Impact of the number of dissected lymph nodes on machine learning-based prediction of postoperative lung cancer recurrence: a single-hospital retrospective cohort study.

BACKGROUND: The optimal number of lymph nodes to be dissected during lung cancer surgery to minimise the postoperative recurrence risk remains undetermined. This study aimed to elucidate the impact of the number of dissected lymph nodes on the risk of postoperative recurrence of non-small cell lung cancer (NSCLC) using machine learning algorithms and statistical analyses. METHODS: We retrospectively analysed 650 patients with NSCLC who underwent complete resection. Five machine learning models were trained using clinicopathological variables to predict postoperative recurrence. The relationship between the number of dissected lymph nodes and postoperative recurrence was investigated in the best-performing model using Shapley additive explanations values and partial dependence plots. Multivariable Cox proportional hazard analysis was performed to estimate the HR for postoperative recurrence based on the number of dissected nodes. RESULTS: The random forest model demonstrated superior predictive performance (area under the receiver operating characteristic curve: 0.92, accuracy: 0.83, F1 score: 0.64). The partial dependence plot of this model revealed a non-linear dependence of the number of dissected lymph nodes on recurrence prediction within the range of 0-20 nodes, with the weakest dependence at 10 nodes. A linear increase in the dependence was observed for ≥20 dissected nodes. A multivariable analysis revealed a significantly elevated risk of recurrence in the group with ≥20 dissected nodes in comparison to those with <20 nodes (adjusted HR, 1.45; 95% CI 1.003 to 2.087). CONCLUSIONS: The number of dissected lymph nodes was significantly associated with the risk of postoperative recurrence of NSCLC. The risk of recurrence is minimised when approximately 10 nodes are dissected but may increase when >20 nodes are removed. Limiting lymph node dissection to approximately 20 nodes may help to preserve a favourable antitumour immune environment. These findings provide novel insights into the optimisation of lymph node dissection during lung cancer surgery.

Nonlinear association between PD-L1 expression levels and the risk of postoperative recurrence in non-small cell lung cancer.

Accurate prediction of postoperative recurrence is important for optimizing the treatment strategies for non-small cell lung cancer (NSCLC). Previous studies identified the PD-L1 expression in NSCLC as a risk factor for postoperative recurrence. This study aimed to examine the contribution of PD-L1 expression to predicting postoperative recurrence using machine learning. The clinical data of 647 patients with NSCLC who underwent surgical resection were collected and stratified into training (80%), validation (10%), and testing (10%) datasets. Machine learning models were trained on the training data using clinical parameters including PD-L1 expression. The top-performing model was assessed on the test data using the SHAP analysis and partial dependence plots to quantify the contribution of the PD-L1 expression. Multivariate Cox proportional hazards model was used to validate the association between PD-L1 expression and postoperative recurrence. The random forest model demonstrated the highest predictive performance with the SHAP analysis, highlighting PD-L1 expression as an important feature, and the multivariate Cox analysis indicated a significant increase in the risk of postoperative recurrence with each increment in PD-L1 expression. These findings suggest that variations in PD-L1 expression may provide valuable information for clinical decision-making regarding lung cancer treatment strategies.

The combination of PD-L1 expression and the neutrophil-to-lymphocyte ratio as a prognostic factor of postoperative recurrence in non-small-cell lung cancer: a retrospective cohort study.

BACKGROUND: While PD-L1 expression and neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers for lung cancer, few studies have considered their interaction. We hypothesized that the product of PD-L1 expression (tumor proportion score) and the NLR (PD-L1 × NLR) might be a postoperative prognostic marker reflecting the immune microenvironment of lung cancer. METHODS: We analyzed the association between PD-L1 × NLR and postoperative recurrence-free survival in 647 patients with NSCLC using multivariable Cox proportional hazards models. RESULTS: In the analysis of PD-L1 × NLR as a categorical variable, the group with PD-L1 × NLR ≥ 25.8 had a significantly higher hazard ratio (HR) than the group with < 25.8 (adjusted HR 1.78, 95% confidence interval [CI] 1.23-2.60). The adjusted HR for PD-L1 × NLR, considered a continuous variable, was 1.004 (95% CI, 1.002-1.006). The risk of postoperative recurrence increased by 1.004-fold for each unit increase in PD-L1 × NLR, and a more than 2-fold increase in risk was observed for values ≥ 170. CONCLUSIONS: PD-L1 × NLR may be used in real-world clinical practice as a novel factor for predicting the risk of postoperative recurrence after lung cancer surgery.

