Prognostic implications of signet ring cell histology in esophageal adenocarcinoma.

BACKGROUND: Signet ring cell esophageal adenocarcinoma histology has been difficult to study in single institution series because of its relative rarity, yet has an anecdotal reputation for poor prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was examined to assess the prognostic implications of this esophageal adenocarcinoma subtype. METHODS: All patients with esophageal adenocarcinoma in the SEER database from 2004 to 2009 were included. Univariate and multivariate analyses examining the relationship of signet ring cell histology with overall survival were performed in all patients, as well as those undergoing surgical resection. RESULTS: A total of 596 of 11,825 (5%) study patients had signet ring cell histology. Patients with signet ring cell histology were similar in age, race, and sex distribution, but had a higher grade (P < .001) and higher stage (P < .001) at diagnosis. In both the all-patient group as well as those undergoing surgical resection, univariate analyses showed a worse survival in patients with signet ring cell esophageal cancer (hazard ratio [HR] = 1.24; 95% confidence interval [CI] = 1.13-1.36 and HR = 1.57; 95% CI = 1.29-1.93, respectively). In multivariate analyses adjusting for covariates, patients with signet ring cell cancer had a worse prognosis than those without (HR = 1.18; 95% CI = 1.07-1.30). In surgically resected patients, this remained a trend, but did not reach statistical significance (HR = 1.16; 95% CI = 0.94-1.42). CONCLUSIONS: This large study of esophageal adenocarcinoma confirms the clinical impression that signet ring cell variant of adenocarcinoma is associated with an advanced stage at presentation and a worse prognosis independent of stage of presentation.

Small cell carcinoma of the esophagus: a SEER database analysis.

BACKGROUND: Small cell cancer (SCC) of the esophagus is an uncommon malignancy with perceived poor prognosis, but there are few data to guide therapeutic decisions. We examined the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for survival. METHODS: All patients with esophageal cancer in the SEER database between 1973 and 2009 were included. Univariate and multivariate analyses were performed in patients with and without SCC, examining the relationship of small cell histology, surgery, and other potential prognostic factors with overall survival (censored at 72 months). RESULTS: Of 64,799 esophageal cancer patients identified in the SEER database, 387 (0.6 %) had small cell histology. As compared with non-small cell histology, patients with small cell histology were similar in age and race but had a higher proportion of women (p < 0.001), had a higher stage at diagnosis (p < 0.001), and were less likely to undergo surgical resection (p < 0.01). Multivariate predictors associated with poor survival in the overall cohort included age, female gender, black race, and stage. In patients treated with surgery, multivariate predictors associated with poor survival included age, male gender, race, and stage but not small cell histology. In patients with small cell histology, both age and stage were associated with poor survival, but surgery and preoperative radiotherapy were associated with improved survival. CONCLUSIONS: SCC of the esophagus presents at an advanced stage and confers a poor prognosis. The survival benefit of surgery and radiotherapy suggests that all esophageal SCC patients should be considered for preoperative radiotherapy and surgery in a stage-appropriate fashion.

Impact of a Thoracic Multidisciplinary Conference on Lung Cancer Outcomes.

BACKGROUND: With the complexity of cancer treatment rising, the role of multidisciplinary conferences (MDCs) in making diagnostic and treatment decisions has become critical. This study evaluated the impact of a thoracic MDC (T-MDC) on lung cancer care quality and survival. METHODS: Lung cancer cases over 7 years were identified from the Roswell Park cancer registry system. The survival rates and treatment plans of 300 patients presented at the MDC were compared with 300 matched patients. The National Comprehensive Cancer Network (NCCN) guidelines were used to define the standard of care. The compliance of care plans with NCCN guidelines was summarized using counts and percentages, with comparisons made using the Fisher exact test. Survival outcomes were summarized using Kaplan-Meier methods. RESULTS: There was improvement in median overall survival (36.9 vs 19.3 months; P < .001) and cancer-specific survival (48 vs 28.1 months; P < .001) for lung cancer patients discussed at the T-MDC compared with controls. These differences were statistically significant in patients with stages III/IV disease but not in patients with stages I/II disease. The NCCN guidelines compliance rate of treatment plans improved from 80% to 94% (P < .001) after MDC discussion. MDC recommendations resulted in treatment plan changes in 123 of 300 patients (41%). CONCLUSIONS: Our results suggest that lung cancer patients have a survival benefit from MDC discussion compared with controls. Patients with advanced disease (stages III and IV) benefited the most. Further research is necessary to understand the precise mechanisms that drive these results.

