[Role of Medical Oncologists in Regional Hospitals].

Medical oncologists are required to propose and implement the optimal treatment for individual patients with cancer in cooperation with doctors and medical staff in each area as the control tower of the cancer treatment team within the medical institute. On the other hand, core hospitals in regional areas have limited numbers of medical oncologists, as well as doctors and staff in each specialized field, and cannot necessarily cover all areas like core cancer hospitals in metropolitan areas. Therefore, it is necessary for each medical facility in the local area to cooperate with the limited number of personnel and equipment and to deal across the region. To this mission, it is desirable to plan and manage areas such as the training of specialists and specialist staff, research and practice activities, enlightenment in cooperation with the government, cancer- related information, cancer education, and cancer advocacy. In order to fulfill this role smoothly, oncologists should take the initiative in demonstrating their social skills.

Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101).

BACKGROUND: Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB-IIIA NSCLC. PATIENTS AND METHODS: Patients with completely resected p-stage IB-IIIA NSCLC were randomly assigned to GEM or UFT. The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and AEs. RESULTS: We assigned 305 patients to the GEM group and 303 to the UFT group. Baseline factors were balanced between the arms. Of the 608 patients, 293 (48.1%) had p-stage IB disease, 195 (32.0%) had p-stage II disease and 121 (19.9%) had p-stage IIIA disease. AEs were generally mild in both groups, and only one death occurred, in the GEM group. After a median follow-up of 6.8 years, the two groups did not significantly differ in survival: 5 year OS rates were GEM: 70.0%, UFT: 68.8% (hazard ratio 0.948; 95% confidence interval 0.73-1.23; P = 0.69). CONCLUSION: Although GEM-based adjuvant therapy for patients with completely resected stage IB-IIIA NSCLC was associated with acceptable toxicity, it did not provide longer OS than did UFT.

[Predictors of Nivolumab-Induced Skin Reactions].

Skin reactions to nivolumab are typical immune-related adverse events. We investigated the relation between patient background and test values before nivolumab administration and skin reactions. From February 2016 to February 2017, we evaluated the clinical outcomes of 21 patients who were administered nivolumab. Patients were divided into 2 groups: 3 cases of skin reactions to nivolumab(skin reaction group)and 18 cases without skin reactions to nivolumab(non-skin reaction group). In the skin reaction group, the numbers of eosinophils and basophils before nivolumab administration were significantly higher than those in the non-skin reaction group(p=0.0015 and p=0.0075, respectively). It was suggested that the numbers of eosinophils or basophils before nivolumab administration might be associated with the appearance of skin reactions.

Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial.

BACKGROUND: Etoposide and irinotecan are key drugs in the treatment of small-cell lung cancer. We did this study to investigate whether combined chemotherapy with cisplatin, etoposide, and irinotecan was superior to topotecan monotherapy as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer. METHODS: We did this open-label, multicentre, randomised phase 3 trial at 29 institutions in Japan. Patients with small-cell lung cancer that responded to first-line treatment but showed evidence of disease relapse or progression at least 90 days after completion of the first-line treatment were eligible to participate. Enrolled patients were randomly assigned (1:1) to receive combination chemotherapy with cisplatin plus etoposide plus irinotecan or topotecan alone. Randomisation was done via the minimisation method with biased-coin balancing for Eastern Cooperative Oncology Group performance status, disease stage at enrolment, and institution. Combination chemotherapy consisted of five 2-week courses of intravenous cisplatin 25 mg/m(2) on days 1 and 8, intravenous etoposide 60 mg/m(2) on days 1-3, and intravenous irinotecan 90 mg/m(2) on day 8, with granulocyte colony-stimulating factor given by hypodermic injection every day starting from day 9 of the first course (except on the days anticancer drugs were given). Topotecan therapy consisted of four courses of intravenous topotecan 1·0 mg/m(2) on days 1-5, every 3 weeks. The primary endpoint was overall survival in the intention-to-treat population, which was analysed with a one-sided α of 5%, and safety was assessed in all patients who received at least one dose of study drug. The trial is registered with University Hospital Medical Information Network Clinical Trials Registry, number UMIN000000828. FINDINGS: Between Sept 20, 2007, and Nov 30, 2012, 180 patients were enrolled, with 90 assigned to each treatment group. The median follow-up for censored patients was 22·7 months (IQR 20·0-35·3). Overall survival was significantly longer in the combination chemotherapy group (median 18·2 months, 95% CI 15·7-20·6) than in the topotecan group (12·5 months, 10·8-14·9; hazard ratio 0·67, 90% CI 0·51-0·88; p=0·0079). The most common grade 3 or 4 adverse events were neutropenia (75 [83%] patients in the combination chemotherapy group vs 77 [86%] patients in the topotecan group), anaemia (76 [84%] vs 25 [28%]), and leucopenia (72 [80%] vs 46 [51%]). Grade 3 or 4 febrile neutropenia was more common in the combination chemotherapy group than in the topotecan group (28 [31%] vs six [7%]), as was grade 3 or 4 thrombocytopenia (37 [41%] vs 25 [28%]). Serious adverse events were reported in four (4%) patients in the topotecan group and nine (10%) in the combination chemotherapy group. Two treatment-related deaths (one each of pneumonitis and pulmonary infection) occurred in the topotecan group and one (febrile neutropenia with sepsis) occurred in the combination chemotherapy group. INTERPRETATION: Combination chemotherapy with cisplatin plus etoposide plus irinotecan could be considered the standard second-line chemotherapy for selected patients with sensitive relapsed small-cell lung cancer. FUNDING: National Cancer Center and the Ministry of Health, Labour and Welfare of Japan.