Increased lactate dehydrogenase reflects the progression of COVID-19 pneumonia on chest computed tomography and predicts subsequent severe disease.

Chest computed tomography (CT) is effective for assessing the severity of coronavirus disease 2019 (COVID-19). However, the clinical factors reflecting the disease progression of COVID-19 pneumonia on chest CT and predicting a subsequent exacerbation remain controversial. We conducted a retrospective cohort study of 450 COVID-19 patients. We used an automated image processing tool to quantify the COVID-19 pneumonia lesion extent on chest CT at admission. The factors associated with the lesion extent were estimated by a multiple regression analysis. After adjusting for background factors by propensity score matching, we conducted a multivariate Cox proportional hazards analysis to identify factors associated with severe disease after admission. The multiple regression analysis identified, body-mass index (BMI), lactate dehydrogenase (LDH), C-reactive protein (CRP), and albumin as continuous variables associated with the lesion extent on chest CT. The standardized partial regression coefficients for them were 1.76, 2.42, 1.54, and 0.71. The multivariate Cox proportional hazards analysis identified LDH (hazard ratio, 1.003; 95% confidence interval, 1.001-1.005) as a factor independently associated with the development of severe COVID-19 pneumonia. Increased serum LDH at admission may be useful in real-world clinical practice for the simple screening of COVID-19 patients at high risk of developing subsequent severe disease.

PIK3CA mutations associated with a poor postoperative prognosis in patients with pulmonary pleomorphic carcinoma: a retrospective cohort study.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small cell lung cancer characterized by high malignancy and a poor prognosis. PPC is associated with a high frequency of postoperative relapse, and shows resistance to chemotherapy. The high malignancy of cancers is associated with genomic instability, which is related to mutations of tumor suppressor genes, such as tumor protein p53 (TP53) and ataxia-telangiectasia mutated (ATM). In addition, signaling pathways involving the oncogenes such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and epidermal growth factor receptor (EGFR) are associated with resistance to chemotherapy. However, the association of PPC with these gene mutations remains unknown. We investigated the impact of TP53, ATM, PIK3CA, and EGFR mutations on the postoperative prognosis of PPC. METHODS: Fifty-five patients with PPC who underwent complete resection were studied. A gene mutation analysis was performed using next-generation sequencing. Postoperative overall survival of patients with gene mutations was evaluated using a multivariable Cox proportional hazards model in which the explanatory variables were the presence of each gene mutation, and the confounding factors were pathological stage and age. The robustness of the results was evaluated by a sensitivity analysis. RESULTS: The frequencies of pathogenic mutations in TP53, ATM, PIK3CA, and EGFR were 47, 0, 7, and 9%, respectively. A multivariable analysis adjusted for pathological stage and age showed a significant difference for only PIK3CA mutations. The hazard ratio (HR) for overall survival in cases with pathogenic mutations of PIK3CA for wild type or non-pathogenic mutations was 4.5 (95% confidence interval [CI] 1.1-18.8). Likewise, sensitivity analyses adjusted for pathological stage and sex (HR, 7.5; 95% CI 1.7-32.4) and for age and sex (HR, 5.4; 95% CI 1.4-21.7) resulted in similar findings. Although three patients with pathogenic mutations of PIK3CA that recurred postoperatively were treated by chemotherapy or immunotherapy, they survived for less than 2 years. CONCLUSIONS: The postoperative prognosis of PPC with PIK3CA pathogenic mutations is particularly poor. Pathogenic mutations of PIK3CA may be a postoperative prognostic marker. Inhibition of signaling pathways associated with PIK3CA mutations may also be a target for chemotherapy after relapse of PPC.

