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Page 6 of 10 Berghen et al. J Cancer Metastasis Treat 2021;7:58 https://dx.doi.org/10.20517/2394-4722.2021.123

Figure 2. An example of a photon treatment plan (A) vs. proton treatment plan (B) of a primary RCC in the upper pole of the right
kidney.

There are two retrospective trials reporting on CIRT in primary RCC. Nomiya et al. reported on 10
[49]
patients treated with CIRT for unilateral RCC. The prescribed dose was 72 GyE in 16 fractions. After a
median follow-up of 58 months, the five-year LC rate, progression-free survival, DSS, and OS were 100%,
100%, 100%, and 74%, respectively. No acute toxicity above Grade 1 was observed. One patient developed a
skin ulcer five years after treatment, which was treated with a skin flap transplantation giving rise to this
Grade 4 toxicity. In two patients with diabetic nephropathy, renal function deteriorated significantly after
CIRT, but this was not the case in the other patients.

[50]
Kasuya et al. updated the results of 19 CIRT treated patients. Fifteen patients were treated with a 16-
fraction scheme, of whom 10 patients received a total dose of 72 Gy (RBE) in 16 fractions. A dose-escalation
to 80 Gy was performed in three patients. A total dose of 64 Gy in 16 fractions, used in case of anatomical
proximity to the gastrointestinal tract, was given in the other two patients. Four patients received a
prescribed fractionation schedule of 66 Gy (RBE) in 12 fractions. For a median follow-up of 6.6 years, the
LC rates, DFS, DSS, and OS rates were 94%, 69%, 100%, and 89%, respectively. Seven patients presented with
Grade 2 CKD, of whom four progressed to Grade 4 CKD. Notably, all four patients who deteriorated to
Grade 4 CKD had definitive renal comorbidities pre-CIRT, such as diabetic nephropathy, renal sclerosis, or
a solitary kidney. While caution is advised in patients with pre-existing renal comorbidities, the authors
noted that progression to Grade 4 took an average of 5.6 years, so the natural course of renal disease cannot
be ruled out. One patient had Grade 4 dermatitis, and one patient had a subcutaneous induration requiring
painkillers. Both patients had undergone dose escalation to 80 Gy in 16 fractions.

Kasuya et al. also reported the results of a prospective clinical trial, in which eight patients were treated
[51]
with CIRT for unilateral RCC. Five patients received 66 Gy in 16 fractions. Since no dose-limiting toxicity
occurred, the following three patients were treated up to 72 Gy in 16 fractions. For a median follow-up of 43
months, the LC and DSS were 100%. No patient developed Grade 3 or higher acute or late toxicity. The
average decrease in eGFR at the end of follow-up was 10.8 mL/min/1.73 m .
2
For follow-up purposes, it should be noted that there was no volume change or even a transient
enlargement during observation in the months following treatment with particle therapy. At long-term
follow-up, a very gradually shrinkage pattern was observed [4,46,49] . Therefore, follow-up imaging after CIRT
should be used with caution so as not to misinterpret local failure.