DART-bid (Dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily)–a novel approach for non-resected NSCLC: final results of a prospective study, correlating radiation dose to tumor volume

Abstract

BackgroundSequential chemo-radiotherapies with intensive radiation components deliver promising results in non-resected non-small cell lung cancer (NSCLC). In general, radiation doses are determined by dose constraints for normal tissues, not by features relevant for tumor control. DART-bid targets directly the doses required for tumor control, correlating doses to tumor volume in a differentiated mode.Materials/MethodsRadiation doses to primary tumors were aligned along increasing tumor size within 4 groups (<2.5 cm/2.5–4.5 cm/4.5–6.0 cm/>6.0 cm; mean number of three perpendicular diameters). ICRU-doses of 73.8 Gy/79.2 Gy/84.6 Gy/90.0 Gy, respectively, were applied. Macroscopically involved nodes were treated with a median dose of 59.4 Gy, nodal sites about 6 cm cranial to involved nodes electively with 45 Gy. Fractional doses were 1.8 Gy twice daily (bid).2 cycles chemotherapy were given before radiotherapy.Between 2004 and 2009, 160 not selected patients with 164 histologically/cytologically proven NSCLC were enrolled; Stage I: 38 patients; II: 6 pts.; IIIA: 69 pts.; IIIB: 47 pts. Weight loss >5%/3 months: 38 patients (24%).Primary endpoints are local and regional tumor control rates at 2 years (as >90% of locoregional failures occur within 2 years). Secondary endpoints are survival and toxicity. With a minimum follow-up time of 2 years for patients alive, the final results are presented.Results32 local and 10 regional recurrences occurred. The local and regional tumor control rates at 2 years are 77% and 93%, respectively.The median overall survival (OS) time is 28.0 months, the 2- and 5-year OS rates are 57% and 19%, respectively. For stage III patients, median OS amounts to 24.3 months, 2- /5-year OS rates to 51% and 18%, respectively.2 treatment-related deaths (progressive pulmonary fibrosis) occurred in patients with pre-existing pulmonary fibrosis. Further acute and late toxicity was mild.ConclusionsThis novel approach yields a high level of locoregional tumor control and survival times. In general it is well tolerated. In all outcome parameters it seems to compare favourably with simultaneous chemo-radiotherapies, at present considered ‘state of the art’; and is additionally amenable for an unselected patient population.

Treatment with Intensity-Modulated Radiation Therapy (IMRT) and Chemotherapy in Advanced Inoperable Non-Small Cell Lung Cancer (NSCLC): Toxicity, Survival and Patterns of Failure in Relation to Treatment with High and Low Radiation Dose

“…Our 80% 1-year OS was equivalent to MSKCC, MDACC, Govaert et al and the DART study [7] [22] [24] [33], yet superior to Kong et al NSCLC 3D-CRT experience [12]. We observed no differences in OS between dose bins, in contrast to earlier studies showing improved survival benefit with dose escalation [11] [12] [24].…”

Pulmonary function decreases moderately after accelerated high‐dose irradiation for stage III non‐small cell lung cancer

“…After induction chemotherapy, all patients received dose‐differentiated accelerated radiotherapy with intensity modulated radiotherapy (IMRT‐DART). The details of this treatment approach were described elsewhere . In brief, the cornerstones of this regimen are the sequential chemoradiation mode, the dose increments from 73.8 to 90 Gy depending on tumor size and twice daily treatment with 1.8 Gy per fraction.…”

“…In the past two decades, concomitant regimens achieved local control (LC) rates of 55–70% and a median overall survival (OS) beyond 30 months . Some single center studies on dose escalation strategies presented similar results with respect to LC and OS . With improved outcome, the maintenance of an adequate pulmonary function (PF) is essential to ensure acceptable quality of life after treatment.…”

Is There a Future for 74 Gy Radiation Treatment of NSCLC after RTOG 0617? A Comparison of the RTOG Study Results with Our Own Department’s 74 Gy NSCLC Cohort

“…Again, the results regarding the benefit of either technique seem to be inconclusive [15]- [19]. Furthermore, the use of modern technologies beyond IMRT to optimize radiation treatment might open up interesting possibilities that might help to improve the still poor outcome of NSCLC patients [20].…”