The Association of Vacuum-Assisted Closure Therapy with Dynamic Volume Change of a Muscle Flap Transposed in an Empyema Cavity for Chronic Empyema: A Case Report.

A 62-year-old woman with a history of lung resection for lung cancer was admitted to our hospital due to cough, which became progressively more severe. She was diagnosed with chronic empyema with bronchopleural fistula (BPF) of the right upper bronchial stump. Although a pedicled muscle flap was transposed to the empyema cavity, the fistula remained. We used a vacuum-assisted closure system after open-window thoracotomy and observed the cavity reduction with expansion of the transposed muscle flap. We quantitatively evaluated the dynamics of the cavity change using a three-dimensional image analysis system. A reduction of the volume of the muscle flap by prolonged empyema and expansion of the muscle flap was observed immediately after vacuum-assisted management. However, expansion of the right residual lung was not recognized. Pedicled muscle flap transposition followed by vacuum-assisted management after open-window thoracotomy may be effective for treating chronic empyema caused by BPF.

A quantitative evaluation of the histological type dependence of the programmed death-ligand 1 expression in non-small cell lung cancer including various adenocarcinoma subtypes: a cross-sectional study.

The association between non-small cell lung cancer histology and programmed death-ligand 1 expression remains controversial. We retrospectively analyzed histological dependence of the programmed death-ligand 1 expression by a multiple regression analysis of 356 non-small cell lung cancer patients. The programmed death-ligand 1 expression patterns of adenocarcinoma were consistent with a pathological predominant growth pattern as a reference to papillary adenocarcinoma: minimally invasive adenocarcinoma[partial regression coefficient (B), 0.17; 95% confidence interval, 0.05-0.59], lepidic adenocarcinoma (B, 0.46; 95% confidence interval, 0.23-0.90), acinar adenocarcinoma (B, 1.98; 95% confidence interval, 1.05-3.76) and solid adenocarcinoma (B, 5.11; 95% confidence interval, 2.20-11.9). In histology other than adenocarcinoma, the programmed death-ligand 1 expression tended to be high with poor differentiation: adenosquamous carcinoma (B, 4.17; 95% confidence interval, 1.05-16.6), squamous cell carcinoma (B, 4.32; 95% confidence interval, 2.45-7.62) and pleomorphic carcinoma (B, 13.0; 95% confidence interval, 4.43-38.2). We showed quantitatively that the programmed death-ligand 1 expression in non-small cell lung cancer tended to be clearly histology-dependent, with more poorly differentiated histology showing a higher expression.

Reduced risk of recurrent pneumothorax for sirolimus therapy after surgical pleural covering of entire lung in lymphangioleiomyomatosis.

BACKGROUND: Patients with lymphangioleiomyomatosis (LAM) frequently experience pneumothorax. Although sirolimus is the standard therapy for LAM, its effect on pneumothorax is controversial. Recently, total pleural covering (TPC) and modified TPC (mTPC) were introduced as surgical treatment options for pneumothorax for patients with LAM. However, the effect of sirolimus on the recurrence of pneumothorax in patients who underwent the treatments is still uncertain. We hypothesized that some clinical factors including sirolimus treatment could predict postoperative recurrence of pneumothorax. In order to clarify this hypothesis, we retrospectively analyzed the clinical data from 18 consecutive patients with LAM who underwent 24 surgical pleural covering of entire lung (SPC) as 17 TPC and 7 mTPC against pneumothoraces from surgical database between January 2005 and January 2019, and we determined the predictors of postoperative recurrence. RESULTS: Of the 24 surgeries of SPC, 14 surgeries (58.3%) had a history of two or more ipsilateral pneumothoraces, and 11 surgeries (45.8%) had a history of ipsilateral pleural procedures before SPC. Sixteen surgeries (66.6%) in 12 patients received treatment of sirolimus after SPC (sirolimus group). With a median follow-up time of 69.0 months after SPC, four surgeries (16.6%) in three patients had a postoperative recurrence, and the 5-year recurrence-free survival (RFS) after SPC was 82.9%. In patients with postoperative recurrence, serum level of vascular endothelial growth factors D was significantly higher than that in those with non-recurrence (3260.5 vs. 892.7 pg/mL, p = 0.02), and the rate of sirolimus treatment in the recurrence group was significantly lower than that in the no-recurrence group (0 vs. 80%, p = 0.006). The log-rank test showed that the RFS of the sirolimus group (sirolimus use after SPC) was significantly better than that of the non-sirolimus group (p = 0.001), and no significant difference was observed for other factors. CONCLUSION: We first reported sirolimus might effectively suppress the recurrence of pneumothoraces in LAM patients who received SPC. Sirolimus induction after SPC (TPC or mTPC) might be a feasible option for frequent pneumothorax in LAM.