Bevacizumab beyond disease progression after first-line treatment with bevacizumab plus chemotherapy in advanced nonsquamous non-small cell lung cancer (West Japan Oncology Group 5910L): An open-label, randomized, phase 2 trial.

BACKGROUND: Bevacizumab combined with platinum-based chemotherapy has been established as a standard treatment option in the first-line setting for advanced nonsquamous non-small cell lung cancer (NSCLC). However, there has been no evidence to support the use of bevacizumab beyond disease progression in such patients. METHODS: West Japan Oncology Group 5910L was designed as a multicenter, open-label, randomized, phase 2 trial of docetaxel versus docetaxel plus bevacizumab every 3 weeks for patients with recurrent or metastatic nonsquamous NSCLC whose disease had progressed after first-line treatment with bevacizumab plus a platinum-based doublet. The primary endpoint was progression-free survival (PFS). RESULTS: One hundred patients were randomly assigned to receive docetaxel (n = 50) or docetaxel plus bevacizumab (n = 50), and this yielded median PFS times of 3.4 and 4.4 months, respectively, with a hazard ratio (HR) of 0.71 and a stratified log-rank P value of .058, which met the predefined criterion for statistical significance (P < .2). The median overall survival also tended to be longer in the docetaxel plus bevacizumab group (13.1 months; 95% confidence interval [CI], 10.6-21.4 months) versus the docetaxel group (11.0 months; 95% CI, 7.6-16.1 months) with an HR of 0.74 (95% CI, 0.46-1.19; stratified log-rank P = .11). No unexpected or severe adverse events were recorded. CONCLUSIONS: Further evaluation of bevacizumab beyond disease progression is warranted for patients with advanced NSCLC whose disease has progressed after treatment with bevacizumab plus a platinum-based doublet.

Phase II study of zoledronic acid combined with docetaxel for non-small-cell lung cancer: West Japan Oncology Group.

The aim of this open-label, multicenter, randomized phase II trial was to evaluate the efficacy and safety of zoledronic acid in combination with docetaxel in previously treated patients with non-small-cell lung cancer (NSCLC) and bone metastases. In this study, patients randomly received docetaxel (60 mg/m(2) ) with (group DZ) or without (group D) zoledronic acid every 21 days. There were 50 patients in each group, and the primary endpoint was progression-free survival. In an efficacy analysis of 94 patients (DZ, 48; D, 46), the median progression-free survival was 2.7 months (95% confidence interval [CI], 1.5-3.5 months) for the DZ group and 2.6 months (95% CI, 1.5-3.4 months) for the D group (stratified log-rank test, P = 0.89). The median overall survival was 10.4 months (95% CI, 7.0-15.8 months) for the DZ group and 9.7 months (95% CI, 6.1-12.5 months) for the D group (stratified log-rank test, P = 0.62). There were no clinically relevant differences in the frequencies of grade 3 or 4 adverse events between the two groups. No treatment-related deaths occurred in the DZ group. Zoledronic acid combined with docetaxel was well tolerated but did not meet the primary endpoint of demonstrating a longer progression-free survival in advanced NSCLC patients with bone metastases compared with docetaxel alone. This trial was registered with the University Hospital Medical Information Network (UMIN000001098).

