Stereotactic Radiation for Lung Cancer: A Practical Approach to Challenging Scenarios

Stereotactic body radiation therapy (SBRT) is an effective and well-tolerated treatment for medically inoperable patients with early stage NSCLC. SBRT is a noninvasive treatment involving the delivery of ablative radiation doses with high precision in the course of a few treatments. Relative to conventionally fractionated radiation, SBRT achieves superior local control and survival. SBRT use has increased dramatically in the past 15 years and is currently considered the standard of care in cases of inoperable early stage NSCLC. It is being increasingly applied to more complex patient populations at higher risk of treatment-related toxicity. In these more complex patients, there is an increasing need to balance patient and treatment factors in selecting the optimal patients for SBRT. Here, we review several challenging clinical scenarios often encountered in thoracic multidisciplinary tumor boards.     

A Biopsychosocial Perspective on the Experience of Lung Cancer

This article examines the effects of an individual's smoking status (current, former, or never-smoker) on the biological, social, and psychological aspects of lung cancer. Current and never-smokers differ in their biological risk factors, responses to treatment, and survival rate. In partial contrast, smoking status does not affect the major social aspect of the disease. The social stigma, which stems from the public perception that lung cancer is a preventable disease, affects social interactions for all patients irrespective of smoking status. The psychological aspects of the disease, including feelings of guilt, vary with smoking status. These observations point to the heterogeneity of lung cancer and underscore the complex links between the disease and smoking behavior.     

The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R): Real-World Data on Stage III Non-Small Cell Lung Cancer Patients Treated With Curative Chemoradiation

IntroductionChemoradiotherapy (CRT) is the standard of care in inoperable non–small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe.MethodsThe Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy.ResultsOut of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality.ConclusionIn this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.     

Vinorelbine in Non-Small Cell Lung Cancer: Real-World Data From a Single-Institution Experience

The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician’s choice; 61.7% were older than 70 years, and 60.5% were affected by 2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p=0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or 2 metastatic lesions. Grade 3–4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.     

肿瘤生物治疗新方法的研究

本文简述“九五”攻关项目间“肿瘤生物治疗新方法”且经协作攻关主要完成的研究工作有：重组人TNF、IL－2及B7重组腺病毒表达载体的构建及其包装体系的建立：腺病毒介导的人TNF－α基因转染对人肝癌细胞凋亡和MHC－Ⅰ类分子表达的影响;瘤体内／瘤周注射TNF－α重组腺病毒和（或）IL－2T重组腺病毒对肝癌小鼠的治疗作用及其免疫机理研究。粘附LAK细胞的制备、体外扩增、冻存及复苏;转染B7、IL－2、TNF－α基因重组腺病毒的肿瘤细胞及A－LAK的生物学特性研究;人肝癌组织中MAG基因的表达及MAGE基因修饰树突状细胞体外抗肿瘤作用;转基因瘤苗临床应用安全性的初步性的初步检测,这些研究工作的完成为肿瘤基因治疗的临床应用打下基础。     

Clinical Studies in Non-small Cell Lung Cancer: The CALGB Experience

Since 1984, the Cancer and Leukemia Group B (CALGB) has focused its clinical research in stage IV non-small cell lung cancer (NSCLC) on investigations of new agents and combinations. Currently, efforts are aimed at identifying non-cisplatin-based combinations with an increased therapeutic index. In stage III disease multimodality therapies have been pursued. Dillman et al. reported a study comparing standard radiotherapy versus induction chemotherapy followed by radiotherapy in patients with unresectable stage III NSCLC. The chemotherapy-treated patients were found to benefit with a 4-month increase in median survival time compared with patients receiving radiotherapy alone (13.8 vs. 9.7 months) and an increased 3-year survival rate of 23% versus 11%. This was the first randomized cooperative group study demonstrating a survival advantage resulting from the use of induction chemotherapy in locoregionally advanced NSCLC. In a subsequent study, the administration of additional “posterior” chemotherapy was not found to be feasible because of early disease progression and toxicity, while the administration of induction chemotherapy followed by concomitant chemoradiotherapy was feasible; therefore, the latter approach was studied further in a randomized phase III setting. This study compared a standard of two cycles of cisplatin and vinblastine followed by radiotherapy with an experimental arm of cisplatin and vinblastine followed by radiotherapy and concomitant carboplatin. Accrual to this study has been completed and results are expected in the near future. In resectable stage III disease, studies have focused on the optimal sequencing of multimodality therapy. A randomized study comparing standard regional therapy with radiotherapy and surgery versus a previously piloted approach combining chemotherapy, surgery, and radiotherapy was closed prematurely due to poor accrual. The next generation of studies in stage III NSCLC will focus on the integration of new chemotherapy agents into the treatment armamentarium for NSCLC. A randomized phase II study investigating paclitaxel, gemcitabine, and vinorelbine in combination with cisplatin in the induction setting and as concomitant chemoradiotherapy has recently been activated.     