PD-L1 expression as a predictor of postoperative recurrence and the association between the PD-L1 expression and EGFR mutations in NSCLC.

Although information on the PD-L1 expression and EGFR mutations in non-small cell lung cancer (NSCLC) is important for therapeutic strategies, the effect of these factors on postoperative recurrence and the association between each factor have remained unclear. We retrospectively assessed the PD-L1 expression and EGFR mutations in 280 NSCLC patients, and analyzed the associations by multivariate analyses. The hazard ratio (HR) of postoperative recurrence in cases with high (≥ 50%) PD-L1 expression regarding negative expression was 4.83 (95% confidence interval [CI] 1.51-15.5). The HR for the PD-L1 expression, considered a continuous variable, was 1.016 (95% CI 1.01-1.03). The HRs in cases with EGFR major and minor mutations were 0.42 (95% CI 0.14-1.25) and 0.63 (95% CI 0.18-2.15), respectively. The high PD-L1 (≥ 50%) expression was significantly associated with exon 21 L858R mutation (Ex21) of EGFR (odds ratio, 0.10; 95% CI 0.01-0.87). The risk of postoperative recurrence increased 1.016-fold for every 1% increase in the PD-L1 expression, and a marked increase in risk was observed for expression levels of ≥ 50%. Whereas EGFR mutations were not an independent risk factor. The high PD-L1 (≥ 50%) expression was negatively associated with Ex21. These findings may help identify NSCLC patients with an increased risk of postoperative recurrence.

Adenocarcinoma with fetal features invading the right superior sulcus treated with neoadjuvant chemoradiotherapy followed by complete video-assisted thoracoscopic right upper lobectomy: a case report.

BACKGROUND: Fetal adenocarcinoma of the lung is a rare lung neoplasm that accounts for only 0.5% of all primary lung cancers. Because of its rarity, effective treatments for the management of the tumor are poorly understood. We herein report a case of adenocarcinoma with fetal features of the lung with invasion of the right superior sulcus that was treated with neoadjuvant chemoradiotherapy followed by surgical resection. CASE PRESENTATION: A 54-year-old man was referred to a medical institution due to right inner forearm pain. On computed tomography of the chest, a 56-mm mass with invasion of right superior sulcus was discovered. Bronchoscopic biopsy revealed non-small cell lung carcinoma. We performed concurrent chemotherapy (2 cycles of cisplatin and vinorelbine) and thoracic radiation therapy (40 Gy in 20 fractions). As the result of extreme tumor reduction after neoadjuvant chemoradiotherapy, we could perform right upper lobectomy by complete video-assisted thoracoscopic surgery. Since no viable cancer cells were detected from the pathological examination of the resected tissue, the specimen obtained by bronchoscopic biopsy was reexamined by immunohistochemistry. The analysis supported a pathologic diagnosis of adenocarcinoma with fetal features. CONCLUSIONS: We experienced a case of adenocarcinoma with fetal features of the lung in which the patient showed a complete response to neoadjuvant chemoradiotherapy. In addition, the tumor invading the right superior sulcus was completely resected by video-assisted thoracoscopic lobectomy. Neoadjuvant chemoradiotherapy followed by surgery may be also an effective treatment for advanced-stage high-grade fetal adenocarcinoma of the lung, similarly to other subtypes of advanced-stage primary lung cancer.

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience.

