Chukwumere Nwogu

Is Video-Assisted Thoracic Surgery Lobectomy Better? Quality of Life Considerations

Video-assisted thoracic surgery lobectomy has controversial advantages over traditional open surgical approaches. Subjective concerns such as pain, dyspnea, physical functioning, and overall satisfaction generally favor VATS but vary depending on survey timing. Independence, a major quality of life component, favors video-assisted thoracic surgery because fewer objective hospital and discharge resources are needed because pulmonary function, activity level, muscle strength, and walking capacity are better. Video-assisted thoracic surgery often hastens return to work and facilitates adjuvant chemotherapy or subsequent urgent surgical procedures. Video-assisted thoracic surgery-related quality of life benefits are amplified by advanced age (or other frailties) and reduced by advanced cancer stage or comorbid illness.

The surgical management of pulmonary metastasis: current concepts

Lung metastases have been found in 25-30% of all patients with cancer at autopsy. Those patients satisfying criteria for surgical resection represent a much smaller subgroup. Given the potentially curative nature of pulmonary metastasectomy in the absence of disseminated disease, it has become widely accepted as an important treatment option for a variety of malignancies with metastasis to the lungs. A standardized approach remains unfounded however, given limited numbers of patients, various histologic subtypes and few published studies utilizing randomized prospective methodology.Ultimately, the development of metastasis represents a major determinant of survival for patients with cancer. Pulmonary metastasectomy is an important treatment modality for patients with metastatic pulmonary disease. The indications for pulmonary metastasectomy and the surgeons role in pulmonary metastatic disease continue to evolve. Future prospective studies and the compilation of comparable data yielding prognostic factors for specific histologies will better define indications for resection.

HER-2/neu Protein Expression and Gene Alteration in Stage I-IIIA Non-Small-Cell Lung Cancer: A Study of 140 Cases Using a Combination of High Throughput Tissue Microarray, Immunohistochemistry, and Fluorescent In Situ Hybridization

Regarding HER-2/ neu expression (gene or protein level) in lung cancer, several studies with inconsistent results have been recently reported, partially due to variable techniques used and/or heterogeneous populations examined. The objective of this study was to examine HER-2/ neu expression in a well-defined cohort of non–small-cell lung cancers (NSCLC) and in nonneoplastic lung tissue utilizing a combination of high-density tissue microarray, immunohistochemistry (IHC), and fluorescent in situ hybridization (FISH) under uniform test conditions. One hundred forty stage I-IIIA primary NSCLCs and 38 non-neoplastic lung samples were examined. IHC, using an FDA-approved Hercept monoclonal antibody kit, was performed and HER-2/ neu gene alteration was assessed by FISH. The association of expression of HER-2/ neu with clinicopathologic parameters was analyzed. Ninety-four percent of tumor samples (131/140) were fully interpretable after tissue processing. Twenty-five of them (19%) overexpressed (2+, 3+) HER-2/ neu, while 106 (81%) had no or weak expression. All thirty-four interpretable non-neoplastic lung samples were negative for HER-2/ neu alteration at protein and gene level. HER-2/ neu protein overexpression correlated well with HER-2/ neu gene amplification (r =.83, P < 0.001). HER-2/ neu overexpression was significantly associated with histologic subtype: 19 adenocarcinomas (19/82, 23%) versus 4 squamous cell carcinomas (4/44, 9%) overexpressed Her-2/ neu (P = 0.04). Statistical significance was observed between HER-2/ neu expression and tumor differentiation, with strong positive (3+) expression observed more frequently in poorly differentiated tumors (P = 0.01). Patients with HER-2/ neu abnormalities, particularly HER-2/ neu gene amplification, exhibited a shorter survival (P = 0.043). The statistically significant difference (P < 0.005) between HER-2/ neu alteration in tumor samples(25/131, 19%) and in the nonneoplastic tissue (0/34, 0%) implies that HER-2/ neu may have a role in the carcinogenesis of NSCLC. The findings provide evidence supporting the hypothesis that the HER-2/ neu receptor may represent a useful molecular target in the treatment of NSCLC. The significant association of HER-2/ neu expression and gene amplification with poorly differentiated carcinoma compared with well differentiated carcinoma suggests that HER-2/ neu may be involved in NSCLC tumor evolution. Patients with HER-2/ neu gene amplification and strong positive expression of HER-2/ neu protein showed a strong tendency toward shorter survival.