Prior Treatment for Non-small Cell Lung Cancer Is Associated With Improved Survival in Patients who Undergo Definitive Stereotactic Body Radiation Therapy for a Subsequent Lung Malignancy: A Retrospective Multivariate and Matched Pair Analysis.

BACKGROUND: Despite occurring commonly, the prognoses of second early-stage non-small cell lung cancers (NSCLC) are not well known. METHODS: The authors retrospectively reviewed the charts of inoperable patients who underwent thoracic stereotactic body radiation therapy (SBRT) from February 2007 to April 2019. Those with previous small cell lung cancers or SBRT treatments for tumors other than NSCLC were excluded. Multivariate Cox regression and a matched pair cohort analyses evaluated the prognoses of patients undergoing definitive SBRT for a new second primary. RESULTS: Of 438 patients who underwent definitive SBRT for NSCLC, 84 had previously treated NSCLC. Univariate log-rank tests identified gender, Karnofksy performance status (KPS), prior lung cancer, anticoagulation use, and history of heart disease to correlate with overall survival (OS) (P<0.05). These factors were incorporated into a multivariate Cox regression model that demonstrated female sex (P=0.004, hazard ratio [HR]=0.68), KPS (P<0.001, HR=2.0), and prior lung cancer (P=0.049, HR=0.7) to be significantly associated with OS. A similar approach found only gender (P=0.017, HR=0.64) and tumor stage (P=0.02, HR=1.7) to correlate with relapse-free survival. To support the Cox regression analysis, propensity score matching was performed using gender, age, KPS, tumor stage, history of heart disease, and anticoagulation use. Kaplan-Meier survival analysis within the matched pairs found prior lung cancer to be associated with improved OS (P=0.011), but not relapse-free survival (P=0.44). CONCLUSIONS: Compared with initial lung cancer SBRT inoperable cases, ablative radiotherapy for new primaries was associated with improved OS. Physicians should not be dissuaded from offering SBRT to such patients.

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

BACKGROUND: Inverse associations between cruciferous vegetable intake and lung cancer risk have been consistently reported. However, associations within smoking status subgroups have not been consistently addressed. METHODS: We 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. RESULTS: Inverse 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. CONCLUSIONS: Our 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.

Analysis of second primary lung cancers in the SEER database.

BACKGROUND: We sought to examine the outcomes of second primary lung cancers in the large population-based Surveillance Epidemiology and End Results (SEER) database. We also sought to study the outcomes of synchronous second non-small-cell lung cancers (NSCLCs), classified as stage IVA (M1A) according to the seventh edition of the TNM staging for lung cancer. METHODS: Data of patients with at least two primary lung cancers were obtained. All available variables potentially associated with the incidence of a second primary lung cancer were examined. The overall survival of patients with synchronous NSCLC was compared with those with metachronous and stage IV NSCLC. RESULTS: A small proportion (1.5%) of patients with lung cancer developed a second primary. A second primary is associated with younger age, female gender, earlier stage, and white race. The median survival of patients with metachronous NSCLCs (n = 3352) was worse than those with synchronous NSCLCs (n = 1858) (median survival 22 mo versus 29 mo, respectively; P < 0.01). After adjusting for age, race, gender, stage, and histology of both primaries, this difference in survival between patients with synchronous and metachronous second primary lung cancers was not statistically significant, but was better than those with stage IV NSCLC (n = 127,654; median survival 4 mo). CONCLUSIONS: The incidence of second primary lung cancer is lower than that previously reported. Factors associated with good prognosis predict a second primary. Synchronous NSCLCs have an outcome better than a stage IV (M1a) designation. These patients should receive appropriate stage-specific multi-modality therapy suitable for the independent stage of each cancer without considering them unresectable.

Sarcopenia is a predictor of outcomes after lobectomy.

