The potential of radiotherapy to enhance the efficacy of renal cell carcinoma therapy

Wolf, Katrien De; Vermaelen, Karim; Meerleer, Gert De; Lambrecht, Bart N.; Ost, Piet

doi:10.1080/2162402x.2015.1042198

Cited by 39 publications

(36 citation statements)

References 116 publications

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“…Immunotherapy with antibodies against the programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) have demonstrated excellent preliminary results (48)(49)(50). Interestingly, SBRT might also be applied to enhance immunogenic the anti-tumor response via the abscopal effect: clinical studies have described regression of non-irradiated distant lesions following SBRT to an RCC metastasis (51)(52)(53). This effect is hypothesized to be immune RCC, renal cell carcinoma; OS, overall survival.…”

Section: Toxicitymentioning

confidence: 99%

“…This effect is hypothesized to be immune RCC, renal cell carcinoma; OS, overall survival. mediated (40,53). However, the abscopal effect occurs rarely after SBRT alone and might be fostered by simultaneous treatment with synergistic immunomodulatory agents (40,53).…”

Section: Toxicitymentioning

confidence: 99%

“…However, the abscopal effect occurs rarely after SBRT alone and might be fostered by simultaneous treatment with synergistic immunomodulatory agents (40,53). Hence, a potential future application of SBRT in patients with metastatic RCC might include the addition of systemic immunomodulatory therapy by inducing persistent anti-tumor immunity and potentially improving long-term survival (40,53).…”

Section: Toxicitymentioning

confidence: 99%

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Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma—a multicenter analysis of the German working group “Stereotactic Radiotherapy”

Hoerner-Rieber¹,

Duma²,

Blanck³

et al. 2017

J. Thorac. Dis.

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Background: Renal cell carcinoma (RCC) is traditionally considered to be radioresistant. Radiotherapy response rates are believed to improve with hypofractionated, high dose stereotactic body radiotherapy (SBRT).However, limited data exist regarding the role of SBRT in the treatment of pulmonary metastases. Methods: The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology analyzed its multi-institutional database of more than 700 patients who received SBRT for pulmonary metastases. Treatment was performed at 10 centers between 2001 and 2016. Patients with metastatic RCC were included in the study. Tumor characteristics, treatment details, and follow-up data including survival, local control (LC), distant metastases, and toxicity were evaluated. Results: A total of 46 RCC patients treated with SBRT for 67 lung metastases were identified, who received a median total biologically effective dose (BED iso ) at planning target volume (PTV) isocenter of 117.0 Gy (range, 48.0-189.0 Gy). A median fractional dose of 20.8 Gy at isocenter (range, 6.0-37.9 Gy) was administered in a median number of 3 fractions (1-8 fractions). After a median follow-up time of 28.3 months for all patients, 1-and 3-year LC rates were 98.1% and 91.9%, with corresponding 1-and 3-year overall survival (OS) of 84.3% and 43.8%, respectively. Pulmonary metastases treated with BEDiso ≥130 Gy showed a trend for superior LC (P=0.054). OS was significantly improved in both uni-and multivariate analysis for patients with higher Karnofsky performance scale, lower maximum pulmonary metastasis diameter and lack of post-SBRT systemic therapy due to progression (P=0.014; P=0.049; P=0.006). Only mild acute and late toxicity was reported.

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Section: Toxicitymentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 99%

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Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma—a multicenter analysis of the German working group “Stereotactic Radiotherapy”

Hoerner-Rieber¹,

Duma²,

Blanck³

et al. 2017

J. Thorac. Dis.

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“…This focus largely overlooks the tumor intrinsic barriers to effective T cell-mediated killing including T cell trafficking to the tumor microenvironment (6), presence of immunosuppressive cells (7), and expression of immunogenic antigens by tumors cells (8). mRCC is characterized as a heavily lymphocyte infiltrated tumor type with low and heterogeneous expression of tumor-associated antigens (TAA) (9, 10).…”

Section: Introductionmentioning

confidence: 99%

A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma

Singh

Winslow

Kermany

et al. 2017

Clinical Cancer Research

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Purpose While stereotactic body radiation therapy (SBRT) can reduce tumor volumes in metastatic renal cell carcinoma (mRCC) patients, little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of mRCC patients and analyze the immunological impact of high-dose radiation. Experimental Design Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, mRCC patients were treated with 15 Gray (Gy) SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930). Results RCC cells treated in vitro with radiation had increased TAA expression compared to untreated tumor cells. Fourteen patients received SBRT followed by surgery and treatment was well tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67+ proliferating CD8+ T cells and FOXP3+ cells were increased in SBRT-treated patient specimens in tumors and at the tumor-stromal interface compared with archived patient specimens. Conclusions It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared to archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC.

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“…Another rationale is that of expected synergy between SBRT and systemic therapies. As SBRT has shown to stimulate tumor-specific immunity, testified by the rare abscopal effect, it might enhance the effect of other immunomodulatory drugs [56,57]. A phase I and II trial combining high dose interleukin 2 (IL2) with SBRT showed increased response rates to IL2 compared with historical data [58,59].…”

Section: Combination Therapymentioning

confidence: 99%

Non-Surgical Ablative Treatment of Distant Extracranial Metastases for Renal Cell Carcinoma: A Systematic Review

Verbiest

Meerleer

Albersen

et al. 2018

KCA

Self Cite

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Abstract.Background: Local ablative treatments of extracranial metastases are increasingly used in renal cell carcinoma (RCC), but their impact on outcome and toxicity remains unclear. Objectives: To perform a systematic review on the efficacy and toxicity of stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) for the treatment of distant extracranial RCC-metastases. Methods: Search strategy: Pubmed, Embase and the national trial register were searched for the combination of metastatic RCC and SBRT or RFA. Eligible studies were original comparative studies with at least 10 patients per treatment arm, published since 2000 and reporting on at least one of: local control, overall or cancer specific survival, symptom control, toxicity. When possible, hazard ratios were calculated from survival curves. Results and limitations:No eligible studies on RFA were found. Eight studies on SBRT were included, all were nonrandomized and seven were observational. Six included only bone metastases. Radiation regime, treatment site and measured outcomes were heterogeneous and intrinsic risks of bias were high. SBRT, especially single dose 24Gy in the spine, seemed more effective than lower dose SBRT or conventional radiotherapy in achieving local control and pain control. Local control rates were 80-90%. The risk of vertebral compression fracture after SBRT for spinal metastases might be as high as 10-25% or more, especially at higher doses. Other toxicities were mild. Conclusion: Due to the poor quality of the existing evidence, no definite recommendations on the use of SBRT in metastatic RCC can be made. SBRT, especially a single high dose, seems well tolerated and efficacious in achieving local control and pain relief, but the risk of vertebral compression fractures in spinal metastases is high. Randomized trials are needed to assess impact on local control, symptom control, survival and toxicity, to determine optimal dosing and assess potential synergistic efficacy or toxicity upon combination with systemic treatment.

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The potential of radiotherapy to enhance the efficacy of renal cell carcinoma therapy

Cited by 39 publications

References 116 publications

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma—a multicenter analysis of the German working group “Stereotactic Radiotherapy”

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma—a multicenter analysis of the German working group “Stereotactic Radiotherapy”

A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma

Non-Surgical Ablative Treatment of Distant Extracranial Metastases for Renal Cell Carcinoma: A Systematic Review

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