The incidence of kidney cancer diagnosis has been increasing over the last years. Surgical resection and local ablation are primary treatment options for localized disease. However, many patients are deemed medically inoperable, technically high risk for surgery or local ablation, or ultimately decline these procedures. Stereotactic body radiation therapy (SBRT) using conventional x-rays has recently been shown to improve outcomes for patients with primary renal cell carcinoma (RCC) in terms of local control and toxicity. However, this treatment may be associated with a significant decline in kidney function that necessitates additional intervention including dialysis in some patients. Proton therapy possesses unique properties that allow the bulk of the energy to be released at the tumor (Bragg peak) while sparing nearby healthy tissues, particularly the remaining ipsilateral and contralateral kidneys. SPARE is a single arm, phase II study. Nineteen patients will be recruited and followed for 2 years. Eligible criteria include a biopsy confirmed diagnosis of primary RCC, if feasible, medically inoperable, technically high-risk patients for surgery or local ablative procedures, or decline surgery or ablation, and no clinical or radiographic evidence of metastatic disease. Radiotherapy treatment planning is undertaken using four dimensional computed tomography scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a proton based SBRT using 40–42 Gy in 3–5 fractions. The primary endpoint is the change in Kidney function following proton based SBRT. The secondary endpoints are local control, toxicity profile, progression and overall survival. SPARE study represents the first trial to our knowledge evaluating the use of proton based SBRT for treatment of primary RCC. We aim to assess the efficacy and toxicity of this approach and to compare our results to historical outcomes established by previous trials. Proton therapy with its unique properties may be able to spare more ipsilateral and contralateral healthy kidney tissue, thus preserving kidney function superior to photon SBRT particularly in patients with challenging situations including patients with a solitary kidney, large tumors close to nearby organs or poor baseline kidney function. Clinicaltrials.gov NCT06376669, registered April 19, 2024.

Background: Limited data inform the outcomes of patients with high-risk neuroblastoma (HR-NBL) who relapse after high-dose chemotherapy, autologous stem cell transplantation (ASCT), and external beam radiotherapy (EBRT). Methods: This is a multi-institutional retrospective study of 84 patients with HR-NBL diagnosed between 1997–2021 with a first recurrence after definitive upfront treatment, including ≥1 ASCT and EBRT. Site(s) of first relapse were defined with relation to a patient’s primary tumor location. Progression-free survival (PFS) and overall survival (OS) outcomes were analyzed using Kaplan–Meier curves and log-rank tests. Cox proportional hazard models were used for univariate and multivariable analyses. Results: Twenty-four patients had local recurrences with or without distant relapses (LR) and 60 had distant relapses only. The LR cohort had higher rates of MYCN amplification (70% vs. 36%, p = 0.016). At relapse, the LR cohort had lower rates of additional radiotherapy (32% vs. 61%, p = 0.029) and higher rates of additional surgery (29% vs. 5%, p = 0.005), with similar rates of chemotherapy for both cohorts. With a median follow-up after first relapse of 1.53 years (range: 0.03–15.82), there were no significant differences in interval PFS and OS between the cohorts. After controlling for age at diagnosis and pattern of recurrence, time to interval relapse ≥ 2 years was a significant predictor of improved OS (HR: 0.50, 95% CI: 0.29–0.85, p = 0.011). Conclusions: Patients with relapsed HR-NBL have poor outcomes with median OS < 2 years. Time to relapse was a significant predictor of OS.

