[en] Combined chemoradiotherapy (CRT) is the standard treatment modality for limited-stage small-cell lung cancer (LSCLC), but the optimal timing of radiation is controversial. Prolonged oral etoposide has the advantage of prolonged exposure, which possibly leads to improved clinical outcome. We conducted a phase II trial of early concurrent CRT, starting from the very beginning of the first cycle of chemotherapy for previously untreated LSCLC. Chemotherapy was given for six cycles, each consisting of oral etoposide (50 mg/m² daily from day 1 to 14) and intravenous cisplatin (75 mg/ m² on day 1), every 3 weeks. Thoracic radiation therapy was given from day 1 of the first cycle of chemotherapy, administered at 2.0 Gy in 22 daily fractions to a total dose of 44 Gy. Forty-four patients were enrolled. The median age was 60 years (range, 42-77 years), including 15 patients (34%) over 65 years-of-age. We observed a complete response rate of 52% (95% confidence interval (CI), 37-67%), and an overall response rate of 88% in an intent-to-treat (ITT) analysis. Median overall survival was 14.9 months (95% CI, 11.4-18.3 months) and the median time to progression was 10.8 months (95% CI, 9.3-12.4 months) for the ITT population. In 220 cycles, grade 3-4 neutropenia was observed in 48% of cycles and grade 3-4 thrombocytopenia in 30% of cycles. Neutropenic fever was observed in 18 patients (41%). Early concurrent CRT, starting from the very beginning of the first cycle of chemotherapy with prolonged oral etoposide and cisplatin failed to show any improvement in survival compared with other CRT regimens. (author)

[en] The present study was performed to assess the usefulness of involved-field irradiation and the impact of ¹⁸F-fluorodeoxyglucose-positron emission tomography-based staging on treatment outcomes in limited-stage small cell lung cancer. Eighty patients who received definitive chemoradiotherapy for limited-stage small cell lung cancer were retrospectively analyzed. Fifty patients were treated with involved-field irradiation, which means that the radiotherapy portal includes only clinically identifiable tumors. The other 30 patients were irradiated with a comprehensive portal, including uninvolved mediastinal and/or supraclavicular lymph nodes, so-called elective nodal irradiation. No significant difference was seen in clinical factors between the two groups. At a median follow-up of 27 months (range, 5-75 months), no significant differences were observed in 3 year overall survival (44.6 vs. 54.1%, P=0.220) and 3 year progression-free survival (24.4 vs. 42.8%, P=0.133) between the involved-field irradiation group and the elective nodal irradiation group, respectively. For patients who did not undergo positron emission tomography scans, 3 year overall survival (29.3 vs. 56.3%, P=0.022) and 3 year progression-free survival (11.0 vs. 50.0%, P=0.040) were significantly longer in the elective nodal irradiation group. Crude incidences of isolated nodal failure were 6.0% in the involved-field irradiation group and 0% in the elective nodal irradiation group, respectively. All isolated nodal failures were developed in patients who had not undergone positron emission tomography scans in their initial work-ups. If patients did not undergo positron emission tomography-based staging, the omission of elective nodal irradiation resulted in impaired survival outcomes and raised the risk of isolated nodal failure. Therefore, involved-field irradiation for limited-stage small cell lung cancer might be reasonable only with positron emission tomography scan implementation. (author)

[en] The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ≤90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.

