M. Salgado

From the limits of the classical model of sensitometric curves to a realistic model based on the percolation theory for GafChromic™ EBT films

PURPOSE Modern radiotherapy uses complex treatments that necessitate more complex quality assurance procedures. As a continuous medium, GafChromic EBT films offer suitable features for such verification. However, its sensitometric curve is not fully understood in terms of classical theoretical models. In fact, measured optical densities and those predicted by the classical models differ significantly. This difference increases systematically with wider dose ranges. Thus, achieving the accuracy required for intensity-modulated radiotherapy (IMRT) by classical methods is not possible, plecluding their use. As a result, experimental parametrizations, such as polynomial fits, are replacing phenomenological expressions in modern investigations. This article focuses on identifying new theoretical ways to describe sensitometric curves and on evaluating the quality of fit for experimental data based on four proposed models. METHODS A whole mathematical formalism starting with a geometrical version of the classical theory is used to develop new expressions for the sensitometric curves. General results from the percolation theory are also used. A flat-bed-scanner-based method was chosen for the film analysis. Different tests were performed, such as consistency of the numeric results for the proposed model and double examination using data from independent researchers. RESULTS Results show that the percolation-theory-based model provides the best theoretical explanation for the sensitometric behavior of GafChromic films. The different sizes of active centers or monomer crystals of the film are the basis of this model, allowing acquisition of information about the internal structure of the films. Values for the mean size of the active centers were obtained in accordance with technical specifications. In this model, the dynamics of the interaction between the active centers of GafChromic film and radiation is also characterized by means of its interaction cross-section value. CONCLUSIONS The percolation model fulfills the accuracy requirements for quality-control procedures when large ranges of doses are used and offers a physical explanation for the film response.

Docetaxel plus fractionated cisplatin is a safe and active schedule as first-line treatment of patients with advanced non-small cell lung cancer: Results of a phase II study

This phase II trial evaluated the efficacy and safety of docetaxel 85 mg/m2 (day 1) and cisplatin 80 mg/m2 (administered as 40 mg/m2 doses each on days 1 and 2) every 3 weeks as first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Forty-two NSCLC patients were enrolled, most of them with stage IV disease (74%). A total of 195 chemotherapy cycles were administered (median 6, range 1–6). All patients were considered evaluable for efficacy and toxicity in an intention-to-treat (ITT) analysis. The overall response rate was 48% (95% CI, 33–64), including one CR (3%) and 19 PRs (45%). Stable disease was found in 6 patients (14%). The median time to disease progression was 4.9 months (95% CI, 4.0–5.7) and the median overall survival was 10.5 months (95% CI, 5.1–16.0). The survival rates at 1 and 2 years were 36.0% (95% CI, 19.9–52.0) and 18.0% (95% CI, 3.9–32.1), respectively. Overall, the combination showed an excellent safety profile. Severe hematological toxicities were uncommon: neutropenia (5% of patients, 1% of cycles) and febrile neutropenia (2% of patients, 0.5% of cycles). Asthenia (12%) was the only grade 3/4 non-hematological toxicity that affected more than 10% of patients. There were no toxic deaths. In conclusion, docetaxel plus fractionated cisplatin as first-line treatment of advanced NSCLC patients showed similar efficacy as the same combination with higher doses of docetaxel but where cisplatin was administered in a single dose. This new schedule shows promise in its excellent hematological and non-hematological toxicity profile. A randomized phase III trial is needed to confirm these results.

