Presence Of N2 Disease Research Articles

Narrative review of patterns of lymphatic drainage in early-stage non-small cell lung cancer

: In non-small cell lung cancer (NSCLC), the presence of metastatic nodal disease has been shown to be the most important predictor of long-term disease-specific survival after surgical resection. In patients with early stage, node-negative NSCLC who undergo complete resection, the current standard of care, a significant portion have recurrence of disease within 24 months after surgery. This has raised interest in better understanding the lymphatic drainage of these cancers to determine the exact patterns of loco-regional spread, and whether sentinel lymph node (SLN) identification can be utilized to aid in management of these diseases. Anatomic studies that have attempted to map the lymphatic drainage of tumors from different locations within the lung have revealed patterns of direct mediastinal drainage, which may help explain the prevalence of skip metastases, which is the presence of N2 disease in the absence of N1 disease. This article will provide a narrative review of primary literature concerning the anatomy of the pulmonary lymphatic system, patterns of nodal metastasis in NSCLC as studied through various techniques (including blue dye, radiocolloid tracers, and near-infrared image-guided SLN mapping), and opportunities for improvement in our understanding of how lung tumors interact with the lymphatic system on a structural level.

Results of radiotherapy in squamous cell laryngeal cancer: A tomotherapy center experience.

Laryngeal cancer is a common type of head and neck cancer (HNC). Radiotherapy (RT) is a mainstay for curative treatment. Intensity-modulated RT (IMRT) is a standard technique today, as it provides of higher survival and local control and lower normal tissue toxicity. One of IMRT devices is helical tomotherapy (HT). The HT treatment results of HNC patients have been reported in few studies. We aimed to investigate the results of squamous cell laryngeal carcinoma patients treated with helical tomotherapy. Forty-five laryngeal cancer patients were selected according to the inclusion criteria. Radiotherapy (RT) plans were set in the Hi-Art HT planning system. Image-gated RT (IGRT) technique was used. Appropriate patients received simultaneous cisplatin. Treatment response rates were evaluated at the post-RT third and sixth months. Survival times were calculated with the Kaplan-Meier method. The factors affecting the treatment results were evaluated using Log-rank and Cox regression tests. A P value of less than 0.05 was accepted as statistically significant. The median age was 65 (28-84) years. The median symptom duration was 6 (1-60) months. The RT dose for the early and the locally advanced disease was median 63 Gy (60.75-66) and 66 Gy (60-70), respectively. The RT interruption was median two (0-20) days. The patients were followed up to 25 (1-45) months. Grade 2 xerostomia and dysphagia rates were 55% and 7%, respectively. The 3-year estimates of overall survival (OS), disease-free survival (DFS), metastasis-free survival (DMFS), and locoregional recurrence-free survival (RRFS) were 71.7%, 60.4%, 84.9%, and 68.5%, respectively. In univariate analysis, the presence of N2 disease was a negative prognostic for DFS (P = 0.05) and DMFS (P = 0.003). RT interruption >2 days was a negative prognostic for OS (P = 0.005), DFS (P = 0.02), and RRFS (P = 0.023). In the multivariate analysis, symptom duration >6 months was found to be the only significant factor for DFS (P < 0.05). Intensity-modulated radiation with HT achieved comparable clinical outcomes with acceptable toxicity in laryngeal carcinoma.

Factors associated with treatment receipt and overall survival for patients with locally advanced large cell neuroendocrine carcinoma of the lung: A National Cancer Database analysis