[en] The objective of this study is to evaluate the efficacy and toxicity of definitive radiotherapy with or without chemotherapy for T3-4 squamous cell carcinoma of maxillary sinus and nasal cavity. Forty-two patients with T3-4N0 squamous cell carcinoma of maxillary sinus (n=30) and nasal cavity (n=12) received definitive radiotherapy. Chemotherapy was used in 34 patients and elective neck irradiation was not used. The 5-year overall survival/local control rates were 34%/29% for maxillary sinus cancer and 50%/52% for nasal cavity cancer. For maxillary sinus cancers, a performance status of Eastern Cooperative Oncology Group ≥2 (P=0.012), biologically equivalent dose <68 Gy (P=0.011) and no use of chemotherapy (P=0.037) were significant worse predictors for overall survival on log-rank analysis. Biologically equivalent dose <68 Gy was independently associated with poor local control (hazard ratio, 3.32; 95% confidence interval, 1.38-7.97; P=0.007) and overall survival (hazard ratio, 2.94; 95% confidence interval, 1.23-7.01; P=0.015). Regional recurrence occurred in only 1 of 30 patients with maxillary sinus cancer and 4 of 12 patients with nasal cavity. Two radiation necrosis in brain, one osteoradionecrosis, and one retinopathy and optic neuropathy occurred. The treatment outcome was poor and local control was a major problem. High radiation dose, effective chemotherapy and elective neck irradiation for advanced nasal cavity cancers may improve disease control. (author)

[en] To investigate the role of radiotherapy for squamous cell carcinomas of the external auditory canal and middle ear. A series of 35 patients who were treated at a single institution from 1981 through 2007 were retrospectively analyzed. Thirteen patients were treated by radiotherapy alone; four by surgery only and 18 by a combination of surgery and radiotherapy. The total radiation dose ranged from 39∼70 Gy (median, 66 Gy) in 13∼35 fractions for radiotherapy alone and 44∼70 Gy (median, 61.2 Gy) in 22∼37 fractions for the combined therapy. Clinical end-points were the cause of specific survival (CSS) and local relapse-free survival (LRFS). The median follow-up time was 2.8 years (range, 0.2∼14.6 years). The 3-year CSS and LRFS rate was 80% and 63%, respectively. Based on a univariate analysis, performance status and residual disease after treatment had a significant impact on CSS; performance status and histologic grade for LRFS. Patients treated by radiotherapy alone had more residual disease following the course of treatment compared to patients treated with the combined therapy; 69% vs. 28%, respectively. Our results suggest that radiation alone was not an inferior treatment modality for CSS compared to the combined therapy for squamous cell carcinoma of the external auditory canal and middle ear. However, local failure after radiotherapy is the main issue that will require further improvement to gain optimal local control

[en] To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.

[en] 

Purpose

We evaluated the predictive role of EGFR mutation on the efficacy of PD-1/PD-L1 inhibitor therapy in patients with advanced pulmonary adenocarcinoma while considering clinical factors such as PD-L1 expression, gender, and smoking status.

Methods

Patients were required to have available data for EGFR mutation, PD-L1 expression, and efficacy of PD-1/PD-L1 inhibitors.

Results

Among 178 patients with EGFR-mutant (n = 38) or wild-type (WT) (n = 140) tumors, the EGFR mutation group had a lower objective response rate (ORR) (15.8% vs. 32.9%, p = 0.04) than the EGFR WT group, similar to the pattern observed for other factors: weak/negative PD-L1 expression vs. strong PD-L1 expression (17.3% vs. 39.2%, p = 0.001); never smokers vs. smokers (19.4% vs. 35.1%, p = 0.03); and females vs. males (21.0% vs. 33.6%, p = 0.08). EGFR mutation and weak/negative PD-L1 expression were associated with a significantly shorter median PFS than EGFR WT (1.9 vs. 3.0 months, p = 0.04) and strong PD-L1 expression (1.6 vs. 3.9 months, p = 0.007), respectively. In multivariate analysis, EGFR mutation predicted worse ORR [hazard ratio (HR) 3.15; 95% confidence interval (CI) 1.15–8.63] and PFS (HR 1.75, 95% CI 1.11–2.75), as did weak/negative PD-L1 expression (ORR, HR 3.46, 95% CI 1.62–7.37; and PFS, HR 1.72, 95% CI 1.17–2.53).

Conclusions

Together with PD-L1 expression, EGFR mutation status is an important factor to predict the efficacy of PD-1/PD-L1 inhibitors in patients with pulmonary adenocarcinoma.

