Cell Lung Cancer Stage Research Articles

Importance of TAK-1 levels in patients with non-small cell lung carcinoma.

In this study, we aimed to investigate the relationship between survival, tumor dimension, grade and stage in respect to transforming growth factor-β-activating kinase (TAK-1) extensity, severity and total score in patients undergoing resection for Stage 1B-2B non-small cell lung cancer. Between January 2000 and December 2014, a total of 70 patients (64 males, 6 females; mean age: 63.4+9.6 years; range, 32 to 78 years) who underwent surgery with resectable non-small cell lung cancer in Stage 1-2b were included. The patients were divided into two groups as Group 1 (n=35) consisting of patients with squamous cell carcinoma and Group 2 (n=35) consisting of patients with adenocarcinoma. The control group consisted of 20 patients (Group 3) who underwent surgery due to non-cancer causes. The relationship between TAK-1 staining (extensity, severity, total scores) and grade, survival time, T factor, N factor, and chemotherapy administration was examined. Pathology specimens of the patients were evaluated for the degree of staining with TAK-1 primary antibody. There was a strong correlation between the tumor grade and TAK-1 primary antibody staining level, independently from histopathological type. A significant correlation was found between dimension, stage, and TAK-1 staining in patients with squamous cell carcinoma. No statistically significant difference was found in the other factors, except for grade factor, in patients with adenocarcinoma. The current study provides precious information about the effects of TAK-1, in clinicopathological behavior and survival of malignant cells, particularly in common histopathological types of lung cancer. We believe that our data can be useful, particularly in evaluating the response to targeted therapies and the prognosis of the disease.

Galectins role as predictive markers for anti-PD-1-based immunotherapy in non-small cell lung cancer.

111 Background: Checkpoint inhibitor-based immunotherapy is opening a promising scenario in oncology with objective responses registered in several tumors. However reliable predictive markers of tumor responsiveness are still lacking. These markers need to be urgently identified for a better selection of patients candidate to immunotherapy. In NSCLC setting, the pleiotropic molecules Galectin 1 and 3 regulate apoptosis and tumor immune-escape and are in the right position to play as predictive marker in anti-PD1 based immunotherapy. Methods: 27 consecutive patients with non small cell lung cancer (NSCLC) stage IV, treatment-naive, selected on the basis of PD-L1 tumor proportion score (TPS) ≥ 50 % were considered for immunotherapy with anti PD-1 antibodies as a first-line treatment. Patients assessments were conducted at baseline and after 3 cycles of therapy (week 12) and classified according to immune-related response criteria (iRECIST). Immunohistochemical analysis was performed on primary tumor biopsies before treatment in order to evaluate Gal-1 and Gal-3 expression both in cancer cells and tumor interstitium. Tumors were grouped in 2 different classes depending on the expression level of these molecules. Results: In our preliminary data there seems to be a strong correlation between the responses to anti-PD-1 treatment and a low-intermediate expression of intratumoral Gal-3 and interstitial Gal-1. In fact, all patients in the intratumoral Gal-3 low-intermediate expression group had an excellent response to immunotherapic treatment (10/10 patients), while 15/17 patients with high intracellular Gal-3 expression had clinical and radiographic progression of the disease after only three cycles of treatment, despite the high expression of PD-L1. In contrast, 8/11 patients with a low-intermediate interstitial expression of Gal-1 had an excellent response to treatment, whereas in the group with high interstitial expression of Gal-1, the response rate was drastically lower (5/15 patients). Conclusions: The expression of interstitial Gal-1 protein and intratumoral Gal-3 protein appear to be a good candidates as predictive markers of response to immunotherapy.