BACKGROUND: As screening for lung cancer rises, an increase in the diagnosis of early stage lung cancers is expected. Lobectomy remains the standard treatment, but there are alternatives, consideration of which requires an estimation of the risk of surgery. Sarcopenia, irrespective of body mass index, confers a worse prognosis in many groups of patients including those undergoing surgery. Here we examine the association of muscle mass with outcomes for patients undergoing lobectomy. METHODS: Consecutive patients undergoing lobectomy were retrospectively reviewed. Preoperative computed tomography scans were reviewed, and cross-sectional area of the erector spinae muscles and pectoralis muscles was determined and normalized for height. Univariate and multivariate analyses were then done to examine for an association of muscle mass with morbidity and short- and long-term mortality. RESULTS: During the study period, there were 299 lobectomies, 278 of which were done by video assisted thoracoscopic surgery. The average age of the patients was 67.5±10.6 years. Overall complication rate was 52.2%, pneumonia rate was 8.7%, and the 30-day mortality rate was 1.3%. Mean height adjusted-erector spinae muscle cross-sectional area was 10.6±2.6 cm2/m2, and mean height adjusted-pectoralis muscle cross sectional area was 13.3±3.8 cm2/m2. The height adjusted cross sectional areas of the erector spinae and pectoralis muscles were not associated with overall complication rate, rate of pneumonia, readmission, or intensive care unit length of stay. The height adjusted-erector spinae muscle cross sectional area was inversely correlated with 30-day mortality risk, odds ratio 0.77 (95% CI, 0.60-0.98, P=0.036). Mean length of stay was 7.0 days (95% CI, 5.5-8.4 days). Multivariate analysis demonstrated a significant inverse association of the height adjusted-erector spinae muscle cross sectional area with length of stay (P=0.019). CONCLUSIONS: The height adjusted-erector spinae muscle cross sectional area was significantly associated with 30-day mortality and length of stay in the hospital. Measurement of muscle mass on preoperative computed tomography imaging may have a role to help predict risk of morbidity and mortality prior to lobectomy.

Malignant gastroparesis: pathogenesis and management of an underrecognized disorder.

Gastroparesis is a disorder of the stomach caused by delayed gastric emptying in the absence of mechanical obstruction. Symptoms of gastroparesis include nausea, vomiting, early satiety, bloating, and abdominal discomfort. Gastroparesis has been described as a complication of several malignancies, including gastric, pancreatic, gallbladder, esophageal, and lung cancers, as well as leiomyosarcoma. The prevalence of malignant gastroparesis (MG) is unknown, and this entity is widely underrecognized and undertreated. Diabetes mellitus is the most common identifiable cause of benign gastroparesis, ie, gastroparesis occurring in the absence of an underlying malignant pathology. In the setting of malignancy, gastroparesis may result from the cancer itself or may be a complication of its treatment with such modalities as surgery, radiation therapy, or chemotherapy. Coexisting conditions, including diabetes, hypothyroidism, and neurologic diseases, may further exacerbate MG. The pathogenesis of MG is not clearly understood at present. However, mechanisms suggested in the literature include postvagotomy syndrome, malignant infiltration of the autonomic nervous system, and paraneoplastic dysmotility with autoantibody-mediated destruction of the enteric nervous system (the interstitial cells of Cajal, also called the intrinsic pacemaker of the gastrointestinal tract, or the myenteric plexus). Appropriate treatment of MG may help to avoid serious consequences, such as cancer cachexia, intolerance of oral anticancer agents, dehydration, and hospitalization. In this article, we will describe our institutional experience with MG and will provide a concise review of the literature. Guidelines for management will be suggested.

Transcervical Extended Mediastinal Lymphadenectomy: Experience From a North American Cancer Center.

