Histological subtypes of lung cancer in Chinese males from 2000 to 2012.

OBJECTIVE: To characterize the histological and epidemiological features of male lung cancer patients in China. METHODS: The demographic and histological information about male lung cancer patients identified from 2000-01-01 to 2012-12-31, was collected from the Cancer Hospital of the Chinese Academy of Medical Sciences. Relative frequencies (RF) were estimated for major histological subtypes and compared according to the years of diagnosis and birth. RESULTS: The RF of adenocarcinoma (ADC) increased from 21.96% to 43.36% and the RF of squamous cell carcinoma (SCC) decreased from 39.11% to 32.23% from 2000 to 2012 in the 15 427 male lung cancer patients included in this study (Z=17.909, P<0.0001; Z=-6.117, P<0.0001). The RF of ADC increased from 28.72% in 2000-2004, 36.88% in 2005-2008 to 48.61% in 2009-2012 in patients born after 1960. The age-adjusted RF of ADC in 2007-2012 increased consistently in all the investigated areas. CONCLUSION: The increased RF of ADC in male lung cancer patients highlights the need for further investigation of the etiologic factors of these tumors. Smoke-free policies rather than modifying tobacco products should be enforced.

[Clinical analysis of intraoperative radiotherapy in breast-conserving surgery of early breast cancer].

OBJECTIVE: To evaluate the safety and feasibility of intraoperative radiotherapy during breast-conserving surgery instead of whole breast radiotherapy in early breast cancer patients. METHODS: From July 2008 to December 2012, 36 early breast cancer patients underwent breast-conserving surgery plus interoperative radiotherapy on a Mobetron 1000 mobile electron accelerator. Postoperative recurrence and metastases, complications and cosmetic outcomes were recorded and analyzed. RESULTS: During a median follow-up period of 27.9 months, 2 patients (5.56%) underwent mastectomy after local relapses. There was no occurrence of distant metastasis or mortality. Their average wound healing time was 17 days and 2 of them (5.56%) developed infection while another 2 (5.56%) had delayed wound healing. And 1 patient (2.78%) showed wound edema and neither necrosis nor hematoma was found. The evaluation of cosmetic outcome shows 32 patients (88.89%) were graded as excellent or good while another 4 (11.11%) fair or poor. None had radiotherapy-related acute hemotological toxicity and 2 patients (5.56%) developed skin pigmentation. CONCLUSION: Intraoperative radiotherapy during breast-conserving surgery instead of whole breast radiotherapy in early breast cancer patients is both safe and reliable with better cosmetic outcomes.

[Value of intraoperative electron radiation therapy in the treatment of malignant bone or soft tissue tumors around the joints].

OBJECTIVE: To evaluate the value of intraoperative radiation therapy with electrons (ELIOT) in treatment of malignant bone or soft tissue tumors around the joints. METHODS: From October 2008 to April 2012, nineteen patients with malignant bone or soft tissue tumors around the joints were treated with ELIOT. The tumors were located around the knee joint in 8 patients, around the hip joint in 6 patients, around the elbow joint in 4 patients and around the shoulder joint in one patient. All of the patients underwent limb salvage surgeries. R0 resections were performed in 18 patients, while R1 resection was performed in one patient. The doses of intraoperative radiation ranged from 10 Gy to 22 Gy. The median dose was 19 Gy. More than one ELIOT fields were used in 10 patients because of the large tumor size. RESULTS: Seven patients suffered wound complications. No grade ≥ 3 acute toxicities were observed. One patient developed radiation ulcer and arterial fistula 15 months after surgery and ELIOT, and resulted in amputation finally (grade 4 late toxicity). The mean Musculoskeletal Tumor Society (MSTS) 93 score was 26.26 ± 4.04 (87.5% ± 13.5%), with excellent to good extremity functions in 18 patients (94.7%). Four patients had local recurrences. The estimated locoregional control rates at 1, 2, and 3 years were 81.9%, 73.7%, and 73.7%, respectively. Seven patients died of the diseases. The estimated overall survivals of the entire group of patients at 1, 2, and 3 years were 76.3%, 61.2%, and 51.0%, respectively. CONCLUSIONS: ELIOT is a safe and well-tolerable technique and could be widely used for patients with malignant bone or soft tissue tumors around the joints with acceptable rates of acute and late toxicity. There is positive significance for controlling the tumor local recurrence, preserving the joint function and improving survival quality.

[Complications and short-term outcomes of intraoperative electron radiotherapy (IOERT) in patients with periarticular soft-tissue sarcomas of the extremities].