Biweekly administration of docetaxel and vinorelbine as second-line chemotherapy for patients with stage IIIB and IV non-small cell lung cancer : a phase II study of the Galician Lung Cancer Group (GGCP 013-02)

The current report aims to evaluate the efficacy and safety profile of a biweekly administration of docetaxel and vinorelbine to patients with advanced non-small cell lung cancer, who had previously been treated for this disease. In a prospective, multicenter, open-label, phase II trial, patients received 40 mg/m2 of docetaxel and 20 mg/m2 of vinorelbine on days 1 and 15, every 28 days. Treatment continued for up to a maximum of six cycles, unless disease progression or unacceptable toxicity occurred, or consent was withdrawn. Fifty patients were enrolled in the study and they received 174 cycles of chemotherapy, with a median of three cycles per patient. All patients were evaluated for efficacy and toxicity in an intention-to-treat analysis. The overall response rate was 10% [95% confidence interval (CI): 1–19], including one complete response (2%) and four partial responses (8%). Previous chemotherapy of 80% of the responders included paclitaxel. Median time to disease progression was 2.7 months (95% CI: 2.2–4.3) and median overall survival was 6.5 months (95% CI: 2.5–9.2). The survival rates at 1 and 2 years were 18% (95% CI: 7–29) and 4% (95% CI: 0–10), respectively. The most frequent severe toxicities were neutropenia (20% of patients) and leukopenia (8% of patients). Other toxicities appeared in 4% or fewer of the patients. Biweekly administration of docetaxel and vinorelbine is feasible as a second-line treatment for non-small cell lung cancer patients, but its level of activity and toxicity does not suggest any advantage compared with the results obtained with single-agent docetaxel in the same setting.

Single‐Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial)

Abstract Lessons Learned. RAS‐ or BRAF‐mutated metastatic colorectal cancers (mCRCs) progressing after first‐line treatment have a poor prognosis. European and U.S. guidelines include the multikinase inhibitor regorafenib as a standard option for second‐line therapy and beyond, based on the results of the randomized phase III CORRECT trial demonstrating improvement in survival. Although stopped prematurely for failing to accrue, the PREVIUM trial, the first prospective interventional study exploring regorafenib as second‐line treatment for patients with mCRC bearing RAS or BRAF mutations, failed to demonstrate clinical activity in the population analyzed. Background. Patients with RAS‐ or BRAF‐mutated (mut) metastatic colorectal cancer (mCRC) progressing on first‐line bevacizumab plus 5‐FU/irinotecan/oxaliplatin (FOLFOXIRI) have a poor prognosis. We aimed to assess the efficacy and safety of regorafenib in this population. Methods. Regorafenib was administered daily for 3 weeks of each 4‐week cycle until disease progression or other reason. The primary endpoint was 6‐month progression‐free survival (PFS). Results. KRAS, NRAS, or BRAF was mutated in mCRC samples in 60%, 20%, and 13% of patients, respectively. Median time from initial diagnosis of metastases to the start of regorafenib and treatment duration was 13.8 months and 7 weeks, respectively. Reasons for discontinuation included disease progression (80%), investigator decision (13%), and adverse events (AEs; 7%). Seven patients (47%) required dose reduction, mostly for asthenia (43%). The most common regorafenib‐related grade 3 AEs were asthenia (33%), dysphonia (13%), and hypertension (13%) (Table 1). There were no grade 4 toxicities. No patient was progression‐free at 6 months. Median PFS, time to progression (TTP), and overall survival (OS) were 2.2, 2.0, and 3.3 months, respectively. Conclusion. Although stopped prematurely for failing to accrue, in the population analyzed, regorafenib failed to demonstrate clinical activity in KRAS‐ or BRAF‐mutated mCRC with progression following first‐line with FOLFOXIRI plus bevacizumab, although tolerability was acceptable. Our trial suggests that exploring regorafenib efficacy in an earlier line of therapy should not be undertaken without better population refinement.

SU‐E‐T‐264: New Concrete Designed and Evaluation for Megavoltage X Radiotherapy Facilities (CONTEK—RFH2)

