Hiroko Tsukada

Treatment of roentgenographically occult endobronchial carcinoma with external beam radiotherapy and intraluminal low-dose-rate brachytherapy: second report

PURPOSE To evaluate the efficacy and toxicity of treatment with external beam radiotherapy and intraluminal low-dose-rate brachytherapy for roentgenographically occult endobronchial carcinoma (ROEC). METHOD AND MATERIALS A total of 79 lesions (71 cases) of ROEC were treated with external beam radiotherapy and intraluminal low-dose-rate brachytherapy from July 1991 to December 1998. Of these lesions, 68 (64 cases) were treated with our standard dose (external beam radiotherapy of 40 Gy and intraluminal low-dose-rate brachytherapy of 25 Gy) and are the subject of this report. All 64 patients were males, and their ages ranged from 55 to 80 (median, 68) years. The histologic diagnosis was squamous cell carcinoma in all patients. RESULTS In all cases, the scheduled treatment was carried out within 2 months. Follow-up period ranged from 4 to 91 (median, 44) months from the beginning of this treatment. Acute toxicity was tolerable. Grade 2 radiation pneumonitis was observed in 4 cases, and there was no case of greater than Grade 2 radiation fibrosis. Nineteen cases of bronchial stenosis and 23 cases of bronchial obstruction were observed on follow-up bronchoscopy. However, no Grade 2 or greater deterioration of respiratory function due to radiotherapy, prolonged symptoms, or fatal toxicity was observed. Nine patients suffered recurrence, 5 of whom were rescued by surgery and external beam radiotherapy, and 4 of whom died of disease. The 5-year cause-specific survival, overall-survival, and disease-free rate were 96.1%, 72.3%, and 87.3%, respectively. CONCLUSION Combined treatment with external beam radiotherapy and intraluminal low-dose-rate brachytherapy is effective and results in acceptable complications for ROEC.

The efficacy of lung cancer screening conducted in 1990s: four case/control studies in Japan

The efficacy of lung cancer screening is still controversial. In order to evaluate efficacy of mass screening for lung cancer in 1990s, the Japanese Ministry of Health and Welfare planned to conduct four independent case-control studies in four different regions; Miyagi, Gunma, Niigata, and Okayama Prefecture. The study design of all the four studies was a matched case-control study in which the decedents from lung cancer were defined as cases. In Gunma Prefecture, a screening examination is annual miniature chest X-ray only, whereas sputum cytology is added for high-risk screenees in others. Matching conditions were gender, year of birth, smoking histories (except Okayama), and municipality. Smoking adjusted odds ratio (OR) of dying from lung cancer for those screened within 12 months before case diagnosis compared with those not screened ranged 0.40-0.68. Three of four studies revealed statistically significant reduction of the risk for lung cancer death. OR of pooled analysis, where all sets were combined and analyzed, was 0.56 (95% confidence interval: 0.48-0.65). Recent mass screening program for lung cancer in Japan could reduce the risk for lung cancer death. However, the possibility exists that some confounding factors affected the results. In order to elucidate whether the results can be applied to Western countries, further studies will be required.

Randomized controlled trial comparing docetaxel–cisplatin combination with weekly docetaxel alone in elderly patients with advanced non-small-cell lung cancer: Japan Clinical Oncology Group (JCOG) 0207

OBJECTIVE Prospective trials specifically designed for elderly patients with advanced non-small-cell lung cancer demonstrating the benefit of platinum-based therapies are still lacking. This trial was designed to clarify whether the addition of cisplatin to monotherapy could improve survival for elderly patients. METHODS Elderly patients (age ≥70 years, ECOG performance Status 0-1) with advanced non-small-cell lung cancer were randomized to receive docetaxel 20 mg/m(2) plus cisplatin 25 mg/m(2) on Day 1, 8 and 15 (docetaxel plus cisplatin) or docetaxel 25 mg/m(2) on the same schedule (docetaxel). Both regimens were repeated every 4 weeks until disease progression. RESULTS One hundred and twenty-six patients were enrolled. Sixty-three were randomly assigned docetaxel plus cisplatin and 63 docetaxel monotherapy. Median age was 76 years (range 70-88). The second planned interim analysis was performed on 112 assessable patients (docetaxel/docetaxel plus cisplatin: 56/56). Although the formal criterion for stopping the trial was not met, the Data and Safety Monitoring Committee recommended study termination on ethical grounds based on the interaction (two-sided P = 0.077, hazard ratios for ≤74/≥75: 0.23/0.72) between age and subgroup and treatment arm, which suggested that docetaxel may not represent an adequate control arm regimen for the age subgroup of 70-74 years. CONCLUSIONS The interpretation of study results is limited due to early stopping. Further study is needed to confirm survival benefit of platinum-based chemotherapy for elderly non-small-cell lung cancer [UMIN-CTR (www.umin.ac.jp/ctr/) ID: C000000146].

Concurrent versus sequential radiotherapy for small cell lung cancer.

Two meta-analyses have shown that thoracic radiotherapy plus chemotherapy is superior to chemotherapy alone in the treatment of limited-stage small cell lung cancer. To minimize the likelihood of emergence of chemotherapy resistance, the optimal schedule for integration of the two modalities might be to introduce radiotherapy early in the course of treatment. The Cancer and Leukemia Group B trial performed from 1981 to 1984 failed to show an advantage for early concurrent chemoradiation. However, three recent controlled trials of thoracic irradiation timing (the National Cancer Institute of Canada trial, the Yugoslavian trial, and the Japan Clinical Oncology Group trial) showed that early radiotherapy is superior to delayed radiotherapy. These three trials used the combination of cisplatin/etoposide and showed that a long-term survival rate greater than 20% is achievable using early integrated chemoradiation. For the present, early concurrent administration of thoracic radiotherapy with a cisplatin/etoposide-based regimen should be standard therapy. Semin Oncol 28 (suppl 4):23-26.