Applicability of a prognostic CT-based radiomic signature model trained on stage I-III non-small cell lung cancer in stage IV non-small cell lung cancer

ObjectivesRecently it has been shown that radiomic features of computed tomography (CT) have prognostic information in stage I-III non-small cell lung cancer (NSCLC) patients. We aim to validate this prognostic radiomic signature in stage IV adenocarcinoma patients undergoing chemotherapy. Materials and methodsTwo datasets of chemo-naive stage IV adenocarcinoma patients were investigated, dataset 1: 285 patients with CTs performed in a single center; dataset 2: 223 patients included in a multicenter clinical trial. The main exclusion criteria were EGFR mutation or unknown mutation status and non-delineated primary tumor. Radiomic features were calculated for the primary tumor. The c-index of cox regression was calculated and compared to the signature performance for overall survival (OS). ResultsIn total CT scans from 195 patients were eligible for analysis. Patients having a prognostic index (PI) lower than the signature median (n = 92) had a significantly better OS than patients with a PI higher than the median (n = 103, HR 1.445, 95% CI 1.07–1.95, p = 0.02, c-index 0.576, 95% CI 0.527–0.624). ConclusionThe radiomic signature, derived from daily practice CT scans, has prognostic value for stage IV NSCLC, however the signature performs less than previously described for stage I-III NSCLC stages. In the future, machine learning techniques can potentially lead to a better prognostic imaging based model for stage IV NSCLC.

Neoadjuvant Radiochemotherapy Followed by Curative Resection in Patients with Advanced Non-Small Cell Lung Cancer in Stage IIIA/IIIB: Prognostic Factors and Results

The role of surgical lung resection following neo-adjuvant radio-chemotherapy (RCT) in patients with locally advanced non-small cell lung cancer (NSCLC) is yet not clearly defined. The aim of our study was to analyze the postoperative survival and to identify relevant prognostic factors. 46 patients underwent curative resections after neo-adjuvant RCT for locally advanced NSCLC (IIIA/IIIB) between February 2008 and February 2015. A retrospective data analysis regarding preoperative regression status, perioperative mortality, postoperative survival, patho-histological remission, relapse pattern and other prognostic factors was performed. A neo-adjuvant RCT with a median radiation dose of 50.4 [range, 45-60] Gy was performed in 44 (96 %) patients. Partial and/or complete regression was observed in 32 (70 %) patients. R0-resection was achieved in 44 (96 %) patients. The 30-day mortality was 4 % and the perioperative morbidity was 37 %. The overall and progression free 5-year survival rate was 47 % and respectively 45 % [in median 58 months]. The 5-year survival rate of 64 % in the "responder"-group was significantly better when compared with 24 % in the "non-responder"-group (p = 0.038). The tri-modality therapy improved the prognosis in patients with locally advanced NSCLC (stage IIIA/IIIB). The complete patho-histological remission is an important prognostic factor for better long term survival. Dividing the patients in "responder" and "non-responder" after neo-adjuvant RCT may have large therapeutically consequences in the future.

Abstract 4334: Elevated lactic acid is a negative prognostic factor in metastatic lung cancer

