Staging in lung cancer: is 3 cm a prognostic threshold in pathologic stage I non-small cell lung cancer? A multicenter study of 1,020 patients

INTRODUCTION: Since 1974, a tumor size of 3 cm in diameter has been regarded as the prognostic threshold in the staging of bronchogenic carcinoma. OBJECTIVE: To study the prognostic behavior of surgical-pathologic tumor size in non-small cell lung cancer (NSCLC) with complete resection. DESIGN: Four-year multi-institutional prospective study from 1993 to 1997. PATIENTS: Consecutive cases of NSCLC in pathologic stages IA-IB (pIA-pIB) treated surgically with complete resection in hospitals belonging to the Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). METHODS: The Schoenfeld procedure was used to identify different prognostic groups, considering 1 cm as the measurement unit. RESULTS: Based on the 1,020 cases evaluated, four prognostic groups were identified: 0 to 2 cm (group A; n = 147), 2.1 to 4 cm (group B; n = 448), 4.1 to 7 cm (group C; n = 336), and > 7 cm (group D; n = 89). At 5 years, survival was 0.63 (95% confidence interval [CI], 0.58 to 0.68), 0.56 (95% CI, 0.53 to 0.59), 0.49 (95% CI, 0.46 to 0.52), and 0.38 (95% CI, 0.32 to 0.44) for groups A, B, C, and D, respectively. Differences between paired groups (log-rank) were significant: 0.0074 between groups A and B, 0.0048 between groups B and C, and 0.0034 between groups C and D. CONCLUSIONS: In initial stages (pIA-pIB) of NSCLC, the 3-cm value was not found to behave as a prognostic threshold; in this study, four surgical-pathologic tumor size groups were identified with strong prognostic differences: from 0 to 2 cm, from 2.1 to 4 cm, from 4.1 to 7 cm, and > 7 cm.     

Can bronchodilator response predict bronchial response to methacholine in preschool coughers?

The aim of the present study was to determine the relationship between bronchodilator response, assessed by interrupter resistance (Rint), and bronchial reactivity in preschool children with chronic cough. Thirty-eight children coughers (median age 5.0 years, range 2.8-6.4) were tested. Bronchodilator response was recorded within 4 months before methacholine challenge. Response to the latter was assessed using transcutaneous partial pressure of oxygen and Rint. Children were considered responders if a 20% fall in transcutaneous partial pressure of oxygen occurred during the bronchial challenge. Bronchodilator response was not different between responders (n = 24) and nonresponders (n = 14) [median (range) -0.11 (-0.44-0.09) vs. -0.08 (-0.21-0.10) kPa L(-1) sec; respectively]. However, none of the nonresponders had a bronchodilator response larger than -0.21 kPa L(-1) sec, this cutoff had a 100% positive and a 44% negative predictive value to predict a positive methacholine challenge. The relationship between bronchodilator response and bronchial methacholine responsiveness reached the limit of significance (P = 0.048). Furthermore, the magnitude of the bronchodilator response was correlated to the level of methacholine-induced level of bronchoconstriction (P = 0.01), and to the postchallenge bronchodilation (P = 0.04), all values expressed as % predicted. Moreover, the postbronchodilator Rint value obtained with preceding methacholine challenge was lower than the postbronchodilator value without preceding methacholine challenge in 71.4% (10/14) of the nonresponders and in only 33.3% (8/24) of the responders. Conclusions in preschool coughers bronchodilator response, assessed by the interrupter technique, was correlated to the bronchial responsiveness to methacholine. Non responders had a bronchodilator response not larger than -0.21 kPa L(-1) sec.     

Can symptoms predict endoscopic findings in GERD?

BACKGROUND: It is difficult to decide which patients with reflux symptoms require endoscopy. The aim of this study was to develop a scoring system to predict esophageal findings at endoscopy. METHODS: A consecutive sample of 1011 adult patients scheduled for upper endoscopy were asked to complete a validated symptom questionnaire. The endoscopy reports were abstracted. Individual logistic regression models were developed to predict esophagitis, Barrett's esophagus (long and short segment) and esophageal stricture, including Schatzki's ring. RESULTS: Reflux esophagitis was independently associated with heartburn frequency (p<0.0001) but not severity or duration (p>0.05). Barrett's esophagus was associated with the duration of acid regurgitation (p<0.005) but not with frequency or severity (p>0.05). Strictures were associated with dysphagia severity (p<0.0001) and duration (p<0.0001) but not frequency (p>0.05). At a sensitivity of 80%, the models had a specificity of 49% for esophagitis, 57% for Barrett's esophagus, and 68% for strictures. At a specificity of 80%, the sensitivities were 51% for esophagitis, 62% for Barrett's esophagus and 71% for strictures. CONCLUSIONS: Endoscopic findings were associated with distinct attributes of reflux symptoms. Symptoms are only modestly predictive of findings at endoscopy.     