[Improvement in quality of life by endobronchial electrocautery using snare in a patient with advanced non-small cell lung cancer].

Endobronchial electrocautery using a polypectomy snare may serve as a useful tool for treating patients with airway obstructing polypoid tumors. An 84-year-old man was admitted to our hospital because of an abnormal shadow observed on chest radiography. He was diagnosed with advanced squamous cell carcinoma, located in the right lower lobe of the lung along with metastatic lesions and obstructive pneumonia. He declined systemic chemotherapy because of his age. Endobronchial electrocautery using a polypectomy snare was performed to treat the obstructive pneumonia. The patient's quality of life improved after polypectomy. This was due to an improvement in malaise and a spontaneous decrease in the size of the hepatic metastasis tumor.

[Late adverse events after concurrent chemoradiation therapy in long-term survivors with non-small cell lung cancer].

Long-term survival in patients with non-small cell lung cancer( NSCLC) can be achieved more frequently with combined modality therapy. However, an increased risk of late treatment-related toxicities has been reported for this treatment strategy. We retrospectively evaluated NSCLC patients treated with chemoradiation therapy from January 1988 to January 2007. Patients who had survived for more than 5 years after treatment were included in an analysis of late adverse events (excluding radiation pneumonitis and pulmonary fibrosis). A total of 188 NSCLC patients treated with chemoradiation therapy were evaluated, with 25 patients having survived for more than 5 years. Of these patients, 4 had stage I disease, 4 had stage IIB disease, 1 had stage IIIA disease, 14 had stage IIIB disease, 1 had stage IV disease, and 1 had disease of unknown stage. The following grade 3 late adverse events were noted: skin ulceration( n=1), skin induration( n=1), brachial plexopathy( n=1), malignant neoplasm( n=1). Adequate management of late adverse events due to chemoradiation therapy is needed for long-term NSCLC survivors.

Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301).

BACKGROUND: It is unknown whether combined chemoradiotherapy improves overall survival in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether radiotherapy plus carboplatin results in longer survival than radiotherapy alone in elderly patients with NSCLC. METHODS: This was a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Patients older than 70 years with unresectable stage III NSCLC were randomly assigned to chemoradiotherapy (60 Gy plus concurrent low-dose carboplatin [30 mg/m(2) per day, 5 days a week for 20 days]) or radiotherapy alone, using a minimisation method with biased-coin assignment balancing on Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), stage (IIIA vs IIIB), and institution. The primary endpoint was overall survival, which was analysed for the eligible population and stratified by ECOG performance status, stage, and institution. The trial was stopped early as a result of the second planned interim analysis. This study is registered with UMIN Clinical Trials Registry, number C000000060, and ClinicalTrials.gov, number NCT00132665. FINDINGS: 200 patients were enrolled from Sept 1, 2003 to May 27, 2010: 100 in the chemoradiotherapy group and 100 in the radiotherapy group. The second planned interim analysis was done 10 months after completion of patient accrual. At this time, median follow-up for censored cases was 19·4 months (IQR 10·3-33·5). In accordance with the prespecified stopping rule, the JCOG data and safety monitoring committee recommended early publication of this trial because the difference in overall survival favoured the chemoradiotherapy group. Median overall survival for the chemoradiotherapy and radiotherapy alone groups were 22·4 months (95% CI 16·5-33·6) and 16·9 months (13·4-20·3), respectively (hazard ratio 0·68, 95·4% CI 0·47-0·98, stratified log-rank test one-sided p value=0·0179). More patients had grade 3-4 haematological toxic effects in the chemoradiotherapy group than in the radiotherapy alone group, including leucopenia (61 [63·5%] vs none), neutropenia (55 [57·3%] vs none), and thrombocytopenia (28 [29·2%] vs two [2·0%]). Grade 3 infection was more common with chemoradiotherapy (12 patients [12·5%]) than with radiotherapy (four patients [4·1%]). Incidences of grade 3-4 pneumonitis and late lung toxicity were similar between groups. There were seven treatment-related deaths: three of 100 patients (3·0%) in the chemoradiotherapy group and four of 100 (4·0%) in the radiotherapy group. INTERPRETATION: For a select group of elderly patients with locally advanced NSCLC, combination chemoradiotherapy provides a clinically significant benefit over radiotherapy alone, and should be considered for this population. FUNDING: Ministry of Health, Labour, and Welfare of Japan.