Abstract Introduction: Hyperlactatemia with or without type B lactic acidosis is a rare complication of malignancy, previously observed most often in hematological malignancies. Underlying pathophysiology involves reduced lactic acid metabolism from metastatic liver dysfunction as well as overproduction of lactic acid from aberrant glycolytic metabolism of tumors. Clinical data to evaluate the potential value of arterial or venous lactic acid (LA) level assessment as a predictor of overall survival (OS) or/and response to treatment are lacking. The aim of this study was to assess the prognostic value of LA in patients with metastatic lung cancer. Methods: Patients diagnosed with stage IV non-small cell lung cancer (NSCLC) or extensive stage small cell lung cancer (SCLC) from 2012 to present, were included in this single center, retrospective study. Patients with sepsis or acute exacerbation of heart failure were excluded from the study. Arterial and venous LA level, bicarbonate, anion gap, urine ketones, serum LDH were recorded for each patient and their associations with demographic and clinical data and OS were analyzed with the Chi-square test, Kaplan-Meier's actuarial method (log-tank test) and Cox proportional hazard model. Results: 85 patients (43 males, mean age 73.1, range 45-96 years) were studied. The maximal levels of arterial or venous LA were significantly associated with presence of ≥2 metastatic sites (p = 0.001), ICU admission or transfer (p = 0.016), intubation (p = 0.029), elevated serum anion gap (p<0.001) and LDH levels (p<0.001). No significant associations emerged between LA level and gender, age, smoking status, histology, tumor size or grade, previous lung resection, location of metastases, COPD, previous metformin use, ketonuria, and previous or ongoing palliative chemotherapy. Hyperlactatemia (p<0.001), histologic subtype (p = 0.019), ICU admission or transfer (p = 0.014), intubation (p = 0.026), number of metastatic sites (p = 0.01), AG (p<0.01) and LDH (p<0.001) were univariately associated with OS. LDH was the only independent prognostic factor [OR = 0.162 (95% CI: 0038-0.687), p = 0.014]. Conclusion: Our results suggest that elevated LA is a predictor of poor OS in metastatic lung cancer patients, irrespective of chemotherapy. Here lie implications for targeting tumor-derived LA production via manipulation of glycolytic enzymes or lactate transporters, with use of LA as a surrogate marker of response. Citation Format: Panagiotis J. Vlachostergios, Nirav Parikh, Katerina Oikonomou, Eugene Gibilaro, George Apergis. Elevated lactic acid is a negative prognostic factor in metastatic lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4334. doi:10.1158/1538-7445.AM2015-4334

The role of ALDH1 and CD133 expression as stem cell tumor marker in early-stage NSCLC.

e13508 Background: A 70% of patients with non-small cell lung cancer (NSCLC) stage I die of their disease within five years of diagnosis. Cancer stem cells (CSC) have been described as poor prognos...

Cytopathological Diagnosis of Non Small Cell Lung Cancer: Recent Advances Including Rapid On-Site Evaluation, Novel Endoscopic Techniques and Molecular Tests

Important advances in non small cell lung cancer (NSCLC) diagnosis, staging and treatment have been made over the last decade. Minimally-invasive endoscopic techniques including endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) and navigational bronchoscopy have emerged as valid alternatives to transthoracic and/or surgical approaches, providing aspiration cytology material instead of histological material for diagnosis and staging of mediastinal and lung lesions. Several drugs designed to target molecular pathways involved in cancer-cell growth and survival have been shown to be effective in a selected fraction of NSCLC patients, mostly with adenocarcinoma (targeted therapy). Somatic activating mutations in several genes involved in those pathways (EGFR/KRAS) can predict patients’ responses to targeted therapies (individualized therapy). Those mutations are commonly detected in histopathological samples (core-needle biopsy/surgical resection). However, when histological tissues are not available, molecular testing can be performed on cytological specimens. This scenario is increasing in frequency, due to the use of less invasive procedure for diagnosis and staging such EBUS-TBNA and/or patients in advanced stage of disease who are not candidates for surgery. Several strategies exist and may be combined to ensure that the less abundant material that results from minimally invasive techniques can be used efficiently for molecular analyses. These include Rapid On-Site Evaluation (ROSE) of EBUS-TBNA cytological material, to ensure optimal sampling and triage of the material (e.g. cell-block preparation), and microdissection techniques, to select an adequate population of tumor cells. Major issues raised by cytological diagnosis of NSCLC and molecular testing on cytological specimen are discussed in this article.

