Phase II study of helical tomotherapy in the multidisciplinary treatment of oligometastatic colorectal cancer

Radiation Oncology Phase II study of helical tomotherapy in the multidisciplinary treatment of oligometastatic colorectal cancer Benedikt Engels 0 Thierry Gevaert 0 Hendrik Everaert 2 Peter De Coninck 0 Alexandra Sermeus 1 Nicolas Christian 0 Guy Storme 0 Dirk Verellen 0 Mark De Ridder 0 0 Department of Radiation Oncology, UZ Brussel, Vrije Universiteit Brussel , Laarbeeklaan 101, B-1090 Brussels , Belgium 1 Department of Gastroenterology, UZ Brussel, Vrije Universiteit Brussel , Laarbeeklaan 101, B-1090 Brussels , Belgium 2 Department of Nuclear Medicine, UZ Brussel, Vrije Universiteit Brussel , Laarbeeklaan 101, B-1090 Brussels , Belgium Background: Complete metastasectomy provides a real chance for long-term survival in patients with oligometastatic colorectal cancer (CRC). For inoperable patients, we evaluated in this study intensity-modulated and image-guided radiotherapy (IMRT-IGRT) by helical tomotherapy. Methods: Twenty-four CRC patients with 5 metastases were enrolled, receiving a dose of 50 Gy in fractions of 5 Gy. No limitations concerning dimension or localization of the metastases were imposed. Whole body PET-CT was performed at baseline and 3 months after the initiation of RT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0. Results: A total of 53 metastases were treated. Seventeen patients (71%) received previously 1 line of chemotherapy for metastatic disease, displaying residual (n = 7) or progressive (n = 10) metabolic active oligometastatic disease at time of inclusion. Most common sites were the lung, liver and lymphnodes. One patient (4%) experienced grade 3 dysphagia. Twenty-two patients were evaluated by post-treatment PET-CT. Twelve patients achieved a complete (n = 6) or partial (n = 6) metabolic response, resulting in an overall metabolic response rate of 55%. At a median follow-up of 10 months, 7 patients (29%) are in remission, of which 5 received previous chemotherapy with residual oligometastatic disease at time of inclusion. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 14% and 78%. Conclusions: Helical tomotherapy delivering 10 fractions of 5 Gy resulted in a metabolic response rate of 55%, and appeared to be attractive as consolidation of inoperable oligometastatic disease after effective chemotherapy. Metastatic colorectal cancer; Oligometastases; Helical tomotherapy; IMRT-IGRT - Background Nearly one fourth of the patients with newly diagnosed colorectal cancer (CRC) present synchronous liver metastases and more than half of the resected CRC patients develop distant recurrence during follow-up [1]. The diagnosis of metastatic CRC (mCRC) does however not equal an acute fatal illness and might be classified more as a chronic disease in patients with a clinical disease state between locoregionally confined and widely spread metastatic disease, so called oligometastatic disease [2,3]. It is well understood today that a complete metastasectomy provides a real chance for long-term survival in those patients, with documented 10-year overall survival (OS) rates in 1 out of 6 mCRC patients which underwent hepatic resection [4]. According to the data of the randomized EORTC intergroup Trial 40983, the perioperative administration of 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) has emerged as a new standard of care in mCRC patients with limited resectable liver metastases, by increasing the 3-year progression-free survival (PFS) with 8% (36% versus 28% without perioperative chemotherapy) [5]. Despite the improvements in surgical procedures and preoperative multi-agent chemotherapy, limitations imposed by localization, multifocal character, size, or comorbidities still exclude the major part of mCRC patients from undergoing metastasectomy [6]. Aiming at ablating metastases while preserving the surrounding healthy tissues, there has been an expansion over the past decade in the use of non-surgical local ablative alternatives such as radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT), the latter a tailored delivery of tumoricidal doses of radiation in a minimal number of fractions to small lesions by the combination of high conformal RT and rigorous localization of the target by image-guided RT (IGRT) [7-10]. In the eradication of liver- and lungmetastases by SBRT, limited toxicity rates and sustained local control (LC) are reported by several authors up [7,8]. However, in order to allow delivery of those cytotoxic doses, SBRT requires carefully selection of the metastases on the base of their localization and dimension. Our institution previously explored in a pilot study the efficacy and toxicity of helical tomotherapy, a technology combining rotational intensity-modulated RT (IMRT) and IGRT by megavoltage (MV) computed tomography (CT) scanning, in patients with oligometastatic CRC who were not amenable for metastasectomy and (further) systemic (...truncated)