S Wanders

Mature Results of an Individualized Radiation Dose Prescription Study Based on Normal Tissue Constraints in Stages I to III Non-Small-Cell Lung Cancer

PURPOSE We previously showed that individualized radiation dose escalation based on normal tissue constraints would allow safe administration of high radiation doses with low complication rate. Here, we report the mature results of a prospective, single-arm study that used this individualized tolerable dose approach. PATIENTS AND METHODS In total, 166 patients with stage III or medically inoperable stage I to II non-small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide >or= 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0. RESULTS The median prescribed TTD was 64.8 Gy (standard deviation, +/- 11.4 Gy) delivered in 25 +/- 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable. CONCLUSION Individualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy.

INDIVIDUALIZED RADICAL RADIOTHERAPY OF NON-SMALL-CELL LUNG CANCER BASED ON NORMAL TISSUE DOSE CONSTRAINTS: A FEASIBILITY STUDY

PURPOSE Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. METHODS AND MATERIALS Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An (18)F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. RESULTS Mean delivered dose was 63.0 +/- 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. CONCLUSIONS Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.

Mature results of a phase II trial on individualised accelerated radiotherapy based on normal tissue constraints in concurrent chemo-radiation for stage III non-small cell lung cancer.

BACKGROUND Sequential chemotherapy and individualised accelerated radiotherapy (INDAR) has been shown to be effective in non-small cell lung cancer (NSCLC), allowing delivering of high biological doses. We therefore performed a phase II trial (clinicaltrials.gov; NCT00572325) investigating the same strategy in concurrent chemo-radiation in stage III NSCLC. METHODS 137 stage III patients fit for concurrent chemo-radiation (PS 0-2; FEV(1) and DLCO ≥ 30%) were included from April 2006 till December 2009. An individualised prescribed dose based on normal tissue dose constraints was applied: mean lung dose (MLD) 19 Gy, spinal cord 54 Gy, brachial plexus 66 Gy, central structures 74 Gy. A total dose between 51 and 69 Gy was delivered in 1.5 Gy BID up to 45 Gy, followed by 2 Gy QD. Radiotherapy was started at the 2nd or 3rd course of chemotherapy. Primary end-point was overall survival (OS) and secondary end-point toxicity common terminology criteria for adverse events v3.0 (CTCAEv3.0). FINDINGS The median tumour volume was 76.4 ± 94.1 cc; 49.6% of patients had N2 and 32.1% N3 disease. The median dose was 65.0 ± 6.0 Gy delivered in 35 ± 5.7 days. Six patients (4.4%) did not complete radiotherapy. With a median follow-up of 30.9 months, the median OS was 25.0 months (2-year OS 52.4%). Severe acute toxicity (≥ G3, 35.8%) consisted mainly of G3 dysphagia during radiotherapy (25.5%). Severe late toxicity (≥ G3) was observed in 10 patients (7.3%). INTERPRETATION INDAR in concurrent chemo-radiation based on normal tissue constraints is feasible, even in patients with large tumour volumes and multi-level N2-3 disease, with acceptable severe late toxicity and promising 2-year survival.

OC-0129: Nitroglycerin decreases the hypoxic fraction of non-small cell lung cancer lesions

ESTRO 35 2016 _____________________________________________________________________________________________________ It is well known that MR data contains detailed information with high tissue contrast and that PET imaging gives molecular/biochemical information with high molecular sensitivity but what is the added value? A major goal with treatment planning is to delineate the tumor volume, which can be done with both MR and PET, but since the both modalities show different characteristics of the tumor the volume might differ between them. Challenges from the imaging point of view will be discussed. The availability to PET/CT is much higher and the challenges with this method are fewer. Some comparison of the two hybrid modalities will be done. The majority of PET studies are done with the tracer fluorodexyglucose, FDG, but beyond FDG a large number of tracer are available, all giving information about different biochemical properties of the tumor. A few of these tracers will be presented and discussed.

PD-0097: Impact of new Dutch guideline on patient selection for WBRT in a large lung cancer cohort

local control (LC), regional control (RC) and metastasis-free survival (MFS). A strong correlation between total lymph node tumour volume and Nstage was found (Rs=0.93, P<0.01). MFS was worse with involvement of the lower neck levels (Rs=0.345, P<0.01). Patients with larger total lymph node tumour volumes had poorer RC and MFS rates, independent of treatment regimen. For total lymph node volumes up to 3.5 cm, MFS can be improved by ARCON (P<0.01). Conclusions: The strong prognostic value of T-stage and primary tumour volume, observed in retrospective analyses was not confirmed in patients treated in a prospective randomised trial with accelerated radiotherapy with or without carbogen breathing and nicotinamide. Results of this study indicate that (biological) factors other than primary tumour volume and T-stage are needed to select patients with laryngeal cancer for treatment intensification.

O-146 Effects of radiotherapy planning with a dedicated combined PET-CT-simulator of patients with non-small cell lung cancer on dose limiting normal tissues and radiation dose-escalation: A planning study

BACKGROUND AND PURPOSE To investigate the effect of radiotherapy planning with a dedicated combined PET-CT simulator of patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS Twenty-one patients underwent a pre-treatment simulation on a dedicated hybrid PET-CT-simulator. For each patient, two 3D conformal treatment plans were made: one with a CT based PTV and one with a PET-CT based PTV, both to deliver 60Gy in 30 fractions. The maximum tolerable prescribed radiation dose for CT versus PET-CT PTV was calculated based on constraints for the lung, the oesophagus, and the spinal cord, and the Tumour Control Probability (TCP) was estimated. RESULTS For the same toxicity levels of the lung, oesophagus and spinal cord, the dose could be increased from 55.2+/-2.0Gy with CT planning to 68.9+/-3.3Gy with the use of PET-CT (P=0.002), with corresponding TCPs of 6.3+/-1.5% for CT and 24.0+/-5.6% for PET-CT planning (P=0.01). CONCLUSIONS The use of a combined dedicated PET-CT-simulator reduced radiation exposure of the oesophagus and the lung, and thus allowed significant radiation dose escalation whilst respecting all relevant normal tissue constraints.