OBJECTIVE: To analyze the complications and short-term outcomes of patients receiving intraoperative electron radiotherapy (IOERT) for locally advanced and recurrent periarticular soft tissue sarcomas of the extremities. METHODS: Twenty-one adult patients with locally advanced and/or recurrent periarticular soft tissue sarcomas of the extremities treated with IOERT were included in this study. Among them 14 patients had recurrent diseases after prior operation and 7 patients with locally advanced disease with primary treatment. The total dose of radiation ranged from 11 Gy to 21 Gy of 6 - 12 MeV beta ray given by intraoperative radiotherapy after complete tumor resection with negative margins. Five patients were given external beam radiotherapy (EBRT) with a total dose of 40 - 50 Gy, and 10 patients received chemotherapy. RESULTS: The median follow-up time was 15 months. Five patients (23.8%) had tumor relapse, including one patients with local recurrence, one patient with regional recurrence, two patients with distant metastasis and one patient with local recurrence and distant metastasis. The actuarial local control rate at 1 year was 95.2% (20/21), and at 2 years was 90.5% (19/21). Acute skin toxicity (RTOG) within 3 months after surgery included grade I in 6 patients and grade II in 3 patients. Two year late skin toxicity (RTOG/EORTC) included grade I in 4 patients and grade II in 2 patients. Fibrosis included grade I in 3 patients and grade II in 3 patients. Six patients had joint dysfunction (3 patients with grade I and 3 with grade II) and 6 patients had healing problems. One patient got ipsilateral schiatic neuritis 9 months after IOERT. No adverse events occurred during surgery. CONCLUSIONS: IOERT brings tolerable complications of acute and late toxicities and favorable local control rate. IOERT should be followed by postoperative radiotherapy or increase the intraoperative radiation dose for locally advanced and recurrent sarcomas to get a better local control. Otherwise, distant metastasis is one of the main reasons of treatment failure, so chemotherapy should be added to the treatment regimen.

[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.

[Value of intraoperative radiotherapy in the treatment of locally advanced pancreatic cancer].

OBJECTIVE: To assess the value of intraoperative radiotherapy (IORT) in the combined treatment of locally advanced pancreatic cancer. METHODS: All patients with locally advanced pancreatic cancer at our hospital from January 2007 to December 2009, judged as unresectable and confirmed by histology or cytology, were recruited into this prospective study. They were randomly assigned into the IORT group (n=31) and control group (n=34). The IORT group received IORT plus internal drainage or laparotomy. The control group had internal drainage or laparotomy only. The evaluation of adverse results of two groups included: intraoperative and postoperative adverse events, recent post-operative side effects, analgesic effect, the level of tumor marker such as CA19-9 and the long-term survival. RESULTS: There was no difference in operation duration, intraoperative hemorrhage and postoperative recovery. Significant differences were found in hematotoxicology, analgesic effect, tumor marker decreasing and long-term survival. CONCLUSION: IORT is a safe, reliable and easy-to-master technique without any obvious side effect. Its analgesic effect is better than the control group. Also IORT can retard the tumor growth and improve the patient survival.

[Clinical analysis of 126 patients with primary small cell carcinoma of the esophagus].

OBJECTIVE: To investigate the prognostic factors and the principles of treatment of primary esophageal small cell carcinoma (SCEC) retrospectively. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Tobacco smoking and trends in histological subtypes of female lung cancer at the Cancer Hospital of the Chinese Academy of Medical Sciences over 13 years.

BACKGROUND: Lung cancer is the leading cause of cancer mortality among women in China, and incidence and mortality continue to rise despite the fact that smoking prevalence is very low among Chinese women. AIM: This study investigated tobacco smoking and trends in histological subtypes of female lung cancer in a central cancer hospital in China. METHODS: Demographic, smoking history and histological information on female lung cancer patients diagnosed or treated from 2000 to 2012 was collected from the Cancer Hospital, Chinese Academy of Medical Science (CHCAMS). The classification of histological subtypes and clinical stages were conducted using the ICD-O-3 and Eighth AJCC Cancer Staging Manuals. Time-trends of histological subtypes were analyzed based on annual percentage change (APC). RESULTS: Overall, 5870 female cases of lung cancer were included in the analysis. The number of female lung cancer patients increased from 509 (2000-2002) to 1744 (2011-2012). The most common histological type of lung cancer was adenocarcinoma (ADC) (72.93%), followed by small cell lung cancer (SCLC) (11.06%), squamous cell carcinoma (SCC) (8.38%) and other (7.63%). Among smokers, the proportion of SCC decreased from 40.5% to 23.7% (P = 0.005), while ADC increased from 35.7% to 50.7% (P = 0.009). In non-smokers, ADC increased from 63.1% to 80.6% (P = 0.006) and SCC decreased from 13.6% to 4.5% (P = 0.016). Among SCC cases, smokers made up a larger proportion of early stage (I/II: 47.1%) compared with late stages (III, 34.3%; IV, 18.6%). CONCLUSION: The number of female lung cancer patients has increased in CHCAMS. In both smoking and non-smoking cases, the proportion of adenocarcinoma increased. Squamous cell carcinomas were more likely to be diagnosed in early stages among smokers.

