Patients had pulmonary function tests before the treatment. Eligible patients were evaluated and staged by a medical team whose members consisted of a surgeon, a radiation oncologist, and a medical oncologist. Before the study, a chemotherapy port was placed and supplemental enteral nutritional support was initiated. Chemotherapy and radiotherapy regimen After the preperatory stage

of the study was completed, neoadjuvant cisplatin and 5-FU were given with 28 day intervals in a total Inhibitors,research,lifescience,medical of three courses with the following administration schedule: 60 mg/m2 cisplatin infusion on day 1, and 600 mg/m2 5-FU infusion (120 hours) on days 1-5. Along with the third course of chemoterapy, hyperfractionated accelerated radiotherapy (HART) was given with the following dose schedule: 5760 cGy/36 fr/16 Inhibitors,research,lifescience,medical day. Patients PKC inhibitor received 3 fractions per day with at least 6-hour intervals between the fractions (07:00-08:00, 13:00-14:00 and 19:00-20:00) for 5 days a week. The treatment was completed in a total of 16 days including weekends. During the entire treatment period patients received a daily dose of 480 cGy/3fr (150-150-180

cGy). A 3D conformal RT was done. In Phase I, AP/PA field and in phase II three (posterior/two oblique) fields were used. In some patients three-field approach was used in both phases. Normal tissues constraints Inhibitors,research,lifescience,medical included 3840 cGy to the spinal cord, lung V20 doses less than 27%, Inhibitors,research,lifescience,medical heart V60 doses less than 30% and a maximum of 4000 cGy to the whole heart. Using computerized tomography and/or PET-CT images, the target volumes and high-risk organs were determined according to the prechemotherapy volumes and the volumes were checked by a radiation oncologist and radiologist in each patient. GTV (Gross Tumor Volume) was the tumor volume seen in PET-CT or computerized tomography.

Inhibitors,research,lifescience,medical During phase I CTV was GTV plus 3 cm and PTV1 was CTV plus 2 cm. For phase II, PTV2 was GTV plus 3 cm. In PTV planning, a 1 cm margin was allowed for GTV in postero-anterior and two lateral directions. Uninvolved regional lymph nodes were not included to treatment volumes. Lymph nodes ≥12 mm on computerized tomography or with FDG pathological uptake on PET (regardless of size) was interpreted as metastatic. A radiation dose higher than conventional RT scheme (5040 cGy/28 fr) was planned based on biological equivalent dose (BED) values and a dose close to CHART Montelukast Sodium scheme was aimed. Dose planning was as follows: BED3, 10580 cGy; BED10, 6430 cGy. Assessment of response and toxicity Toxicity was assessed at Days 5, 10, 12 and 16 during treatment, and at each follow-up visit after the treatment. Reactions occurring within the first month after completion of CRT were considered as “early reactions”, while those occurring between months 1 and 6 and after month 6 were designated as subacute and late reactions, respectively.