contribute only a small fraction to the total nrPRS events. To detect a hazard ratio of 0.62, which corresponds under exponential distribution assumptions to an absolute 15% improvement in one-year nrPFS from 50% in the control group to 65% in the experimental arm (SABR plus immunotherapy), a total sample size of 240 patients will be enrolled. This design will provide 90% power, based on a one-sided logrank test at the 0.05 alpha level, with three years of accrual and two further years of follow-up. The expected number of nrPFS events is E=175. The calculations allow for a 10% non-eligible/early dropout rate. The trial is currently open and accruing through the NRG oncology cooperative group (NCT05327686).

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.

Dataset Information

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases.

Publications

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases.

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