PURPOSE The most common material for shielding is concrete, which can be made using various materials of different densities as aggregates. New techniques in radiotherapy, as IMRT and VMAT, require more monitor units and it is important to develop specifically designed shielding materials. METHODS Arraela S.L. has developed new concrete (CONTEK®-RFH2), which is made from an arid with a high percentage in iron (> 60%), and using the suitable sieve size, enables optimum compaction of the material and a high mass density, about 4.1-4.2 g/cm3 . Moreover, aluminate cement, used as base, gives high resistance to high temperatures what makes this product be structurally resistant to temperatures up to 1200 ° C. The measurements were made in a LINAC Elekta SL18 to energies 6MV and 15 MV with a field size of 10×10 cm2 for concrete samples in the form of tile 25cm×25cm with variable thickness. RESULTS The linear attenuation coefficient, μm, was determined for each energy by fitting the data to Eq. 1, where Xxm is the exposure in air behind a thickness xm of the material, and X0 is the exposure in the absence of shielding. These results are compared with the ordinary concrete (2.35 g cm-3) for 6MV and 15MV energies (Ref. NCRP Report No.151). Results are tabulated in Table1. Results of attenuation are compared with ordinary concrete in Fig. 1. CONCLUSIONS The new concrete CONTEK®-RFH2 increases photon attenuation and reduces the size of a shielded wall. A very high percentage in iron and a suitablesieve size approximately double the density of ordinary concrete. High mass attenuation coefficient makes this concrete an extremely desirable material for use in radiation facilities as shielding material for photon beam, and for upgrading facilities designed for less energy or less workload.

SU‐E‐T‐388: Verification of Monitor Units and Dose Distributions in IMRT Plans Using Monte Carlo Algorithms on the E‐IMRT Web Platform

PURPOSE Currently, quality control (QC) for each IMRT treatment is performed by dose distribution measurements. These techniques are very time-consuming and require long accelerator downtime. QC could be only based in verification of monitor units and dose distributions, if precise control of MLC is carried out. In such a manner, the e-IMRT platform (http://eimrt.cesga.es/) is a remote distributed computing tool, which allows comparison between the dose distributions calculated by a TPS and those calculated by Monte Carlo (MC). METHODS Previously, our linear accelerator (Oncor Impression, Siemens) was commissioned. For this purpose, comparison of experimental and MC simulated data was carried out. Several IMRT treatments plans were calculated in superposition algorithm (TPS Xio®CMS 4.60.00) and used as input data for the e-IMRT platform. These treatment plans were previously verified employing a 2D array MapCheckTM, Sun Nuclear. The gamma index (3%, 3mm) was used for validating results. RESULTS The platform displays calculated doses using MC, also gamma map (in the CT images, not only statistical data) and histogram shown in Figures 1a), b) and d). The gamma map illustrates the differences between the input and calculated doses. According to the legend in Figure 1 d), these differences correspond to less than 1%. Results show good agreement between the doses calculated by TPS and those computed by e-IMRT platform. CONCLUSIONS If a rigorous quality control is established for MLC and optimisation criteria (number of gantry angles, minimum segment size, levels of intensity for fluency map) are used. Then, QC for IMRT standard treatment plans would be only based on the verification of monitor units and dose distributions using e-IMRT II.This work has been funded by the Xunta de Galicia, Project R&D Grant 09SIN007CT. We would like to thank Centro de SupercomputaciÃ3 n de Galicia for the computational resources and support.

Phase II study of biweekly docetaxel and cisplatin combination chemotherapy in first-line advanced gastric cancer

15601 Background: Docetaxel and cisplatin, as single agents, have demonstrated activity in patients with advanced gastric cancer. Docetaxel and cisplatin have shown a different toxicity profile; consequently the combination of these drugs could be a safe and effective treatment. Therefore, we conducted a phase II study to assess efficacy and toxicity of a biweekly regimen of docetaxel plus cisplatin in patients with advanced gastric cancer who have never been treated with palliative chemotherapy. Methods: Fifty-two patients with advanced gastric cancer were enrolled, histologically confirmed of gastric adenocarcinoma, at least one measurable lesion, ECOG PS ≤2, no prior palliative chemotherapy and adequate bone marrow, renal and hepatic function. Docetaxel 50 mg/m2 and cisplatin 50 mg/m2 were administered every two weeks until progression disease, unbearable toxicity or a maximum of 12 cycles. The objective response was evaluated according to RECIST criteria and toxicity was assessed according to the NCI-...