Jima Lv

Randomized phase II study of concurrent cisplatin/etoposide or paclitaxel/carboplatin and thoracic radiotherapy in patients with stage III non-small cell lung cancer

OBJECTIVE To evaluate the activity and safety of concurrent thoracic radiotherapy (TRT) plus weekly paclitaxel/carboplatin (PC) regimen compared with widely used cisplatin/etoposide (PE) regimen in patients with unresectable stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Patients were randomly assigned to receive the following treatments: PE arm, cisplatin (50mg/m(2)) on days 1, 8, 29, and 36 and etoposide (50 mg/m(2)) on days 1-5 and 29-33 plus 60 Gy of TRT; PC arm, weekly concurrent carboplatin (AUC = 2) and paclitaxel (45 mg/m(2)) plus 60 Gy of TRT. RESULTS A total of 65 patients were randomized (PE arm, n = 33; PC arm, n = 32). The 3-year overall survival (OS) was significantly better in the PE arm than in the PC arm (33.1% vs. 13%, P = .04). The incidence of Grade 3/4 neutropenia was 78.1% in the PE arm and 51.5% in the PC arm (P = .05). The rate of Grade 2 or greater radiation pneumonitis was 25% in the PE arm and 48.5% in the PC arm (P = .09). CONCLUSIONS Compared to PE regimen, weekly PC regimen cannot be recommended since it failed to achieve an improvement in either OS or PFS.

Primary small cell carcinoma of the esophagus.

Introduction: Primary small cell esophageal carcinoma (SCEC) is a rare and aggressive disease for which there is no recommended standard treatment at this time. Methods: A total of 126 patients with SCEC, diagnosed histologically between May 1985 and June 2005 at our institution, were analyzed retrospectively. All were staged according to the Veterans’ Administration Lung Study Group staging system. The TNM system for esophageal carcinoma (6th edition, American Joint Committee on Cancer) was also used for those who underwent esophagectomies. SPSS (10.0) software was used for statistical analysis. Cox’s hazard regression model was performed to identify prognostic factors. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. The &khgr;2 test was performed to examine frequencies between different groups. Results: Through a median follow-up of 13 months, 108 patients died, 10 were alive, and 8 were lost to follow-up. Of the entire study population, the overall median survival time (MST) and 1-, 3-, and 5-year overall survival rates were 12.5 months and 52.2%, 15.9%, and 12.2%, respectively. For limited disease, the MST and 1-, 2-, and 3-year overall survival rates were 14.0 months and 62.1%, 30.8%, and 22.4%, respectively; for extensive disease, the respective values were 7.0 months and 29.3%, 13.6%, and 2.7% (p = 0.0001). The MST of 14.5 months for cases who received chemotherapy was superior to that of 5.2 months for cases who did not (p = 0.0001). Tumor stage, length of the primary lesion, and chemotherapy, but not surgery were independent prognostic factors in a multivariate analysis. Conclusions: SCEC is systemic disease. Tumor stage and chemotherapy were independent prognostic factors. Systemic therapy, based on chemotherapy with radiotherapy, is recommended.

Thoracic radiation therapy improves the overall survival of patients with extensive-stage small cell lung cancer with distant metastasis.

The authors conducted a retrospective study to evaluate the effects of thoracic radiation therapy (TRT) for patients with extensive‐stage small cell lung cancer (ED‐SCLC).

Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial.

Objective To determine the safety and therapeutic effects of nimotuzumab (h-R3) combined with radiotherapy in esophageal cancer. Methods This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery) to stage IV (supraclavicular lymph node metastasis only) esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy. Results There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50–70 Gy radiation; 37 patients (88.1%) received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events) included esophagitis and gastrointestinal, dermatological and hematological toxicities. Complete response, partial response, stable disease, and progressive disease were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients at 1 month after the treatment. The epidermal growth factor receptor (EGFR) overexpression rate was 95.2%. After a median follow-up of 37 months, the median survival time (MST) was 14 months. The 2 year and 3 year overall survival (OS) rates were 33.3% and 26.2%, respectively. The median progression-free survival (PFS) time was 10 months. The 2 year and 3 year PFS rates were 24.5% and 22.1%, respectively. The MST in the 13 patients with (+++) EGFR expression (group A) and 7 patients with (++) EGFR expression (group B) was 15 and 11 months, respectively. The 2 year and 3 year OS rates were 46.2% and 38.5% in group A and 28.6% and 28.6% in group B, respectively (P = 0.405). Conclusion Although concurrent chemoradiotherapy was the standard care for locally advanced esophageal cancer, radiotherapy was the choice for those who were refused or could not tolerate chemoradiotherapy. Our study shows that nimotuzumab combined with radiotherapy was well tolerated in patients with esophageal cancer. EGFR overexpression was more common than previously reported. OS was higher after combined therapy than after historical control radiotherapy alone. Further studies are required to confirm the therapeutic efficacy of nimotuzumab in esophageal cancer.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial

Background The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients and methods Patients were randomly received 60–66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1–5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. Results A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%–28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55–1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). Conclusion EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. Trial registration ID NCT01494558.

Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

PURPOSE We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. METHODS AND MATERIALS The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. RESULTS The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). CONCLUSIONS Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

BackgroundBrain metastases (BM) is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC) after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2) NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset.MethodsBetween 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM.ResultsFifty-three (24.4 %) patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001) and the ratio of metastatic to examined nodes or lymph node ratio (LNR) ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000) were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %.ConclusionsIn NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

Selection of proper candidates with resected pathological stage IIIA-N2 non-small cell lung cancer for postoperative radiotherapy

To establish a prediction model in selecting fit patients with resected pIIIA‐N2 non‐small cell lung cancer (NSCLC) for postoperative radiotherapy (PORT), and evaluate the model in clinical practice.

Risk factors for radiation-induced lung toxicity in patients with non-small cell lung cancer who received postoperative radiation therapy

BACKGROUND AND PURPOSE To evaluate the risk factors for radiation-induced lung toxicity (RILT) from post-operative radiation therapy (PORT) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS Ninety NSCLC patients who received PORT with or without chemotherapy from November 2002 to March 2006 were retrospectively analyzed. Each individuals radiotherapy plans were reviewed to determine the percentage of the whole lung volume that received more than a specific dose of irradiation (V(dose)). The endpoint was RILT of grade 2 or higher. Data of potential risk factors for RILT were extracted from the medical records and evaluated by logistic regression modeling, the t-test, and the Chi-square test. RESULTS A total of 20 patients received pneumonectomy, while the remaining 70 received lobectomy. In the lobectomy group, 9 patients (10%) developed ≥grade 2 RILT. Among the clinical factors, only adjuvant chemotherapy was significantly correlated with RILT (p=0.039). For lung dosimetric factors, V(20) through V(40) were all significantly higher in the RILT group than in the non-RILT group. In the lobectomy group, the incidence of RILT was 27.3% in patients who received adjuvant chemotherapy and whose V(20) was greater than 20%. It was 9.7% in lobectomy patients with one of the risk factors, and 0.0% in those with no risk factors (p=0.032). CONCLUSIONS The lung toxicity of PORT was found to be acceptably low. Adjuvant chemotherapy and lung dosimetric factors of V(20)-V(40) were significantly correlated with RILT risk in NSCLC patients.

Radical thoracic radiotherapy may provide favorable outcomes for stage IV non‐small cell lung cancer

This study investigates the outcome of synchronous stage IV non‐small cell lung cancer (NSCLC) patients who received radical thoracic radiotherapy (TRT).