BACKGROUND: Accurate staging of the mediastinum is a critical element of therapeutic decision making in non-small cell lung cancer. We sought to determine the utility of transcervical extended mediastinal lymphadenectomy (TEMLA) in staging non-small cell lung cancer for large central tumors and after induction therapy. METHODS: A retrospective record review was performed of all patients who underwent TEMLA at our institution from 2010 to 2015. Clinical stage as assessed by positron emission tomography integrated with computed tomography (PET-CT), stage as assessed by TEMLA, final pathologic stage, lymph node yield, and clinical characteristics of tumors were assessed along with TEMLA-related perioperative morbidity. Accuracy of staging by TEMLA for restaging the mediastinum after neoadjuvant therapy was compared with that of PET-CT. RESULTS: Of 164 patients who underwent TEMLA, 157 (95.7%) were completed successfully. Combined surgical resection along with TEMLA was performed in 138 of these patients, with 131 (94.2%) undergoing a video-assisted thoracoscopic resection. The recurrent laryngeal nerve injury rate was 6.7%. TEMLA was performed in 118 of 164 patients for restaging after neoadjuvant therapy, and 101 of these patients were also restaged by PET-CT. Based on TEMLA, 7 patients did not go on to have resection. Of the 101 patients who did have a resection, TEMLA was more accurate than PET-CT in staging the mediastinum (95% vs 73%, p < 0.0001). However, the pneumonia rate in this subgroup of patients was 13%. CONCLUSIONS: TEMLA is a safe procedure and superior to PET-CT for restaging of the mediastinum after neoadjuvant therapy for non-small cell lung cancer. However, this increased accuracy comes with a high postoperative pneumonia rate.

Palliation of malignant dysphagia in esophageal cancer: a literature-based review.

Esophageal cancer is a lethal malignancy and adenocarcinoma of the esophagus is increasing in incidence. Most patients present with locally advanced, unresectable or metastatic disease. The 5-year survival rate of patients with esophageal cancer is < 20%. Dysphagia is the most common presenting symptom of this disease and leads to nutritional compromise, pain, and deterioration of quality of life. Palliation is an important goal of esophageal cancer therapy. Severity is commonly measured using a dysphagia grade, and dysphagia is an integral component of quality-of-life instruments, such as FACT-E and EORTC-OES 24. Investigation of dysphagia includes radiographic studies such as barium or Gastrografin swallow, esophagogastroduodenoscopy, endoscopic ultrasonography, and other staging studies for esophageal cancer. Current management options for the palliation of dysphagia include esophageal dilatation, intraluminal stents, Nd:YAG laser therapy, photodynamic therapy, argon laser, systemic chemotherapy, external beam radiation therapy, brachytherapy, and combined chemoradiation therapy. The clinical situation, local expertise, and cost effectiveness play an important role in choosing the appropriate treatment modality. The benefits and disadvantages of these approaches along with a concise review of the literature are presented.

Photodynamic Therapy of Non-Small Cell Lung Cancer. Narrative Review and Future Directions.

Photodynamic therapy (PDT) is an established treatment modality for non-small cell lung cancer. Phototoxicity, the primary adverse event, is expected to be minimized with the introduction of new photosensitizers that have shown promising results in phase I and II clinical studies. Early-stage and superficial endobronchial lesions less than 1 cm in thickness can be effectively treated with external light sources. Thicker lesions and peripheral lesions may be amenable to interstitial PDT, where the light is delivered intratumorally. The addition of PDT to standard-of-care surgery and chemotherapy can improve survival and outcomes in patients with pleural disease. Intraoperative PDT has shown promise in the treatment of non-small cell lung cancer with pleural spread. Recent preclinical and clinical data suggest that PDT can increase antitumor immunity. Crosslinking of signal transducer and activator of transcription-3 molecules is a reliable biomarker to quantify the photoreaction induced by PDT. Randomized studies are required to test the prognosis value of this biomarker, obtain approval for the new photosensitizers, and test the potential efficacy of interstitial and intraoperative PDT in the treatment of patients with non-small cell lung cancer.

Role of Private Enterprise in Cancer Control in Low to Middle Income Countries.

Background. About 65% of cancer deaths globally occur in low to middle income countries (LMICs) where prioritization and allocation of resources to cancer care are often quite poor. In the absence of governmental focus on this problem, public-private partnerships may be an avenue to provide effective cancer control. Methods. This manuscript highlights the establishment of a nongovernmental organization (NGO) to stimulate the development of partnerships between oncology professionals, private enterprise, and academic institutions, both locally and internationally. Examples of capacity building, grant support, establishment of collaborative networks, and the development of a facility to provide clinical care are highlighted. Results. Collaborations were established between oncology professionals at academic institutions in the US and Nigeria. Cancer control workshops were conducted in Nigeria with grant support from the Union for International Cancer Control (UICC). A monthly tumor board conference was established at LASUTH in Lagos, and further capacity building is underway with grant support from the United States NCI. An outpatient, privately funded oncology clinic in Lagos has been launched. Conclusion. In LMICs, effective partnership between public and private institutions can lead to tangible strides in cancer control. The use of creative healthcare financing models can also support positive change.