Surgical resection for non-small cell lung cancer: clinical features and outcomes for a consecutive series at an Irish tertiary referral centre

Few patients diagnosed with lung cancer are still alive 5 years after diagnosis. The aim of the current study was to conduct a 10-year review of a consecutive series of patients undergoing curative-intent surgical resection at the largest tertiary referral centre to identify prognostic factors. Case records of all patients operated on for lung cancer between 1998 and 2008 were reviewed. The clinical features and outcomes of all patients with non-small cell lung cancer (NSCLC) stage I-IV were recorded. A total of 654 patients underwent surgical resection with curative intent during the study period. Median overall survival for the entire cohort was 37 months. The median age at operation was 66 years, with males accounting for 62.7 %. Squamous cell type was the most common histological subtype, and lobectomies were performed in 76.5 % of surgical resections. Pneumonectomy rates decreased significantly in the latter half of the study (25 vs. 16.3 %), while sub-anatomical resection more than doubled (2 vs. 5 %) (p < 0.005). Clinico-pathological characteristics associated with improved survival by univariate analysis include younger age, female sex, smaller tumour size, smoking status, lobectomy, lower T and N status and less advanced pathological stage. Age, gender, smoking status and tumour size, as well as T and N descriptors have emerged as independent prognostic factors by multivariate analysis. We identified several factors that predicted outcome for NSCLC patients undergoing curative-intent surgical resection. Survival rates in our series are comparable to those reported from other thoracic surgery centres.

Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice.

Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages. Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society. There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010). The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.

Utility of PET/CT for mediastinal staging of non-small cell lung cancer in stage III (N2)

Purpose To evaluate the accuracy of integrated positron emission tomography with 18F-fluoro-2-deoxy- d-glucose (FDG) and computed tomography (PET/CT) in mediastinal lymph node staging in patients with potentially operable (N2) non-small cell lung cancer (NSCLC) and to ascertain the role of invasive staging in verifying positron emission tomography (PET)/computed tomography (CT) results. Material and methods A retrospective study of consecutive patients with pathologically-proven NSCLC and N2 staging by enhanced CT was performed. A PET/CT scan was performed for all the patients. Lymph node staging was pathologically confirmed when it was possible or by consensus in the Thoracic Cancer Committee. Sensitivity, specificity, negative predictive value and positive predictive value of PET/CT in N2 cases were determined. Results A total of 34 patients with N2 by CT were evaluated. PET/CT showed N2 in 30 patients. Discrepancies were found in four patients, two patients were classified as N1 in PET/CT and two patients as N0. Lymph node staging was pathologically confirmed in 20 patients. No false positives were found in PET/CT study. Sensitivity was 94.7%, specificity and positive predictive values were 100% and negative predictive value was 50%. Conclusions Our data show that integrated PET/CT provides high sensitivity and positive predictive value in mediastinal nodal staging of NSCLC patients. Therefore, in patients with potentially resectable lung cancer, neoadjuvant chemotherapy candidate, mediastinoscopy could be reserved for restaging after induction therapy.

Endostar in combination with radiotherapy and paclitaxel/carboplatin in patients with unresectable non-small cell lung cancer of stage III: Preliminary results of a phase II study.

7043 Background: A feasibility study was performed to examine the safety and activity profile of Endostar in combination with radiotherapy and Paclitaxel/Carboplatin in patients with unresectable non-small cell lung cancer(NSCLC) of stage III. Methods: Patients with unresectable stage III NSCLC will receive thoracic radiation therapy in 2Gy fractions five times weekly to a total dose of 60-66 Gy and concurrent with Endostar 7.5 mg/m2 over 3 hours d1-14, paclitaxel 50 mg/m2 weekly over 1 hour, carboplatin AUC=2 mg/mL/min over 30 min weekly. Followed by Endostar 7.5 mg/m2 d1-14, paclitaxel 175 mg/m2 d1 and carboplatin AUC=5 mg/mL/min d1 every 3 weeks for 2 cycles as consolidation treatment. Objective response rate according to the RECIST criteria was recorded and toxicity was evaluated using the NCI Common Toxicity Criteria. Results: 12 eligible patients enrolled in the study received concurrent Endostar, paclitaxel/carboplatin and definitive thoracic radiation therapy (TRT). Three patients were unable to complete the followed consolidation treatment (two because of pulmonary toxicity and one because of progressive disease). 9 patients (75.0%) had a partial response, while 2 patient’s disease remained stable and 1 patient had progression of the disease. The overall response rate (75.0%,95% confidence interval (CI): 51%-97%) didn’t exceed the goal per study design (85.0%), and the study was therefore closed according to the protocol definition. Main toxicity (grade 3 or greater, %): neutropenia 5 (41.7%); thrombocytopenia 2 (16.7%); anaemia 2 (16.7%); nausea/vomiting 1 (8.3%); anorexia 2 (16.7%), dysphagia 2 (16.7%), radiation pneumonitis 4 (33.3%) and fatigue 1 (8.3%). Conclusions: Our results do not support further trials of Endostar in combination with radiochemotherapy in patients with Stage III NSCLC. Endostar likely enhances radiation pneumonitis. The impact of Endostar on survival as a first-line treatment in combination with radiochemotherapy remains to be determined.

