Hypofractionated radiotherapy for medically inoperable stage I non-small cell lung cancer.

BACKGROUND: To investigate the clinical outcomes and toxicity of hypofractionated radiotherapy for medically inoperable stage I non-small cell lung cancer (NSCLC). METHODS: Patients treated with radiotherapy at a dose of 4-6 Gy per fraction using fixed-field intensity modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT) at our hospital from June 2005 to December 2013 were analyzed. The total prescription doses ranged from 50-78 Gy with 4-6 Gy per fraction. The median follow-up period was 24 months. RESULTS: A total of 65 patients with stage I NSCLC were analyzed, including 43 primary NSCLC patients and 22 patients with recurrent or second primary NSCLC. An objective response (complete or partial response) was achieved at six months in 84.6% of patients. The three-year local control rate was 90.8%. Kaplan-Meier estimates of local failure-free, progression-free, overall, and cancer-specific survival rates at three years were 90.3%, 64.3%, 68.9%, and 88.8%, respectively. The rate of symptomatic radiation pneumonitis was 16.9%, and no grade 4-5 toxicity was observed. CONCLUSION: Favorable local control and outcome was achieved with hypofractionated radiotherapy in patients with inoperable stage I NSCLC with acceptable toxicity. The most common schedule of 6 Gy × 12 fractions may be a promising regimen, and a prospective study is in process.

MicroRNA-related polymorphisms in apoptosis pathway genes are predictive of clinical outcome in patients with limited disease small cell lung cancer.

We examined the impact of single nucleotide polymorphisms (SNPs) at miRNA binding sites in the 3'-UTRs of genes in the apoptosis pathway on the prognosis of patients with limited disease-small cell lung cancer (LD-SCLC). Twelve tagSNPs in seven genes were genotyped using blood samples from 146 LD-SCLC patients treated with chemoradiotherapy. Cox proportional hazard regression models and recursive partitioning analysis were performed to identify SNPs significantly associated with overall survival. Three SNPs, CASP8: rs1045494 (C > T), PIK3R1: rs3756668 (A > G) and CASP7: rs4353229 (T > C), were associated with longer overall survival in LD-SCLC patients after chemoradiotherapy. The adjusted hazard ratios (95% confidence intervals) were 0.480 (0.258-0.894), 0.405 (0.173-0.947) and 0.446 (0.247-0.802), respectively, and remained significant after multiple comparison correction. Moreover, subset analysis showed these SNPs were still predictive of overall survival in stage III patients. Recursive partitioning analysis enabled patients to be classified into three risk subgroups based on unfavorable genotype combinations of the rs1045494 and rs4353229 SNPs. These findings suggest miRNA-related polymorphisms in the apoptosis pathway may be useful biomarkers for selection of LD-SCLC patients likely to benefit from chemoradiotherapy.

Patterns and predictors of recurrence after radical resection of thymoma.

BACKGROUND: Recurrence of thymomas even after complete resection is common, but the relapse patterns remain controversial. This study aimed to define the patterns and predictors of relapse after complete resection of thymoma. METHODS: A single-institution retrospective study was performed with 331 patients who underwent radical resection of thymoma between 1991 and 2012. RESULTS: After a median follow-up of 59 months, the recurrence rate was 6.9% (23/331). Relapse occurred in 23 patients with the pleura (14) and tumor bed (6) as the most common sites of recurrence. According to the definitions of the International Thymic Malignancy Interest Group, 10 (43.5%) patients had local relapse, 15 (65.2%) had regional relapse, 10 (43.5%) had distant relapse. The difference in survival following relapse between lung and regional relapse was statistically significant (P=0.027) but that between lung and distant relapse was not (P=0.808). The recurrence rates correlated with the initial Masaoka stage. Further, recurrence also correlated with World Health Organization (WHO) tumor type. The recurrence-free survival rates in patients with tumor size ⩾8 cm were worse than those of patients with tumor size <8 cm (P=0.007). Tumor size was also correlated with stage (r=0.110). As tumor becomes larger, the stage is more advanced (P=0.023). Multivariate analysis showed that Masaoka stage (P=0.005), tumor size (P=0.033), and WHO histological type (P=0.046) were predictive factors of relapse. CONCLUSION: Regional recurrence is the most common relapse pattern but local and distant relapse are also common. Advanced Masaoka stage, larger tumor size, and type B3 are risk factors of recurrence. Lung relapse should be considered distant relapse. Further, tumor size was correlated with Masaoka stage and therefore should be considered in the staging system.