Fluorescent human lung macrophages analyzed by spectral confocal laser scanning microscopy and multispectral cytometry.

Numerous highly fluorescent macrophages (MPhi), designated "smoker cells," exist in the lungs of smokers and subjects who have quit smoking within 5 years. The brightly fluorescent MPhi, however, are not present in the lungs of never smokers. Some investigators have speculated that the intense fluorescence of the MPhi is due to smoke-induced changes in the autofluorescence of naturally occurring (i.e., endogenous) compounds (e.g., NADP). In contrast, other researchers have theorized that the fluorescence is due to the uptake of tobacco smoke particulates (i.e., "tar"). Studies reported herein were undertaken to test the hypothesis that the origin of the MPhi fluorescence could be profiled with the novel technologies afforded by spectral confocal laser scanning microscopy (sCLSM) and multispectral cytometry (MSC). To this end, spectral emissions were obtained by sCLSM of optical sections of live MPhi isolated from fresh surgically excised human lung tissue and in air-dried lung tissue imprints. Confirmation of spectral profiles of these single cell observations was obtained in population studies with the use of high-throughput MSC in which multispectral analyses were performed with three different lasers. Proof of concept experiments demonstrated that relatively nonfluorescent MPhi from the lungs of nonsmokers became fluorescent upon short-term ex vivo exposure to tobacco smoke tar. Summarily, the studies reported herein document that the fluorescence of human lung MPhi is due to tobacco tar.

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. McNemar's 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.

Discharge independence with minimally invasive lobectomy.

BACKGROUND: The effects of video-assisted thoracic surgery (VATS) pulmonary lobectomy on after-hospital care are not well known. METHODS: In a retrospective case-control study, 20 consecutive VATS cases were matched to 38 standard thoracotomies (open cases). RESULTS: Ages were 73.8 +/- 7.8 years with no initial differences between the groups. No hospital deaths occurred. Excluding 2 VATS and 6 open outliers, VATS cases had fewer hospital days (4.6 +/- 1.9 vs. 6.4 +/- 2.2, P <0.01), chest tube days (3.0 +/- 1.1 vs. 4.2 +/- 1.7, P = 0.01), and prolonged pain complaints (28% vs. 56%, P = 0.05). Transfer to care facilities or home nursing support was needed for 63% of open patients and only 20% of VATS patients (P = 0.015). Less personal care (10% vs. 21%), wound/medical care (0% vs. 13%), occupational/physical therapy (5% vs. 13%), or other home support (5% vs. 18%) was needed for VATS patients. CONCLUSIONS: In older populations, more independence and fewer resources after discharge favor VATS lobectomy over standard thoracotomy.

Thoracoscopic pneumonectomy: an 11-year experience.

BACKGROUND: It is unclear whether thoracoscopic (video-assisted thoracoscopic surgery [VATS]) pneumonectomy improves outcomes compared with open approaches. METHODS: One hundred seven consecutive pneumonectomies performed at an experienced center from January 2002 to December 2012 were studied retrospectively. Forty cases were open, and 50 successful VATS and 17 conversions were combined (intent-to-treat [ITT] analysis). RESULTS: The VATS cohort had more preoperative comorbidities (three vs two, P = .003), women (57% vs 30%, P = .009), and older ages (65 years vs 63 years, P = .07). Although advanced clinical stage was less for VATS (26% vs 50% stage III, P = .035), final pathologic staging was similar (25% vs 38%, P = .77). Pursuing a VATS approach yielded similar complications (two vs two, median, P = .73) with no catastrophic intraoperative events like bleeding. Successful VATS pneumonectomy rates rose from 50%-82% by the second half of the series (P < .001). Completion pneumonectomy cases (13.4% VATS, 7.5% open) had similar outcomes. Having similar initial discomforts as patients undergoing open surgery, more patients undergoing VATS were pain-free at 1 year (53% vs 19%, P = .03). Conversions resulted in longer ICU stays (4 days vs 2 days, P = .01). Advanced clinical stage (III-IV) ITT VATS had longer median overall survival (OS) (42 months vs 13 months, log-rank P = .042). Successful VATS cases with early pathologic stage (0-II) had a median OS of 80 vs 16 months for converted and 28 months for open (log rank = 0.083). CONCLUSIONS: Attempting thoracoscopic pneumonectomy at an experienced center appears safe but does not yield the early pain/complication reductions observed for VATS lobectomy. There may be long-term pain/survival advantages for certain stages that warrant further study and refinement of this approach.

