Stereotactic ablative radiotherapy: a game-changer in primary renal cancer therapy.
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ABSTRACT:
SUBMITTER: Castronovo FM
PROVIDER: S-EPMC11291405 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Stereotactic ablative radiotherapy: a game-changer in primary renal cancer therapy.
Castronovo Francesco Mosè FM Zilli Thomas T Angrisani Antonio A Bosetti Davide Giovanni DG
Translational andrology and urology 20240716 7
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Project description: Not available
| S-EPMC10698523 | biostudies-literature
Project description:BackgroundMost renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.ObjectiveTo investigate whether SAbR is effective in the management of primary RCCs.Design, setting, and participantsPatients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.Outcome measurements and statistical analysisThe primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 mm/yr on active surveillance) and pathologic evidence of tumor response at 1 yr. Secondary endpoints included LC by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), safety, and preservation of kidney function. Exploratory tumor cell-enriched spatial protein and gene expression analysis were conducted on pre- and post-treatment biopsy samples.Results and limitationsTarget accrual was reached with the enrollment of 16 ethnically diverse patients. Radiographic LC at 1 yr was observed in 94% of patients (15/16; 95% confidence interval: 70, 100), and this was accompanied by pathologic evidence of tumor response (hyalinization, necrosis, and reduced tumor cellularity) in all patients. By RECIST, 100% of the sites remained without progression at 1 yr. The median pretreatment growth rate was 0.8 cm/yr (interquartile range [IQR]: 0.3, 1.4), and the median post-treatment growth rate was 0.0 cm/yr (IQR: -0.4, 0.1, p < 0.002). Tumor cell viability decreased from 4.6% to 0.7% at 1 yr (p = 0.004). With a median follow-up of 36 mo for censored patients, the disease control rate was 94%. SAbR was well tolerated with no grade ≥2 (acute or late) toxicities. The average glomerular filtration rate declined from a baseline of 65.6 to 55.4 ml/min at 1 yr (p = 0.003). Spatial protein and gene expression analyses were consistent with the induction of cellular senescence by radiation.ConclusionsThis clinical trial adds to the growing body of evidence suggesting that SAbR is effective for primary RCC supporting its evaluation in comparative phase 3 clinical trials.Patient summaryIn this clinical trial, we investigated a noninvasive treatment option of stereotactic radiation therapy for the treatment of primary kidney cancer and found that it was safe and effective.
| S-EPMC10440291 | biostudies-literature
Project description:PurposeTo conduct an international survey of radiation oncologists treating primary renal cell carcinoma (RCC) with SABR to ascertain the general patterns of SABR use, common dose/treatment/follow-up details, and expected outcomes.Materials and methodsA 51-question survey was created containing the following themes: prevalence and clinical scenarios in which RCC SABR is used, dose-fractionation schedules, treatment delivery details, follow-up/outcome assessments, and implementation barriers. The survey was distributed widely across multiple influential radiation oncology societies and social media, and ran from January to April 2023.ResultsA total of 255 respondents participated, mostly from academic centers within Europe/North America. Of these, 40 % (n = 102) currently offer SABR (50 % having begun within the last 3 years). Common barriers in non-users included lack of referrals by urologists and lack of supportive practice guidelines. Of respondents who do offer SABR, 77 % treat both small (4 cm or less) and large (>4 cm) renal masses. Dose-fractionation strategies varied from 27-52 Gy (3-5 fractions) for multifraction regimens, and 15-34 Gy for single fractions. Apart from treatment for medically inoperable disease, scenarios in which SABR was likely to be offered were for recurrence post surgery/thermal ablation and for oligometastatic kidney lesions. Uncommon scenarios included RCC with renal vein/inferior vena cava thrombosis, and as cytoreductive therapy in metastatic RCC. Expected local control outcomes were generally above 70 %, higher for small versus large renal masses.ConclusionsSABR is a relatively newer indication for primary RCC, offered by less than 50% of respondents, with both consistent and variable practice patterns observed.
| S-EPMC11648799 | biostudies-literature
Project description:PurposeOligoprogression, defined as limited sites of progression on systemic therapy, in patients with metastatic renal cell carcinoma (mRCC) is not uncommon, possibly because of inter- and intratumoral heterogeneity. We evaluated the effect of stereotactic ablative radiation therapy (SAbR) for longitudinal control of oligoprogressive mRCC.Methods and materialsPatients with extracranial mRCC were included in this retrospective analysis if they progressed in ≤3 sites on systemic therapy while demonstrating response/stability at other sites and received SAbR to all progressing sites without switching systemic therapy. Our primary endpoint was modified progression-free survival (mPFS), which we calculated from the start of SAbR to the start of a subsequent systemic therapy, death, or loss to follow-up.ResultsWe identified 36 patients with a median follow-up of 20.4 months (interquartile range, 10.9-29.4). Forty-three sites were treated with SAbR with a median dose of 36 Gy (range, 18-50) in 3 fractions (range, 1-5). Median time to SAbR from the start of systemic therapy was 11.4 months (interquartile range, 6.1-17.1). Median mPFS was 9.2 months (95% confidence interval [CI], 5.9-13.2). Patients receiving SAbR while on immunotherapy exhibited a longer median mPFS (>28.4 months, log-rank P = .0001) than patients not on immunotherapy (9.2 months). Median overall survival from SAbR administration was 43.4 months (95% CI, 21.5-not Reached). The 1-year local control rate was 93% (95% CI, 78.7-97.5). Most SAbR-related toxicities were grade 1 to 2 (33% of patients), with one grade 5 hemoptysis event possibly related to SAbR or disease progression.ConclusionsSAbR has the potential to extend the the duration of current systemic therapy for selected patients with mRCC, preserving subsequent therapies for later administration possibly enabling longer treatment duration.