Invasive Bladder Cancer: Our Experience With Bladder Sparing Approach

Purpose: Muscle-invasive bladder cancer (MIBC) is a disease associated with several unresolved therapeutic questions. Radical cystectomy still represents the most frequent treatment approach. The aim of our study was to evaluate the effect and feasibility of bladder-sparing treatment by transurethral resection (TUR) and sequential chemoradiotherapy in patients with biopsy-proven invasive bladder cancer.Methods and Materials: After maximal TUR, 105 patients were treated with two to four cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders, the treatment was continued by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas in nonresponders, cystectomy was performed when feasible.Results: Complete response after TUR and chemotherapy was achieved in 52% of patients. After a median follow-up of 42 months, 52 of 75 patients (69%) selected for bladder preservation were without evidence of disease in the bladder. Freedom from local failure in complete responders to chemotherapy was 80% [95% confidence interval (CI), 69–91%) at 4 years. The actuarial survival of the entire group was 58% (95% CI, 47–69%), whereas the survival rate with the bladder intact was 45% (95% CI, 34–56%) at 4 years. Survival was significantly better in patients who responded to chemotherapy (79%) than in nonresponders (35%, p < 0.0001). There was no significant difference in survival between nonresponders who underwent cystectomy and nonresponders who completed treatment with radiotherapy (approximately 30% at 3 years).Conclusion: The present study confirms that MIBC is a heterogeneous disease, and that in more than half of patients who are affected, a bladder-sparing approach is safe. Our study has also demonstrated that in nonresponders, radical cystectomy as the treatment of choice is questionable.     

Clinicopathological Characteristics of Iranian Patients with Lung Cancer a Single Institute Experience

Background Lung cancer has long been a leading cause of cancer related death in both women and men worldwide. The focus of this study was to review clinicopathological features of Iranian patients diagnosed with lung cancer. Materials and Methods Clinicopathological data of 1353 primary lung cancer patients diagnosed during 17 years (1997-2014) in the National Institute of Tuberculosis and Lung Disease (NRITLD), Tehran, Iran, were retrospectively reviewed. Results The median age of patients was 60 (mean 58.95 years, range 16- 99) and adenocarcinoma was the most prevalent pathology (45.2%). Male/female ratio was 3.22 and 57.2% of patients were smokers (men 70.3%, women 15%). The majority (85.3%) were referred in advanced stages (stage IIIB and IV). Conclusions Although some of our ndings are in concordance with other studies in lung cancer but there are some discrepancies particularly in terms of smoking status and median age of Iranian patients. Further clinical and epidemiological studies are warranted to elucidate etiologic and factors other than smoking contributing to development of lung cancer such as environmental exposures or genetic predisposition.     

Lung Cancer in Women: A Single Institution Experience with 50 Patients

Background: Lung cancer is the most common cause of cancer-related death worldwide. The incidence oflung cancer is aproximately 7-8 thousand percent in Turkish women. In this study, we aimed to evaluate theclinical, pathological properties and survival data of female patients with lung cancer who were treated in ourcenter. Materials and Methods: From 2007 to 2012, 50 women with lung cancer were enrolled. Patient data wereevaluated retrospectively. Results: The median age was 61 (40-81). Forty patients (80%) were diagnosed withnon small cell lung cancer (NSCLC), 10 patients (20%) were small cell carcinoma (SCC). Twelve (24%) patientswere smokers and 13 of 16 non-smokers had a history of exposure to asbestos. The most common histologicsubtype was adenocarcinoma (46%) and this accounted for 71% in patients with exposure to asbestos. The mostcommon initial Eastern Cooperative Oncology Group (ECOG) performance score was 1 (24 patients, 48%) andinitial stage was IV (25 patients, 50%) in the study group. During the median 15 months (1-96 months) followupperiod: 1 year overall survival (OS) was 68%, 2yearoverall survival was 36% and the median survival time was19 months. According to univariate analysis, poor ECOG performance status, advanced stage, anemia and weightloss at time of diagnosis were negative prognostic factors. However, adenocarcinoma sub-type was a positiveprognostic factor. Conclusions: In this study NSCLC sub-type, poor ECOG performance score, advanced stage,anemia and weight loss were prognostic factors in Turkish women with lung cancer.     

Survival Outcomes Among Lung Cancer Patients Treated Using a Multidisciplinary Team Approach

Background

Evidence favoring a multidisciplinary team (MDT) approach in the treatment of lung cancer is scarce, especially in the United States. The purpose of the present investigation was to evaluate survival outcomes of lung cancer patients treated with an MDT compared with a traditional care model.