[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.

[Three-dimensional conformal radiotherapy for locoregionally recurrent non-small cell lung cancer after initial radiotherapy].

OBJECTIVE: To evaluate the feasibility, therapeutic effects and normal tissue complications of three-dimensional conformal radiotherapy (3DCRT) for locoregionally recurrent non-small cell lung cancer after initial radiotherapy. METHODS: Between August 1999 and August 2003, 27 such patients were treated with 3DCRT after initial radiotherapy. This series consisted of 25 men and 2 women with a median age of 64 years. Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week, to a median dose of 50 Gy. Treatment results and normal tissue complications were assessed with WHO and RTOG/EORTC criteria. RESULTS: Based upon a median follow-up time of 20.6 months, 25 patients (92.6%) completed the planned 3DCRT treatment. Their clinical symptom relief rate was 79.1%, and the response rate was 59.3% with a complete remission rate of 14.8% (4/27), partial remission rate of 44.4% (12/27). The overall 1- and 2-year survival (OS) rates were 73.8% and 25.4% with a median survival time (MST) of 20 months. The 1- and 2-year local progression free survival (LPFS) rates were both 88.8%. Grade 2 and grade 3 acute radiation pneumonitis developed in 7.4% (2/27) and 11.1% (3/27). Grade 2 late radiation pneumonitis developed in 11.1% (3/27). CONCLUSION: 3DCRT is feasible and advisable for locoregionally recurrent non-small-cell lung cancer, giving a good immediate tumor response and acceptable normal tissue complications.

[SPECT lung perfusion scans in predicting radiation pneumonitis in lung cancer patients].

OBJECTIVE: To evaluate single photon emission computed tomography (SPECT) lung perfusion in predicting radiation pneumonitis in lung cancer patients. METHODS: From April 2003 to March 2004, 31 lung cancer patients treated with radical radiotherapy received SPECT lung perfusion scans, among whom, 23 had had perfusion scans both before and at the time of 40 Gy irradiation. The perfusion changes in the region of interest (ROI) after irradiation were obtained through comparing post-radiotherapy with pre-radiotherapy average proportion of SPECT counts within the ROI relative to average counts of the whole lung. Endpoint was defined as grade 2 and above radiation pneumonitis according to RTOG criteria. RESULTS: Lung perfusion defect was observed in all the patients at baseline. > or = grade 2 lung perfusion defect was found in 68.2% (15/22) of patients with central lesion and in 22.2% (2/9) of patients with peripheral lesions (P = 0.04). Seventy percent of the patients (16/23) experienced improved perfusion at 40 - 50 Gy. > or = grade 2 radiation pneumonitis was observed in 12 patients (38.7%) in the whole group, with 6 in those with grade 1 perfusion defects and another 6 in > or = grade 2 group, respectively; Of the 23 patients who had had both pre- and post-radiotherapy SPECT perfusion scan, 5 > or = grade 2 radiation pneumonitis occurred in the 16 perfusion-improved patients and 3 in the 7 unimproved patients. CONCLUSION: There is no significant correlation between radiation pneumonitis and the extent of perfusion defect either before or after 40 - 50 Gy irradiation based on our limited data analysis in this series.

Role of radiotherapy in treating patients with primary malignant mediastinal non-seminomatous germ cell tumor: A 21-year experience at a single institution.

BACKGROUND: The aim of this study was to investigate the clinical characteristics and outcomes of patients with primary malignant mediastinal non-seminomatous germ cell tumor (MMNSGCT) by comparing the efficacies of different treatment modalities. METHODS: The charts of 62 consecutive patients with MMNSGCT between 1990 and 2010 were reviewed. Analyses included Kaplan-Meier survival and Cox multivariate regression. RESULTS: There was sufficient data of 61 patients for inclusion in the study. The median age was 25 years. At diagnosis, 35 patients had tumors located in the mediastinum, 26 had lung and/or distant metastases. At a median follow-up of 47.2 months, 32 patients had died and 43 had developed progressive disease. The one, three, and five-year overall survival (OS) and progression-free survival (PFS) rates were 72.1%, 50.8%, 49.2% and 47.5%, 32.8%, 32.8%, respectively. Patients who received radiotherapy in the primary treatment regimen showed improved five-year OS (68.2% vs. 38.5%, P = 0.043), PFS (45.5% vs. 20.5%, P = 0.023), and local recurrence-free survival (LRFS) (77.3% vs. 38.5%, P = 0.003) compared with those who did not receive radiotherapy. Multivariate analysis revealed that radiotherapy was an independent prognostic factor of five-year OS (hazard ratio [HR] 0.39, P = 0.037), PFS (HR 0.42, P = 0.017), and LRFS (HR 0.31, P = 0.019). CONCLUSION: Radiotherapy in a chemotherapy-based treatment regimen could significantly reduce local recurrence and improve survival of MMNGCT patients.

