Treatment outcome, toxicity, and quality of life of patients with bronchus-associated lymphoid tissue lymphoma.

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p = .160), 30.8% (p = .017), and 31.3% (p = .039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma.

BALT lymphoma has a favorable prognosis but a persistent progression and relapse risk.Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life.

Explainable artificial intelligence (XAI) for exploring spatial variability of lung and bronchus cancer (LBC) mortality rates in the contiguous USA.

Machine learning (ML) has demonstrated promise in predicting mortality; however, understanding spatial variation in risk factor contributions to mortality rate requires explainability. We applied explainable artificial intelligence (XAI) on a stack-ensemble machine learning model framework to explore and visualize the spatial distribution of the contributions of known risk factors to lung and bronchus cancer (LBC) mortality rates in the conterminous United States. We used five base-learners-generalized linear model (GLM), random forest (RF), Gradient boosting machine (GBM), extreme Gradient boosting machine (XGBoost), and Deep Neural Network (DNN) for developing stack-ensemble models. Then we applied several model-agnostic approaches to interpret and visualize the stack ensemble model's output in global and local scales (at the county level). The stack ensemble generally performs better than all the base learners and three spatial regression models. A permutation-based feature importance technique ranked smoking prevalence as the most important predictor, followed by poverty and elevation. However, the impact of these risk factors on LBC mortality rates varies spatially. This is the first study to use ensemble machine learning with explainable algorithms to explore and visualize the spatial heterogeneity of the relationships between LBC mortality and risk factors in the contiguous USA.

Effective Radiotherapy in Tracheobronchial Adenoid Cystic Carcinoma With Positive Surgical Margin.

BACKGROUND: The study aimed to evaluate the role of postoperative radiotherapy (PORT) in the treatment of trachea and main bronchus adenoid cystic carcinoma (ACC) with a positive surgical margin. METHODS: Patients with pathologically confirmed trachea or main bronchus ACC operated on at Shanghai Chest Hospital were enrolled. Survival, univariate, and multivariate analyses were performed. The χ2 test was applied to analyze the failure patterns among different groups (R0/0: negative margin resection without PORT; R1/0: positive margin resection without PORT; R1/1: positive margin resection with PORT). RESULTS: From January 2001 to December 2014, 77 patients were deemed eligible for the study. Pairwise comparisons showed that the overall survival rate of group R1/1 was comparable to that of group R0/0 (P = .438), and significantly longer than the rate of group R1/0 (P = .032). Additionally, the local disease-free survival rate of group R1/1 was much higher than that of group R0/0 (P = .023) and R1/0 (P = .001). Cox multivariate analysis identified the radiologic feature (P = .012) and PORT (P = .006) as significantly favorable prognostic factors for locoregional disease-free survival. By contrast, for overall survival, PORT (P = .032) was the only corresponding variable identified by univariate analysis. Furthermore, PORT significantly decreased the locoregional recurrence rate (P = .002) but not distant metastases (P > .999). CONCLUSIONS: PORT helped patients with tracheobronchial ACC and microscopic positive surgical margins to achieve a similar outcome as patients with complete resection. R0 resection may not be necessary for tracheobronchial ACC if it is difficult to be completely resected.

NEP-Score Thresholds Predict Survival of Patients With Bronchial Carcinoids.

Survival prognostic markers are extremely needed to better define therapeutic strategies in patients with bronchial carcinoids (BC). We aim to verify the applicability of the NEP-Score in a homogeneous BC cohort and identify a derivative prognostic marker, the NEP-Score at diagnosis (NEP-D) that does not consider new metastases during follow-up. Sixty-four patients (38 females, and 26 males, mean age at diagnosis 58.9 ± 1.7 years) with BC were retrospectively evaluated. NEP-Score was calculated at the end of follow-up (NEP-T). A derivative score, the NEP-Score at diagnosis (NEP-D) that does not consider new metastases during follow-up, was then assessed. Patients were subdivided according to their living status at the end of follow-up. A NEP-Score threshold was investigated to predict survival. Mean NEP-T and mean NEP-D were significantly lower in live patients at end of follow-up. A NEP-T cut-off >138 significantly predicts survival. Atypical BC relapsed more frequently than Typical BC. Male gender and previous malignancy were negative prognostic factors for survival. We confirmed NEP-Score applicability in BC and NEP-D utility, being the latter a simple, quick, and cheap prognostic score that can help clinicians in decision making. The identified NEP-D threshold can predict NEN aggressiveness and may be used to define the best personalized therapeutic strategy. In this context, a validation study is needed.

Pediatric airway tumors: A report from the International Network of Pediatric Airway Teams (INPAT).

