Carbon-ion radiotherapy for lymph node oligo-recurrence: a multi-institutional study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS)

Abstract

Background The efficacy of carbon-ion radiotherapy (C-ion RT) for lymph node (LN) oligo-recurrence has only been evaluated in limited single-center studies. We aimed to investigate the benefit of C-ion RT for LN oligo-recurrence in a large multi-center study. Methods Patients who received C-ion RT between December 1996 and December 2015 at 4 participating facilities and who met the following eligibility criteria were included: (i) histological or clinical diagnosis of LN recurrence; (ii) controlled primary lesion; (iii) no recurrence other than LN; (iv) LN recurrence involved in a single lymphatic site; and (v) age ≥ 20 years. Results A total of 323 patients were enrolled. Median follow-up period was 34 months for surviving patients. The most common dose fractionation of C-ion RT was 48.0 Gy (relative biological effectiveness) in 12 fractions. Forty-seven patients had a history of RT at the recurrent site. The 2-year local control (LC) and overall survival (OS) rates after C-ion RT were 85% and 63%, respectively. Only 1 patient developed grade-3 toxicity. Factors such as LN diameter, histology, and history of previous RT did not correlate with LC. Smaller diameters (< 30 mm) and numbers (≤ 3) of LN metastases as well as longer disease-free intervals post-primary therapy (≥ 16 months) were associated with significantly better OS. Conclusions C-ion RT for LN oligo-recurrence appeared to be effective and safe. C-ion RT may provide a survival benefit to patients with LN oligo-recurrence, particularly to those with few LN metastases, smaller LN diameters, and longer disease-free intervals. Electronic supplementary material The online version of this article (10.1007/s10147-019-01440-y) contains supplementary material, which is available to authorized users.

The rationale for a carbon ion radiation therapy facility in Australia

“…The clinical efficacy of CIRT has been demonstrated for many tumours, both for toxicity reduction and for improved local control and survival. 3,4,27,38,42,62,[86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] However, all discussion recognises that direct high-level clinical evidence for CIRT benefit is limited, 117 since most clinical CIRT investigations are retrospective single arm studies. This is similar in principle to many PBT applications, although PBT phase III trial numbers are increasing.…”

“…Six additional Japanese CIRT facilities opened between 2002 and 2021, incorporating advancing technologies as they were developed at NIRS, so there are almost 1.5 CIRT centres per 25 million population (Japan also has roughly four PBT centres per 25 million population, with 19 operational and two under construction) 7 . The Japan Carbon‐ion Radiation Oncology Study Group (J‐CROS) was set up in 2014 and has carried out many multi‐centre retrospective and prospective studies, including on locally recurrent rectal cancer, 89 mucosal melanoma of the head and neck (H&N), 90 locally advanced pancreatic cancer, 91 lymph node oligo‐recurrence, 92 cholangiocarcinoma 93 adenoid cystic carcinoma (ACC) of the H&N, 94 locally advanced sinonasal malignant tumours, 95 prostate cancer, 96 sacral chordoma 97 and inoperable stage 1 non‐small cell lung cancer (NSCLC) 98 . NIRS and wider Japanese clinical experience has been summarised in specific reports 44,57,86,87,99 or in wider overviews of international CIRT experience (Section ‘Clinical indications, patient numbers and application to Australia’).…”

“…The clinical efficacy of CIRT has been demonstrated for many tumours, both for toxicity reduction and for improved local control and survival 3,4,27,38,42,62,86–102 . However, all discussion recognises that direct high‐level clinical evidence for CIRT benefit is limited, 117 since most clinical CIRT investigations are retrospective single arm studies.…”

Three discipline collaborative radiation therapy (3DCRT) special debate: The United States needs at least one carbon ion facility

“…The pioneering investigations at LBNL showed that fractionated delivery of heavy ion therapy, generally as a boost at relatively low doses, was well tolerated across diverse tumor sites, including locally advanced prostate cancer, bone and soft tissue sarcomas, and head and neck tumors of the salivary gland and paranasal sinus . Subsequent phase I/II trials conducted largely in Japan and Germany employing higher doses and conducted primarily solely with CIRT have demonstrated negligible toxicity and encouraging tumor control rates in diverse histologic tumor types, including adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, and bone and soft tissue sarcomas, tumors which are often resistant to conventional photon irradiation . Additional difficult to treat tumor sites with early favorable outcomes include tumors of the lung, liver, and pancreas.…”

Carbon-ion Radiotherapy for Isolated Lymph Node Metastasis After Surgery or Radiotherapy for Lung Cancer

“…Previously, the safety and efficacy of carbon-ion RT were reported for early stage and locally advanced lung cancer (7, 8). Moreover, a few retrospective studies demonstrated the usefulness of carbon-ion RT for isolated lymph node recurrence of esophageal cancer, colorectal cancer, and several tumors (9–11). Therefore, carbon-ion RT might be a promising treatment for lung cancer patients with isolated lymph node metastasis after initial treatments.…”