[Therapeutic efficacy of three-dimensional conformal radiation therapy for patients with locally advanced non-small cell lung cancer].

OBJECTIVE: To compare the treatment results of three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (2D) for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: Five hundred and twenty seven patients with stage III NSCLC treated between Jan 2000 and Dec 2006 were included in this study. Among them, 253 cases were treated with 3D-CRT, and 274 with conventional radiotherapy. In the 3D group, 159 (62.8%) patients received chemoradiotherapy, 77 with total radiotherapy dose of > 60 Gy, 49 with 50 - 60 Gy. In the 2D group, 127 (46.4%) patients received chemoradiotherapy, 48 with total radiotherapy dose of > 60 Gy, 75 with 50 - 60 Gy. RESULTS: The 1-, 3-, 5-year overall survival rates (OS) and median survival time for patients treated with 3D-CRT were 73.3%, 26.1%, 14.4% and 20.1 months, respectively, and that of patients treated with 2D radiotherapy were 61.0%, 13.8%, 8.0% and 15.6 months, respectively (P = 0.002). The 1-, 3-, 5-year cause-specific survival rates (CSS) were 79.0%, 33.3%, and 20.8% for the 3D group and 65.1%, 16.7%, 11.2%, respectively, for the 2D group (P = 0.000). The 1-, 3-, and 5-year locoregional control rates were 71.6%, 34.3% and 31.0% for patients treated with 3D radiotherapy and 57.3%, 22.1% and 19.2%, respectively, for patients treated with 2D treatment (P = 0.002). The results of multivariate analysis showed that 3D-CRT, KPS, clinical tumor response and pretreatment hemoglobin level were independently associated with increased OS and CSS. No statistically significant differences were found between the radiation complications in the two groups. CONCLUSIONS: The results of our study demonstrate that 3D-conformal radiotherapy improves the survival rate in patients with stage III NSCLC compared with that of 2D radiation therapy.

[Thoracic radiation therapy improves the prognosis for patients with extensive stage small-cell lung cancer].

OBJECTIVE: To evaluate the effect of thoracic radiation therapy (TRT) on patients with extensive stage small-cell lung cancer (SCLC). METHODS: One hundred and fifty-four patients with extensive stage SCLC treated in our department between January 2003 and December 2006 were enrolled in this study. Eighty nine patients received chemotherapy and thoracic radiation therapy (ChT/TRT), and 65 patients were treated with chemotherapy alone (ChT without TRT). The chemotherapy was CE (carboplatin and etoposide), PE (cisplatin and etoposide) or CAO (CTX, ADM and VCR) regimens. The total dose of thoracic irradiation was 40-60 Gy with 1.8 - 2.0 Gy per fraction. RESULTS: For the whole group, the median survival time (MST) was 13.7 months, the 2-year and 5-year overall survival rates were 27.9% and 8.1%, respectively. The MST, overall survival rates at 2 years and 5 years in the ChT/TRT group and ChT without TRT group were 17.2 months, 36.0%, 10.1% and 9.3 months, 16.9%, 4.6%, respectively (P = 0.001). The median progression-free survival (PFS) for all patients was 8.0 months, the 2-year and 5-year PFS were 13.6% and 8.2%, respectively. The median PFS, 2-year and 5-year PFS in the ChT/TRT group and ChT without TRT group were 10.0 months, 17.4%, 10.5% and 6.2 months, 9.8%, 4.9%, respectively (P < 0.001). The incidence of intra-thoracic local failure was 29.6% in the ChT/TRT group and 70.0% in the ChT/without TRT group (P = 0.000). CONCLUSIONS: Chemotherapy plus thoracic radiation therapy can improve the overall survival, progress free survival and reduce local regional failure rate in patients with extensive stage SCLC compared with that by chemotherapy alone.