PurposeLarge cell neuroendocrine carcinoma (LCNEC) is a rare pulmonary malignancy with clinicopathologic features of both non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Given the paucity of available data regarding LCNEC management, we queried the National Cancer Database (NCDB) to describe trends in management, identify predictors of treatment receipt, and compare outcomes in patients receiving chemotherapy (ChT) and chemoradiotherapy (CRT). MethodsWe identified patients with locally advanced (Stage III) LCNEC of the lung treated with definitive ChT or CRT between the years of 2004−2015. Odds ratios were calculated to determine predictors of CRT receipt. Multivariable cox regression was used to determine predictors of overall survival. ResultsUsing the above criteria, 5797 patients were identified, 54 % of whom received CRT (n = 3153) while 46 % (n = 2644) received ChT alone. Most patients had T4 (35 %) and N2 (59 %) disease. Median overall survival was 11.9 months (11.3–12.6) in patients receiving ChT compared to 16.1 months (15.4–16.9) in patients receiving CRT (p < 0.0001). Overall survival at 1, 3, and 5 years was 50 %, 20 %, and 13 % versus 60 %, 27 %, and 18 %, in patients receiving ChT and CRT, respectively. Older patients and those with higher comorbidity scores were less likely to receive CRT; whereas patients with higher education level, treatment receipt at an academic/research program facility, N2 disease, and later treatment year were more likely to receive CRT. On multivariable analysis, older age, greater comorbidity score, presence of N2 disease, and presence of T4 disease were all associated with decreased OS. CRT receipt was an independent predictor of increased overall survival. ConclusionsDefinitive CRT was an independent predictor of increased overall survival in patients with locally advanced LCNEC of the lung. Findings from our study may help guide potential areas of future investigation to help define an ideal treatment approach for LCNEC.

Trends in management of locally advanced large cell neuroendocrine carcinoma of the lung.

e21073 Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare pulmonary malignancy with clinicopathologic features of both non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The optimal treatment approach for LCNEC is not well established, likely a result of the histology’s underrepresentation in randomized clinical trials. Given the paucity of available data regarding LCNEC management, we queried the National Cancer Database (NCDB) to describe trends in management, identify predictors of treatment receipt, and compare outcomes in patients receiving chemotherapy (ChT) and chemoradiotherapy (CRT). Methods: We identified patients with locally advanced (Stage III) LCNEC of the lung treated with definitive ChT or CRT between the years of 2004-2015. Odds ratios were calculated to determine predictors of CRT receipt. Multivariable cox regression was used to determine predictors of overall survival. Results: Using the above criteria, 6,802 patients were identified, 46% of whom received CRT (n = 3,153) while 39% (n = 2,644) received ChT alone. Median age of the entire cohort was 68 years old. Most patients had T4 (35%) and N2 (59%) disease. Median overall survival was 11.9 months (11.3-12.6) in patients receiving ChT compared to 16.1 months (15.4-16.9) in patients receiving CRT (p &lt; 0.0001). Overall survival at 1, 3, and 5 years was 50%, 20%, and 13% versus 60%, 27%, and 18%, in patients receiving ChT and CRT, respectively. Older patients and those with higher comorbidity scores were less likely to receive CRT; whereas patients with higher education level, treatment receipt at an academic/research program facility, N2 disease, and later treatment year were more likely to receive CRT. On multivariable analysis, older age, greater comorbidity score, presence of N2 disease, and presence of T4 disease were all associated with decreased OS, whereby female sex, private insurance, higher income, lower T stage, and more recent treatment were associated with increased overall survival. CRT receipt was an independent predictor of increased overall survival. Conclusions: Definitive CRT was an independent predictor of increased overall survival in patients with locally advanced LCNEC of the lung. Findings from our study may help guide potential areas of future investigation to help define an ideal treatment approach for LCNEC.

Surgical Treatment of Superior Sulcus Tumors: Results and Prognostic Factors

This study aims to investigate the treatment modalities and factors influencing survival in surgically treated superior sulcus tumors. Sixty-five cases of surgically treated non-small cell carcinoma of the lung occurring as superior sulcus tumors between 1994 and 2007 were retrospectively reviewed. Twenty-five patients underwent induction radiotherapy (RT), 10 had induction chemoradiotherapy (CT/RT). In thirty patients surgery was performed directly. The mortality rate was 6.2 %. Pathological stage was T3 in 55, T4 in 10, N0 in 52, and N1 in 5 and N2 in 8 patients. Overall 5- and 10-year survival rates were 31 % and 28 %, respectively. Complete resection rate was 90 % for patients who received induction CT/RT and 80 % for patients who either received induction RT alone or patients in whom surgery was performed directly. In patients who received neoadjuvant therapy with complete tumor resection, the median survival time was 33 months (28 months for patients who received induction RT alone and 36 months for patients who received induction CT/RT), and the 5-year survival rate was 41 %. Median survival time and 5-year survival rate of patients treated by direct surgery with complete resection was 24 months and 37 %, respectively ( P = 0.87). Five-year survival and 10-year survival rates were significantly higher after complete resection than after incomplete resection (38 % and 34 % vs. 0 %, P = 0.0001). In multivariate analysis, only N2 disease ( P = 0.04) and incomplete resection ( P = 0.03) were found to be poor prognostic factors. The presence of N2 disease and incomplete resection are the two most important factors affecting survival. Induction CT/RT may increase the ability to achieve complete surgical resection.

