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Introduction Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) is a recent addition to the already available treatment options. In order to be able to deliver ablative doses, a tracking of the lesion is required. The CyberKnife is a SBRT system that allows for real-time tracking of the tumor. The purpose of this study was to evaluate the safety and efficacy of this system for the treatment of primary hepatocellular carcinoma. Methods From July 2007 to November 2011, 75 patients with 96 liver-confined HCC were treated with SBRT at the Oscar Lambret Comprehensive Cancer Center. Three to four gold seeds were implanted inside the patients' liver before treatment and were used as markers to follow the movement of the lesion due to respiration. Treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control and overall survival were calculated according to the method of Kaplan and Meier. Results There were 67 patients with Child-Turcotte-Pugh (CTP) Class A and 8 patients with CTP Class B. Treatment was administered in three sessions. A total dose of 40 to 45Gy at the 80% isodose was delivered with a median number of 146 beams. The average follow-up was 10 months (min : 3 – max : 44). The local control rate was 89.8% at 1 and 2 years. Overall survival was 78.5% and 50.4% at 1 and 2 years. Treatment toxicity was low. The most common toxicities were pain and asthenia. 1 patient had a gastric ulcer. No grade 3 toxicity was observed. Conclusion This treatment, while minimally invasive, presents tumoral local control and overall survival rates comparable to other treatments. The toxicity was low for our patients. It could be considered for patients not amenable to surgery or chemoembolization. A randomized trial comparing SBRT to the other available treatments should be conducted to validate this results.

Introduction: R1507 has single agent activity and remarkable chemo- and radiosensitizing effect in defined SCLC cell lines in vitro. It exhibits a dramatic antitumoral effect when combined to IR and cisplatin in vivo. The molecular mechanisms underlying these effects remain unknown. Materials and methods: Three SCLC cell lines (H69, H146 and H526) were selected according to their specific mutational profile (H146 and H69 cells are mutated for MAP2K4 and both PIK3CA and C-MET, respectively). The effects of R1507 on IGF1R downstream signaling were explored using western blots. Both genomic (HG-U133 plus 2 microarray, Affymetrix) and classical functional analyses were performed on the following conditions: (A) R1507 alone short-term (ST-R1507) (3 hours) vs. long-term (LT-R1507) (4 weeks) exposure, (B) R1507 combined with cisplatin, (C) and with ionizing radiation (IR). Results: (A) ST-R1507 disrupts IGF1R signaling through Akt and MAPK pathways in a dose dependent manner in selected SCLC cell lines. High IGF-1R basal expression is not correlated with sensitivity to R1507. Only cell lines with IGF1R gene amplification (H526 and H146) exhibit sensitivity to R1507. The addition of either MK-2206 (Akt inhibitor) or PHA665752 (c-Met tyrosine kinase inhibitor) to R1507 does not restore the sensitivity to IGF-1R inhibition in H69 cells. The addition of U0126 (MEK inhibitor) to R1507 does not restore the sensitivity to IGF-1R inhibition in H146 cells. LT- vs. ST-R1507 analyses reveal evidence of adaptive mechanisms susceptible to promote tumor escape to R1507 as single agent: (i) activation of cell-cell adhesion, beta-arrestin and MAPK gene expression pathways, (ii) activation of multiple cell surface receptors and intracellular proteins implicated in proliferation, angiogenesis and survival, (iii) transient reduction of phosphorylated IGF-1R staining intensity, in H526 xenografts in vivo. Regarding combination regimens, we identified: (B) the apoptotic mitochondrial and the NER pathways as majorly sensitizing the effects of LT- R1507 to Cisplatin, and (C) the TGF-beta pathway as the key mediator of the sensitization of LT-R1507 to IR. Conclusion: Combined genomic and functional approaches performed under LT-R1507 exposure unravel the activation of multiple alternative signaling pathways that are expected to promote tumor escape. Our study also provides key biological basis for translating the R1507 combined with Cisplatin and IR in the SCLC clinical setting. To analyze both short- and long-term drug exposure appears critical when evaluating new antitumoral regimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2866. doi:1538-7445.AM2012-2866

e14013 Background: Surgery together with systemic chemotherapy remains the standard treatment for liver metastases from colorectal cancer (CRC). Other local therapies include intra-arterial chemoth...

7050 Background: Stereotactic radiation therapy is a promising treatment for early stage lung cancer occurring in medically inoperable patients (pts). Robotic radiosurgery with the CyberKnife allow...

The SFjRO was created ten years ago to promote radiation oncology teaching in France. Our society has now more than 120 members from all around the country. Each year, two national courses are organized where all members are invited.

Background The first-line treatment of a pelvic recurrence in a previously irradiated area is surgery. Unfortunately, few patients are deemed operable, often due to the location of the recurrence, usually too close to the iliac vessels, or the associated surgical morbidity. The objective of this study is to test the viability of robotic image-guided radiotherapy as an alternative treatment in inoperable cases. Methods Sixteen patients previously treated with radiotherapy were reirradiated with CyberKnife® for lateral pelvic lesions. Recurrences of primary rectal cancer (4 patients), anal canal (6), uterine cervix cancer (4), endometrial cancer (1), and bladder carcinoma (1) were treated. The median dose of the previous treatment was 45 Gy (EqD2 range: 20 to 96 Gy). A total dose of 36 Gy in six fractions was delivered with the CyberKnife over three weeks. The responses were evaluated according to RECIST criteria. Results Median follow-up was 10.6 months (1.9 to 20.5 months). The actuarial local control rate was 51.4% at one year. Median disease-free survival was 8.3 months after CyberKnife treatment. The actuarial one-year survival rate was 46%. Acute tolerance was limited to digestive grade 1 and 2 toxicities. Conclusions Robotic stereotactic radiotherapy can offer a short and well-tolerated treatment for lateral pelvic recurrences in previously irradiated areas in patients otherwise not treatable. Efficacy and toxicity need to be evaluated over the long term, but initial results are encouraging.