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.

A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury.

Radiation therapy (RT) is an important therapeutic modality in the treatment of thoracic tumors. The maximum doses to these tumors are often limited by the radiation tolerance of lung tissues. Lung injury from ionizing radiation is believed to be a consequence of oxidative stress and a cascade of cytokine activity. Superoxide dismutase (SOD) is a key enzyme in cellular defenses against oxidative damage. The objective of this study was to determine whether the SOD mimetic AEOL 10113 [manganese (III) mesotetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP(5+))] increases the tolerance of lung to ionizing radiation. AEOL 10113 was able to significantly reduce the severity of RT-induced lung injury. This was strongly supported with histopathology results and measurements of collagen deposition (hydroxyproline content). There was a significant reduction in the plasma level of the profibrogenic cytokine transforming growth factor-beta (TGF-beta) in the group of rats receiving RT + AEOL 10113. In conclusion, the novel SOD mimetic, AEOL 10113, demonstrates a significant protective effect from radiation-induced lung injury.

Radioprotection of lungs by amifostine is associated with reduction in profibrogenic cytokine activity.

Radiation-induced pulmonary toxicity causes significant morbidity and mortality in patients irradiated for lung cancer, breast cancer, lymphoma or thymoma. Amifostine is an important drug in the emerging field of cytoprotection. Recent advances in our understanding of the mechanism of radiation-induced injury at the molecular and cellular levels have stimulated interest in the development of effective radioprotective strategies. Accumulation of macrophages with associated production of reactive oxygen species (ROS) and production and activation of cytokines is a key process involved in the pathophysiology of radiation injury in the lung. The purpose of this study was to determine whether the mechanism of radioprotection by amifostine includes reduction in both macrophage activity and the expression and activation of profibrogenic cytokines. Our results demonstrated a reduction in both functional and histological radiation-induced lung injury by amifostine. In addition, this study is the first to demonstrate that amifostine given prior to irradiation reduced both the accumulation of macrophages and the expression/activation of lung tissue Tgfb1 which was followed by the reduction of plasma Tgfb1 levels during the development of radiation-induced lung injury. Future studies are needed to determine whether administration of amifostine both during and after radiotherapy may further increase its radioprotective effect.

[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.

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.

Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity.

The objective of this study was to assess the radioprotective effects of amifostine in the rat model of radiation-induced lung injury using fractionated doses of radiation, to determine whether amifostine given before irradiation protects tumor from radiation cytotoxicity, and to determine whether changes in plasma levels of transforming growth factor (TGF)-beta correlate with radioprotective effect of amifostine. R3230 AC mammary adenocarcinoma was transplanted on the right posterior chest wall of female Fisher-344 rats. Both tumor-bearing and non-tumor-bearing animals were irradiated to the tumor or right lung using 4 MV photons and fractionated dose of 35 Gy/5 fractions/5 days. Animals with tumors and those without were randomized into 4 groups, respectively (8 to 10 rats per group), to receive (1) radiation alone; (2) radiation + amifostine; (3) amifostine alone; (4) sham radiation. Amifostine (150 mg/kg) was given intraperitoneally 30 minutes before each fraction of irradiation. The tumor size was measured twice a week. Breathing rate was assessed every 2 weeks. TGF-beta levels in plasma were assessed monthly after treatment. Six months after irradiation, animals were euthanized and lung tissue was processed for hydroxyproline content analysis. A significant increase in breathing frequency started 9 weeks after irradiation in animals that received radiation only. In the radiation + amifostine group, there was both a delay and a significantly lower peak in breathing frequency (P < .001). Hydroxyproline content was higher in the radiation-alone group than in rats given amifostine prior to radiation (P < .05). The TGF-beta levels in plasma showed an increase from 1 to 3 months after radiation, peaking at 2 months in the rats with (2.80 +/- 0.23) or without (5.32 +/- 1.21) amifostine compared to sham irradiation. TGF-beta levels were significantly lower at 1 to 3 months in rats receiving amifostine plus radiation versus those receiving radiation alone. Tumor growth delay and regrowth rate after radiation were not different between radiation-alone and radiation + amifostine groups. This study confirms the protective effect of amifostine in reducing radiation-induced pulmonary toxicity. No tumor protection was demonstrated after fractionated radiotherapy. The reduction in pulmonary injury with amifostine in paralleling lower plasma levels of TGF-beta, suggesting that monitoring plasma levels of this cytokine may reflect the efficacy of an intervention aimed at preventing radiation-induced lung injury.