Abstract 4158: SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer in plasma

Abstract Analysis of DNA methylation at the SHOX2 locus has been shown to identify lung cancer in bronchial aspirates of patients with disease, and can potentially provide more definitive information to clinicians when histologic and cytologic findings from bronchoscopy are ambiguous. In a previous training study on bronchial aspirate samples, valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 discriminated malignant from benign lung disease (e.g. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses) with 68% sensitivity and 95% specificity. A SHOX2 assay performance was then validated in a blinded and randomized case control study comprised of Saccomanno-fixed bronchial lavage samples from 250 patients (125 cases, 125 controls). Results showed the SHOX2 assay reliably identified patients with lung cancer (AUC = 0.95, sensitivity 78%, specificity 96%). Computed tomography (CT) is currently being evaluated as a screening tool for early detection of lung cancer in several large ongoing trials. The randomized National Lung Screening Trial (NLST) in the United States was halted early after 8-year results showed that screening heavy smokers with low-dose helical CT significantly reduced deaths from lung cancer when compared with chest x-ray screening. However, CT scans fail to detect pre-invasive lesions and early lung cancer in the central airways, specifically small cell lung cancer (SCLC) and early stages of squamous cell carcinoma, which comprise 17-29% of all lung cancers. The use of a biomarker assay in conjunction with a CT might help to identify these patients. This study aimed to develop a modified SHOX2 assay which detects circulating methylated SHOX2 in blood and to analyze the performance of this optimized SHOX2 assay in plasma. Quantitative real-time PCR was used to analyze DNA methylation of SHOX2 assay in plasma samples from a total of 371 individuals (lung cancer patients, healthy individuals, benign lung diseases and prostate cancer patients). Performance of the assay was calculated to determine sensitivity and specificity based on a clinical cut-off. Valid measurements were obtained from a total of 343 patient samples (155 controls, 188 cases). DNA methylation of SHOX2 discriminated malignant lung disease from controls at a sensitivity of 62% and a specificity of 90%. SCLC (80%) and squamous cell carcinoma (63%) were detected at higher sensitivity as compared to adenocarcinoma (42%). SHOX2 DNA methylation is a sensitive and specific biomarker for detecting the presence of malignant lung disease in blood plasma, with highest sensitivity for detection of small cell and squamous cell lung cancer. A blood-based test for detection of SHOX2 DNA methylation could be a useful tool to identify patients with lung cancer alone or in conjunction with CT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2011-4158

Anatomic thoracoscopic lung resection for non-small cell lung cancer in stage I is associated with less morbidity and shorter hospitalization than thoracotomy

