partial volume high-dose irradiation in renal cell carcinoma for intra-tumoural control alongside current management

Conditions: Renal Cell Carcinoma; Renal Cell Carcinoma Metastatic

Summary: prospective, randomised, feasibility study of patients with localised or metastatic renal cell carcinoma (rcc) comparing standard palliative dose radiotherapy to a high-dose hypofractionated regime. primary aim • to demonstrate feasibility of a randomised study comparing high-dose hypofractionated radiotherapy versus standard palliative dose radiotherapy in localised or metastatic renal cell carcinoma the aim is to recruit a minimum of 24 patients; 12 to the control arm and 12 to the high-dose regime. 2 treatment arms, no placebo: * control arm - standard palliative-dose radiotherapy, 30gy in 10 fractions in 3gy per fraction over 2 weeks * high-dose arm - high-dose radiotherapy, 30gy in 5 fractions in 6gy per fraction on alternate days/2-3 fractions a week over 2 weeks

hypothesis the investigators hypothesise that it is feasible to recruit to a study of localised and metastatic renal cell carcinoma comparing a high-dose short fractionation radiotherapy regime (30gy in 5 fractions in alternate day fractions over 2 weeks) in comparison to the standard palliative dose-fractionation (30gy in 10 fractions in daily fractions over 2 weeks). aims primary aim • to demonstrate feasibility of a randomised study comparing high-dose hypofractionated radiotherapy versus standard palliative dose radiotherapy in localised or metastatic renal cell carcinoma secondary aim * to report acute and late toxicity in both treatment groups * to demonstrate completion of quality of life (qol) validated eortc forms by patients under study study design * randomised 1:1 * the study is unblinded for the trial investigators and participants. visits (in line with routine standard care): * 1 pre-treatment appointment * 1 ct planning scan (immobilisation/mould room as required dependent on anatomical site) * 10 radiotherapy treatment appointments (control arm) / 5 radiotherapy treatment appointments (experimental arm) * 2 on-treat clinic reviews (week 1 and week 2) * end of treatment/safety follow up (4 weeks post-radiotherapy) * follow-up at 3 months, 6 months, and 12 months investigations * quality of life questionnaires * blood tests * clinical/physical examination

Eligibility criteria:
inclusion criteria: * histologically confirmed renal cell carcinoma (rcc) (histological confirmation of metastasis not required) or clinically consistent with rcc as per multidisciplinary team (mdt) diagnosis. * not suitable for surgical resection, metastasectomy or ablative therapy due to tumour or patient factors * all extracranial sites which clinically require radiotherapy (as per clinician discretion) * age ≥18 years * karnofsky performance status (kps) ≥50 * adequate baseline organ function applicable to site-of irradiation * haemaglobin ≥90g/dl * platelets ≥50 * bilirubin \<3x uln * inr \<1.4 or correctable with vitamin k * ast or alt \<5x normal range * creatinine \<200umol/l (or established on dialysis). note patients on dialysis are unable to have dynamic contrast enhanced mri. * the use of concurrent systemic therapy is acceptable * ability of the research subject to understand and the willingness to sign a written informed consent document * able to undergo all mandated staging and follow-up investigations * negative pregnancy test (for women of childbearing potential) exclusion criteria: * expected prognosis \<6 months * uncontrolled intracranial metastases * previous radiotherapy, such that the delivery of further radiotherapy is not feasible * unable to have necessary radiotherapy planning, radiotherapy related investigations/fiducials (if required) * co-morbidities or any psychological, familial, sociological or geographical condition which may preclude ability to undergo/attend investigations, treatment or follow-up * other active primary cancer * pregnant or lactating * requiring ongoing treatment with a concomitant medication, which is contraindicated alongside radiotherapy (e.g. methotrexate)

Keywords: standard palliative dose radiotherapy high-dose hypofractionated radiotherapy radiotherapy unblinded