[Review of chemoradiotherapy followed by surgical resection in locally advanced non-small-cell lung cancer].

Chemoradiotherapy is recommended for locally advanced non-small-cell lung cancer(NSCLC). However, the overall median survival time remains poor(<20 months). We evaluated the outcome and complications of chemoradiotherapy, followed by surgical resection, in locally advanced NSCLC. Eight patients(7 men and 1 woman; median age, 59.5 years (range, 47-68 years) who underwent chemoradiotherapy followed by surgical resection for locally advanced NSCLC from 2002 to 2011 were retrospectively analyzed. In all cases, chemotherapy consisted of platinum-based combination therapy. Postoperatively, bronchopleural fistula occurred in 1 patient and Horner syndrome was observed in 1 patient. No treatment -related deaths were observed. The median of progression-free survival was 34.2 months. In conclusion, chemoradiotherapy should be the standard of care for locally advanced NSCLC. Trimodality therapy is still experimental but seems to be promising for certain subgroups of patients with locally advanced NSCLC.

A phase II study of cisplatin and irinotecan as induction chemotherapy followed by concomitant thoracic radiotherapy with weekly low-dose irinotecan in unresectable, stage III, non-small cell lung cancer: JCOG 9706.

OBJECTIVE: It is important to identify optimal regimens of cisplatin-based, third-generation chemotherapy and thoracic radiotherapy for patients with unresectable, Stage III, non-small cell lung cancer. METHODS: Patients with unresectable, Stage III non-small cell lung cancer were treated with the following regimen: cisplatin 80 mg/m(2) on days 1 and 29, with irinotecan 60 mg/m(2) on days 1, 8, 15, 29, 36, and 43 and 30 mg/m(2) on days 57, 64, 71, 78, 85 and 92. Thoracic radiotherapy was started on day 57 at 2 Gy/day (total 60 Gy). RESULTS: From February 1998 to January 1999, 68 patients were enrolled. Grade 3/4 toxicities during induction chemotherapy primarily included neutropenia (73.5%) and diarrhea (20.6%), while Grade 3/4 toxicities during concomitant thoracic radiotherapy with irinotecan consisted of neutropenia (18.4%), esophagitis (4.1%) and hypoxia (6.5%). There was one treatment-related death due to radiation pneumonitis. The response rate was 64.7% (95% confidence interval, 52.2-75.9%). The median survival time was 16.5 (95% confidence interval, 12.6-19.8) months. The 1- and 2 year survival rates were 65.8% (95% confidence interval, 54.4-77.1%) and 32.9% (95% confidence interval, 21.6-44.1%), respectively. Overall, only 36 (56%) completed both the scheduled chemotherapy and thoracic radiotherapy. CONCLUSIONS: Induction chemotherapy with cisplatin plus irinotecan followed by low-dose irinotecan and concomitant thoracic radiotherapy was feasible according to the prespecified decision criteria in this study for patients with unresectable Stage III non-small cell lung cancer. We did not decide to select this regimen for further investigations because approximately half of the patients completed the scheduled treatment.

[Stereotactic radiotherapy following chemo-radiotherapy for lymph node metastasis of stage III non-small-cell lung cancer].

It has been expected that stereotactic radiotherapy (SRT) is one of the useful treatments for non-resectable early lung cancer. In the case radiotherapy was thought to be difficult due to the wideness of irradiation area, it is probable to undergo chemo-radiotherapy safely using SRT for a primary lesion. We report two cases of Stage III non-small-cell lung cancer, which underwent SRT for primary tumors following chemo-radiotherapy for the lymph node metastasis. In both two cases, a reduction of V20 (the normal pulmonary volume to receive radiation exposure: more than 20 Gy) was a possibility, and symptomatic radiation pneumonitis was not observed.

Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial.

IMPORTANCE: Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer. OBJECTIVE: To evaluate survival and late toxic effects 10 years after patients were treated with curative CRT. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3 West Japan Thoracic Oncology Group (WJTOG) 0105 randomized clinical trial was conducted between September 2001 and September 2005 in Japan. Patients with histologically or cytologically confirmed non-small-cell lung cancer with unresectable stage III disease were assessed for eligibility. Additional data were analyzed from January 2018 to December 2019. INTERVENTIONS: A total of 440 eligible patients were randomly assigned to groups as follows: A (control), 4 cycles of mitomycin/vindesine/cisplatin plus thoracic radiotherapy (TRT) of 60 Gy; B, weekly irinotecan/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of irinotecan/carboplatin consolidation; or C, weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of paclitaxel/carboplatin consolidation. MAIN OUTCOMES AND MEASURES: The primary outcome was 10-year survival probability after CRT. The secondary outcome was late toxic effects that occurred more than 90 days after initiating CRT. RESULTS: From September 2001 to September 2005, 440 patients (group A, n = 146 [33.2%; median (range) age, 63 (31-74) years; 18 women (12.3%)]; group B, n = 147 [33.4%; median (range) age, 63 (30-75) years; 22 women (15.0%)]; group C, n = 147 [33.4%; median (range) age, 63 (38-74) years; 19 women (12.9%)]) were enrolled. The median (range) follow-up was 11.9 (7.6-13.3) years. In groups A, B, and C, median (range) overall survival times were 20.5 (17.5-26.0), 19.8 (16.7-23.5), and 22.0 (18.7-26.2) months, respectively, and 10-year survival probabilities were 13.6%, 7.5%, and 15.2%, respectively. There were no significant differences in overall survival among treatment groups. The 10-year progression-free survival probabilities were 8.5%, 6.5%, and 11.1% in groups A, B, and C, respectively. Grade 3 or 4 late toxic effect rates were 3.4% (heart, 0.7%; lung, 2.7%) in group A, and those only affecting the lung represented 3.4% and 4.1% in groups B and C, respectively. No other cases of late toxic effects (grades 3/4) were observed since the initial report. CONCLUSION AND RELEVANCE: In this 10-year follow-up of a phase 3 randomized clinical trial, group C achieved similar efficacy and toxic effect profiles as group A 10 years after initiating treatment. These results serve as a historical control for the long-term comparisons of outcomes of future clinical trials of CRT. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000030811.

[The efficacy and safety of stereotactic radiotherapy for non-resectable non-small cell lung cancer].

Stereotactic radiotherapy (SRT) has recently been used for the treatment of small lung tumors. We retrospectively evaluated the efficacy and safety of SRT for non-small cell lung cancer (NSCLC) treated in our hospital. Between October 2007 and December 2009, 31 tumors of 29 patients were treated by SRT (mean age, 75 years: stage IA, n=13; stage IB, n=5; stage IIIA, n=1; stage IIIB, n=1; recurrence, n=11). All of the patients completed the treatment. In one patient who had radiation pneumonitis before SRT, a progression of pulmonary fibrosis was observed, and treated with steroid therapy. In evaluable 29 tumors of 27 patients, the recurrence rates are 11/29 (37.9%). Median progression free survival time was 8 months. The recurrence rate and median progression free survival time of stage IA and IB subgroups were 4/17 (23.5%) and 12 months, respectively. SRT is thought to be a safe and effective treatment for stage I NSCLC. For patients with stage I NSCLC, SRT can be a complemental therapy for surgical resection.

Site-Specific and Targeted Therapy Based on Molecular Profiling by Next-Generation Sequencing for Cancer of Unknown Primary Site: A Nonrandomized Phase 2 Clinical Trial.