Background. Patients undergoing surgery for non-small cell lung cancer (NSCLC) are often elderly with co-morbid conditions and decreased performance status. Thus, the morbidity of lung resection via thoracotomy may be unacceptable for some patients. This is the reason why video-assisted thoracoscopic surgery (VATS) instead of open thoracotomy has gained more use and acceptance, especially in patients with stage I disease. The aim of this study was to evaluate the difference between VATS and open thoracotomy in treatment outcomes of stage I NSCLC patients. Methods. A total of 328 stage I NSCLC patients underwent lobectomy, bilobectomy or segmentectomy between January 2000 and February 2010. VATS was implemented in 116 patients, of which 16 were converted to thoracotomy. Muscle-sparing anterolateral thoracotomy was performed in 212. Propensity-matched groups were analyzed based on preoperative variables and stage. Results. VATS was associated with lower postoperative morbidity in both overall (p = 0.020) and propensity-matched analysis (p = 0.026) and shorter hospitalization (both p < 0.001). Patients selected for VATS were older (p = 0.001) with a significantly higher Charlson comorbidity index (p = 0.007) and poorer diffusion capacity (p < 0.001). The conversion rate was 14%. Between the two groups, no significant difference was observable in two-year overall and progression-free survival. Conclusions. Despite the VATS lobectomy and segmentectomy patients’ being older, with more comorbid condition and poorer pulmonary function, the incidence of major complications was lower and hospitalization shorter than for open thoracotomy patients. For stage I NSCLC, VATS should be considered the primary surgical approach.

Non-Small Cell Lung Cancer in Stages I–IIIB

To investigate therapeutic outcome of dose escalation ≥ 80 Gy in nonresected non-small cell lung cancer (NSCLC). 124 consecutive patients with histologically/cytologically proven NSCLC were enrolled. Tumor stage I, II, IIIA, and IIIB was diagnosed in 30, eight, 39, and 47 patients, respectively. 38 patients (31%) had weight loss > 5% during the 3 months before diagnosis. A median dose of 88.2 Gy (range 80.0-96.0 Gy), 69.3 Gy (63.0-88.0 Gy) and 56.7 Gy was applied to primary lesions, involved lymph nodes, and elective nodes (within a region of about 6 cm cranial to macroscopically involved nodes), respectively. Daily fractional ICRU doses of 2.0-2.2 Gy were delivered by the conformal target-splitting technique. 58 patients (47%) received induction chemotherapy, in median two cycles prior to radiotherapy. Median follow-up time of all patients was 19 months, of patients alive 72.4 months (69-121 months). The cumulative actual overall survival rate at 2 and 5 years amounts to 39% and 11.3%, respectively, resulting in a median overall survival time of 19.6 months. According to stages I, II, IIIA, and IIIB, the median overall survival times are 31.8, 31.4, 19.0, and 14.5 months, respectively. The locoregional tumor control rate at 2 years is 49%. Apart from one treatment-related death (pneumonitis), acute toxicity according to EORTC/RTOG scores was moderate: lung grade 2 (n = 7), grade 3 (n = 3); esophagus grade 1 (n = 11); heart grade 3 (n = 1, pericarditis). No late toxicity grade > 1 has been observed. Sequential, conventionally fractionated high-dose radiotherapy by conformal target splitting is well tolerated. The results for survival and locoregional tumor control seem to at least equalize the outcome of simultaneous chemoradiation approaches, which, at present, are considered "state of the art" for patients with nonresected NSCLC. A higher potential of radiation therapy might be reached by accelerated fractionation regimens.

Clinical study of non-18F-FDG positron imaging in lung cancer diagnosis and treatment

18F-FDG PET-CT is of great significance in non-small cell lung cancer diagnosis, staging, treatment options, efficacy evaluation and prediction of prognosis. But it has non-specificity, and its application is limited. In recent years, a number of new non-18F-FDG imaging agents is constantly developed and used clinically, which contributes to the PET -CT's further development and application in lung cancer. Key words: Lung neoplasms; Fluorodeoxyglucose F18; Tomography, X-ray computed

Effect of informing the diagnosis on depressive state in patients with non-small cell lung cancer of stage III.