BACKGROUND: In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features. MATERIALS AND METHODS: We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells. RESULTS: In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive. CONCLUSIONS: The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.

A High PD-L1 Expression in Pulmonary Pleomorphic Carcinoma Correlates with Parietal-pleural Invasion and Might Predict a Poor Prognosis.

Objective Pleomorphic carcinoma (PC) is a rare pulmonary epithelial malignant tumor with a poor prognosis. The objective of the present study was to investigate the programmed death-ligand 1 (PD-L1) expression in PC and its correlation between the clinicopathological factors and prognosis. Methods Clinical and pathological data of 35 patients with surgically resected PC encountered from 2002 to 2016 at our institution were collected. The PD-L1 expression on tumor cells was evaluated via immunohistochemistry (clone 22C3). We examined the correlation between the PD-L1 expression and patients' clinicopathological factors and their prognosis. Results A high PD-L1 expression (≥50%) was seen in 21 (60%) patients, and parietal-pleural invasion was significantly correlated with a high PD-L1 expression (p=0.012). The 5-year overall survival and relapse-free survival were 68.2% and 43.2%, respectively. Tumor size ≥50 mm (p=0.021), lymph node metastasis (p=0.023), and a high PD-L1 expression (p=0.047) were correlated with a short relapse-free survival. Since lymph node metastasis was an independent risk factor of a poor overall survival (p=0.012), patients with a high PD-L1 expression also tended to have a worse overall survival than those with low levels (p=0.081). Conclusion A high PD-L1 expression is frequently seen in PC. The PD-L1 expression is associated with parietal-pleural invasion and might indicate a poor prognosis.

Assessment of ALK gene rearrangement in lung cancer using a new rapid automated SureFISH (Dako Omnis) assay.

The ALK fluorescence in situ hybridisation (FISH) method is the examination essential for pathological diagnosis and choice of molecular-targeted therapy in ALK-rearranged lung cancer. Here, for detection of ALK gene rearrangement in patients with lung cancer, we evaluated the rapid FISH technology (ALK SureFISH), a newly developed assay for the automated staining platform Dako Omnis, using 21 formalin-fixed paraffin-embedded (FFPE) samples. All cases could be evaluated with the SureFISH method. SureFISH provided excellent quality signals without any background staining. The SureFISH assay was able to offer a rapid turnaround time (approximately 3.5 hours) and was 100% concordant with prior Vysis FISH results in our laboratory.

A Case of Solitary Well-Differentiated Papillary Mesothelioma with Invasive Foci in the Pleura.

Well-differentiated papillary mesothelioma (WDPM) is a rare, distinct tumor consisting of mesothelial cells with a papillary architecture, bland cytological features, and a tendency toward superficial spread without invasion. Rare cases with superficial invasion are termed WDPM with invasive foci. We report a case of solitary WDPM with invasive foci in the pleura. A 61-year-old woman presented with a lung adenocarcinoma. A small papillary lesion measuring 29 × 10 × 8 mm was incidentally found in the parietal pleura during a lobectomy for the lung adenocarcinoma. The fibrovascular core of the small papillary lesion was surrounded by a single layer of cuboidal cells with mild to moderate atypia and large nucleoli. Atypical mesothelial cells focally invaded the submesothelial layer. The cells of the papillary lesion were positive for cytokeratins and mesothelial markers. The Ki67 index was <1 %. The lesion did not show p16 loss on fluorescence in situ hybridization. We could not detect atypical mesothelial cells in the specimen from an extrapleural pneumonectomy. WDPM with invasive foci is prone to multifocality; however, our case represents a solitary case in the pleura.

Life-threatening and Rapidly Growing Teratoma in the Anterior Mediastinum.

This report describes the case of a 23-year-old man with a mediastinal teratoma. Five months before admission, a chest radiograph during a routine health checkup was normal. Four months before admission, the patient developed sudden onset of mild right-sided chest pain. He gradually developed dyspnea and was admitted to our hospital. Computed tomography revealed a giant tumor that was markedly compressing the right atrium. Urgent surgery was performed, and a ruptured, benign mature teratoma was diagnosed. Mature mediastinal teratomas are benign tumors, but they can rupture and have the potential to grow rapidly, potentially leading to life-threatening complications.