Prognostic Factors in Resected T3 Non-Small Cell Lung Carcinoma: Perineural Invasion as a New Prognostic Factor

Currently the best prognostic indicator for resected non-small cell lung cancer (NSCLC) is the TNM stage. Moreover, certain histopathological properties of the tumor (such as lymphatic, vascular and perineural invasion) can help to predict the survival of the patients. Between 1997 and 2004, the results of surgical treatment were retrospectively analyzed for 153 patients with T3 non-small cell lung cancer. One hundred and twenty-four of them had had complete (R0) resections, and 29 had had incomplete (R1) resections. The prognostic factors evaluated by univariate and multivariate analysis were: type of resection; N status; subgroup of pT3; effect of adjuvant therapy; tumor size; histological type; tumor differentiation; lymphatic invasion; vascular invasion; and perineural invasion. The overall 5-year survival rate was 32 % in R0 patients, and 8 % in R1 patients ( P = 0.0002). The presence of N2 disease, vascular invasion, and perineural invasion were found to be significant prognostic indicators in univariate analysis ( P = 0.0058, P = 0.033, and P = 0.0058, respectively). Among these indicators, N2 disease and perineural invasion were also found to be significant prognostic factors in multivariate analyses ( P = 0.013, and P = 0.003, respectively). Incomplete resection, N2 disease, vascular and perineural invasion were found to be prognostic indicators for the survival of T3 NSCLC patients. Of these indicators, perineural invasion was found to be the strongest predictor of poor prognosis and independently affected the patients' survival.

Morbidity, mortality, and long-term survival after sleeve lobectomy for non-small cell lung cancer

Sleeve lobectomy is a widely accepted procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study is to assess operative mortality, morbidity, and long-term results of sleeve lobectomies performed for non-small cell lung carcinoma (NSCLC). A retrospective review of 218 patients who underwent sleeve lobectomy for NSCLC between 1981 and 2005 was undertaken. There were 186 (85%) men and 32 women with a mean age of 61.9 years (range, 19-82 years). Eighty patients (36.6%) had a preoperative contraindication to pneumonectomy. Right upper lobectomy was the most common operation (45.4%). Vascular sleeve resection was performed in 28 patients (12.8%) and was commonly associated with left upper lobectomy (n=20; 9.1%; p=0.0001). The histologic type was predominantly squamous cell carcinoma (n=164; 75%), followed by adenocarcinoma (n=46; 21%). Resection was incomplete in nine (4.1%) patients. There were nine operative deaths; the operative mortality and the morbidity rates were 4.1% and 22.9%, respectively. A total of 14 (6.4%) patients presented with bronchial anastomotic complications: two were fatal postoperatively, seven patients required reoperation, three required a stent insertion, and two were managed conservatively. Multivariate analysis showed that compromised patients (p=0.001), current smoking (p=0.01), right sided resections (p=0.003), bilobectomy (p=0.03), squamous cell carcinoma (p=0.03), and presence of N1 or N2 disease (p=0.01) were risk factors for mortality and morbidity. Follow-up was complete in 208 patients (95.4%). Overall 5-year and 10-year survival rates were 53% and 28.6%, respectively. After complete resection, recurrence was local in 10 patients, mediastinal in 20, and distant in 25. By multivariate analysis, two factors significantly and independently influenced survival: nodal status (N0-N1 vs N2; p=0.01) and the stage of the lung cancer (stage I-II vs III, p=0.02). For patients with NSCLC, sleeve lobectomy achieves local tumor control, even in patients with preoperative contraindication to pneumonectomy and is associated with low mortality and bronchial anastomotic complication rates. Postoperative complications are higher in compromised patients, smokers, N disease, right sided resections, bilobectomies, and squamous cell cancers. The presence of N2 disease and stage III significantly worsen the prognosis.

Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma

Background Computed tomography and magnetic resonance imaging often fail to predict resectability in patients with malignant pleural mesothelioma. Small studies suggest that fluorodeoxyglucose-positron emission tomography may improve staging. We analyzed our experience to determine more definitively the potential utility of fluorodeoxyglucose-positron emission tomography. Methods Patients with malignant pleural mesothelioma who underwent fluorodeoxyglucose-positron emission tomography scanning were identified from an institutional database. All patients fasted and received a minimum of 10 mCi of F-18-fluorodeoxyglucose. Whole-body emission studies were acquired, followed by whole-body transmission studies, allowing iterative reconstruction. Blinded review of positron emission tomography scans was performed for clinical staging, which was then correlated with surgical and pathologic findings. Sensitivity and specificity were determined for tumor and nodal status. Results From 1998 to 2002, 63 patients underwent positron emission tomography scans, 60 preoperatively and 3 to assess disease recurrence after surgery. Increased fluorodeoxyglucose uptake was seen in all but 1 tumor, which was very early stage (IA). Positron emission tomography findings yielded sensitivities of only 19% and 11% for tumor and nodal status, respectively. However, a high standard uptake value in the primary tumor correlated with the presence of N2 disease. Positron emission tomography correctly identified supraclavicular N3 or M1 disease in 6 patients. Conclusions Positron emission tomography does not identify the local extent of tumor or mediastinal nodal metastases reliably but detects extrathoracic metastases, thereby obviating inappropriate thoracotomy. Further studies of the association between tumor standard uptake value and the presence of N2 disease are warranted.

The significance of tumour markers as an indication for mediastinoscopy in non-small cell lung cancer.

The purpose of this study was to verify the significance of tumour markers as indicators for mediastinoscopy in non-small cell lung cancer. In the past 4 years, 205 patients with non-small cell lung carcinoma (NSCLC) underwent surgical resection at Chiba Cancer Center, Chiba, Japan. The correlation between the serum levels of eight tumour markers (CEA, AFP, CA19-9, SCC, NSE, CA125, CYFRA, ProGRP) and the presence of N2 disease was analysed. Univariate and multivariate analyses were performed to determine the relationship between both marker levels and clinical findings and N2 disease. In multivariate analysis, positive CEA was significantly associated with the diagnosis of N2 disease. We also demonstrated that when CA125, CYFRA and ProGRP were positive, they were individually significantly associated with N2 disease. However, CEA was superior to the other markers and equivalent to a combination of various tumour markers. It was concluded that evaluation of CEA in addition to CT is of use in the diagnosis of N2 disease in NSCLC patients and should be used as an indication for mediastinoscopy.

Prognostic significance of pleural lavage cytology after resection for non-small cell lung cancer.

In the staging of lung cancer, pleural effusion that is malignant on cytologic examination is regarded as T4 disease, and curative resection cannot be performed. We conducted this study to determine whether cancer cells can be present in the pleural cavity with no pleural effusion, to investigate the factors contributing to that occurrence, and to evaluate its prognostic significance. Eighty-five patients (77 males, eight females) with a median age 60.1-+/--7.9 years (31--74 years) underwent a major lung resection, due to lung cancer in our department. From January 1998 to December 1999, 30 pneumonectomies, seven bilobectomies, 46 lobectomies and two wedge-resections were performed. Chest wall resection was performed in four patients. After performing a posterolateral thoracotomy and lung resection with extended mediastinal lymph node dissection, the pleural cavity was filled with 1 l physiologic saline solution (PSS) and the fluid was shaken. The lavage fluid was suctioned off (S1). Immediately after the lavage, the pleural cavity was refilled with 3 l PSS. The surgeon washed out the pleural cavity by hand for 1 min and the fluid was suctioned off. Finally, the pleural cavity was refilled with 1 l PSS and a new lavage fluid was suctioned off (S2). A cytologic examination was carried out for each sample. The pathology report showed 39 adenocarcinomas, 33 squamous-cell, two adenosquamous, four large-cell, two neuroendocrine and five undifferentiated carcinomas. S1 was positive in eight patients (9.4%), while S2 was positive in four patients (4.7%). The correlation of positive pleural lavage and infiltrated lymph nodes demonstrated a statistically significant relation between presence of N2 disease and positive S2 sample (P = 0.049). No significant correlation existed between positive lavage sample (S1 or S2) and TNM stage, level of T, extent of tumor invasion, kind of operation, histological type or differentiation of the cancer (Chi square test). The mean follow-up is 11.3 +/- 6.2 months (4--22 months). There are 78 patients alive. A significance difference in survival was identified in-patients with positive S1 (P = 0.0081), and positive S2 (P = 0.0251) (Kaplan--Meier). The cytologic results of lavage were positive for malignant cells in eight of 85 patients (9.4%). The existence of cancer cells in the pleural cavity can be the result of their exfoliation or surgical manipulations. The mechanical irrigation subdivides the percentage of positive samples. Our study supports that the positive findings on pleural lavage cytology is an essential prognostic factor.