Role of adjuvant radiotherapy for stage II thymoma after complete tumor resection.

PURPOSE: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. METHODS AND MATERIALS: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. RESULTS: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. CONCLUSIONS: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

[Effect of different chemotherapy regimens for concurrent chemoradiotherapy on locally advanced non-small cell lung cancer].

OBJECTIVE: To retrospectively analyze the effects of different chemotherapy regimens for concurrent chemoradiation on locally advanced non-small cell lung cancer (NSCLC). METHODS: The data from 106 patients diagnosed as locally advanced NSCLC (IIIa: 29, IIIb: 77), who received various chemotherapy regimens for concurrent chemoradiotherapy, were retrospectively analyzed. Paclitaxel-based chemotherapy regimen was administered in 55 patients, topotecan regimen in 21 patients, PE (cisplatin and etopside) regimen in 26 patients, and other regimens in the remaining 4 patients. The effect of different chemotherapy regimens on overall survival and toxicity was analyzed. RESULTS: The median survival time was 18.6 months, and the overall 1- and 3-year survival rates were 72.2% and 27.5%, respectively. The median survival time of 102 patients treated with paclitaxel-containing, topotecan-containing or PE regimens was 16.3, 27.3 and 29.1 months, respectively. The overall survival times of topotecan and PE groups were superior to that of paclitaxol-based group, but not significantly different (P = 0.32). Both univariate and multivariate analysis showed that paclitaxol-based chemotherapy regimen was significantly associated with a poorer survival (P < 0.05). N stage was another significant prognostic factor determined by COX multivariate regression model. Compared with the other regimens (10.6%), paclitaxel-based regimen (27.3%) had more acute radiation pneumonitis (grade >or= 2, P = 0.03), but no significant differences were observed in blood toxicity and esophagitis. CONCLUSION: There is a correlation between different chemotherapy regimens for concurrent chemoradiotherapy and the overall survival and acute radiation pneumonitis in patients with locally advanced NSCLC.

[Postoperative three-dimensional conformal radiotherapy for resected non-small cell lung cancer].

OBJECTIVE: To investigate the association between survival and postoperative three-dimensional conformal radiotherapy (3DCRT) in patients with resected non-small cell lung cancer (NSCLC). METHODS: Eighty-four patients were treated with surgery and postoperative 3DCRT for NSCLC. Sixty-five (77.4%) patients received lobectomy, and 19 (22.6%) received pneumonectomy. Fifty-four (64.3%) patients achieved R0 resection and 30 cases (35.8%) received R1/R2 resection. Fifty-two patients were of stage IIIA and 24 patients were of stage IIIB. Photon energy of 6 MV was used for all the patients. The median 3DCRT dose was 60 Gy (40 - 70 Gy) with a fraction size of 2 Gy. Thirty-seven patients received median 3 cycles of adjuvant chemotherapy. The median follow-up was 35.5 months for survivors. RESULTS: The overall 3-year survival rate was 58.6%, and the 4-year overall survival rate was 43.9%. Of the 43 patients who had treatment failure, only 8 (9.9%) patients showed intrathoracic recurrence, but 38 (46.9%) patients had distant metastasis. The univariate analysis for all patients showed that sex, age, weight loss, tumor size, pathology and stage were not correlated with prognosis. R1/R2 resection was associated with a significantly worse survival. Toxicities were acceptable, with 9 (11.1%) patients appeared higher than NCI CTC grade 2 radiation pneumonitis. CONCLUSION: In a population-based cohort, postoperative 3DCRT for NSCLC provides a good prognosis, and the radiation-related pneumonitis is acceptable.

[Prognosis of locally advanced non small cell lung cancer treated with three dimentional conformal radiotherapy].