Surgical results for centrally-located early stage lung cancer

BACKGROUND With the increasing use of mass screening programs for lung cancer, and especially the use of sputum cytology, the incidence of roentgenographically occult lung cancer has been increasing. These occult cancers comprise mainly histologically centrally-located early stage lung cancers. This study examined the clinicopathologic characteristics and surgical results of centrally-located early stage lung cancer. RESULTS From 1980 to 1998, there were 98 patients and 99 lesions of centrally-located early stage lung cancer resected. A total of 64 patients were detected by mass screening. Histologic examination revealed that 96 lesions were squamous cell carcinoma, and in these patients, there were 10 lesions of carcinoma in situ. The 5-year survival rate was 81.4% in all patients, and 88.9% in carcinoma in situ patients. In the postoperative follow-up period, a second lung cancer occurred in 13 patients. CONCLUSIONS The surgical results for centrally-located early lung cancer were good. However, sometimes these cancers are accompanied by a second centrally-located primary lung cancer, so it is necessary to follow-up with sputum cytology to allow early detection of additional centrally-located lung cancer.

Diagnostic yield of preoperative computed tomography imaging and the importance of a clinical decision for lung cancer surgery

PurposeThis study aimed to evaluate the diagnostic yield of preoperative computed tomography (CT) imaging and the validity of surgical intervention based on the clinical decision to perform surgery for lung cancer or suspected lung cancer.MethodsWe retrospectively evaluated 1755 patients who had undergone pulmonary resection for lung cancer or suspected lung cancer. CT scans were performed on all patients. Surgical intervention to diagnose and treat was based on a medical staff conference evaluation for the suspected lung cancer patients who were pathologically undiagnosed. We evaluated the relation between resected specimens and preoperative CT imaging in detail.ResultsA total of 1289 patients were diagnosed with lung cancer by preoperative pathology examination; another 466 were not pathologically diagnosed preoperatively. Among the 1289 patients preoperatively diagnosed with lung cancer, the diagnoses were confirmed postoperatively in 1282. Among the 466 patients preoperatively undiagnosed, 435 were definitively diagnosed with lung cancer, and there were 383 p-stage I disease patients. There were 38 noncancerous patients who underwent surgery with a diagnosis of confirmed or suspected lung cancer. Among the 1755 patients who underwent surgery, 1717 were pathologically confirmed with lung cancer, and the diagnostic yield of preoperative CT imaging was 97.8%. Among the 466 patients who were preoperatively undiagnosed, 435 were compatible with the predicted findings of lung cancer.ConclusionDiagnostic yields of preoperative CT imaging based on clinical evaluation are sufficiently reliable. Diagnostic surgical intervention was acceptable when the clinical probability of malignancy was high and the malignancy was pathologically undiagnosed.

Prognostic value of Lung Cancer Subscale in older patients with advanced non-small cell lung cancer: An integrated analysis of JCOG0207 and JCOG0803/WJOG4307L (JCOG1414A)

OBJECTIVE The Lung Cancer Subscale (LCS) of the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire is commonly used for evaluating lung cancer-specific symptoms. The objective of this study was to elucidate the prognostic value of the LCS in older patients with advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS We conducted an integrated analysis of data from two randomized phase III trials (JCOG0207, JCOG0803/WJOG4307L) including patients aged 70 years or older with advanced NSCLC to evaluate the prognostic value of LCS scores at baseline (Aim 1) and for symptom improvement (an increase in LCS of two points or more during treatment) (Aim 2). Multivariable analyses for survival, adjusted for baseline factors, were performed using a stratified Cox regression model with treatment regimen as a stratum. RESULTS A total of 327 patients were included in the analysis for Aim 1 and 373 patients for Aim 2. Approximately 70% of patients were aged 75 or older. In Aim 1, use of descriptive statistics determined a cutoff point for baseline LCS score of 21. Multivariable analysis showed that higher baseline LCS was associated with favorable overall survival (OS) (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.52-0.89) and progression-free survival (HR: 0.68; 95% CI: 0.52-0.89). In Aim 2, symptom improvement was not associated with favorable OS (HR: 0.97; 95% CI: 0.72-1.23). CONCLUSION It is recommended to consider baseline LCS scores while determining treatment strategies for older patients with advanced NSCLC.

Carboplatin Has Equivalent Efficacy to Cisplatin in the Treatment of Advanced Non-small-cell Lung Cancer?

目的. シスプラチン(CDDP)の腎毒性・神経毒性・催吐作用を軽減した誘導体として開発されたカルボプラチン(CBDCA)が, 進行非小細胞肺癌化学療法においてCDDPと同等の効果があるか否かを検討する. 研究方法. 対象が進行非小細胞肺癌で,併用化学療法におけるCDDPとCBDCAの比較がなされている無作為化比較試験のうち, 併用薬が共通である7つの試験をとりあげ, 両者の奏効率・生存期間・毒性について検討した.結果.毒性の面では悪心・嘔吐がCDDP群で多かったが神経毒性. 重篤な腎毒性では差がなく血小板減少はCBDCA群の方で発現頻度が高かった. 奏効率はすべての試験でCDDP群が上回っており, 生存期間では同等または有意差はないもののCDDP群が長い傾向がみられた. 結論. 進行非小細胞肺癌の化学療法においてCBDCAがCDDPと同等であるとはいえない. 今後のより有効な治療法の開発をめざす臨床試験においては現時点ではCDDPを含む併用療法を基本としていくことが望ましいであろう. しかし実地診療においては患者の腎機能・心機能,簡便性などを考慮して選択するのが適切と考えられる.