Phase I/II clinical trials of carbon ion therapy for prostate cancer

TLDR

Heavy ion beams deliver high linear energy transfer and a pronounced Bragg peak, yielding higher relative biological effectiveness and superior dose distribution in the human body. The study aimed to establish carbon ion therapy techniques for prostate cancer by conducting phase I/II trials in 96 patients with T1b–T3 disease, delivering three carbon ion beams to the prostate and seminal vesicles over 20 fractions in five weeks, with or without endocrine therapy. Patients received escalating doses from 54 to 72 GyE, with monotherapy for early‑stage disease, neoadjuvant endocrine therapy for intermediate stages, and combined neoadjuvant/adjuvant endocrine therapy for more advanced stages; the median follow‑up was 47 months, and after observing Grade 3 toxicity at 66–72 GyE the dose was reduced to 66 GyE and the field coned down. At five years, overall, cause‑specific, clinical recurrence‑free, and biochemical recurrence‑free survival were 87.7 %, 94.9 %, 90.0 %, and 82.6 % respectively, with local control in all but one patient (who received 54 GyE) and only one Grade 3 rectal and five Grade 3 bladder/urethral toxicities, demonstrating that carbon ion therapy is effective and well tolerated.

Abstract

Heavy ion beams possess high linear energy transfer components and a prominent Bragg peak in the human body, resulting in higher relative biological effectiveness and improved dose distribution. To establish heavy ion therapy techniques for the treatment of prostate cancer, phase I/II clinical trials were initiated.For 96 patients with T1b-T3 prostate cancer, three carbon ion beams were used to irradiate the prostate and seminal vesicles (20 times/5 weeks) with or without endocrine therapy. Radiation dose was expressed in GyE which was initially thought to be equivalent to photon dose. Total dose was gradually increased from 54 to 72 GyE.Carbon ion therapy was completed in 20 cases of T1b/T1c/T2aN0M0 as monotherapy, in 8 cases of T2b/T3pN0M0 with neoadjuvant endocrine therapy, and in 68 cases of T2b/T3N0/pN1M0 with neoadjuvant and adjuvant endocrine therapy. Median observation period was 47 months. Grade 3 late radiation morbidity of rectum and/or bladder/urethra developed in one and five cases who received 66 and 72 GyE of radiation, respectively. After these adverse effects were observed, total dose was decreased to 66 GyE and the radiation field was coned down during the treatment course. At 5 years, overall, cause-specific, clinical recurrence-free, and biochemical recurrence-free survival rates were 87.7, 94.9, 90.0, and 82.6%, respectively. Local control was achieved in all patients except one patient who received 54 GyE of radiation.The therapeutic techniques of carbon ion therapy have been established for patients with prostate cancer. Carbon ion therapy may exert excellent effect to the tissues of prostate cancer.