This is a prospective, interventional, monocentric, clinical study of Stereotactic Body Radiation Therapy (SBRT) for primary or secondary renal tumors, delivering from 25-26 Gy/1 fraction to 42-48 Gy/3-4 fractions or 40-50 Gy/5 fractions (standard prescriptions for the internationl guidelines, according to tumor size), using a robotic accelerator -CyberKnife® (Accuray, Sunnyvale, CA)-, with fiducial-tracking, to observe the acute and late toxicity reduction (as primary objectives), due to the maximum precision of the treatment. Secondary objectives are Local Relpase-Free Survival (LRFS), Regional Relapse-Free Survival (RRFS), Distant Metastasis-Free Survival (DMFS), Disease-Free Survival (DFS), Cancer Specific Survival (CSS), Overall Survival (OS) and Quality-of-Life (QoL). A total of 60 participants are expected to be enrolled over four years, and the follow-up of enrolled patients will be three years.

Renal Cell Carcinoma (RCC) is the eighth most common cancer diagnosed in Europe, with a rising incidence, particularly in old patients. The standard of care for operable patients with primary RCC is surgical resection, however, not all patients are suitable candidates for surgery. Alternative approaches, such as thermal ablation, present significant limitations, as reduced efficacy for lager tumors (>3-4 cm) and those located near the renal hilum.

Traditionally, Radiotherapy (RT) has not been considered an effective treatment for RCC due to its perceived radioresistance. High dose radiation therapy RCC leads to both direct cancer cell death and indirect cancer death from vasculature disruption.

The paradigm of radioresistance has shifted significantly with the advent of stereotactic body radiotherapy/ ablative radiotherapy (SBRT/SABR), which has demonstrated promising efficacy in local control while preserving renal function. The radiosensitivity varies in laboratory studies, with low α/β values (2.6 Gy - 6.9 Gy), thus RCC's lines are more responsive to increased radiation fraction size.

SBRT is non-invasive, delivers high doses with precision, using a steep dose gradient over a small number of treatment sessions. This approach has recently demonstrated promising local control (LC), and acceptable toxicity, even for large tumors.

IROCK (the International Radiosurgery Consortium of the Kidney) included 223 patients pooled from nine institutions, with a median follow up of 30 months. No difference in LC and toxicity was observed between patients receiving single fraction SBRT at 25 Gy (range 14-26 Gy) and multiple fractions SBRT at a median of 40 Gy (range 24-70 Gy) in four fractions was observed.

In 2022, IROCK reported the 5-year outcomes of 190 patients with primary RCC. The 7-year cumulative local failure rate was 8.4%, with no significant difference in the incidence of grade ≥2 between single fraction SBRT (5%) and multi-fraction SBRT (6%).

The TransTasman Radiation Oncology Group (TROG) 15.03 FASTRACK II trial was a non-randomized, phase 2, multicenter study with 71 pts enrolled, and 70 underwent SBRT. Treatment was delivered according to tumor size, with 23 patients (33%) received a single- fraction dose of 26 Gy (for tumors ≤ 4 cm) and 47 patients received 42 Gy in 3 fractions (for tumors >4 and ≤10 cm). Median follow up was 43 months. Local Control was 100%, with no observed local failures during the study protocol. Cancer specific survival was 100%, while freedom from distant failure was 97% at 36 months. Overall Survival was 82% at 36 months. SBRT was well tolerated with no grade 4 or 5 adverse events. The systematic review conducted for the International Society of Stereotactic Radiosurgery (ISRS) guidelines analyzed 36 studies with 822 patients. The median LC was 94.1 % (range 70-100%), 5-year progression-free survival was 80.5 % (range 72-92%), and 5- year Overall Survival was 77.2 %. SBRT was associated with minimal impact on renal function, with only a 3.9% of patients requiring post treatment dialysis across studies. Abancourt et al. analyzed 144 patients treated between 2008 and 2020, mainly with 26 Gy/ 1 fraction and 42 Gy/ 3 fractions, and with a 43 month median follow-up (IQR 24-81.2) local control at 5 years was 96%. Overall survival was 58 months and 5-year cumulative incidence of cancer related deaths was 8% (95% CI 3-15%). As much as 49% of patients experienced at least one toxicity, of which 32% were grade 1, 14% grade 2 and 1% grade 3. Two patients (1%) underwent dialysis. Median eGFR loss was 7 ml/min (IQR -17; 0) at the last follow-up.

The proposed clinical study involves a cutting-edge dose delivery method and a precise treatment planning. The high-dose conformation and real-time imaging accuracy for target identification and adjustment during treatment ensure the validity of this approach.

The treatment will be performed according to current guidelines. For primary disease definitive radiation therapy using SBRT will be considered as a treatment option for non-optimal surgical candidates, for patients with T1 tumors (<10 cm in diameter, according to FASTRACK II trial). SBRT will be delivered using 1-5 fractions. Dose and fractionation options will attempt to keep the biologically effective dose (BED) to ≥80 Gy assuming an α/β ratio of 10 due to association with improved local control.

This is a prospective, interventional, monocentric, clinical study of SBRT for primary or secondary renal tumors, delivering from 25-26 Gy/1 fraction to 40-50 Gy/5 fractions (according to tumor size), using CyberKnife with fiducial-tracking. The primary objective is acute and late toxicity reduction, due to the maximum precision of the treatment. Secondary objectives concern loco-regional and distant control, overall and specific survival, quality-of-life.

The study plans to enroll a total of 60 patients, needed for the ≥ G2 toxicity analysis , according to the study design, and with 20% compensation for potential drop-outs.

Inclusion Criteria:

1. Histological or clinical diagnosis of primary or secondary kidney tumors
2. Patients aged ≥18 years
3. Signed informed consent
4. Tumor up to 10 cm in the greatest diameter (sum of diameters in case of multiple lesions)
5. PS (ECOG) ≤2
6. No prior local radiotherapy
7. Fertile women using contraception methods previously initiated (a pregnancy test will be prescribed)

Exclusion Criteria:

1. Patients aged < 18 years
2. Tumors > 10 cm
3. PS ECOG ≥3
4. Psychiatric or other disorders that may prevent the patient from signing informed consent
5. Previous invasive cancer, except for skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the oral cavity or bladder)
6. Pregnant women
7. Collagen diseases
8. Sjogren's syndrome