Final results of a Phase I/II dose escalation trial in non–small-cell lung cancer using three-dimensional conformal radiotherapy

Belderbos, J.; Heemsbergen, Wilma D.; Jaeger, Katrien De; Baas, Paul; Lebesque, Joos V.

doi:10.1016/j.ijrobp.2006.04.034

Cited by 191 publications

(119 citation statements)

References 31 publications

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“…The median GTV was 47.3 cm 3 . N0 status and female gender were associated with better tumor responses.…”

Section: Methodsmentioning

confidence: 98%

“…The distribution of the GTV was as follows: ≤45 cm 3 in 79 (49%) and >45 cm 3 in 82 (51%) of 161 patients. The median GTV was 47.3 cm 3 .…”

Section: Methodsmentioning

confidence: 99%

“…The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (≤45 cm 3 ) vs. larger (>45 cm 3 )…”

Section: Methodsmentioning

confidence: 99%

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Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Werner‐Wasik

Swann

Bradley

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

101

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Recommended CitationWerner-Wasik, Maria; Swann, R. Suzanne; Bradley, Jeffrey; Graham, Mary; Emami, Bahman; Purdy, James; and Sause, William, "Increasing tumor volume is predictive of poor overall and progressionfree survival: Secondary analysis of the Radiation Therapy Oncology Group 93-11 phase I-II radiation dose-escalation study in patients with inoperable non-small-cell lung cancer" (2008 Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome. Methods and Materials:The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (≤45 cm 3 ) vs. larger (>45 cm 3 )tumors.Results:The distribution of the GTV was as follows: ≤45 13.3 months, p < 0.0001; and 15.8 vs. 8.3 months, p < 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p < 0.0001; and HR, 1.39, p < 0.0001, respectively). Conclusions:Radiation dose escalation up to 90.3Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume.

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“…The median GTV was 47.3 cm 3 . N0 status and female gender were associated with better tumor responses.…”

Section: Methodsmentioning

confidence: 98%

“…The distribution of the GTV was as follows: ≤45 cm 3 in 79 (49%) and >45 cm 3 in 82 (51%) of 161 patients. The median GTV was 47.3 cm 3 .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Werner‐Wasik

Swann

Bradley

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

101

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“…1 In previous hypofractionated dose-escalation trials, escalation was performed using 3-dimensional conformal radiotherapy (CRT). [25][26][27] The use of CRT can be insufficient for large and/or centrally located lesions or for patients who have widespread lymph node involvement and can lead to increased toxicity rates and the inability to reach an appropriate dose. [28][29][30] Liu et al demonstrated that IMRT could reduce the irradiated volumes of normal lung tissue and other critical structures significantly while maintaining an adequate dose to the target volume.…”

Section: Discussionmentioning

confidence: 99%

Toxicity report of a phase 1/2 dose‐escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy

Bral

Duchateau

Versmessen

et al. 2009

Cancer

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BACKGROUND:The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system).METHODS:This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity.RESULTS:Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade ≥3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group‐European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images.CONCLUSIONS:The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction. Cancer 2010. © 2010 American Cancer Society.

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“…High tumor dose is normally inaccessible because of possible lung injury,10, 11, 12, 13, 14, 15, 16, 17 especially for large tumors. Discrepancy in lung volume among patients may cause differences in toxicity and potential of dose escalation for patients with approximate tumor volumes suggesting the need for an individualized treatment mode.…”

Section: Introductionmentioning

confidence: 99%

Impacts of lung and tumor volumes on lung dosimetry for nonsmall cell lung cancer

Lei

Jia

Cao

et al. 2017

J Applied Clin Med Phys

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The purpose of this study was to determine the impacts of lung and tumor volumes on normal lung dosimetry in three‐dimensional conformal radiotherapy (3DCRT), step‐and‐shoot intensity‐modulated radiotherapy (ssIMRT), and single full‐arc volumetric‐modulated arc therapy (VMAT) in treatment of nonsmall cell lung cancers (NSCLC). All plans were designed to deliver a total dose of 66 Gy in 33 fractions to PTV for the 32 NSCLC patients with various total (bilateral) lung volumes, planning target volumes (PTVs), and PTV locations. The ratio of the lung volume (total lung volume excluding the PTV volume) to the PTV volume (LTR) was evaluated to represent the impacts in three steps. (a) The least squares method was used to fit mean lung doses (MLDs) to PTVs or LTRs with power‐law function in the population cohort (N = 32). (b) The population cohort was divided into three groups by LTRs based on first step and then by PTVs, respectively. The MLDs were compared among the three techniques in each LTR group (LG) and each PTV group (PG). (c) The power‐law correlation was tested by using the adaptive radiation therapy (ART) planning data of individual patients in the individual cohort (N = 4). Different curves of power‐law function with high R2 values were observed between averaged LTRs and averaged MLDs for 3DCRT, ssIMRT, and VMAT, respectively. In the individual cohort, high R2 values of fitting curves were also observed in individual patients in ART, although the trend was highly patient‐specific. There was a more obvious correlation between LTR and MLD than that between PTV and MLD.

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Final results of a Phase I/II dose escalation trial in non–small-cell lung cancer using three-dimensional conformal radiotherapy

Cited by 191 publications

References 31 publications

Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non–Small-Cell Lung Cancer

Toxicity report of a phase 1/2 dose‐escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy

Impacts of lung and tumor volumes on lung dosimetry for nonsmall cell lung cancer

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