DART-bid for loco-regionally advanced NSCLC

Abstract

BackgroundTo report acute and late toxicity with long-term follow-up, and to describe our experiences with pulmonary dose constraints.MethodsBetween 2002 and 2009, 150 patients with 155 histologically/cytologically proven non-small cell lung cancer (NSCLC; tumor stages II, IIIA, IIIB in 6, 55 and 39%, respectively) received the following median doses: primary tumors 79.2 Gy (range 72.0–90.0 Gy), lymph node metastases 59.4 Gy (54.0–73.8 Gy), nodes electively 45 Gy; with fractional doses of 1.8 Gy twice daily (bid). In all, 86% of patients received 2 cycles of chemotherapy previously.ResultsFive treatment-related deaths occurred: pneumonitis, n = 1; progressive pulmonary fibrosis in patients with pre-existing pulmonary fibrosis, n = 2; haemorrhage, n = 2. In all, 8% of patients experienced grade 3 and 1.3% grade 4 pneumonitis; 11% showed late fibrotic alterations grade 2 in lung parenchyma. Clinically relevant acute esophagitis (grade 2 and 3) was seen in 33.3% of patients, 2 patients developed late esophageal stenosis (G3). Patients with upper lobe, middle lobe and central lower lobe tumours (n = 130) were treated with V20 (total lung) up to 50% and patients with peripheral lower lobe tumours (n = 14, basal lateral tumours excluded) up to 42%, without observing acute or late pulmonary toxicity >grade 3. Only patients with basal lateral lower lobe tumours (n = 5) experienced grade 4/5 pulmonary toxicity; V20 for this latter group ranged between 30 and 53%. The mean lung dose was below the QUANTEC recommendation of 20–23 Gy in all patients. The median follow-up time of all patients is 26.3 months (range 2.9–149.4) and of patients alive 80.2 months (range 63.9–149.4.). The median overall survival time of all patients is 26.3 months; the 2-, 5- and 8‑year survival rates of 54, 21 and 15%, respectively. The local tumour control rate at 2 and 5 years is 70 and 64%, the regional control rate 90 and 88%, respectively.Discussion and conclusionGrade 4 or 5 toxicity occurred in 7/150 patients (4.7%), which can be partially avoided in the future (e.g. by excluding patients with pre-existing pulmonary fibrosis). Tolerance and oncologic outcome compare favourably to concomitant chemoradiation also in long-term follow-up.

Re-Irradiation for Locally Recurrent Lung Cancer: A Single Center Retrospective Analysis

“…Organs at risk (OAR), such as the esophagus, central vessels and airways, spinal cord, lungs, and heart were routinely contoured, and dose volume histograms of both initial and re-irradiation plans were used to determine the cumulative radiation exposure of each critical organ. On the basis of a previous evaluation of long-term toxicity after a single course of high-dose chemo-radiation, which revealed that a dose maximum of 80 Gy to the esophagus was associated with a 33.5% clinically relevant grade 2 or 3 toxicity, the D max was set at 100 Gy [12,16]. Okamoto et al showed in a small cohort of long-term survivors that a D max of 110 Gy to trachea and main bronchi can be well tolerated, and therefore we adopted the same constraints [17].…”

“…The maximum volume that could receive more than the above-specified cumulative dose was set at 1 mL. As for the lungs, a V20 total lung < 50% was used on the basis of a previous publication by our group [16]. Regarding cardiac toxicity, QUANTEC suggests dose constraint of V25 heart < 10%, which is associated with a risk of 1% cardiac mortality in 15 years [19].…”

Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

“…Accordingly, lung toxicity remains a crucial dose limiting factor, and dose escalation trials with conventionally fractionated radiotherapy have been limited by severe lung toxicity [ 25 – 27 ]. Due to the development of novel radiotherapy techniques, including intensity modulated radiotherapy (IMRT) [ 5 , 6 ] and volumetric modulated arc therapy (VMAT) [ 20 ], and radiation qualities, such as and proton therapy [ 28 ], radiation exposure of normal lung tissue can be significantly reduced.…”