As other tumors, unresectabe lung cancer can cause many psychological problems to the patients, such as depression and anxiety. The present paper aims to evaluate the status of depression before and after knowing the state of illness in patients with non-small cell lung cancer of stage III. 43 cases of newly diagnosed non-small cell lung cancer (NSCLC) with stage III were enrolled in the study. All the patients were distributed into three groups and given different intervention, that was completely unknowing the state of illness (group A), partly knowing the state of illness (group B) and completely knowing the state of illness (group C). Before and after knowing the state of illness, the depression status was assessed with the Hamilton depression rating scale for depression (HAMD). The mean total score of HAMD was unchanged both in group A and C, while significantly reduced in group B. The scores of anxiety somatization, cognitive disorder, retardation and feeling of despair were all significant lower in the group B after the patients partly knowing the state of illness, while the scores of sleep disorder was obviously higher in group C after the patients completely knowing the state of illness. The hypochondriasis was much severer in the group A, and in the group C, the score of suicidal idea became significantly higher after the patient knowing the diagnosis. Depression is very common in the NSCLC patients with stage III. Partly knowing the state of illness can obviously ameliorate the symptoms of depression, while completely knowing or completely unknowing the state of illness have no effect on relieving the patients' depression.

Efficacy of induction chemoradiotherapy with carboplatin and docetaxel for non-small cell lung cancer in stage III

18510 Background: The aim of this study was to assess the usefulness of induction chemoradiotherapy with carboplatin and docetaxel for non-small cell lung cancer (NSCLC) in stage III. Methods: The clinicopathologic efficacy in 24 patients (a mean age of 62.7(56–80), 19 men and 5 female, 14 adenocarcinoma and 10 squamous cell carcinoma, clinical stage: 16 IIIA and 8 IIIB) with clinical N2 (diagnosed under 6 mediastinoscope, 2 thoracoscope, 7 FDG-PET, 1 CT guided biopsy, and 1 TBNA) or T4 (invasion to vertebra body) who received induction therapy from April 2001 through October 2007 were evaluated. The patients who evaluated as SD or PR or CR after induction chemotherapy [2 cycles of carboplatin (AUC 6)+docetaxel (60 mg/m2) every monthly or 4 cycles of carboplatin (AUC 3)+docetaxel (30 mg/m2) every biweekly] with concurrent thoracic radiotherapy (TD 40 Gy/20 fr.), underwent surgical lung resection. Results: Total response rate of induction therapy was 83%, including down stage rate in 50%, surgical resection rate in 96% and complete resection rate in 69%. Pathologic effect was EF 1 in 9, EF 2 in 8 and EF 3 in 6. Median survival was 10.9 months in EF1 and 25 months in EF2. All EF 3 patients still alive with a mean survival of 60 months (32–76 months). From the point of survival time, there was a significant difference between EF 3 and EF 1 (p<0.05), but there was no significant difference in age, gender, PS, pathologic type, clinical stage and complete or incomplete resection. Conclusions: Pathologic effect was correlated with prognosis after induction therapy in stage III NSCLC. No significant financial relationships to disclose.

Surgery and Chemotherapy for Small Cell Lung Cancer in Stages I–II with or without Radiotherapy

To analyze the effectiveness of surgery and chemotherapy with or without radiotherapy in the management of limited small cell lung cancer (LSCLC) in stages I and II. 39 patients (median age 62 years) with LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA-IIB) who had a tumor resection and systematic lymph node dissection were reviewed retrospectively. The median follow-up period was 29 months. 35 patients (90%) received a median of four cycles of a platinum-containing chemotherapy postoperatively. 16 patients (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy). The median overall survival for all patients was 47 months, resulting in actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively. Distant metastases were found in 13 patients (33%) after a median of 16 months. Patients who received an adjuvant TRT showed a trend toward improved thoracic recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07) compared to those treated with surgery and chemotherapy only. Brain metastasis-free survival (p = 0.01) and overall survival (p = 0.01) were improved significantly in patients who received a PCI. Surgical tumor resection may be considered for carefully selected patients. Adjuvant chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently used in patients with positive lymph nodes (pN1), because the probability of a subclinical involvement of the mediastinal lymphatic system appears to be increased in these patients.