IMPORTANCE: Although profiling of gene expression and gene alterations by next-generation sequencing (NGS) to predict the primary tumor site and guide molecularly targeted therapy might be expected to improve clinical outcomes for cancer of unknown primary site (CUP), to our knowledge, no clinical trial has previously evaluated this approach. OBJECTIVE: To assess the clinical use of site-specific treatment, including molecularly targeted therapy based on NGS results, for patients with CUP. DESIGN, SETTING, AND PARTICIPANTS: This phase 2 clinical trial was conducted at 19 institutions in Japan and enrolled 111 previously untreated patients with the unfavorable subset of CUP between March 2015 and January 2018, with 97 patients being included in the efficacy analysis. Eligibility criteria included a diagnosis of unfavorable CUP after mandatory examinations, including pathological evaluation by immunohistochemistry, chest-abdomen-pelvis computed tomography scans, and a positron emission tomography scan. INTERVENTIONS: RNA and DNA sequencing for selected genes was performed simultaneously to evaluate gene expression and gene alterations, respectively. A newly established algorithm was applied to predict tumor origin based on these data. Patients received site-specific therapy, including molecularly targeted therapy, according to the predicted site and detected gene alterations. MAIN OUTCOMES AND MEASURES: The primary end point was 1-year survival probability. Secondary end points included progression-free survival (PFS), overall survival (OS), objective response rate, safety, efficacy according to predicted site, and frequency of gene alterations. RESULTS: Of 97 participants, 49 (50.5%) were women and the median (range) age was 64 (21-81) years. The cancer types most commonly predicted were lung (21 [21%]), liver (15 [15%]), kidney (15 [15%]), and colorectal (12 [12%]) cancer. The most frequent gene alterations were in TP53 (45 [46.4%]), KRAS (19 [19.6%]), and CDKN2A (18 [18.6%]). The 1-year survival probability, median OS, and median PFS were 53.1% (95% CI, 42.6%-62.5%), 13.7 months (95% CI, 9.3-19.7 months), and 5.2 months (95% CI, 3.3-7.1 months), respectively. Targetable EGFR mutations in tumor specimens were detected in 5 patients with predicted non-small-cell lung cancer (5.2%), 4 of whom were treated with afatinib; 2 of these patients achieved a durable PFS of longer than 6 months. CONCLUSIONS AND RELEVANCE: This study's findings suggest that site-specific treatment, including molecularly targeted therapy based on profiling gene expression and gene alterations by NGS, can contribute to treating patients with the unfavorable subset of CUP. TRIAL REGISTRATION: UMIN Identifier: UMIN000016794.

Prospective analysis of the association between skeletal-related events and quality of life in patients with advanced lung cancer (CSP-HOR13).

A prospective study has previously reported on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients with advanced lung cancer. The aim of the present study was to prospectively investigate how the quality of life (QOL) of patients with advanced lung cancer was affected by SREs. Patients with stage IIIB or IV non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) at any stage were followed up every four weeks to determine if they had developed SREs. QOL questionnaires were conducted at enrollment, at 3- and 12-months later and at 1 month after the onset of SREs, using QOL scores including the EuroQOL-5 Dimension (EQ-5D), Functional Assessment of Cancer Therapy-General (FACT-G) and activities of daily living (ADL) scores obtained by the Barthel Index. A total of 274 patients were enrolled in the study. At enrollment the EQ-5D and Barthel Index scores were lower in patients with SREs compared with patients without SREs. A chronological analysis revealed no statistically significant changes in either QOL or ADL in any of the patients. For 14 patients in whom QOL data was collected following the onset of SREs, the evaluation undertaken on the four subscales of the FACT-G revealed a significant decline in emotional functioning following the onset of SREs.

Opioid Dose and Survival of Patients with Incurable Nonsmall Cell Lung Cancer: A Prospective Cohort Study.