Can micronucleus technique predict the risk of lung cancer in smokers?

Smoking is the main etiological factor in the carcinogenesis process of lung cancer. But genetically defined factors such as increased levels of oxidase enzymes or chromosome aberrations have been shown to correlate with the higher possibility of contracting lung cancer among smokers. In this study, chromosome aberrations measured by micronucleus (MN) technique following in vitro irradiation were investigated in peripheral blood lymphocytes of long term smokers with or without lung cancer. Our aim is to establish the role of MN scores in identifying the individuals who might develop cancer among smokers. Twelve lung cancer patients and appropriately matching 10 healthy controls were evaluated. Spontaneous and radiation induced MN frequencies were evaluated in the two groups. An increase in the amounts of MN after 3 Gy irradiation was observed in the patient and control group when compared to spontaneous frequencies. Absolute MN frequencies as a determinant of radiosensitivity were calculated by subtraction of spontaneous aberration frequencies from the frequencies that were obtained following 3 Gy of irradiation. Absolute MN frequency range was between 0.0116 and 0.3883 with the average value of 0.1114 +/- 0.0390 (SE) for the lung cancer patients, and was between 0.0216 and 0.2291 with the average value of 0.1410 +/- 0.0234 (SE) for the controls. When the comparison was made between the absolute MN frequencies of both groups, there was no difference (p=0.159) between the two groups. In our study, it can be concluded that radiation induced MN scores in peripheral blood lymphocytes of long term smokers do not predict the risk of lung cancer.     

The elderly patient with surgically resected non-small cell lung cancer - A distinct situation?

The worldwide population shift towards older ages will inevitably lead to more elderly patients being diagnosed with cancer. Lung cancer is the number one cause for cancer mortality and surgical resection is the treatment of choice whenever possible. This study investigates whether elderly patients with non-small cell lung cancer (NSCLC) are characterized by distinct clinical and pathologic features and different clinical course after resection. Special emphasis is placed on disease recurrence, which is an important, but rarely described parameter for biological tumor behavior. Sex, stage, histology, differentiation grade, smoking status, performance status, hemoglobin, C-reactive protein, lactate dehydrogenase, Ki-67 index, recurrent disease and overall survival were analyzed in 383 surgically resected NSCLC patients. Calculations were performed comparing patients <70 to ≥70 years. A postoperative follow-up period of 15 years enabled detailed correlations. Rate of disease recurrence and disease-free survival did not differ between any age groups and was not influenced by clinico-pathologic parameters. Elderly patients with a Ki-67 index of >3% were associated with significantly decreased overall survival time when compared to younger patients (36.3 and 47.3 months respectively, p=0.029). The biological behavior of NSCLC as reflected by characteristics of disease recurrence is similar for surgically resected patients among different age groups and does not warrant specific recommendations for the elderly surgical patient. The Ki-67 index offers prognostic information for overall survival in the elderly.     

Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan

AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan.METHODS: Using published data,a total of 252 patients,126 in the United Kingdom and 126 in Japan,aged 20 to 80 years,were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system.RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibili ty,wi th a weighted kappa value of 0.76(P 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio(OR) 0.22,95% confidence interval(CI) 0.11-0.43],older age(OR = 0.32,95%CI: 0.16-0.66) and endoscopic atrophy(OR = 0.10,95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy,assessed by cancer risk-oriented grading,was reproducible,with a kappa value of 0.81(95%CI: 0.75-0.87). Only nine patients(3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives.CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives,indicating that precancerous conditions can be identified during screening endoscopy,particularly in patients in western countries.     

Update on anti-angiogenic therapy in non-small cell lung cancer: Are we making progress?

Non-small cell lung cancer (NSCLC) remains a leading cause of death worldwide among patients diagnosed with malignancy. Despite new chemotherapy regimens and new cytotoxic combinations investigated in multiple clinical trials in recent years, no significant improvement in the prognosis of patients with lung cancer was achieved. The five-year survival rate for all patients diagnosed with NSCLC is about 15%, only 5% better than that of more than 40 years ago. New therapeutic approaches that target various different aspects of tumor progression and metastasis are of particular interest in to NSCLC patients. Drugs that block tumor vascularization (angiogenesis) or interfere with the activity of growth factor receptors and molecular pathways that are triggered by activation of these receptors are already used in clinical practice. In this review we will briefly discuss briefly the basic mechanisms of lung cancer angiogenesis, rationale for using drugs that block this process and present the most current recent data on their clinical efficacy.     

Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for surgical morbidity?

