Phase III Study of the Eastern Cooperative Oncology Group (ECOG 2597): Induction Chemotherapy Followed by Either Standard Thoracic Radiotherapy or Hyperfractionated Accelerated Radiotherapy for Patients With Unresectable Stage IIIA and B Non–Small-Cell Lung Cancer
ABSTRACT To compare once-daily radiation therapy (qdRT) with hyperfractionated accelerated radiation therapy (HART) after two cycles of induction chemotherapy.
Eligible patients were treatment naive, and had stage IIIA and B unresectable non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and normal organ function. Induction chemotherapy consisted of two cycles of carboplatin area under time-concentration curve 6 mg/mL . min plus paclitaxel 225 mg/m2 on day 1. RT consisted of arm 1 (qdRT), 64 Gy (2 Gy/d), versus arm 2 (HART), 57.6 Gy (1.5 Gy tid for 2.5 weeks). A total of 388 patients were needed to detect a 50% increase in median survival from 14 months of qdRT to 21 months of HART; accrual was not achieved and the study closed prematurely.
Of 141 patients enrolled, 83% were randomly assigned after chemotherapy to qdRT (n = 59) or HART (n = 60). Median survival was 20.3 and 14.9 months for HART and qdRT, respectively (P = .28). Overall response was 25% and 22% for HART and qdRT, respectively (P = .69). Two- and 3-year survival was 44% and 34% for HART, and 24% and 14% for qdRT, respectively. Grade > or = 3 toxicities included esophagitis in 14 v nine patients, and pneumonitis in 0 v 6 patients for HART and qdRT, respectively. Any subsequent trials of the HART regimen must address the issues that led to early closure, including slow accrual, logistics of HART, mucosal toxicity, and the fact that concurrent chemoradiotherapy now seems more effective than sequential treatment.
After two cycles of induction chemotherapy with carboplatin-paclitaxel, HART is feasible with an acceptable toxicity profile. Although statistical significance was not achieved and the study closed early, there was a positive statistical trend suggesting a survival advantage with the HART regimen.
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- "Interestingly we note that the only randomised trial which compared sequential with concurrent chemotherapy using an accelerated radiotherapy scheme, found no difference in survival between the arms . Furthermore, the best results reported in a phase III study of chemoradiation in locally advanced NSCLC have come from the combination of 2 cycles of carboplatin-paclitaxel followed by hyperfractionated accelerated radiation therapy (HART) . We think that this approach warrants further investigation. "
ABSTRACT: We conducted a phase II study combining induction chemotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) in locally advanced non-small-cell lung cancer (NSCLC). A total of 40 patients with stage III NSCLC were enrolled. All patients received 3 cycles of chemotherapy followed by CHART (56 Gy in 36 fractions over 12 days). The primary outcome measure was radiation toxicity. Secondary endpoints were response rate, overall survival, disease-free survival and loco-regional progression-free survival. Acute radiation toxicity was minimal and there were no significant late toxicities. The response rate after completion of chemoradiation was 65%. The median and 2-year overall survival, progression-free survival and loco-regional progression-free survivals were 15.7 months, 28%; 12.1 months, 23%; and 26.4 months, 51%, respectively. Induction chemotherapy can be safely combined with CHART. The survival results are consistent with previous studies of chemotherapy followed by accelerated radiotherapy. This approach should be compared with synchronous chemoradiation to determine if it represents a less toxic alternative.Radiotherapy and Oncology 06/2009; 93(3):396-401. DOI:10.1016/j.radonc.2009.04.002 · 4.36 Impact Factor
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- "In prospective trials this was shown to be equivalent to conventional fractionation for patients with squamous cell head and neck cancer and superior to conventional fractionation for both local control and overall survival for patients with NSCLC. A subsequent trial conducted in the US compared a modification of CHART called HART, which eliminated the weekend treatments and increased total dose to 57.6 Gy in 36 fractions over 2.5 weeks, to conventional fractionation in patients with Stage III NSCLC following two cycles of induction carboplatin and paclitaxel and found an improvement in median survival of 14.9 to 20.3 months and three-year survival from 14% to 34% . These differences unfortunately did not reach statistical significance because the trial was closed prematurely with only half of its planned accrual. "
ABSTRACT: Translational research in medicine aims to inform the clinic and the laboratory with the results of each other's work, and to bring promising and validated new therapies into clinical application. While laudable in intent, this is complicated in practice and the current state of translational research in cancer shows both striking success stories and examples of the numerous potential obstacles as well as opportunities for delays and errors in translation. This paper reviews the premises, promises, and problems of translational research with a focus on radiation oncology and suggests opportunities for improvements in future research design.Biomedical Imaging and Intervention Journal 07/2008; 4(3):e47. DOI:10.2349/biij.4.3.e47
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- "In the CHART-study reduction of the OTT from 6 weeks to 12 days resulted in improved outcome with radiotherapy alone, indicating an influence of repopulation . Several other studies report about improved results while shortening the OTT, for radiotherapy alone or for chemo-radiation [18,45-47]. Assuming that accelerated repopulation begins 28 days after start of treatment and that each day of prolongation hereafter should be compensated by 0.5 Gy, 66 Gy administered in 32 days could be equivalent to a BED10 of 93 Gy [Dische 02, Hermann 04, Fowler 04]. "
ABSTRACT: Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995-2004. Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt). Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m(2): 56 pts (standard).Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m(2) d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts. The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications. In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.Radiation Oncology 02/2007; 2(1):27. DOI:10.1186/1748-717X-2-27 · 2.55 Impact Factor