Long-term follow-up after first-line bronchoscopic therapy in patients with bronchial carcinoids.

BACKGROUND: Carcinoid of the lung is considered to be a low-grade malignancy. A subgroup presents as an endobronchial tumour. Surgical resection is considered the standard approach because of its metastatic potential and the possibility of an iceberg phenomenon for the endobronchial subgroup. Advances in non-invasive and minimally invasive technologies seem to justify a more lung parenchyma-sparing approach. METHODS: In patients presenting with bronchial carcinoids, initial bronchoscopic treatment (IBT) is first attempted for complete tumour eradication and sufficient tissue sampling for the proper differentiation of typical (TC) versus atypical (AC) histological type. Furthermore in cases with postobstruction problems the desobstruction is aimed at improving the patient's condition and by that alleviate surgery if that is needed. High resolution CT is performed 6 weeks post IBT to determine local tumour growth. Surgical resection follows in case of extraluminal disease, residual carcinoid inaccessible for IBT, or late recurrences not salvaged by repeat IBT. RESULTS: Minimum follow-up was 5 years from start of treatment for 112 patients (65 women, 47 men), with a median age of 47 years (range 16-77 years). Eighty-three patients (74%) had TC, and 29 (26%) AC. IBT only was ultimately curative in 42% of the cases (47/112): 42 TC, 5 AC. Disease-specific mortality including surgical mortality has been 2.6% (3/112) in patients with extraluminal carcinoids (3 AC). CONCLUSIONS: IBT, if with unsuccessful rescue surgery, is justifiable with excellent long-term outcome. IBT made surgery unnecessary in 42% of the cases. Iceberg phenomenon and metastatic potential in this group of patients with bronchial carcinoids are clinically insignificant.

Can quantifying free-circulating DNA in plasma be used to identify subjects with high-grade pre-invasive endobronchial lesions?

Increased concentrations of free-circulating plasma DNA (cpDNA) are observed in patients with invasive cancer, including lung cancer. Whether cpDNA levels are elevated in subjects with high-grade pre-invasive lesions of lung squamous cell carcinoma (SqCC) and whether its detection may be of value for identifying subjects at the highest risk of developing lung SqCC is currently unknown. The present study assessed cpDNA levels in subjects with high- and low-grade pre-invasive squamous endobronchial lesions relative to patients with clinically overt lung SqCC and healthy controls using real-time quantitative PCR methodology. The median cpDNA levels of the patients with invasive lung SqCC (n=16) were significantly higher compared with those of the healthy controls (n=16; P<0.01), whereas the cpDNA levels in the subjects with pre-invasive lesions (n=20) did not differ from those of the controls (P=0.29). The cpDNA levels in subjects with high-grade pre-invasive lesions were highly similar to those diagnosed with low-grade pre-invasive lesions (P=0.85). Our data suggest that cpDNA levels are not increased during the pre-invasive stages of lung squamous carcinogenesis.

Primary lung cancer after treatment of head and neck cancer without lymph node metastasis: is there a role for autofluorescence bronchoscopy?

BACKGROUND: Head and neck cancer (HNC) is the 5th most common cancer worldwide. As good locoregional tumor control can be achieved with current treatment strategies, patients who develop second primary tumors from field cancerization have poorer prognosis. OBJECTIVES: To determine if autofluorescence bronchoscopy (AF) played a role in the detection of second primary lung cancer (SPLC), and impact of SPLC on survival of patients with HNC and no cervical lymph node metastasis (N0). METHODS: Patients with HNC(N0) referred for symptoms and/or radiology suspicious for lung cancer were assessed with AF. Data on patient demographics, smoking, cancer characteristics, and outcome were prospectively collected. RESULTS: Fifty-one patients (44 males) with curatively treated HNC(N0) were evaluated. Median age was 70 years, all were current or former smokers of 35 pack years, and 25 had chronic obstructive lung disease. Over a median follow up of 60 months, 8 patients were diagnosed with synchronous and 26 with metachronous SPLC. Forty-two SPLC were found; 12 (29%) affected the tracheobronchial tree and 30 (71%) involved the lung parenchyma. Median time to metachronous SPLC was 22 months. Most of SPLC were surgically resectable. Five radiographically occult lung cancers detected by AF were successfully treated with endobronchial therapy. Lung cancer mortality was 24%. HNC patients who developed synchronous and metachronous SPLCs had significantly shorter survival (51 and 144 months) compared to those without (240 months) (p=0.0005). CONCLUSION: SPLC impacted negatively on the survival of patients with HNC. Close surveillance with AF and CT for SPLC combined with aggressive treatment of early stage lung cancer might be a strategy to improve outcome.

