Non-Small Cell Lung Cancer in Stages I–IIIB

Wurstbauer, Karl; Weise, Hannes; Deutschmann, H.; Kopp, Peter; Merz, Florian; Studnicka, Michael; Nairz, Olaf; Sedlmayer, Felix

doi:10.1007/s00066-010-2108-3

Cited by 17 publications

(5 citation statements)

References 35 publications

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“…Often only the patterns of first relapses are reported. Simultaneous radio-/chemotherapies seem to achieve definitive local tumor control in about 30–40% of the patients [1,20,21], sequential high-dose treatments with conventional fractionation in about 40–50% [12,22]. …”

Section: Discussionmentioning

confidence: 99%

“…Fowler estimates a loss of local tumor control of 11% per week for treatment times beyond 4 weeks [4]. This reflects the drawback of dose escalation protocols performed with conventional fractionation [3,6,12] (Table 4). One way to lower radiation treatment time is treating patients more often than once daily [7,13,31] (Table 4).…”

Section: Discussionmentioning

confidence: 99%

“…Initially, high dose radiation therapies with conventional fractionation rendered encouraging results [12]. Thereafter, in order to lower treatment times, in a phase I/II trial up to 90 Gy to primary tumors and 63 Gy to nodes in 1.8 Gy bid fractions were applied, preceded by 2 cycles chemotherapy [13].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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

et al. 2013

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“…Some studies explored accelerated radiotherapy after induction chemotherapy reporting a median OAS above 20 months [ 6 , 7 ]. Additionally, loco-regional control can be increased from about 40 % in conventional dose escalation [ 8 , 9 ] to 70 % [ 7 ], yet at the potential cost of increased toxicity.…”

Section: Introductionmentioning

confidence: 99%

Normal tissue complication models for clinically relevant acute esophagitis (≥ grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

et al. 2015

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BackgroundOne of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade ≥ 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC).Patients and methods66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: <2.5 cm 73.8 Gy, 2.5–4.5 cm 79.2 Gy, 4.5–6 cm 84.6 Gy, >6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP), two Lyman models and the cutoff-logistic regression model were fitted to the data with AE ≥ grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AICc), which calculates the model’s quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG.ResultsThe median follow up was 686 days (range 84–2921 days), 23/66 patients (35 %) experienced AE ≥ grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (Dc = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2–57.3) was the most significant predictor of AE ≥ grade 2 (HR = 1.05, CI 1.01–1.09, p = 0.007).ConclusionFollowing high-dose accelerated radiotherapy the rate of AE ≥ grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the additional benefit of markedly increased loco-regional tumor control. In the current patient cohort the most significant predictor of AE was found to be V38. A second clinically useful parameter in treatment planning may be MED (mean esophageal dose).Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0429-1) contains supplementary material, which is available to authorized users.

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“…The theoretical solution of simply increasing radiation doses to high biologically effective doses (BED), ideally above the threshold of 100 Gy in 2-Gy fractions, which has been suggested by several groups [5-8], is hampered by the tolerance of surrounding normal tissues that must be respected if a favourable therapeutic ratio is to be maintained. Under such circumstances, simultaneous administration of radiosensitizing agents that increase tumour cell kill might improve the therapeutic ratio, provided these agents do not sensitize critical normal tissues in the same fashion.…”

Section: Introductionmentioning

confidence: 99%

A review of clinical trials of cetuximab combined with radiotherapy for non-small cell lung cancer

et al. 2012

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Treatment of non-small cell lung cancer (NSCLC) is challenging in many ways. One of the problems is disappointing local control rates in larger volume disease. Moreover, the likelihood of both nodal and distant spread increases with primary tumour (T-) stage. Many patients are elderly and have considerable comorbidity. Therefore, aggressive combined modality treatment might be contraindicated or poorly tolerated. In many cases with larger tumour volume, sufficiently high radiation doses can not be administered because the tolerance of surrounding normal tissues must be respected. Under such circumstances, simultaneous administration of radiosensitizing agents, which increase tumour cell kill, might improve the therapeutic ratio. If such agents have a favourable toxicity profile, even elderly patients might tolerate concomitant treatment. Based on sound preclinical evidence, several relatively small studies have examined radiotherapy (RT) with cetuximab in stage III NSCLC. Three different strategies were pursued: 1) RT plus cetuximab (2 studies), 2) induction chemotherapy followed by RT plus cetuximab (2 studies) and 3) concomitant RT and chemotherapy plus cetuximab (2 studies). Radiation doses were limited to 60-70 Gy. As a result of study design, in particular lack of randomised comparison between cetuximab and no cetuximab, the efficacy results are difficult to interpret. However, strategy 1) and 3) appear more promising than induction chemotherapy followed by RT and cetuximab. Toxicity and adverse events were more common when concomitant chemotherapy was given. Nevertheless, combined treatment appears feasible. The role of consolidation cetuximab after RT is uncertain. A large randomised phase III study of combined RT, chemotherapy and cetuximab has been initiated.

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Non-Small Cell Lung Cancer in Stages I–IIIB

Cited by 17 publications

References 35 publications

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

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

Normal tissue complication models for clinically relevant acute esophagitis (≥ grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

A review of clinical trials of cetuximab combined with radiotherapy for non-small cell lung cancer

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