Phase II Multi-institutional Clinical Trial on a New Mixed Beam RT Scheme of IMRT on Pelvis Combined with a Carbon Ion Boost for High-risk Prostate Cancer Patients

Abstract

The present clinical trial aims at improving the current treatment for high-risk prostate cancer, evaluating safety and feasibility of a new RT mixed-beam scheme including photons and carbon ions. Encouraging results are coming from carbon ion facilities worldwide on the treatment of different tumors including prostate cancers. Carbon ions combine physical properties allowing for high dose conformity and advantageous radiobiological characteristics. The proposed mixed beam treatment has the advantage to combine a photon high conformity standard of care IMRT phase with a hypofractionated carbon ion RT boost delivered in a short overall treatment time.

Preliminary exploration of clinical factors affecting acute toxicity and quality of life after carbon ion therapy for prostate cancer

“…The inclusion criteria were men with pathologically confirmed localized prostate cancer who received CIRT as the radical treatment. Patients with visceral or bone metastases [10], pelvic nodes metastases [11], postoperative radiotherapy [4], and recurrence after either surgery or radiotherapy [7] were excluded. Finally, 64 eligible patients participated in this study.…”

Therapeutic Sequences in the Treatment of High-Risk Prostate Cancer: Paving the Way Towards Multimodal Tailored Approaches

“…The NCT02672449 is a prospective, multicentric, phase II open-label trial that might provide novel insights on a new mixed beam RT scheme of a carbon ion boost followed by pelvic photon RT ( 76 ), and details about this ongoing trial are reported in Table 1 . Overall, data about CIRT in HR setting seems encouraging and could provide novel insight for the treatment of these patients.…”

Clinical trials involving carbon‐ion radiation therapy and the path forward

“…4) The higher RBE and sharper lateral fields of CIRT, permitting biologic and physical dose escalation, should improve local control more than might be expected with photon‐based or proton‐based SBRT . 5) Hypoxia and other mechanisms of radiation resistance thought to confer resistance to photon‐based EBRT may be overcome with CIRT . And 6) intermediate endpoints, such as prostate‐specific antigen nadir and/or time to metastatic disease, could be used to support the viability of CIRT …”

“…40 5) Hypoxia and other mechanisms of radiation resistance thought to confer resistance to photon-based EBRT may be overcome Cancer December 1, 2018 with CIRT. 27,[49][50][51] And 6) intermediate endpoints, such as prostate-specific antigen nadir and/or time to metastatic disease, could be used to support the viability of CIRT. 38,40,52,53 Patients with prostate cancer (including those from the United States) initially would receive treatment with 4 or 5 fractions of SBRT using photons (x-rays) versus protons versus CIRT (with photons considered the standard to which the others are compared), as noted above.…”

“…One site under discussion by our own group (NAPTA), in collaboration with the leadership of a number of centers with CIRT capability involves the design of a large phase II/III clinical trial for unfavorable intermediate and high-risk prostate cancer. The rationale for choosing this cancer site is as follows: (1) prostate cancer is one of the most common cancers treated definitively with radiation in the world, and is the most common cancer treated with CIRT 3,29 ; (2) increasingly SBRT is being used to treat both intermediate and high grade prostate cancer either as a monotherapy in 4 to 5 fractions or as a boost with 2 fractions after pelvic radiotherapy and recently a number of investigators have begun studying the feasibility of treating prostate cancer with a single fraction 39 (ClinicalTrials.gov Identifier: NCT03294889); (3) there are theoretical reasons to believe that CIRT, due to the tighter penumbra, should allow increased sparing of neurovascular structures and the penile bulb resulting in improved erectile function and favorably impacting quality of life 45–47 ; (4) the higher RBE and sharper lateral fields of CIRT, permitting biological and physical dose escalation, should improve local control more than might be expected with photon or proton based SBRT 43,44 ; (5) hypoxia and other mechanisms of radiation resistance thought to confer resistance to photon based EBRT may be overcome with CIRT 26,48–50 ; (6) intermediate endpoints such as PSA nadir and /or time to metastatic disease could be used to support the viability of CIRT 37,39,51,52 .…”