Surgical treatment for octogenarians with lung cancer: results from a population-based series of 124 patients.

INTRODUCTION: With the increasing life span in the Western world, the number of octogenarians with resectable, localized non-small cell lung cancer is increasing. Previous reports on the outcome of surgery for lung cancer in octogenarians were mainly derived from single institutions. In contrast, this study presents results for all hospitals in a region of 3 million inhabitants. METHODS: General data on all patients diagnosed with lung cancer in the period 1989 to 2004 were retrieved from the Amsterdam Cancer Registry. Incidence and type of treatment were tabulated and tested for significance with chi2 analysis. Survival was calculated using actuarial analysis. Absolute and relative survival for octogenarians relative to other age groups and relative to other treatment modalities in octogenarians with clinical stage I/II lung cancer was performed. RESULTS: Non-small cell lung cancer was diagnosed in 1993 octogenarians (14% of all lung cancer patients). One hundred twenty-four patients (6%) underwent surgery. Five patients died within 30 days of surgery (4%). Relative survival after 1, 2, and 5 years was 83%, 69%, and 47%, respectively. These relative survival figures are comparable with other age groups. There was a survival benefit for surgical resection versus radiotherapy and other or no treatment (relative 5-year survival of 47% versus 3% and 0%, respectively). CONCLUSIONS: Resection rates in octogenarians are low but satisfactory postoperative mortality and acceptable survival suggest that selection criteria should be adapted. Until effective alternative treatment becomes available, surgical resection, preceded by a thorough preoperative assessment, should be considered in the "old but fit" octogenarian.

Dual digital video-autofluorescence imaging for detection of pre-neoplastic lesions.

AIM: The incorporation of autofluorescence (AF) to white light bronchoscopy has led to improved sensitivity for the detection of pre-neoplastic lesions in the airways. However, AF has difficulty distinguishing benign epithelial changes such as bronchitis, previous biopsy, and airway fibrosis from pre-invasive lesions, which necessitates extensive biopsy. This frequently results in longer procedural time and need for additional sedation that may compromise patient safety, increase the risk of bronchospasm, and bleeding from multiple endobronchial biopsies. We postulate that dual imaging with simultaneous video and AF bronchoscopy of the tracheobronchial tree could improve the low specificity observed with AF in the detection of pre-invasive lesions, leading to targeted biopsy, good correlation with pathological diagnosis and shorter procedural time. METHODS: Forty-eight patients with known or suspected of lung cancer underwent video and AF bronchoscopy, which were provided as real-time dual images with SAFE 3000 (Pentax, Tokyo) between March and August 2006. Biopsy specimens were taken from all suspicious areas with two random specimens from normal areas. Values were expressed as median and range, and p<0.05 was considered statistically significant. RESULTS: Twenty-five suspicious sites were detected by dual imaging bronchoscopy, and 126 endobronchial biopsies were evaluated, of which 22 (17.5%) were graded as moderate dysplasia and worse. Sensitivity and specificity of dual imaging for the detection of high-grade dysplasia were 86% and 94%, respectively, with good correlation between bronchoscopic assessment and pathology (r=0.77, p<0.0001). However, there were three random biopsy specimens obtained from normal or abnormal sites that showed severe dysplasia in two and moderate dysplasia in one. Median time taken for airway examination was 4 min (range, 4-4.8), and 5 min (range, 4-5) for biopsy, giving a total procedural time of 9 min (range, 8-10). There were no procedure-related complications noted. CONCLUSION: Dual imaging that allows simultaneous real-time assessment of the lesion with video and AF bronchoscopy not only achieves satisfactory sensitivity for the detection of pre-neoplastic lesions, importantly it improves specificity by allowing targeted biopsy, which has led to a marked decrease in procedural time and better patient safety.

Initial bronchoscopic treatment for patients with intraluminal bronchial carcinoids.

