Search PubMed⌕ Search

Biomedical subjects

Frank C Detterbeck

Publications and source records attributed to Frank C Detterbeck.

At least 19 recordsLinked to original sources

Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database.

PURPOSE: To investigate the association between survival and postoperative radiotherapy (PORT) in patients with resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database, we selected patients with stage II or III NSCLC who underwent a lobectomy or pneumonectomy. Only those patients coded as receiving PORT or observation were included. To account for perioperative mortality, we excluded patients who survived less than 4 months. As a result of our inclusion criteria, we selected a total of 7,465 patients, with a median follow-up time of 3.5 years for patients still alive. RESULTS: Predictors for the use of PORT included age less than 50 years, higher American Joint Committee on Cancer stage, T3-4 tumor stage, larger tumor size, advanced node stage, greater number of lymph nodes involved, and a ratio of lymph nodes involved to lymph nodes sampled approaching 1.00. On multivariate analysis, older age, T3-4 tumor stage, N2 node stage, male sex, fewer sampled lymph nodes, and greater number of involved lymph nodes had a negative impact on survival. The use of PORT did not have a significant impact on survival. However, in subset analysis for patients with N2 nodal disease (hazard ratio [HR] = 0.855; 95% CI, 0.762 to 0.959; P = .0077), PORT was associated with a significant increase in survival. For patients with N0 (HR = 1.176; 95% CI, 1.005 to 1.376; P = .0435) and N1 (HR = 1.097; 95% CI, 1.015 to 1.186; P = .0196) nodal disease, PORT was associated with a significant decrease in survival. CONCLUSION: In a population-based cohort, PORT use is associated with an increase in survival in patients with N2 nodal disease but not in patients with N1 and N0 nodal disease.

Adult↗

Smoking is associated with increased telomerase activity in short-term cultures of human bronchial epithelial cells.

Telomerase plays an important role in the maintenance of telomere ends in normal and tumor cells and ectopic expression can immortalize human bronchial epithelial (HBE) cells. We assessed telomerase activation, growth properties and methylation status in the hTERT promoter in a panel of HBE cell cultures in relation to smoking and previous lung cancer history. HBE cells were obtained from a total of 26 subjects, six of whom were lifelong non-smokers, while 20 subjects had a smoking history, including seven who had lung carcinoma. Telomerase activity was determined using the telomeric repeat amplification protocol (TRAP). Maximum passage number and time to senescence were also determined through extended culturing. The distribution of the telomerase activity between ever-smokers and never-smokers was significantly different (P=0.03, F-test), and there was a strong correlation between telomerase activity and the number of pack-years smoked (P=0.0012, F-test for slope). A small difference in telomerase activity was observed according to lung cancer status (P=0.02, F-test). Telomerase activity was not correlated with maximum passage number after extended culturing or with time to senescence. None of the HBE cultures demonstrated methylation of the hTERT promoter. Our results indicate an association between tobacco carcinogen exposure and telomerase activity in normal bronchial epithelium, although a causative role of tobacco smoking in the (re)activation of telomerase can not be proven. An increase in telomerase activity in normal bronchial epithelium might extend the lifespan of cells at risk for malignant transformation, and thus contribute to lung carcinogenesis.

Adolescent↗

Invited commentary.

Explore the source record for details and available documents.

Carcinoma, Non-Small-Cell Lung↗

Clinical value of the WHO classification system of thymoma.

Since the World Health Organization (WHO) histologic classification system for thymoma was introduced in 1999, several centers have published results using this system. This review of the published experience with the WHO system examines whether the classification is reproducible, whether the WHO system defines clinically distinct patient groups, assesses the independent prognostic value of the WHO type by multivariate analysis, and discusses the impact of the WHO system on clinical management decisions.

Aged↗

Airway complications after pulmonary resection.

Airway complications following pulmonary resection remain a challenging problem. A high degree of clinical suspicion, contrasted CT imaging, and early reoperation are crucial in preserving viable lung parenchyma following the anatomic compromise of lobar torsion. Likewise, early recognition and expeditious drainage of the pleural space in the setting of bronchial dehiscence may help prevent the aspiration pneumonia and consequent respiratory failure that is the leading cause of death in this patient population; A variety of interventions to manage stump dehiscence are possible, but successful management still remains difficult and requires an individualized approach. Attention to technical details and avoidance of extensive dissection and tension should yield acceptably low rates of postoperative stenosis following bronchoplastic resection. These common themes of precise surgical technique, vigilance in the perioperative period, and classic sound judgment in addressing problems effectively and expeditiously remain pivotal in the minimization of sequelae from morbid airway complications.

Bronchi↗

Evaluation and definitive management of medically inoperable early-stage non-small-cell lung cancer. Part 1: Assessment and conventional radiotherapy.