Study of proton stereotactic body radiation therapy (SBRT) for spinal metastasis has been limited, largely due to concerns of increased risk of spinal cord injury given the challenges of end of range relative biological effectiveness (RBE). Although the 1.1 RBE constant for proton beam has been adopted for clinical use, data indicate that proton RBE is variable and dependent on technical-, tissue-, and patient factors. To better understand the safety of proton SBRT for spinal metastasis, this dosimetric analysis compares plans using photon robotic techniques and proton therapy accounting for RBE-weighted dose (D_{RBE}). Nine patients with spinal metastasis were selected to be representative of a broad range of complex clinical practice (3 cervical, 3 thoracic, 3 lumbar) that are uniquely challenging to treat with SBRT were identified. Each vertebral level contained a case with paraspinal extension, a reirradiation case, and a case with high-grade epidural disease (Bilsky grade ≥1c) given that such complex cases in current practice often require target volume under-coverage with photon SBRT (PH-SBRT) in order to meet organ at risk (OAR) dose constraints. All selected patients were treated with PH-SBRT using a robotic system to a prescription dose of 30 Gy in 5 fractions despite our institutional preference for further dose escalation, because further dose escalation was not feasible in the original planning process while keeping normal tissues below acceptable dose constraints. To see if superior target coverage could be achieved with proton treatment, comparative intensity modulated proton therapy (IMPT) plans were generated with the same prescription dose as what was clinically delivered using the 1.1 RBE constant. Dose escalated IMPT plans were then generated to 45 Gy(RBE) in 5 fractions. Variable RBE models (Carabe, McNamara, and Wedenberg) were then utilized to generate RBE-weighted dose D_{RBE} distribution for 30 Gy(RBE) and 45 Gy(RBE) plans using the α/β value (which was 3.76 in this study), physical dose, linear energy transfer (LET) value, and dose per fraction parameters. Proton plans used the robust optimization parameters of ±3.5% range and 2-mm setup uncertainties. Planning target volume (PTV) coverage and OARs sparing were compared using the Wilcoxon signed-rank test. Planning target volume coverage was significantly improved when comparing PH-SBRT at 30 Gy in 5 fractions (median: 25 Gy) to IMPT at 30 Gy[RBE] in 5 fractions (median: 30.3 Gy[RBE], P = .02) and 45 Gy(RBE) in 5 fractions (median 35.6 Gy[RBE], P = .001). Maximum dose of the spinal cord (cord Dmax) was significantly lower with IMPT at 30 Gy(RBE) (median: 17.6 Gy[RBE], P = .04) and 45 Gy(RBE) (median: 16.1 Gy[RBE], P = .04) compared to conventional plan at 30 Gy (median: 18 Gy). Spinal cord expansion (cord + 2 mm) maximum dose did not change in both photon (median 21.5 Gy) and proton plans (median 22.5, P = .27). Other OARs were better spared with the same and dose-escalated proton plans. No difference was seen in cord Dmax when comparing the PH-SBRT at 30 Gy to D_{RBE} at 30 and 45 Gy(RBE) using Carabe-, McNamara-, or Wedenberg models. However, for spinal cord expansion (cord + 2 mm), there was significant difference between PH-SBRT and D_{RBE} at 30 Gy(RBE) and 45 Gy(RBE) in 5 fractions using Carabe- (median: 25.4 Gy[RBE], P = .002), McNamara- (median: 25.1 Gy[RBE], P = .003), or Wedenberg (median: 24.8 Gy[RBE], P = .0001) models. The average increase in the spinal cord expansion maximum dose using these models compared to the fixed RBE plans was 5.3%. We report the first dosimetric analysis of proton SBRT for spine metastasis using variable RBE dose models. Compared to photon SBRT, IMPT may provide improved target coverage and better spare adjacent OARs, though fixed RBE models can underestimate the maximum dose to adjacent OARs. Future prospective studies are needed to validate these results.

Photon based Stereotactic Body Radiotherapy (PH-SBRT) has emerged as a promising option for treatment of primary renal cell carcinoma (RCC), however is associated with decrements in long-term kidney function and toxicity to adjacent organs at risk (OARs). We compared proton (PT) based SBRT versus PH-SBRT regarding target coverage, OARs, and maximum peak doses of 125% and 142%. All variables were compared using student t-tests. Target coverage was comparable between plans for gross tumor volume (GTV) and clinical target volume (CTV). OARs were greatly spared by PT-SBRT including small bowel; V5 Gy to V25 Gy and maximum dose (10.47, 20.22, P = .02), large bowel; V5 Gy to V25 Gy and maximum dose (16.16, 23.90, P = .03), all volumes of uninvolved ipsilateral kidney and maximum dose to heart, lungs, esophagus, stomach, duodenum, ipsilateral ureter, and spinal canal. The ratio of ipsilateral kidney V50%/Vtot (volume receiving 50% of the dose/total volume), which is correlated with glomerular filtration rate loss in prospective trials, was significantly lower with PT-SBRT for both maximum dose of 125% (25.41, 19.97, P < .01) and 142% (23.33, 19.18, P < .01). Integral dose was significantly lower with protons. PT-SBRT with higher peak dose allowed for additional sparing of OARs: stomach V 10 Gy, liver V 25 Gy, large bowel V 30 Gy, V 35 Gy, ipsilateral kidney cortex. PT-SBRT improved target coverage while reducing dose to the involved kidney and adjacent OARs. Protons allow delivery of maximum peak dose escalated plans without exceeding the normal tissues limit and have the potential to better preserve renal function. Prospective studies are warranted to validate these findings and potential clinical benefits.