Koichi Kurishima

PROTON BEAM THERAPY OF STAGE II AND III NON-SMALL-CELL LUNG CANCER

PURPOSE The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. PATIENTS AND METHODS Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). RESULTS Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. CONCLUSION PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

High-dose concurrent chemo–proton therapy for Stage III NSCLC: preliminary results of a Phase II study

The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC.

Outcomes and Prognostic Factors for Recurrence After High-Dose Proton Beam Therapy for Centrally and Peripherally Located Stage I Non–Small-Cell Lung Cancer

INTRODUCTION This study was conducted to determine disease control rates and prognostic factors associated with recurrence of centrally and peripherally located stage I NSCLC treated using high-dose PBT. PATIENTS AND METHODS Seventy-four patients with 80 centrally or peripherally located stage I NSCLCs were treated with PBT. A protocol using 72.6 Gy (RBE) in 22 fractions was used for centrally located tumors, and 66 Gy (RBE) in 10 or 12 fractions was used for peripherally located tumors. Data were collected and control rates and prognostic factors for recurrence were evaluated retrospectively. RESULTS The median follow-up period was 31.0 months. The overall survival, disease-specific survival, and progression-free survival rates were 76.7%, 83.0%, and 58.6% at 3 years, respectively. Disease recurrence was noted in 30 patients and local recurrence of 11 tumors occurred. The 3-year local control rate was 86.2% for stage IA tumors and 67.0% for stage IB tumors. Radiation dose was identified as a significant prognostic factor for disease recurrence and local recurrence. Tumor diameter and age were only significantly associated with disease recurrence. The 3-year local control rate was 63.9% for centrally located tumors irradiated with 72.6 Gy (RBE) and 88.4% for peripherally located tumors irradiated with 66 Gy (RBE). CONCLUSION Radiation dose was shown to be the most significant prognostic factor for tumor control in stage I NSCLC treated using high-dose PBT. Tumor diameter was not significant for local control. Further evaluation of PBT for centrally located tumors is warranted.

Postoperative Follow-Up for Patients with Non-Small Cell Lung Cancer

Background: It is unclear whether postoperative follow-up by thoracic surgeons or chest physicians for non-small cell lung cancer (NSCLC) alters survival. Patients and Methods: The charts of 1,398 NSCLC patients, diagnosed between 1980 and 2008, were reviewed. Prognostic factors contained therein were evaluated using univariate and multivariate analyses. Patients were divided into 2 groups according to the doctor in charge of their postoperative follow-up: the thoracic surgeon group and the chest physician group. The doctors in charge of following up the patients were also analyzed for prognostic significance. Results: In the univariate and multivariate analyses, age 65 years or younger, female sex, early pathological stage, Charlson Index score of 0–1, absence of adjuvant therapy, and follow-up by a chest physician were significantly favorable prognostic factors. Exam-ined overall, NSCLC patients in the chest physician group had longer survival than those in the thoracic surgeon group. The difference in survival of patients with advanced disease was also statistically significant between these 2 groups. Conclusions: Our results indicate that early detection of asymptomatic disease by regular follow-up including chest computed tomography scan may improve the chance of treatment with curative intent and thus may increase survival, irrespective of the doctor in charge of follow-up.

Lung cancer in patients aged 80 years and over

OBJECTIVES The purpose of this study is to examine clinical and pathological features, treatment modality approaches in the elderly, especially in patients aged 80 years and older. METHODS From the databases at two educational hospitals during the period from January 1978 and December 2007, medical records of lung cancer patients were retrospectively reviewed. The patient population was divided into three age groups: less than 70 years (the <70 age group), 70-79 years (the 70-79 age group), and 80 years or older (the > or =80 age group). Time trends were also studied in two-time intervals: first study period up to 1997, which represents past practice standards, the second study period up to 2007, which represents contemporary practice. RESULTS Patients aged 80 years and older comprised 7.5% of 2775 consecutive patients with lung cancer, and there was a rapid increase in the proportion of patients aged 80 years or older from the earlier to the later time period. The > or =80 age group had higher proportion of poor performance status (PS) and comorbid disease than the <70 age group and the 70-79 age group. Unchanged proportion of patients with poor PS and advanced disease at presentation were observed in the > or =80 age group. The > or =80 age group was less likely to be subjected to surgery or chemotherapy, and had inferior outcomes when compared with the 70-79 age group and the <70 age group. Survival improvement was not observed in the > or =80 age group. Multivariate analysis showed good PS, early clinical stage and surgery were favorable prognostic factors in the > or =80 age group. CONCLUSION In order to improve the outcome, detection of early stage lung cancer in patients with good PS and thorough pretreatment evaluation for appropriate treatment are indeed essential even for the > or =80 age group of patients.