Background Increasing the rate of pathological complete remissions after neoadjuvant chemoradiation of rectal cancer has become a strategy to further improve the long-term oncological outcome of patients. This report evaluates the influence of preoperative intensified radiochemotherapy on the rate and outcome of surgical complications. Materials and Methods Patients with primary rectal cancer at stages cT3/4cNx or N+ without metastasis were preoperatively treated either with capecitabine and irinotecan or with capecitabine, irinotecan and ceutximab with a concurrent radiation (50.4 Gy). Surgery was scheduled 4–7 weeks after completion of the chemoradiation. Perioperative complications were prospectively documented during the patient’s hospital stay. Results Fifty-nine patients (median age 60; male/female: 46/13) undergoing surgery at a single center were analysed. The median distance of the tumour from the dentate line was 5 cm. The operations performed were low anterior resection (n=45), Hartmann’s procedure (n=4) and abdominoperineal resection (n=10). Total mesorectal excision with R0-resection was accomplished in all but one patients. Histopathological regression was described in four grades (0–3) as defined by the Japanese Society for Cancer of the Colon and Rectum. Tumors were called major responsive when assigned to the regression grades 3 or 2, and minor or nonresponsive at regression grades 1 or 0. In total, 33 patients (55.9%) had a regression grade 2 or 3. Among them, 12 patients showed a pathological complete response without any residual cancer cell (20.3%). Seven out of 45 patients (15.5%) with sphincter-preserving surgery suffered from suture breakdown; they all had previously shown a major response of the resected tumor. Two of them died during the hospital stay. Conclusions While in general, patients undergoing neoadjuvant intensified treatment suffer from a slight increase in surgical complications, this is markedly enhanced in patients with good treatment responses. Our results underline the oncological benefit of intensified neoadjuvant chemoradiation, but the severity of complications in low rectal anastomosis of patients with good response after neoadjuvant therapy should alert surgeons and oncologists. R.D. Hofheinz contributed equally with K. Horisberger to the study.     

Can we predict pathologic complete response before surgery for locally advanced rectal cancer treated with preoperative chemoradiation therapy?

Background

Pathologic complete response has been proven to have oncological benefits for locally advanced rectal cancer treated with chemoradiation therapy. The aims of this study are to analyze and determine the factors to predict pathologic complete response for patients treated with preoperative neoadjuvant therapy.

Methods

Patients with biopsy-proven, locally advanced rectal cancer were treated neoadjuvantly followed by radical surgical resection. Tumors were re-assessed after completing chemoradiation, including pelvic magnetic resonance images, colonoscopic examination, and re-biopsy. The results of examination were compared with the final pathologic status.

Results

A retrospective chart review of 166 patients was conducted. Twenty-five patients (15.1%) had pathologic complete response after chemoradiation. The 5-year overall survival rates were better in the complete response group than the residual tumor group (91.1% vs. 70.8%; P?=?0.047), and there were also significant differences in the 5-year disease-free survival rates between these two groups (91.1% vs. 70.2%; P?=?0.027). The prediction rates for pathologic complete response by re-biopsy, magnetic resonance images, and colonoscopy were 21.4%, 33.3%, and 53.8%, respectively. In addition, when we further combine the results of colonoscopic findings and re-biopsy, the prediction rate for pathologic complete response reached 77.8% (P?=?0.009).

Conclusions

Combining the results of the re-biopsy and post-treatment colonoscopic findings, we can achieve a good prediction rate for pathologic complete response. Post-treatment magnetic resonance images are not useful tools in predicting tumor clearance following chemoradiation.     

Real-time endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal staging of non-small cell lung cancer: how many aspirations per target lymph node station?

OBJECTIVE: The goal of this study was to determine the optimal number of aspirations per lymph node (LN) station during endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) for maximum diagnostic yield in mediastinal staging of non-small cell lung cancer (NSCLC) in the absence of rapid on-site cytopathologic examination. METHODS: EBUS-TBNA was performed in potentially operable NSCLC patients with mediastinal LNs accessible by EBUS-TBNA (5 to 20 mm). Every target LN station was punctured four times. RESULTS: We performed EBUS-TBNA in 163 mediastinal LN stations in 102 NSCLC patients. EBUS-TBNA confirmed malignancy in 41 LN stations in 30 patients. Two malignant LN stations were missed in two patients. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of EBUS-TBNA in predicting mediastinal metastasis were 93.8%, 100%, 100%, 96.9%, and 97.9%, respectively. Sample adequacy was 90.1% for one aspiration, and it reached 100% for three aspirations. The sensitivity for differentiating malignant from benign LN stations was 69.8%, 83.7%, 95.3%, and 95.3% for one, two, three, and four aspirations, respectively. The NPV was 86.5%, 92.2%, 97.6%, and 97.6% for one, two, three, and four aspirations, respectively. Maximum diagnostic values were achieved in three aspirations. When at least one tissue core was obtained by the first or second aspiration, the sensitivity and NPV of the first two aspirations were 91.9% and 96.0%, respectively. CONCLUSIONS: Optimal results can be obtained in three aspirations per LN station in EBUS-TBNA for mediastinal staging of potentially operable NSCLC. When at least one tissue core specimen is obtained by the first or second aspiration, two aspirations per LN station can be acceptable.