The International Epidemiology of Lung Cancer: Latest Trends, Disparities, and Tumor Characteristics

Introduction: Our aim was to update global lung cancer epidemiology and describe changing trends and disparities. Methods: We presented country‐specific incidence and mortality from GLOBOCAN 2012 by region and socioeconomic factors via the Human Development Index (HDI). Between‐ and within‐country incidence by histological type was analyzed by using International Agency for Research on Cancer data on cancer incidence on five continents. Trend analyses including data from the International Agency for Research on Cancer, cancer registries, and the WHO mortality database were conducted using joinpoint regression. Survival was compared between and within countries and by histological type. Results: In 2012, there were 1.82 and 1.59 million new lung cancer cases and deaths worldwide, respectively. Incidence was highest in countries with a very high HDI and lowest in countries with a low HDI (42.2 versus 7.9 in 100,000 for males and 21.8 versus 3.1 in 100,000 for females, respectively). In most countries with a very high HDI, as incidence in males decreased gradually (ranging from –0.3% in Spain to –2.5% in the United States each year), incidence in females continued to increase (with the increase ranging from 1.4% each year in Australia to 6.1% in recent years in Spain). Although histological type varied between countries, adenocarcinoma was more common than squamous cell carcinoma, particularly among females (e.g., in Chinese females, the adenocarcinoma‐to–squamous cell carcinoma ratio was 6.6). Five‐year relative survival varied from 2% (Libya) to 30% (Japan), with substantial within‐country differences. Conclusions: Lung cancer will continue to be a major health problem well through the first half of this century. Preventive strategies, particularly tobacco control, tailored to populations at highest risk are key to reducing the global burden of lung cancer.

Cruciferous vegetable intake is inversely associated with lung cancer risk among smokers: a case-control study

BackgroundInverse associations between cruciferous vegetable intake and lung cancer risk have been consistently reported. However, associations within smoking status subgroups have not been consistently addressed.MethodsWe conducted a hospital-based case-control study with lung cancer cases and controls matched on smoking status, and further adjusted for smoking status, duration, and intensity in the multivariate models. A total of 948 cases and 1743 controls were included in the analysis.ResultsInverse linear trends were observed between intake of fruits, total vegetables, and cruciferous vegetables and risk of lung cancer (ORs ranged from 0.53-0.70, with P for trend < 0.05). Interestingly, significant associations were observed for intake of fruits and total vegetables with lung cancer among never smokers. Conversely, significant inverse associations with cruciferous vegetable intake were observed primarily among smokers, in particular former smokers, although significant interactions were not detected between smoking and intake of any food group. Of four lung cancer histological subtypes, significant inverse associations were observed primarily among patients with squamous or small cell carcinoma - the two subtypes more strongly associated with heavy smoking.ConclusionsOur findings are consistent with the smoking-related carcinogen-modulating effect of isothiocyanates, a group of phytochemicals uniquely present in cruciferous vegetables. Our data support consumption of a diet rich in cruciferous vegetables may reduce the risk of lung cancer among smokers.

Number of Lymph Nodes and Metastatic Lymph Node Ratio Are Associated With Survival in Lung Cancer

BACKGROUND The non-small cell lung cancer TNM classification system uses only the anatomic extent of lymph node (LN) metastases to define the N category. The number of LNs resected and the ratio of positive LNs to total examined LNs are prognostic in other solid tumors. We used the Surveillance, Epidemiology and End Results database to investigate the effect of these factors on the overall survival of non-small cell lung cancer. METHODS All patients with non-small cell lung cancer in the Surveillance, Epidemiology and End Results database from 1988 through 2007 who had curative resections and had at least one LN examined were included. The prognostic value of age, race, sex, tumor size, histologic grade, number of examined LNs, and ratio of positive LNs to total examined LNs was assessed using a multivariate Cox proportional hazards model for overall survival. The number of LNs examined was categorized into four levels. The percentage of positive LNs was stratified into three levels. RESULTS Among patients with localized disease, fewer LNs examined corresponded with a worse prognosis. Prognosis improved as more LNs were examined. For patients with regional disease, the differences were significant only at the extremes. Older patients, males, and those with higher grade or larger tumors did worse. Patients with low or moderate ratios of positive to total LNs had better prognoses than those with high ratios. CONCLUSIONS More LNs resected and lower ratios of positive LNs to total examined LNs are associated with better patient survival after non-small cell lung cancer resection independent of age, sex, grade, tumor size, and stage of disease.