OBJECTIVE: Carcinoid of the lung is considered low-grade malignancy, and less invasive treatment may therefore be considered. We analyzed the long-term outcome of initial bronchoscopic treatment in patients with intraluminal bronchial carcinoids. METHODS: Initial bronchoscopic treatment was applied to improve presurgical condition, to obtain tissue samples for proper histologic classification, and to enable less extensive parenchymal resection. For intraluminal bronchial carcinoid, complete tumor eradication with initial bronchoscopic treatment was attempted. High-resolution computed tomography in addition to bronchoscopy was used to determine intraluminal versus extraluminal tumor growth. Surgery followed in cases of atypical carcinoid, residue, or recurrence. RESULTS: Seventy-two patients, 43 of them female, have been treated (median age 47 years, range 16-80 years). Median follow-up has been 65 months (range 2-180 months). Fifty-seven (79%) had typical carcinoids and 15 (21%) had atypical carcinoids. Initial bronchoscopic treatment resulted in complete tumor eradication in 33 of 72 cases (46%), 30 typical and 3 atypical. Thirty-seven of 72 cases (51%), 11 atypical, required surgery (2 for late detected recurrences). Two patients had metastatic atypical carcinoid, 1 already at referral. Of the 6 deaths, 1 was tumor related. CONCLUSIONS: Initial bronchoscopic treatment is a potentially more tissue-sparing alternative than immediate surgical resection in patients with intraluminal bronchial carcinoids. For successful tumor eradication with initial bronchoscopic treatment in central carcinoids, assessment of intraluminal versus extraluminal growth may be of much more importance than histologic division between typical and atypical carcinoid. Disease-specific mortality is low, and long-term outcome has been excellent. Implementation of initial bronchoscopic treatment had no negative impact on surgical treatment outcome.

Detection and staging of preinvasive lesions and occult lung cancer in the central airways with 18F-fluorodeoxyglucose positron emission tomography: a pilot study.

PURPOSE: To evaluate the role of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in radiologically occult preinvasive lesions and lung cancer in the central airways. EXPERIMENTAL DESIGN: Twenty-two patients with 24 preinvasive lesions and early squamous cell cancer (SCC) being occult on high-resolution computed tomography were studied. All lesions were diagnosed based on histology sampled using autofluorescence bronchoscopy. FDG-PET findings were correlated with WHO histologic classification. FDG-PET was considered true-positive when the final diagnosis was SCC and true-negative when the lesions were classified as severe dysplasia or less. RESULTS: FDG-PET was true-positive in 8 of 11 and true-negative in 11 of 13 cases corresponding with a sensitivity of 73% [95% confidence interval (CI), 0.43-0.91] and specificity of 85% (95% CI, 0.57-0.97). Positive and negative predictive values were 80% (95% CI, 0.48-0.96) and 79% (95% CI, 0.52-0.93), respectively. CONCLUSIONS: Our very preliminary data suggest that FDG-PET might be useful for the evaluation of early central airway lesions, being positive in most SCC and negative in cases of severe dysplasia. Validation in a larger multicenter study is needed.

Cost-effectiveness of early intervention: comparison between intraluminal bronchoscopic treatment and surgical resection for T1N0 lung cancer patients.

BACKGROUND: For patients with early-stage lung cancer (ESLC) and severe comorbidities, the cost-effectiveness of early intervention may be reduced by screening and treatment-related morbidity and mortality in addition to the risk for non-cancer-related deaths. OBJECTIVES: The use of bronchoscopic treatment (BT) for centrally located ESLC as minimally invasive technique has raised questions whether this approach will be more cost-effective than standard surgical resection in the above-mentioned cohort of patients. METHODS: The cost-effectiveness of BT of 32 medically inoperable patients with intraluminal tumor has been compared to a matched control group of surgically treated stage IA cancer patients. RESULTS: Median follow-up after BT for ESLC has been 5 years (range 2-10) versus 6.7 years (range 2-10) for the surgical group. Five patients (16%) developed subsequent primaries/local recurrences after BT versus 4 (12.5%) in the surgical group. The respective percentages of actual survival during follow-up have been 50 and 41%, non-lung-cancer-related death 22 and 31% and lung-cancer-related death 28% in both groups, respectively. So far, the average costs per individual for early management by BT have been Euro 22,638 by surgery, and total expenses have been Euro 209,492 and Euro 724,403, respectively. CONCLUSIONS: Despite the worse initial health status of patients treated with BT, actual survival rates and costs for early intervention underscore the superior cost-effectiveness of BT as early intervention in properly selected individuals with ESLC in the central airways.