Resection of lung cancer invading the diaphragm

Each year, stage III non-small-cell lung cancer (NSCLC) is diagnosed in approximately 30,000 patients. Locally advanced NSCLC (stage IliA) includes a group of biologically diverse tumors with subgroups of truly locally advanced disease--T3 tumors and advanced locoregional disease with the presence of N2 disease. The prognosis of patients with a diagnosis of stage III lung cancer is mainly dependent on the status of the mediastinal nodes. Good long-term results are achieved in patients with NO disease, whereas patients with N2 disease are poor candidates for resection as a primary treatment. 1-3 Information is not available on results of surgical treatment of patients with stage III disease and tumors involving the diaphragm. Patients and methods. From January 31, 1974, to August 17, 1995, a total of 4668 patients underwent exploration for resection of NSCLC at Memorial Hospital. By analyzing our database we identified eight patients (0.17%) who had exploratory thoracotomy for resection of NSCLC invading the diaphragm. The medical records of these eight patients were retrospectively analyzed. Data are reported as mean -+ standard deviation. Survival data are reported as mean and 95% confidence interval (CI) for the mean. The Kaplan-Meier method was used to calculate actuarial survival. Results. The demographics of these eight patients are shown in Table I. The mean age at diagnosis was 65.8 + 10.2 years, ranging from 52.6 to 82.4 years. The most common symptoms were cough in four patients, hemoptysis in two patients, and chest pain in one patient. One patient had clubbing of the fingers. Three patients were free of symptoms. All patients smoked. The mean time from first symptoms to referral for treatment was 25.1 -+ 16.6 weeks, ranging from 5.3 to 49 weeks. The histologic diagnosis was made by bronchoscopic examination in four patients and by fluoroscopic guided needle biopsy in two. In two patients the diagnosis was made in the operating room. Four tumors were on the right side and four on the left side. Two patients underwent mediastinoscopy, both studies yielding negative results. The other six did not undergo preoperative mediastinoscopy. Among the eight patients, diaphragmatic invasion was not suspected at exploration in six and it was suspected before the opera-

Pleural dissemination in non‐small cell lung cancer: Results of radiological evaluation and surgical treatment

The aims of this study are to evaluate the diagnostic ability of chest computed tomography (CT) in the early detection of pleural disease and to analyze the results of surgical treatment for lung cancer with pleural dissemination. Twenty-three non-small cell lung cancer patients with pleural dissemination, but without distant metastasis, underwent pleuropulmonary resection during the past 15 years. Chest CT scans were obtained preoperatively in 21 of those patients. In eight patients without pleural effusion, small pleural nodules, about 3-5 mm in size, were found in their chest CT. However, during surgery, small nodules were more frequently observed on the parietal pleura than on the visceral pleura in five of them. Therefore, early detection of the dissemination by chest CT seemed limited to only those of the visceral pleura. In the survival curve after resection, there was no difference among the patients with n2 disease, but there was a significant difference between the patients without n2 disease and those with it (P < 0.05). The presence of n2 disease appeared to be a poor prognostic sign in this form of advanced lung cancer.