Escalated dose for non-small-cell lung cancer with accelerated hypofractionated three-dimensional conformal radiation therapy

Thirion, P.; Holmberg, Ola; Collins, Conor D; O'Shea, Carmel; Moriarty, M.; Pomeroy, M.; O'Sullivan, Catriona; Buckney, Steve; Armstrong, John G.

doi:10.1016/j.radonc.2003.09.006

Cited by 50 publications

(28 citation statements)

References 15 publications

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“…Most fraction sizes are 3-3.5 Gy/fraction [10,11,13] and the results are comparable to those of the present study. However, Sandhu et al [12] used 2.2-2.69 Gy/fractions in most patients (84.8%) and the resulting local control with a median value of 21.2 months was inferior to those reported in other studies [10-14].…”

Section: Discussionsupporting

confidence: 89%

“…These results are similar to the dose-response relationship shown in the present study. In terms of safety, no severe toxicities over grade 3 were observed in the present study, and low incidence of toxicities was also reported by Thirion et al [13] (BED of HFRT, 93.6 Gy). Accordingly, HFRT with high BED over 90 Gy may improve tumor control without increasing toxicities, similar to SABR.…”

Section: Discussionsupporting

confidence: 88%

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Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer

Lee

Kim

et al. 2013

Radiat Oncol J

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PurposeThe purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors.Materials and MethodsWe performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients.ResultsThe median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ≤90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed.ConclusionRadical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 88%

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer

Lee

Kim

et al. 2013

Radiat Oncol J

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“…Thirion et al [31] conducted a study of accelerated hypofractionation using 3 Gy per fraction in which a 72 Gy radiation dose was delivered in 24 fractions over five weeks. The 25 NSCLC cases that Thirion et al examined included 16 cases of stage III NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Dose escalation of accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I trial

et al. 2013

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BackgroundAccelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated repopulation of tumour cells during radiotherapy. This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the optimal fractionation scheme remains uncertain. The purpose of this phase I trial was to explore the maximum tolerated dose (MTD) of accelerated hypofractionated three-dimensional conformal radiotherapy (3-DCRT) (at 3 Gy/fraction) administered in combination with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for unresectable stage III NSCLC.MethodsPreviously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT, delivered at 3 Gy per fraction, once daily, with five fractions per week. The starting dose was 66 Gy and an increment of 3 Gy was utilized. Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity (DLT). The MTD was regarded as the dose that was one step below the dose at which DLT occurred. Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP.ResultsA total of 13 patients were enrolled and progressed through three dose escalation groups: 66 Gy, 69 Gy, and 72 Gy. No treatment-related deaths occurred. The major adverse events included radiation oesophagitis, radiation pneumonitis, and neutropenia. Nausea, fatigue, and anorexia were commonly observed, although the magnitude of these events was typically relatively minor. Among the entire group, four instances of DLT were observed, including two cases of grade 3 radiation oesophagitis, one case of grade 3 radiation pneumonitis, and one case of grade 4 neutropenia. All of these cases of DLT occurred in the 72 Gy group. Therefore, 72 Gy was designated as the DLT dose level, and the lower dose of 69 Gy was regarded as the MTD.ConclusionsFor unresectable stage III NSCLC 69 Gy (at 3 Gy/fraction) was the MTD of accelerated hypofractionated 3-DCRT administered in combination with concurrent NVB and CBP chemotherapy. The toxicity of this chemoradiotherapy regimen could be tolerated. A phase II trial is recommended to further evaluate the efficacy and safety of this regimen.

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“…Thirion et al [26] conducted a study of high-dose accelerated hypofractionation at 3 Gy/fraction in which a 72 Gy radiation dose was delivered in 24 fractions over 5 weeks. The regimen was tolerated.…”

Section: Discussionmentioning

confidence: 99%

High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study

et al. 2013

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BackgroundIncreasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC.MethodsUntreated patients with unresectable stage IIIA/IIIB NSCLC or patients with a recurrence of NSCLC received accelerated hypofractionated three-dimensional conformal radiotherapy. The total dose was greater than or equal to 60 Gy. The accelerated hypofractionated radiotherapy was conducted once daily at 3 Gy/fraction with 5 fractions per week, and the radiotherapy was completed in 5 weeks. In addition to radiotherapy, the patients also received at least 1 cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP.ResultsA total of 26 patients (19 previously untreated cases and 7 cases of recurrent disease) received 60Gy-75Gy radiotherapy with concurrent chemotherapy. All of the patients underwent evaluations for toxicity and preliminary therapeutic efficacy. There were no treatment-related deaths within the entire patient group. The major acute adverse reactions were radiation esophagitis (88.5%) and radiation pneumonitis (42.3%). The percentages of grade III acute radiation esophagitis and grade III radiation pneumonitis were 15.4% and 7.7%, respectively. Hematological toxicities were common and did not significantly affect the implementation of chemoradiotherapy after supportive treatment. Two patients received high dose of 75 Gy had grade III late esophageal toxicity, and none had grade IV and above. Grade III and above late lung toxicity did not occur.ConclusionHigh-dose accelerated hypofractionated three-dimensional conformal radiotherapy with a dose of 60 Gy or greater with concurrent NVB and CBP chemotherapy might be feasible. However esophagus toxicity needs special attention. A phase I trial is recommended to obtain the maximum tolerated radiation dose of accelerated hypofractionated radiotherapy with concurrent chemotherapy.

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Escalated dose for non-small-cell lung cancer with accelerated hypofractionated three-dimensional conformal radiation therapy

Cited by 50 publications

References 15 publications

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer

Dose escalation of accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I trial

High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study

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