| S-EPMC8498727 | biostudies-literature
Project description:Prostate is the most common non-cutaneous cancer diagnosed among men in North America. Fortunately most prostate cancers are screen detected and non-metastatic on diagnosis. Treatment options for men with localized prostate cancer include surgery ± postoperative radiation or radiation ± androgen deprivation therapy (ADT). Brachytherapy ± external beam radiation treatment (EBRT) appears to have superior long-term disease control over EBRT alone likely because of higher biologic effective dose delivered. Stereotactic ablative body radiation (SABR) is a novel, non-invasive, high-precision EBRT technique that allows safe delivery of biologic doses similar to brachytherapy with similar or lower side effects [measured using toxicity or quality of life (QOL) scales]. Efficacy for SABR appears to be similar to brachytherapy including positive biopsy rates 2-3 years post treatment, biochemical failure (BF) rates out to 10-year and incidence of metastases. SABR dose escalation reduces biopsy positivity and prostate-specific antigen (PSA) nadirs but increases genitourinary (GU) and gastrointestinal (GI) toxicity-no effect on BF has been realized yet. The overall treatment time (OTT) varies in many protocols. Phase 2 randomized data shows that QOL is better in the acute setting with a weekly course of treatment compared to an every other day treatment regimen with no difference in late setting. Follow-up data are immature and likely underpowered to determine efficacy differences. SABR is cheaper and uses less resource than any other radiation technique. Given the healthcare resource challenges (including financial resources), SABR would be a welcomed addition if studies show non-inferiority to other radiation techniques. For patients with de novo or metastatic disease on relapse, there is much enthusiasm regarding the use of SABR in the setting of oligometastatic prostate cancer. SABR appears to be feasible to deliver, well tolerated and may delay the next line of therapy. However, until adequately powered randomized studies confirm a benefit, such an approach cannot be considered standard of care treatment at this time. Enrollment of eligible prostate cancer patients onto SABR clinical trials should be encouraged.
| S-EPMC6043737 | biostudies-literature
Project description:Stereotactic ablative radiotherapy (SABR) has challenged the conventional wisdom surrounding the radioresistance of renal cell carcinoma (RCC). In the past decade, there has been a significant accumulation of clinical data to support the safety and efficacy of SABR in RCC. Herein, we review the use of SABR across the spectrum of RCC. We performed an online search of the Pubmed database from January 1990 through April 2023. Studies of SABR/stereotactic radiosurgery targeting primary, extracranial, and intracranial metastatic RCC were included. For SABR in non-metastatic RCC, this includes its use in small renal masses, larger renal masses, and inferior vena cava tumor thrombi. In the metastatic setting, SABR can be used at diagnosis, for oligometastatic and oligoprogressive disease, and for symptomatic reasons. Notably, SABR can be used for both the primary renal tumor and metastasis-directed therapy. Management of RCC is evolving rapidly, and the role that SABR will have in this landscape is being assessed in a number of ongoing prospective clinical trials. The objective of this narrative review is to summarize the evidence corroborating the use of SABR in RCC.
| S-EPMC10742565 | biostudies-literature
Project description:Stereotactic ablative radiotherapy (SABR) planning for adrenal metastases aims to minimize doses to the adjacent kidney. Renal dose constraints for SABR delivery are not well defined. In 20 patients who underwent MR-guided breath-hold SABR in five daily fractions of 8-10 Gy, ipsilateral renal volumes receiving ≥20 Gy best correlated with loss of renal volumes, with median renal volume reduction being 6% (range: 3%-11%, 10th-90th percentiles). Organ function did not deteriorate in 18 patients, who had post treatment renal function tests available. This suggests that the ipsilateral renal volume receiving 20 Gy can be used as partial organ dose constraint for SABR to targets in the upper abdomen.
| S-EPMC8473532 | biostudies-literature
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.
| S-EPMC7647381 | biostudies-literature
Project description: Not available
| S-EPMC5864629 | biostudies-literature
Project description:Background and aimsLiver cancer is the third leading cause of cancer related death due to treatment resistance and late onset of symptoms (Rumgay in J Hepatol 77: 1598-1606, 2022). The role of external beam radiotherapy (EBRT) in treatment of unresectable liver cancer needs to be defined. The use of particle therapy such as carbon ion radiation therapy (CIRT) with high linear energy transfer (LET) could increase efficacy of EBRT while limiting the toxic effects of radiation on non-cancerous liver tissue. Promising effects of CIRT have been described in several studies during the past decades, mostly in Japan. To date, no standardized treatment protocol has been established and European data on CIRT for liver cancer is lacking. This retrospective analysis aims to investigate efficacy and safety of hypofractionated CIRT compared to photon-based stereotactic body radiation (SBRT) in primary liver cancer.MethodThirty-six (n = 36) and twenty (n = 20) patients with primary malignant liver tumors were treated with hypofractionated CIRT (4 fractions) and photon-based SBRT, respectively, between 2011 and 2022 and were retrospectively evaluated for survival, local control, and toxicity.ResultsTwo-year local control rate after CIRT was 92.3%. Compared to photon- based SBRT, CIRT scores with a significantly longer median distant progression free survival (3.1 versus 0.9 years). In a matched pair comparison of the two treatment regimens, the CIRT cohort demonstrated both longer 2-year overall survival (100% versus 59.6%) and longer 2-year distant PFS (75.7% versus 22.9%). No significant impairment of liver function was observed in either cohort.ConclusionIn this retrospective analysis, patients who received CIRT presented excellent local tumor control and had better oncologic outcomes than patients who received photon-based SBRT. SBRT with carbon ions is a promising local ablative treatment option that needs further investigation in large prospective trials.
| S-EPMC11834390 | biostudies-literature