OBJECTIVE: To summarize our experience and evaluate the prognostic factors of locally advanced non small cell lung cancer (LA-NSCLC) treated with three dimentional conformal radiotherapy (3D-CRT). METHODS: 118 patients with stage IIImA/IIIB non small cell lung cancer were treated with 3D-CRT from Nov. 2001 to Mar. 2005. 113 patients with complete clinical data were eligible for analysis, 45 of them received radiotherapy alone; 39 were treated by concurrent chemoradiation with paclitaxol plus carboplatin in 32 patients and topotecan in 7 patients, and 29 by sequential chemoradiation with platinum-based regiment in most of them. The dose of radiation for the thoracic field ranged from 26 Gy to 75 Gy with a median dose of 60 Gy. GTV and PTV were collected from the 3D treatment plans in 79 and 101 patients, respectively. Overall survival (OS) was calculated using the Kaplan-Meier method. Comparisons among the curves were made using a two-tailed long-rank test. The Cox model was used for multivariate analysis. RESULTS: The 1-, 2- and 3-year overall survival rate was 60.7%, 31.6% and 22.4%, respectively, with a median survival time of 17 months. In univariate analysis, the following characteristics were significantly associated with longer survival: absence of chest pain, good karnofsky performance status (KPS), albumin > 4.2 g/L, hemoglobin > or = 140 g/L (male) or 130 g/L (female), response to radiotherapy and GTV < 100 cm3. However, multivariate analysis revealed that only good KPS was an independent risk factor predicting the survival. CONCLUSION: Three-dimensional conformal radiotherapy is effective in the treatment of locally advanced non-small cell lung cancer with acceptable complications. Karnofsky performance status is the only independent prognositic factor.

[Preliminary results of three-dimensional conformal radiotherapy for small-cell lung cancer].

OBJECTIVE: To evaluate the feasibility, therapeutic effects and complications of three-dimensional conformal radiotherapy (3DCRT) for small-cell lung cancer (SCLC). METHODS: The data of 19 SCLC patients treated between June 2001 and August 2003, with 3DCRT were reviewed and analyzed. Eighteen patients were treated by radiotherapy plus chemotherapy while only 1 patient by radiotherapy alone. Radiotherapy was delivered at 2 Gy/fraction, 5 fractions per week with a median total dose of 54 Gy. Chemotherapy consisted of 4 - 6 cycles of etoposide and cisplatin or carboplatin. The median follow-up time was 24 months. RESULTS: (1) The overall response rate after 3DCRT was 79.0%, with a complete remission rate of 31.6% (6/19), partial remission rate of 47.4% (9/19). The 1- and 2-year overall survival (OS) was 71.7% and 35.8% respectively, with a median survival time (MST) of 19 months, and both the 1- and 2-year local progression free survival (LPFS) were 94.7%. (2) Of these 19 patients, grade 2 acute radiation pneumonitis developed in 5.3%, grade 2 late radiation pneumofibrosis in 5.3%, grade 2 acute radiation esophagitis in 10.5% and grade 2 acute hematologic toxicity in 10.5%. CONCLUSION: Three-dimensional conformal radiotherapy is feasible in the treatment of SCLC with high response rate and acceptable complications. Further observation, more patients treated by 3DCRT and prolonged follow-up are needed to evaluate remote survival.

Comparison of conformal and intensity-modulated techniques for simultaneous integrated boost radiotherapy of upper esophageal carcinoma.

AIM: To compare intensity-modulated radiotherapy (IMRT) with conformal radiotherapy (CRT) by investigating the dose profiles of primary tumors, electively treated regions, and the doses to organs at risk. METHODS: CRT and IMRT plans were designed for five patients with upper esophageal carcinoma. For each patient, target volumes for primary lesions (67.2 Gy) and electively treated regions (50.4 Gy) were predefined. An experienced planner manually designed one CRT plan. Four IMRT plans were generated with the same dose-volume constraints, but with different beam arrangements. Indices including dose distributions, dose volume histograms (DVHs) and conformity index were compared. RESULTS: The plans with three intensity-modulated beams were discarded because the doses to spinal cord were lager than the tolerable dose 45Gy, and the dose on areas near the skin was up to 50Gy. When the number of intensity beams increased to five, IMRT plans were better than CRT plans in terms of the dose conformity and homogeneity of targets and the dose to OARs. The dose distributions changed little when the beam number increased from five to seven and nine. CONCLUSION: IMRT is superior to CRT for the treatment of upper esophageal carcinoma with simultaneous integrated boost (SIB). Five equispaced coplanar intensity-modulated beams can produce desirable dose distributions. The primary tumor can get higher equivalent dose by SIB technique. The SIB-IMRT technique shortens the total treatment time, and is an easier, more efficient, and perhaps a less error-prone way in delivering IMRT.

