Huan-Jun Yang

Three-dimensional conformal radiotherapy for locoregionally recurrent lung carcinoma after external beam irradiation: a prospective phase I-II clinical trial.

OBJECTIVES To observe in a clinical trial the feasibility, tolerance, and efficacy of reirradiation by three-dimensional conformal radiotherapy (3D-CRT) for locoregionally recurrent lung carcinoma after external beam radiotherapy (EBRT). MATERIALS AND METHODS Between June 1999 and March 2001, 23 lung carcinoma patients with locoregional recurrence after EBRT were enrolled in this study. Of the 23 patients, 21 were men and 2 were women (median age 68 years, range 43-79). At the first course of RT, 9 patients had squamous cell carcinoma, 7 adenocarcinoma, and 7 small cell carcinoma. The interval between the first course of RT and recurrence varied from 6 to 42 months (median 13). The median dose of the first course of RT was 66 Gy (range 30-78). Reirradiation was carried out using 3D-CRT and only covered the radiographic lesions. The median dose of reirradiation was 51 Gy (range 46-60), which was delivered by a conventionally fractionated schedule (i.e., 1.8-2.0 Gy/fraction, 5 fractions/wk). The toxicity was assessed according to the Radiation Therapy Oncology Group criteria. RESULTS The median follow-up time was 15 months (range 2-37). Acute radiation esophagitis occurred in 9% of patients (Grade 1-2). Acute radiation pneumonitis developed in 22% of patients (Grade 1-2). No cases of acute Grade 3 or greater toxicity had been recorded at last follow-up. Pulmonary fibrosis was observed in 26% of patients (Grade 2-3); no other severe late complications have been observed. The 1- and 2-year survival rate was 59% and 21%, respectively. The locoregional progression-free rate at 1 and 2 years was 51% and 42%, respectively. CONCLUSIONS Reirradiation using 3D-CRT was tolerated by this group of recurrent lung carcinoma patients without severe complications. The 2-year outcome was encouraging. Reirradiation with 3D-CRT can be considered an option for the management of locoregionally recurrent lung carcinoma.

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.

Is involved-field radiotherapy based on CT safe for patients with limited-stage small-cell lung cancer?

PURPOSE To examine the pattern of failures in patients with limited-stage small-cell lung cancer (LS-SCLC) treated with involved-field radiotherapy (IFRT) and chemotherapy, with the aim of investigating the safety of IFRT. METHODS AND MATERIALS Two consecutive clinical phase II trials in patients with LS-SCLC conducted in our center from 1997 to 2010 were reviewed retrospectively. Both trials had the same inclusion criteria. All patients (n=108) received combined chemotherapy and thoracic radiotherapy. Only the primary tumor and involved lymphatic regions based on computed tomography (CT) scan were irradiated. Isolated nodal failure (INF) was defined as a failure in an initially uninvolved lymph node region in the absence of local recurrence or distant metastasis. RESULTS With a median follow-up of 21 months, 78 patients experienced treatment failures. Out of 28 patients with local-regional recurrences, 16 in-field, 10 out-of-field, and 2 both in-field and out-of-field recurrences were observed. INF occurred in 5 patients (4.6%), all in the ipsilateral supraclavicular area. Four patients developed simultaneously supraclavicular nodal failures and distant metastases. The median overall survival was 27 months (95% confidence interval, 24-30 months) and the median progression-free survival was 16 months (95% confidence interval, 12-21 months). For the 5 patients with INF, the median time to INF from the end of thoracic radiotherapy was 5 months (range, 1-18 months). CONCLUSIONS IFRT based on CT scan in our patients resulted in a low rate of INF (4.6%), all in the ipsilateral supraclavicular area; but another four supraclavicular nodal failures with simultaneously distant metastases were also observed. The modern imaging with higher diagnostic capabilities of lymph node especially for supraclavicular area should be incorporated in the assessment of LS-SCLC when IFRT is being contemplated.

The effect of bioequivalent radiation dose on survival of patients with limited-stage small-cell lung cancer

BackgroundTo investigate the biological radiation dose-response for patients of limited-stage small-cell lung cancer (LS-SCLC) treated with high radiation dose.MethodsTwo hundred and five patients of LS-SCLC treated with sequential chemotherapy and thoracic radiotherapy with involved-field between 1997 and 2006 were reviewed retrospectively. Biologically effective dose (BED) was calculated for dose homogenization and was corrected with the factor of overall radiation time. Patients were divided into low BED group (n = 70) and high BED group (n = 135) with a cut-off of BED 57 Gy (equivalent to 60 Gy in 30 fractions over 40 days). Outcomes of the two groups were compared.ResultsMedian follow-up was 20.7 months for all analyzable patients and 50.8 months for surviving patients. Considering all patients, median survival was 22.9 months (95% confidence interval, 20.6-25.2 months); 2- and 5-year survival rates were 47.2% and 22.3%, respectively. Patients in high BED group had a significantly better local control (p = 0.024), progression-free survival (p = 0.006) and overall survival (p = 0.005), with a trend toward improved distant-metastasis free survival (p = 0.196). Multivariable Cox regression demonstrated that age (p = 0.003), KPS (p = 0.009), weight loss (p = 0.023), and BED (p = 0.004) were significant predictors of overall survival.ConclusionsOur data showed that a high BED was significantly associated with favourable outcomes in the Chinese LS-SCLC population, indicating that a positive BED-response relationship still existed even in a relatively high radiation dose range.

Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

PURPOSE To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. METHODS AND MATERIALS Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. RESULTS Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. CONCLUSION Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.

Comparison of paclitaxel in combination with cisplatin (TP), carboplatin (TC) or fluorouracil (TF) concurrent with radiotherapy for patients with local advanced oesophageal squamous cell carcinoma: a three-arm phase III randomized trial (ESO-Shanghai 2)

Introduction Concurrent chemoradiation is the standard therapy for patients with local advanced oesophageal carcinoma unsuitable for surgery. Paclitaxel is an active agent against oesophageal cancer and it has been proved as a potent radiation sensitiser. There have been multiple studies evaluating paclitaxel-based chemoradiation in oesophageal cancer, of which the results are inspiring. However, which regimen, among cisplatin (TP), carboplatin (TC) or fluorouracil (TF) in combination with paclitaxel concurrent with radiotherapy, provides best prognosis with minimum adverse events is still unknown and very few studies focus on this field. The purpose of this study is to confirm the priority of TF to TP or TF to TC concurrent with radiotherapy in terms of overall survival and propose a feasible and effective plan for patients with local advanced oesophageal cancer. Methods and analysis ESO-Shanghai 2 is a three-arm, multicenter, open-labelled, randomised phase III clinical trial. The study was initiated in July 2015 and the duration of inclusion is expected to be 4 years. The study compares two pairs of regimen: TF versus TP and TF versus TC concurrent with definitive radiotherapy for patients with oesophageal squamous cell carcinoma (OSCC). Patients with histologically confirmed OSCC (clinical stage II, III or IVa based on the sixth Union for International Cancer Control-tumour, node, metastasis classification) and without any prior treatment of chemotherapy, radiotherapy or surgery against oesophageal cancer will be eligible. A total of 321 patients will be randomised and allocated in a 1:1:1 ratio to the three treatment groups. Patients are stratified by lymph node status (N0, N1, M1a). The primary endpoint is overall survival and the secondary endpoint is progression-free survival and adverse events. Ethics and dissemination This trial has been approved by the Fudan University Shanghai Cancer Centre Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations. Trial status The trial was initiated in July 2015 and is currently recruiting patients in all of the participating institutions above. Trial registration number NCT02459457.