Sen Zhao

The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer

PURPOSE A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS From Jan. 1990 to Dec. 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. RESULTS OTT had been shortened in 64 patients because of an accelerated hyperfractioned irradiation, while OTT was prolonged i n 114 patients due to interruptions of irradiation courses. The main ca uses of interruption were machine breakdown or delayed preparations of c errobend block for boost fields (55%), holidays (11%) and treatment toxi city and side effects (34%). Patients tre ated with prolonged OTT (> 45 days) had significant poorer local progression-free survival than whom with OTT of </=45 days, 1, 3 and 5 year actuarial local progression-free survivals being 49, 17 and 15% for the former, and 74, 35 and 25% for the latter, respectively (P<0.001). BED-T that contained the factor of OTT correlated directly to local controls, which implied that BED-T represented radiobiological effects accurately, in other words, OTT had played a role in determining the radiobiological effects. Linear-regression on 103 cases treated with BED of 80-85 Gy(10) showed that 3 year local progression-free survival decreased by 9% per week with prolongation of OTT, or vice versa it increased by 9% per week with shortening OTT in an OTT range of 30-76 days. Cox multivariate analyses confirmed that OTT was an independent prognostic factor for local controls. CONCLUSION OTT may have played an important role in determining local controls in radiotherapy for NSCLC. One should always keep in mind to make the OTT as short as possible, provided the patients can tolerate it, and to reduce irradiation interruptions for whatever reasons to a minimum.

A phase II trial of accelerated hypofractionated three-dimensional conformal radiation therapy in locally advanced non-small cell lung cancer

PURPOSE The aim of this study is to evaluate the safety and efficacy of accelerated hypofractionated radiotherapy (HypoRT) combined with sequential chemotherapy in locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS A total of 34 patients with stage III NSCLC were enrolled. All patients received accelerated HypoRT (initially 50Gy/20 fractions, then a fraction dose of 3Gy) using three-dimensional conformal radiation therapy (3D-CRT), omitting elective nodal irradiation (ENI), to a total dose of 65-68Gy. All patients received two cycles of induction chemotherapy; 1-2 cycles of consolidation chemotherapy were given to 31 patients. The primary outcome measure was a profile of radiation toxicity. The secondary endpoints included overall survival (OS), progression-free survival (PFS), locoregional PFS (LR-PFS) and the pattern of initial failure. RESULTS Radiation toxicity was minimal. The median and 3-year OS, PFS were 19.0 months, 32.1%; 10.0 months, 29.8%, respectively. The 1-, 2-, and 3-year LR-PFS were 69.6%, 60.9% and 60.9%, respectively. No patient experienced isolated elective nodal failure as the first site of failure. CONCLUSION This study suggests that accelerated HypoRT using 3D-CRT omitting ENI can be used in combination with sequential chemotherapy in locally advanced NSCLC.

[Phase I clinical trial of dose escalation on three dimensional conformal radiation therapy for non-small cell lung cancer].

BACKGROUND To establish the technique of 3-dimensional conformal radiation therapy (3DCRT) for non-small cell lung cancer (NSCLC) in stage II-IIIB,and to assess its acute side-effects and to obtain the maximum tolerance dose (MTD). METHODS From June,1999 to June,2000,38 cases of NSCLC in stage II-IIIB were enrolled in this study.MTD was identified by dose escalation study.After 42Gy/21Fx/4.2wks by conventional fractionated irradiation through AP/PA fields,which covered the primary tumor and lymph nodes,the technique of 3DCRT was used as boost.The boost fields encompassed the clinical lesions showed on chest CT.The planning of total dose escalation depended on the percentage,i.e.,<25%,25%-37%,and >37% of normal lung volume irradiated to over 20Gy.The scheduled dose escalation ranged from 69 to 81Gy.The criteria for stopping dose escalation was grade III or more worse radiation pneumonitis (RTOG).The boost doses were delivered with 3Gy/fraction,once a day,5 fractions a week. RESULTS Thirty-three cases had completed their treatments and could be evaluated by now.Acute radiation pneumonitis occurred in 26% of patients with grade I-II and 3% with grade III,and acute radiation esophagitis in 61% with grade I-II and 9% with grade III,and the hematopoietic toxicity in 58% with grade I-II and 9% with grade III.The current doses implemented were 78,78,and 75Gy respectively for patients with <25%,25%-37%,and >37% of normal lung volume irradiated.The overall immediate response rate of tumors was 88%(29/33). CONCLUSIONS Dose escalation in a volume-dependent organ as the lungs is acceptable and applicable.The immediate response is encouraging.MTD is to be determined.The long-term follow-up is needed to observe late complications and treatment efficacy.