BACKGROUND: Preclinical studies show that opioids promote angiogenesis, tumor progression, and metastasis, resulting in shorter survival. OBJECTIVE: To explore whether opioids are associated with the overall survival (OS) of patients with incurable nonsmall cell lung cancer (NSCLC). DESIGN: Prospective cohort study of patients with NSCLC. SETTING: We investigated patients newly diagnosed with advanced or post-operative recurrent NSCLC between April 2013 and December 2015 at a single institute. MEASUREMENTS: We evaluated OS, opioid requirements, opioid doses, pain levels, and prognostic factors of advanced NSCLC. The effects of variables on survival were analyzed using univariable and multivariable models. Patients were stratified according to oral morphine equivalents (OMEs)/day (<60 or ≥60 mg) to assess the association between opioid dose and OS. RESULTS: We analyzed 150 patients, including 64 who received opioid treatment during follow-up. The median OS was 242 days in the opioid group and 627 days in the no-opioid group (log-rank p < 0.001). Multivariable models revealed that the opioid requirement was an independent predictor of shorter OS, after adjustment for prognostic variables, including sex, histology, stage, history of systemic chemotherapy, and performance status (hazard ratio 1.73, 95% confidence interval 1.137-2.631). There was no significant difference in OS between patients who received ≥60 mg OME/day for 250 days versus <60 OME/day for 242 days. CONCLUSIONS: The opioid dose does not shorten the survival of patients with advanced NSCLC. The opioid requirement is associated with shorter survival when opioids are administered any time during the clinical course, independent of the influence of other key factors.

Chemoradiotherapy in Elderly Patients With Non-Small-Cell Lung Cancer: Long-Term Follow-Up of a Randomized Trial (JCOG0301).

INTRODUCTION: In the phase III JCOG0301 trial, chemoradiotherapy (CRT) with daily low-dose carboplatin showed significant benefits in elderly patients with locally advanced non-small-cell lung cancer (NSCLC) compared with radiotherapy (RT) alone. However, the long-term patterns and cumulative incidences of toxicity associated with CRT and RT in elderly patients are not well elucidated. We report long-term survival data and late toxicities after a minimum follow-up of 6.4 years. PATIENTS AND METHODS: Eligible patients were older than 70 years and had unresectable stage III NSCLC. They were randomly assigned to RT or CRT. Prognosis and adverse events data were collected beyond those in the initial report. Late toxicities were defined as occurring more than 90 days after RT initiation. RESULTS: From September 2003 to May 2010, 200 patients (RT arm, n = 100; CRT arm, n = 100) were enrolled. Consistent with the initial report, the CRT arm had better overall survival than the RT arm (hazard ratio, 0.743; 95% confidence interval, 0.552-0.998; 1-sided P = .0239). The proportion of Grade 3/4 late toxicities were 7.4% (heart 2.1%, lung 5.3%) in the RT arm (n = 94) and 7.5% (esophagus 1.1%, lung 6.5%) in the CRT arm (n = 93). No additional cases of late toxicity (Grade 3/4) and treatment-related death have been seen since the initial report that was published. CONCLUSION: Long-term follow-up confirmed the survival benefits of CRT for elderly patients with locally advanced NSCLC. There was no observed increase in late toxicity with CRT compared with RT alone.

Spiritual Well-Being and Correlated Factors in Subjects With Advanced COPD or Lung Cancer.

BACKGROUND: Spiritual care for patients with COPD has rarely been discussed, and thus much remains unknown about their needs. The aims of this study were to identify the factors associated with spiritual well-being and to compare the levels of spiritual well-being between subjects with advanced COPD and those with inoperable lung cancer. METHODS: A total of 96 subjects with COPD or lung cancer participated in this study, which was conducted between December 2014 and April 2016. Measures included the Japanese version of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, the McGill Quality of Life Questionnaire (MQOL), the modified Medical Research Council (mMRC) dyspnea scale, and various other medico-social factors. RESULTS: No significant differences were found between subjects with COPD and those with lung cancer in median FACIT-Sp-12 scores (COPD, 27; lung cancer, 26; P = .81). However, significant differences were found in the 2 MQOL domains, suggesting that subjects with COPD had a better psychological state (P = .01) and that subjects with lung cancer had a better support state (P = .002). Multiple regression analysis revealed that mMRC was significantly associated with FACIT-Sp-12 scores in subjects with COPD. CONCLUSIONS: These results suggest that subjects with advanced COPD experience spiritual well-being similar to that of subjects with inoperable lung cancer.

[Bronchofiberscopic treatment for malignant tracheobronchial tumor].

We evaluated bronchofiberscopic treatment for 38 cases with malignant tracheobronchial tumor. We performed bronchofiberscopic ethanol injection therapy in 13 cases, endoscopic diode laser treatment in 19 cases and airway stent insertion in 9 cases. Each treatment was comparatively easy and improved symptoms such as dyspnea effectively.