Molecular analysis of human papillomavirus in never-smokers with non-small cell lung cancer.

The causes of lung cancer in never-smokers remain unclear. The potential contribution of human papillomavirus (HPV) to the carcinogenesis of non-small cell lung cancer (NSCLC) has been reported. In 2008, a prospective registry of never-smokers with NSCLC was established at the Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan. Never-smokers with NSCLC were consecutively enrolled onto the registry. Of these patients, 114 with large tumor specimens, the majority of which were surgical tissues, were selected. In total, 23 of the most clinically relevant HPV types were assayed using polymerase chain reaction amplification of the viral genome. Following exclusion of samples with suboptimal quality, DNA was extracted from 96 formalin-fixed paraffin-embedded samples. These 96 cases consisted of 82 females (85.4%) and 14 males (14.6%), with a median age of 67 years (range, 29-83). Almost all cases (93.8%) were of the adenocarcinoma histological subtype. Despite confirmation of the quality and amount of DNA, HPV type 6 was detected in only one case (1.1%). Furthermore, no other samples examined were positive for any other HPV types. The results therefore suggest that HPV does not play a major role as the driving oncogenic event in never-smokers with NSCLC.

Small calcifying fibrous pseudotumor of the heart confined to the epicardium.

A calcifying fibrous pseudotumor (CFPT) is a rare benign lesion that often presents in the upper and lower extremities of children and young adults. In the present report, we describe a case of a small CFPT arising from the epicardium (visceral pericardium) in a 32-year-old woman. The tumor presented as a 25-mm polypoid mass protruding into the pericardial cavity, without extending into the myocardium. A complete resection was performed, and the patient has not experienced any relapse for more than 2 years. On histological examination, the lesion contained densely hyalinized collagen with psammomatous and dystrophic calcifications, as well as patchy chronic inflammatory infiltrate. The localization in the epicardium with no involvement of the myocardium was confirmed by the elastic stain. Amyloid was negative by the Congo red stain. On immunohistochemical analysis, the lesional cells indicated diffuse positive staining for vimentin and factor XIIIa and focal positive staining for CD34, but did not indicate positive staining for other pertinent antigens such as cytokeratins, calretinin, desmin, α-smooth muscle actin, ALK, and estrogen and progesterone receptors as well as IgG4 in plasma cells. To our knowledge, only three cases of CFPT in the heart have been reported in the literature, all of which developed in young females as a large mass involving the epicardium; the lesion also extended to the parietal pericardium in two cases. Moreover, all cases presented with few symptoms, despite the large lesion. In the present case, the CFPT developed also in a young woman, but the lesion was much smaller than those previously published and was localized in the visceral serous membrane of the heart. The findings of this case suggest a potential preferable site of origin of CFPTs of the heart.

A pilot study of cisplatin and etoposide with and without radiotherapy for advanced malignant thymoma.

AIM: Thymoma is a rare neoplasm of the mediastinum, for which very few data on the efficacy and safety of chemotherapy and chemoradiotherapy are available. The objective of this pilot study was to assess the safety and efficacy of cisplatin, etoposide, and radiotherapy for thymoma. PATIENTS AND METHODS: Patients with advanced, previously-untreated thymoma (Masaoka classification), measurable disease, and a performance status of 0-2 were eligible, and were treated with cisplatin-plus-etoposide, together with radiotherapy when possible. RESULTS: One patient achieved complete response, and seven achieved partial responses. Progression-free survival was 37.7 months (95% confidence interval = 18.6-56.8 months). Ten patients had grade 4 neutropenia, and five patients had grade 3 febrile neutropenia. However, other toxicities were relatively mild. To date, only five patients (45.5%) have died, and the median survival time is 128.1 months (95% confidence interval = 51.6-204.6 months). Patients treated with chemoradiotherapy had a good response and long progression-free survival. CONCLUSION: The combination of cisplatin and etoposide with or without radiotherapy is effective for advanced thymoma, and has an acceptable toxicity.