OBJECTIVE: Primary tracheobronchial tumors (PTTs) are rare heterogeneous lesions arising from any part of the tracheobronchial tree. Nonspecific symptoms may lead to delayed diagnosis that requires more aggressive surgical treatment. An analysis of cases collected by the International Network of Pediatric Airway Team was undertaken to ensure proper insight into the behavior and management of PTTs. METHODS: Patients <18 years of age with a histological confirmation of PTT diagnosed from 2000 to 2015 were included in this multicenter international retrospective study. Medical records, treatment modalities, and outcomes were analyzed. The patient presentation, tumor management, and clinical course were compared between malignant and benign histotypes. Clinical and surgical variables that might influence event-free survival were considered. RESULTS: Among the 78 children identified, PTTs were more likely to be malignant than benign; bronchial carcinoid tumor (n = 31; 40%) was the most common histological subtype, followed by inflammatory myofibroblastic tumor (n = 19; 25%) and mucoepidermoid carcinoma (n = 15; 19%). Regarding symptoms at presentation, wheezing (P = 0.001) and dyspnea (P = 0.03) were more often associated with benign growth, whereas hemoptysis was more frequently associated with malignancy (P = 0.042). Factors that significantly worsened event-free survival were age at diagnosis earlier than 112 months (P = 0.0035) and duration of symptoms lasting more than 2 months (P = 0.0029). CONCLUSION: The results of this international study provide important information regarding the clinical presentation, diagnostic workup, and treatment of PTTs in children, casting new light on the biological behavior of PTTs to ensure appropriate treatments. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E243-E251, 2020.

The role of surgery for atypical bronchopulmonary carcinoid tumor: Development and validation of a model based on Surveillance, Epidemiology, and End Results (SEER) database.

OBJECTIVES: The rarity of atypical carcinoid (AC) of lung and the lack of prospective clinical trials lead to limited knowledge of its biology, treatment information and prognosis. The current study analyzed AC patients from the Surveillance, Epidemiology, and End Results (SEER) database to better understand the clinical characteristics of this disease and build a prognostic nomogram for clinical practice. MATERIALS AND METHODS: A total of 507 AC patients with pathological confirmation from SEER database were performed with univariate Cox regression analyses for both overall survival (OS) and lung cancer specific survival (LCSS) analyses. Of the 507 observations, 464 were used in the multivariable Cox proportional hazards model as training cohort of new nomogram. A new nomogram was constructed based on the training cohort and validated by an external validation cohort to predict the 3-, 5- and 10-year OS of ACs. The accuracy and clinical practicability were separately tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Lobectomy and segmental resection were found to be protective factors for AC patients. Age, primary tumor size, N stage, M stage, surgery and regional lymph nodes examination were shown as significant prognostic factors in Cox regression analyses and included in the nomogram as predictors. The C-index in the training cohort for 3-, 5-, and 10-year OS were 0.722, 0.737 and 0.712, respectively. The internal and external calibration plots for predictions of the 3-, 5-, and 10-year OS were in excellent agreement. An online webserver was built based on the proposed nomogram for convenient clinical use. CONCLUSION: AC patients with lobectomy or segmental resection tended to have better OS and LCSS. A nomogram was constructed and validated to predict the OS for AC patients and to provide accurate and individualized survival predictions.

Associations of county-level cumulative environmental quality with mortality of chronic obstructive pulmonary disease and mortality of tracheal, bronchus and lung cancers.

Chronic obstructive pulmonary disease (COPD) and tracheal, bronchus, and lung (TBL) cancers are among the leading causes of mortality worldwide. Many environmental factors have been linked to COPD and TBL cancers. This study examined the associations of cumulative environmental quality indices with COPD mortality and TBL cancers mortality, respectively. Environmental Quality Index (EQI) was constructed to represent cumulative environmental quality for the overall environment and 5 major environmental domains (e.g., air, water, built). Associations of each EQI indices with COPD mortality and TBL cancers mortality, across 3109 counties in the 48 contiguous states of the US, were examined using simultaneous autoregressive (SAR) models. Stratified analyses were conducted in females versus males and according to rural-urban continuum codes (RUCC) to assess the heterogeneity across the overall population. Overall poor environmental quality was associated with a percent difference (PD) of 0.75 [95% confidence intervals (95% CI), 0.46, 1.05] in COPD mortality and an PD of 1.22 (95% CI, 0.97, 1.46) in TBL cancers mortality. PDs were higher in females than in males for both COPD and TBL cancers. The built domain had the largest effect on COPD mortality (PD, 0.85; 95% CI, 0.58, 1.12) while the air domain had the largest effect on TBL cancers mortality (PD, 1.54; 95% CI, 1.31, 1.76). The EQI-mortality associations varied among different RUCCs, but no consistent trend was found. This result suggests that poor environmental quality, particularly poor air quality and built environment quality may increase the mortality risk for COPD and that for TBL cancers. Females appear to be more susceptible to the effect of cumulative environmental quality. Our findings highlight the importance of improving overall and domain-specific cumulative environmental quality in reducing COPD and TBL cancer mortalities in the United States.