Interstitial lung disease in patients with small cell lung cancer.

Interstitial lung disease (ILD) and lung cancer are two of the most common respiratory diseases. The aim of this study was to demonstrate the prognostic significance of the presence of ILD in patients with small cell lung cancer (SCLC). All the patients with SCLC who were admitted to our hospitals over a 23-year period up to 2008 were retrospectively analyzed. During the study period, 332 SCLC patients were consecutively admitted to our hospitals. Among them, 15 (4.5%) were diagnosed as having both SCLC and ILD. In univariate and multivariate analysis, female sex, early stage, good performance status, and chemotherapy were favorable prognostic factors. The presence of ILD was confirmed as an unfavorable prognostic factor. Existing ILD adversely affects the outcome of SCLC. When deciding whether to offer a standard therapy that may increase treatment-related mortality, the patient’s medical condition, including ILD, should be taken into consideration.

Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer

To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41–57 days) and 5.3 months (134–181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.

Serum KL-6 levels in lung cancer patients with or without interstitial lung disease

Background: It is not known whether lung cancer patients with interstitial lung disease (ILD) might have higher serum levels of KL‐6, a high molecular weight glycoprotein classified as a polymorphic epithelial mucin. In addition, prognosis of these patients with elevated serum KL‐6 levels might be poorer than that with normal KL‐6 levels, but it has not been well clarified. Methods: Serum KL‐6 levels in 273 lung cancer patients with or without ILD, and prognostic significance of elevated serum KL‐6 levels in these patients were studied using uni‐ and multivariate analyses. Results: Serum KL‐6 levels were elevated (>500 U/ml) in 73.5% of lung cancer patients with ILD and in 33.7% of those without ILD. Serum KL‐6 levels in lung cancer patients with ILD were significantly higher than those without ILD. In lung cancer patients with ILD, elevated serum KL‐6 has no prognostic significance, but in those without ILD, however, it was one of the unfavorable prognostic factors. Conclusions: Elevated serum KL‐6 levels can be observed in lung cancer patients both with and without ILD. Having ILD has strong prognostic impact in patients with lung cancer. In those without ILD, however, elevated KL‐6 levels may be related to poor prognosis. J. Clin. Lab. Anal. 24:295–299, 2010.

Lung Cancer in the Octogenarian

Background: Older patients with lung cancer tend to have significant coexisting diseases and less aggressive treatment is often advisable. Objective: To investigate the clinicopathological features of lung cancer in patients aged 80 years and over. Methods: The medical records of 966 patients with lung cancer between 1976 and 1999 were reviewed retrospectively. Results: There were 56 (5.8%) patients 80 years old or over. Thirty-nine (70%) were male, and 22 (39%) patients had poor performance status (2–4). Some of the patients had a medical history of cardiovascular disease (n = 23; 41%), cerebrovascular disease (n = 5; 9%), diabetes mellitus (n = 11; 20%), or malignant disease (n = 8; 14%). Twenty-one (35%) patients were diagnosed as having surgically resectable disease and 20 patients underwent radiotherapy, but 25 patients only received supportive care because of concomitant illnesses. Only 9 and 2 patients, respectively, had chemotherapy and surgery. There was no statistical difference in the survival rate of the two groups of patients receiving radiotherapy or supportive care. Conclusion: Adequate palliative care to provide prolonged quality survival is an appropriate primary goal of therapy for lung cancer in the octogenarian until less invasive treatments are developed.

Erlotinib for elderly patients with non-small-cell lung cancer: Subset analysis from a population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The incidence and mortality of lung cancer have increased worldwide over the last decades, with an observed increased incidence particularly among elderly populations. It has not yet been determined whether erlotinib therapy exhibits the same efficacy and safety in elderly and younger patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective subgroup analysis of data from a population-based observational study was to assess the efficacy and safety of erlotinib in an elderly (≥75 years, n=74) and a younger group of patients (<75 years, n=233) who received treatment for NSCLC. The time to treatment failure was similar in the elderly [median, 62 days; 95% confidence interval (95% CI): 44–80 days] compared with the younger group (median, 46 days; 95% CI: 35–53 days) (P=0.2475). The overall survival did not differ between the elderly and younger groups (median, 170 days; 95% CI: 142–239 days vs. median, 146 days; 95% CI: 114–185 days, respectively) (P=0.7642). The adverse events did not differ in incidence between the groups and were manageable, regardless of age. Among the NSCLC patients receiving erlotinib treatment, the outcomes of the elderly (≥75 years) and younger (<75 years) groups of patients were similar in our population-based observational study.