[en] Studies about the biology, treatment pattern, and treatment outcome of metastatic/recurrent neuroendocrine tumor (NET) have been few. We enrolled patients with metastatic/recurrent NET diagnosed between January 1996 and July 2007 and retrospectively analyzed. A total of 103 patients were evaluated. Twenty-six patients (25.2%) had pancreatic NET, 27 (26.2%) had gastrointestinal NET, 2 (1.9%) had lung NET, 28 (27.2%) had NET from other sites, and 20 (19.4%) had NET from unknown origin. The liver was the most common metastatic site (68.9%). Thirty-four patients had grade 1 disease, 1 (1.0%) had grade 2 disease, 15 (14.6%) had grade 3 disease, 9 (8.7%) had large cell disease, and 7 (6.8%) had small cell disease. Sixty-six patients received systemic treatment (interferon, somatostatin analogues or chemotherapy), 64 patients received local treatment (TACE, radiofrequency ablation, metastasectomy, etc.). Thirty-six patients received both systemic and local treatments. Median overall survival (OS) was 29.0 months (95% confidence interval, 25.0-33.0) in the103 patients. OS was significantly influenced by grade (p = .001). OS was 43.0, 23.0, and 29.0 months in patients who received local treatment only, systemic treatment only, and both treatments, respectively (p = .245). The median time-to-progression (TTP) was 6.0 months. Overall response rate was 34.0% and disease-control rate was 64.2%. TTP was influenced by the presence of liver metastasis (p = .011). OS of metastatic/recurrent NET was different according to tumor grade. TTP was different according to metastasis site. Therefore, development of optimal treatment strategy based on the characteristics of NET is warranted

[en] We report the results of a systematic study to understand low drive current of Ge-nMOSFET (metal-oxide-semiconductor field-effect transistor). The poor electron transport property is primarily attributed to the low dopant activation efficiency and high contact resistance. Results are supported by analyzing source/drain Ohmic metal contacts to n-type Ge using the transmission line method. Ni contacts to Ge nMOSFETs exhibit specific contact resistances of 10^-3-10^-5 Ω cm², which is significantly higher than the 10^-7-10^-8 Ω cm² of Ni contacts to Ge pMOSFETs. The high resistance of Ni Ohmic contacts to n-type Ge is attributed mainly to insufficient dopant activation in Ge (or high sheet resistance) and a high tunneling barrier. Results obtained in this work identify one of the root causes of the lower than expected Ge nMOSFET transport issue, advancing high mobility Ge channel technology.

[en] This study investigated the correlations between parameters of ¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan and indices of genetic properties, heterogeneity index (HI), and tumor mutation burden (TMB), in patients with lung cancer. We produced 106 PET indices for each tumor site that underwent genomic analysis in a total of 176 study subjects (age, 62.0 ± 10.0 y; males, 68.2%), comprising 101 adenocarcinoma (ADC), 29 squamous cell carcinoma (SQCC), and 46 small cell lung cancer (SCLC) patients. We then examined the correlations of the PET parameters with genetic properties of HI and TMB, according to pathology and tumor site. Comparisons between PET parameters and the genetic properties with false discovery rate (FDR) correction revealed that the surface standard uptake value (SUV) entropy of SUV statistics had a significant correlation with HI only in patients with SCLC who underwent a genetic test in lymph nodes (r = 0.592, p = 0.028), whereas PET parameters did not show a significant correlation with HI or TMB in patients with SCLC who underwent a genetic test in lung tissue. In patients with ADC and SQCC, there was no significant correlation between PET parameters and the genetic properties. Although SUV_max showed raw p values less than 0.05 in correlation with HI (r = 0.315, raw p = 0.048) and TMB (r = 0.206, raw p = 0.043) in ADC, and SUV_peak had a raw p value less than 0.05 in correlation with HI (r = 0.394, raw p = 0.046) in SQCC, these parameters were not significant when corrected by FDR. In this study, surface SUV entropy had a significant correlation with HI in SCLC. Regarding other PET parameters and tumors, no significant correlation with genetic parameters existed. (orig.)