Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Therapeutic efficacy of three-dimensional conformal radiation therapy for patients with locally advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Thoracic radiation therapy improves the prognosis for patients with extensive stage small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of thoracic radiation therapy (TRT) on patients with extensive stage small-cell lung cancer (SCLC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Clinical analysis of 126 patients with primary small cell carcinoma of the esophagus / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors and the principles of treatment of primary esophageal small cell carcinoma (SCEC) retrospectively.</p><p><b>METHODS</b>The data of 126 patients with histologically confirmed SCEC treated in our department between May 1985 and June 2005 were retrospectively analyzed. 85 patients were in limited disease stage (LD) and 41 patients as extensive disease stage (ED) according to the Veterans Administration Lung Study Group staging system. Among the 84 patients treated with esophagectomy, 8 cases were in stage I, 16 in stage IIa, 10 in stage IIb, 40 in stage III, 4 in stage IVa and 6 in stage IVb, according to the TNM system (6(th) edition, AJCC). Cox's hazard regression model was used to identify the prognostic factors, and Chi-square test to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank methods were used to estimate and compare the survival rates.</p><p><b>RESULTS</b>The median follow-up duration of this series was 13 months. One hundred and eight patients died of the disease during the follow-up, 10 were still alive and 8 were lost to follow-up. The 1-, 3-, and 5-year overall survival rates (OS) were 52.2%, 15.9%, and 12.2%, respectively, with a median survival time (MST) of 12.5 months. The 1-, 2-, and 3-year OS were 62.1%, 30.8%, and 22.4% with a MST of 14.0 months for LD, and 29.3%, 13.6% and 2.7% with a MST of 7.0 months for ED, respectively. There was a statistically significant difference in OS between LD and ED (P = 0.0001). The MST of the patients treated with chemotherapy was 14.5 months, significantly longer than the 5.2 months of the patients without (P = 0.0001). Multivariate analysis showed that stage (HR 1.91, 95% CI 1.26 approximately 2.91, P = 0.002), length of the primary lesion (HR 1.75, 95% CI 1.17 approximately 2.63, P = 0.007), and chemotherapy (HR 0.42, 95% CI 0.28 approximately 0.65, P = 0.000) were independent prognostic factors.</p><p><b>CONCLUSION</b>Esophageal small cell carcinoma is a systemic disease. The tumor stage (LD or ED), length of the primary lesion and chemotherapy are independent prognostic factors. Therefore, a systemic therapy based on chemotherapy should be recommended.</p>

Postoperative three-dimensional conformal radiotherapy for resected non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association between survival and postoperative three-dimensional conformal radiotherapy (3DCRT) in patients with resected non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>In a population-based cohort, postoperative 3DCRT for NSCLC provides a good prognosis, and the radiation-related pneumonitis is acceptable.</p>

Prognosis of locally advanced non small cell lung cancer treated with three dimentional conformal radiotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Preliminary results of three-dimensional conformal radiotherapy for small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility, therapeutic effects and complications of three-dimensional conformal radiotherapy (3DCRT) for small-cell lung cancer (SCLC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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%.</p><p><b>CONCLUSION</b>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.</p>

Influence of the number of lymph node metastasis on survival and significance of postoperative radiotherapy for esophageal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the influence of the number of lymph node metastasis on survival and prophylactic postoperative radiotherapy after radical resection of thoracic esophageal carcinoma.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Evidence-based clinical practice of radiotherapy of small-cell lung cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effects of radiotherapy in the treatment of small-cell lung cancer and the optimal radiation doses, irradiation volume and fractionations.</p><p><b>METHODS</b>Using evidence-based principles to search and evaluate clinical evidence on radiotherapy of small-cell lung cancer and giving grades of recommendation in clinical practice.</p><p><b>RESULTS AND CONCLUSION</b>The combination of chemotherapy and thoracic irradiation were the treatment strategy in limited stage small-cell lung cancer (LD SCLC). There were no clear answers on optimal irradiation dose and volume. Early thoracic irradiations were better than later ones. Radiotherapy should be started at the first or second cycle of chemotherapy. Hyperfractionated irradiation may have therapeutic benefit compared with conventional irradiation. Prophylactic cranial irradiation could improve survival for patients with complete response after chemotherapy and radiotherapy.</p>