VATS Lobectomy Has Better Perioperative Outcomes Than Open Lobectomy: CALGB 31001, an Ancillary Analysis of CALGB 140202 (Alliance)

BACKGROUND The short-term superiority of video-assisted thoracoscopic surgery lobectomy compared with open lobectomy for early-stage lung cancer has been suggested by single-institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared with open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. METHODS Five hundred nineteen patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, sex, performance status, comorbidities, histology, tumor stage, and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemars test for binary variables and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. Probability values of less than 0.05 were considered significant. RESULTS The matched data on length of hospital stay, complications, and discharge dispositions significantly favored the video-assisted thoracoscopic surgery group. There was no statistically significant difference in survival between the two approaches. CONCLUSIONS This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer perioperative complications, and greater likelihood of independent home discharge compared with open lobectomy for early-stage lung cancer. Survival was comparable between the two groups.

Automated tobacco assessment and cessation support for cancer patients

Tobacco assessment and cessation support are not routinely included in cancer care. An automated tobacco assessment and cessation program was developed to increase the delivery of tobacco cessation support for cancer patients.

Pilot study of gefitinib, oxaliplatin, and radiotherapy for esophageal adenocarcinoma: tissue effect predicts clinical response.

Purpose:Overexpression of epidermal growth factor receptor (EGFR) in esophageal cancer is associated with poor prognosis. Preclinical studies indicate synergism between the EGFR inhibitor gefitinib and oxaliplatin or radiotherapy (RT). We report here early results of a planned phase I/II study of gefitinib, oxaliplatin, and RT for locally advanced, unresectable esophageal cancer. Methods and Materials:The protocol consisted of oral gefitinib 250 mg daily for 1 year plus intravenous oxaliplatin 85 or 100 mg/m2 on days 1, 15, and 29, and RT (50.4 Gy in 28 1.8-Gy fractions). Four-quadrant biopsies were obtained at 1-cm intervals along the length of the tumor before and after treatment and the specimens were immunostained for EGFR, Erk, Akt, and their phosphorylated (activated) forms. Results:Enrollment was halted at 6 evaluable cases [all male; median age, 72.5 years (range, 51–75); and all with Eastern Cooperative Oncology Group performance status of 1]. All 6 tumors were adenocarcinomas; 5 were stage III and 1 stage IVA. Oxaliplatin was given at 85 mg/m2 in 3 cases and at 100 mg/m2 in 3 cases. Gefitinib therapy lasted a median 24 weeks; the median number of oxaliplatin doses was 6.5. Best responses were mucosal complete response (n = 1), partial response (n = 1), stable disease (n = 1), and progressive disease (n = 3). EGFR was expressed by tumor in 5 cases and Erk and Akt in 6 cases before treatment; no changes were noted after treatment. EGFR expression did not correlate with survival or response. No grade 4 toxicities were noted; grade 3 toxicities were diarrhea (n = 1), vomiting (n = 1), fatigue (n = 1), and constipation (n = 2). Median overall and disease-free survival times were 10.8 months and 8.4 months. Conclusions:Gefitinib in combination with oxaliplatin and RT was tolerable, but had limited clinical activity and did not down-regulate total or activated EGFR, Akt, or Erk in esophageal tumor samples.

Is Sublobar Resection Sufficient for Carcinoid Tumors

BACKGROUND The existing guidelines for extent of resection of carcinoid tumors are based on other, more malignant non-small cell lung cancers. Because of the small number of patients in any single institution, we analyzed the Surveillance Epidemiology and End Results (SEER) database to study the effect of the extent of resection of these tumors on overall survival. METHODS All patients with lung cancer in the SEER database from 1973 to 2006 with carcinoid tumors as their only cancer were included. Variables examined included age, race (white, black, others), gender, histologic type (atypical versus typical carcinoid), stage (localized, regional, and distant), extent of resection (sublobar resection, lobectomy, or more extensive) and survival. Univariate analyses (Kaplan-Meier method) were used to select variables for multivariate analysis (Cox regression analysis). Associations were considered significant with an alpha error < 5%. In addition, propensity score-matched Cox regression analysis was performed for patients with typical carcinoid disease. RESULTS Most patients with carcinoid tumors did not acquire any other cancers (4,785/6,819; 70.2%). Of these, 797 patients had sublobar resection and 2,681 patients had lobectomy or more extensive resections. On univariate analysis, gender (p = 0.014), race (p < 0.001), stage (p < 0.001), histologic type (p < 0.001) and extent of resection (p = 0.04) were associated with overall survival. Multivariate analysis demonstrated that age, gender, race, stage, and histologic type remain statistically associated with overall survival and disease-specific survival, whereas extent of resection is not. Propensity score-matched analysis demonstrates that for typical carcinoid, extent of resection is not associated with overall survival when adjusted for age, gender, race, and stage. CONCLUSIONS Sublobar resection of carcinoid tumors did not compromise oncologic outcomes in a large population-based database. Lobectomy for typical carcinoid tumors is not mandatory as long as complete resection and adequate mediastinal staging are performed.