[Influence of the number of lymph node metastasis on survival and significance of postoperative radiotherapy for esophageal carcinoma].

OBJECTIVE: To analyze the influence of the number of lymph node metastasis on survival and prophylactic postoperative radiotherapy after radical resection of thoracic esophageal carcinoma. METHODS: Four hundred and ninety-five patients with thoracic esophageal squamous cell cancer who had undergone radical resection were randomly divided into surgery group alone (S, 275) and surgery plus radiotherapy group (S + R, 220). The patients were classified into three groups: Group A: 234 patients (47.2%) without lymph node involvement; Group B: 146 patients (29.5%) with 1 to 2 involved lymph nodes and Group C: 115 patients (23.2%) with >or= 3 involved lymph nodes. RESULTS: 1. The 5-year survival rate in Groups A, B and C for the same T stage (T3) was 52.6%, 28.8% and 10.9%, respectively (P = 0.0000); the 5-year survival rate in group C was 0% in S group and 19.3% in S + R group (P = 0.0336); 2. In the positive lymph node group, the metastatic rate of intra-thoracic and supraclavicular lymph node was 35.9% and 21.2% in S group and 19.7% and 4.4% in S+R group (P = 0.014 and P = 0.000). In the negative lymph node group, the metastatic rates of intra-thoracic lymph node was 27.8% in S group and 10.3% in S + R group (P = 0.003). The metastatic rate of intra-abdominal lymph node in Groups A, B and C was 3.9%, 9.4% and 17.5%, respectively (P = 0.0000). The occurrence of hematogenous metastasis was most frequent in group C (27.8%) with >or= 3 positive lymph nodes. CONCLUSION: 1. The number of metastatic lymph node is one of the important factors which affects the survival of thoracic esophageal carcinoma. 2. Chemotherapy might be given to the patients with three or more lymph nodes involved who have the possibility of developing hematogenous metastasis. Postoperative radiotherapy can reduce the occurrence of intra-thoracic and supraclavicular lymph node metastasis and improve the survival of patients with three or more lymph nodes involvement.

[Comparison of SIB-IMRT treatment plans for upper esophageal carcinoma].

OBJECTIVE: To implement simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT) plans for upper esophageal carcinoma and investigate the dose profiles of tumor and electively treated region and the dose to organs at risk (OARs). METHODS: SIB-IMRT plans were designed for two patients with upper esophageal carcinoma. Two target volumes were predefined: PTV1, the target volume of the primary lesion, which was given to 67.2 Gy, and PTV2, the target volume of electively treated region, which was given to 50.4 Gy. With the same dose-volume constraints, but different beams arrangements (3, 5, 7, or 9 equispaced coplanar beams), four plans were generated. Indices, including dose distribution, dose volume histogram (DVH) and conformity index, were used for comparison of these plans. RESULTS: The plan with three intensity-modulated beams could produce good dose distribution for the two target volumes. The dose conformity to targets and the dose to OARs were improved as the beam number increased. The dose distributions in targets changed little when the beam number increased from 7 to 9. CONCLUSIONS: Five to seven intensity-modulated beams can produce desirable dose distributions for simultaneous integrated boost (SIB) treatment for upper esophageal carcinoma. The primary tumor can get higher equivalent dose by SIB treatments. It is easier and more efficient to design plans with equispaced coplanar beams. The efficacy of SIB-IMRT remains to be determined by the clinical outcome.