Phase I dose escalation study of vinorelbine and topotecan combination chemotherapy in patients with recurrent lung cancer

BackgroundA platinum doublet is the current standard treatment for good performance status patients with advanced non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC) with good performance status. However, platinum-based treatment may be associated with significant toxicities, therefore alternative platinum-free combinations should be investigated. Topotecan is a topoisomerase I inhibitor that exerts its cytotoxic effect through stabilization of the topoisomerase I-DNA complex. Preclinical data suggests synergy between topoisomerase I inhibitors and mitotic spindle poisons. Considerable hematologic toxicities have been reported with topotecan dosed for 5 consecutive days in combination with vinorelbine. Therefore, the aim of this study was to evaluate the optimal dosage and the maximal tolerated dose (MTD) of topotecan and vinorelbine in patients with relapsed or refractory non-small cell or small cell lung cancer administered on an alternate dosing schedule.MethodsFrom February, 2004 to March, 2007 eighteen patients with advanced or recurrent NSCLC or SCLC previously treated with chemotherapy were enrolled. Patients were heavily pretreated with 22% having received at least 3 prior lines of chemotherapy. Vinorelbine was administered at a fixed dose (20 mg/m2) and topotecan at escalating doses (2, 2.5, 3, 3.5, and 4 mg/m2) on days 1 and 8 every 21 days.ResultsThe MTD was not reached in any of the 5 cohorts, with only one dose limiting toxicity (DLT) occurring in cohort 4. Non-hematological toxicities were manageable. One patient had a partial response with four patients (27%) achieving stable disease. The median progression-free and overall survival for all patients, were 2.7 months (95% CI: 1.6, 9.1) and 10.5 months (95% CI: 4.2, 22.7), respectively.ConclusionVinorelbine and topotecan administered on days 1 and 8 every 21 days is well tolerated without any DLT seen with previously investigated topotecan schedules. This doublet provides a potentially active non-platinum containing doublet for the treatment of patients with advanced SCLC and NSCLC. Vinorelbine and topotecan should therefore be investigated in subsequent phase II studies at a dose of 20 mg/m2 and 4 mg/m2, respectively.Trial Registration NumberNCT00287963.

Communication and understanding of prognosis among stage IV lung and GI cancer patients

9024 Background: Patients' understanding of prognosis is essential to informed decision making about treatment options. There is little data on what prognostic information oncologists communicate to patients and what patients actually understand about their prognosis. Methods: We audio taped consultations between 90 newly diagnosed stage IV non small cell lung cancer patients and stage IV GI cancer patients and medical oncologists at academic teaching hospitals. Interactions were audio taped until patients arrived at a treatment decision. Audiotapes were digitized, coded and analyzed using the RIAS system. All conversation relating to prognosis was blocked, coded and analyzed. After meeting with an oncologist patients were surveyed about their understanding of prognosis and desire for information about life expectancy. Results: 276 patients were contacted of whom 190 consented to participate. 87 patients were ineligible, 13 patients withdrew from the study, and complete data were obtained on 90 patients. The mean age of participants was 62 years (±11), 65% were women. Analysis of the audiotapes revealed that in 78% of cases oncologists told patients that their cancer was not curable. When patients were surveyed, however, only 32% of those who were told that their cancer was not curable actually understood that there was no cure for their cancer (CI 0.19–0.45). Patients’ age, gender, education, and marital status were not associated with an understanding of prognosis. Patient factors associated with understanding of prognosis included a desire for good and bad medical information (CI 0.75–0.99; p&lt;0.0001), an interest in knowing the likelihood that treatment would cure their disease (CI 0.54–0.94; p&lt;0.01), and a belief that information about life expectancy would influence their medical decisions (CI 0.56–0.94; p&lt;0.01). Conclusion: In a majority of cases oncologists actually told patients that their cancer is not curable. Most patients, however, did not understand what was communicated. Patients’ understanding of prognosis is determined not only by what oncologists communicate, but also by patients’ desire for prognostic information. No significant financial relationships to disclose.