Lung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading cause of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this two-part article. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities will be addressed in part 2.

Carcinoma, Non-Small-Cell Lung↗

Evaluation and definitive management of medically inoperable early stage non-small-cell lung cancer. Part 2: newer treatment modalities.

Lung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading causes of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this article, which appeared in last month's issue. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities are addressed in part 2.

Carcinoma, Non-Small-Cell Lung↗

Assessment of real-time 3D visualization for cardiothoracic diagnostic evaluation and surgery planning.

RATIONALE AND OBJECTIVES: Three-dimensional (3D) real-time volume rendering has demonstrated improvements in clinical care for several areas of radiological imaging. We test whether advanced real-time rendering techniques combined with an effective user interface will allow radiologists and surgeons to improve their performance for cardiothoracic surgery planning and diagnostic evaluation. MATERIAL AND METHODS: An interactive combination 3D and 2D visualization system developed at the University of North Carolina at Chapel Hill was compared against standard tiled 2D slice presentation on a viewbox. The system was evaluated for 23 complex cardiothoracic computed tomographic (CT) cases including heart-lung and lung transplantation, tumor resection, airway stent placement, repair of congenital heart defects, aortic aneurysm repair, and resection of pulmonary arteriovenous malformation. Radiologists and surgeons recorded their impressions with and without the use of the interactive visualization system. RESULTS: The cardiothoracic surgeons reported positive benefits to using the 3D visualizations. The addition of the 3D visualization changed the surgical plan (65% of cases), increased the surgeon's confidence (on average 40% per case), and correlated well with the anatomy found at surgery (95% of cases). The radiologists reported fewer and less major changes than the surgeons in their understanding of the case due to the 3D visualization. They found new findings or additional information about existing findings in 66% of the cases; however, they changed their radiology report in only 14% of the cases. CONCLUSION: With the appropriate choice of 3D real-time volume rendering and a well-designed user interface, both surgeons and radiologists benefit from viewing an interactive 3D visualization in addition to 2D images for surgery planning and diagnostic evaluation of complex cardiothoracic cases. This study finds that 3D visualization is especially helpful to the surgeon in understanding the case, and in communicating and planning the surgery. These results suggest that including real-time 3D visualization would be of clinical benefit for complex cardiothoracic CT cases.

Confidence Intervals↗

Of buffaloes, horseshoes, and having no connections.

We report a patient with multiple congenital pulmonary anomalies, including unilateral pulmonary artery agenesis with an atretic left lung, "buffalo chest," and a variant of the anatomic anomaly "horseshoe lung," discovered during double lung transplantation. Both hemithoraces were filled by the right lung. The right chest was occupied primarily by the anatomic right lower lobe, and the left chest by the right middle lobe at the apex and the anatomic right upper lobe at the base.

Abnormalities, Multiple↗

Efficacy of methods of intercostal nerve blockade for pain relief after thoracotomy.

Intercostal nerve blockade for postthoracotomy pain relief can be accomplished by continuous infusion of local anesthetics through a catheter in the subpleural space or through an interpleural catheter, by cryoanalgesia, and by a direct intercostal nerve block. A systematic review of randomized studies indicates that an extrapleural infusion is at least as effective as an epidural and significantly better than narcotics alone. The other techniques of intercostal blockade do not offer an advantage over narcotics alone.

Anesthetics, Local↗

Chromosomal abnormalities in bronchial epithelium from smokers, nonsmokers, and lung cancer patients.

The identification of individuals who are at greatest risk of developing lung cancer would greatly improve diagnosis and possibly lead to early treatment. To study the use of karyotypes for this purpose, we used short-term human bronchial epithelial (hBE) cell cultures from nonsmokers, smokers, and lung cancer patients. Twenty-five metaphases were scored for hBE cell cultures obtained from 32 patients: 8 were nonsmokers, and 24 had a history of smoking (of whom 11 had had lung cancer surgery). The number of abnormal metaphases ranged from 0 to 4 per cell culture. No overall differences in the number of abnormal metaphases were observed between nonsmokers and smokers or between lung cancer patients and non-lung cancer patients. The most commonly observed abnormalities were structural changes in chromosome 1 (six cultures), loss of chromosome 17 (six cultures), and trisomy of chromosome 20 (three cultures). These specific alterations were found almost exclusively in patients with a history of tobacco smoking. The results did not indicate that general chromosomal abnormalities are a useful marker for tobacco smoke exposure or cancer risk.

Adolescent↗

Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer.

PURPOSE: We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing. METHODS: Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods. RESULTS: Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS. CONCLUSION: A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.

Carcinoma, Non-Small-Cell Lung↗

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PURPOSE: Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. PATIENTS AND METHODS: Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. RESULTS: Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.

Antineoplastic Combined Chemotherapy Protocols↗