Phase II study of perioperative chemotherapy with cisplatin and pemetrexed in non-small-cell lung cancer.

INTRODUCTION: Pathologic complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated pCR rate of cisplatin with pemetrexed in non-small-cell lung cancer. METHODS: Patients with stages IB to IIIA non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1 were enrolled in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of more than or equal to 10%. Pretreatment mediastinal lymph node biopsy was required. Patients received three cycles of cisplatin 75 mg/m with pemetrexed 500 mg/m (day 1 every 21 days) preoperatively and additional two cycles within 60 to 80 days after surgery. The primary end point was pCR. Polymorphisms in FPGS, GGH, SLC19A1, and TYMS genes were correlated with treatment outcomes. RESULTS: Thirty-eight patients were enrolled, with median age of 62.5 years. Preoperatively, 26% had squamous histology, and 34% had biopsy-proven N2 involvement. R0 resection was achieved in 94% of the 34 patients who underwent surgery, and 54% had documented N2 clearance. There was no pCR seen. Median disease-free survival (DFS) and overall survival of these patients have not yet been reached in contrast to median of 13.8 and 24.2 months, respectively, in patients with persistent N2 disease (p = 0.3241 and p = 0.1022, respectively). There was a statistically significant association between DFS and postoperative tumor, node, metastasis stage (p = 0.0429), SLC19A1 rs3788189 TT genotype (p = 0.0821), and viable tumor defined as less than or equal to 10% of resected specimen (p = 0.026). CONCLUSION: The primary end point was not met. Patients with N2 clearance, less than or equal to 10% viable tumor in the resected specimen, and SLC19A1 rs3788189 TT genotype have favorable DFS outcomes.

Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: correlation with vascular endothelial growth factor expression.

OBJECTIVES: Lymph node staging provides critical information in patients with non-small cell lung cancer (NSCLC). Lymphangiogenesis may be an important contributor to the pathophysiology of lymphatic metastases. We hypothesized that the presence of lymph node micrometastases positively correlates with vascular endothelial growth factors (VEGFs) A, C, and D as well as VEGF-receptor-3 (lymphangiogenic factors) expression in lymph nodes. METHODS: Forty patients with NSCLC underwent preoperative positron emission tomography-computed tomography and mediastinoscopy. Real-time polymerase chain reaction (RT-PCR) assays for messenger RNA expression of epithelial markers (ie, cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; and palate, lung, and nasal epithelium carcinoma-associated protein) were performed in selected fluorodeoxyglucose-avid lymph nodes. VEGF-A, VEGF-C, VEGF-D, and VEGF receptor-3 expression levels were measured in primary tumors and lymph nodes. Wilcoxon rank sum test was run for the association between the RT-PCR epithelial marker levels and VEGF expression levels in the lymph nodes. RESULTS: RT-PCR for cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; or palate, lung, and nasal epithelium carcinoma-associated protein indicated lymph node micrometastatic disease in 19 of 35 patients (54%). There was a high correlation between detection of micrometastases and VEGF-A, VEGF-C, VEGF-D, or VEGF receptor-3 expression levels in lymph nodes. Median follow-up was 12.6 months. CONCLUSIONS: RT-PCR analysis of fluorodeoxyglucose-avid lymph nodes results in up-staging a patient's cancer. Micrometastases correlate with the expression of VEGF in lymph nodes in patients with NSCLC. This may reflect the role of lymphangiogenesis in promoting metastases.

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.