Poor survival of non-small-cell lung cancer patients with main bronchus tumor: a large population-based study.

Aim: In this study, we evaluated the association between tumor location and prognosis in non-small-cell lung cancer patients. Patients & methods: The SEER database was used to screen for suitable patients using our inclusion criteria. The χ2 test was used to compare baseline patient characteristics and the Kaplan-Meier method as well as the log-rank test were used to compare survival differences. At last, univariate and multivariate Cox proportional hazards regression models were used to analyze the influence of different variables on overall survival. Results: The results found no significant difference in overall survival between patients in laterality (p = 0.071). However, patients with main bronchial tumors had worse prognosis than tumors at other locations (p < 0.001). Our results also showed that tumor location including main bronchus, upper lobe, middle lobe, lower lobe and overlapping lesion was a significant factor affecting survival (p < 0.001). Subgroup analysis revealed that regardless of histology or M stage, patients with main bronchial tumors had a worse survival compared with other tumor locations (all; p < 0.001). Interestingly, we found that patients with tumor main bronchial tumors were more likely to be squamous carcinoma and terminal Tumor, Node, Metastasis stage (all; p < 0.001). Conclusion: Non-small-cell lung cancer patients' prognosis was related to the tumor location. And patients with tumors located in main bronchus had worse outcomes than those located in other locations. Tumor primary site should be considered in treatment management and prognosis assessment.

Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence.

BACKGROUND: Bronchopulmonary neuroendocrine tumours are divided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC). AIM: To thoroughly describe a cohort of 252 patients with TC, AC and LCNEC (SCLC excluded). MATERIAL AND METHODS: Collection of data from 252 patients referred to and treated at Rigshospitalet 2008-2016. Data was collected from electronic patient files and our prospective NET database. Statistics were performed in SPSS. RESULTS: 162 (64%) had TC, 29 (12%) had AC and 61 (24%) had LCNEC. Median age at diagnosis was 69 years (range: 19-89) with no difference between genders. Thoraco-abdominal CT was performed in all patients at diagnosis. FDG-PET/CT was performed in 207 (82%) at diagnosis and was positive in 95% of the entire cohort, with no difference between tumour types. Synaptophysin was positive in 98%, chromogranin A in 92% and CD56 in 97%. Mean Ki67 index was 5% in TC, 16% in AC and 69% in LCNEC (p < 0.001). Metastatic disease was found in 4% of TC, 27% of AC and 58% of LCNEC at time of initial diagnosis (p < 0.001). In total 179 patients (71%) underwent surgical resection; TC: 87%, AC: 72% and LCNEC: 28% (p < 0.001). Of the resected patients, 11 (6%) had recurrence. Five-year survival rate was 88% for TC, 63% for AC and 20% for LCNEC. CONCLUSION: In this comprehensive study of a cohort of 252 patients, one of the largest until date, with TC, AC and LCNEC, the gender distribution showed female predominance with 68%. FDG-PET/CT was positive in 95% of the patients independent of tumour type, which confirms that FDG-PET/CT should be a part of the preoperative work-up for TC, AC and LCNEC. Tumour type was the single most potent independent prognostic factor.

CP*Trends: An Online Tool for Comparing Cohort and Period Trends Across Cancer Sites.

Cohort or period components of trends can provide a rationale for new research or point to clues on the effectiveness of control strategies. Graphical display of trends guides models that quantify the experience of a population. In this paper, a method for smoothing rates by single year of age and year is developed and displayed to show the contributions of period and cohort to trends. The magnitude of the contribution of period and/or cohort in a model for trends may be assessed by the percentage of deviance explained and the relative contributions of cohort (C) and period (P) individually, known as the C-P score. The method is illustrated using Surveillance, Epidemiology, and End Results data (1975-2014) on lung and bronchial cancer mortality in females and prostate and colorectal cancer incidence in males. Smoothed age-period and age-cohort rates provide a useful first step in studies of etiology and the impact of disease control without imposing a restrictive model. We found that, in this data set, cohort predominates for female lung and bronchial cancer and period predominates for male prostate cancer. However, the effects change with age for male colorectal cancer incidence, indicating an age shift in relevant exposures. These methods are applied on an interactive website for both incidence and mortality at over 20 cancer sites in the United States.

Tracheobronchial Adenoid Cystic Carcinoma: 50-Year Experience at the National Cancer Center, China.

BACKGROUND: Only a small series of studies has investigated primary tracheobronchial adenoid cystic carcinoma (TACC), and its prognosis and prognostic factors have not been well defined. METHODS: Patients with TACC diagnosed histologically between January 1967 and December 2017 at our institution were retrospectively analyzed. RESULTS: A total of 191 consecutive patients were included in our study. One hundred sixty-three patients underwent surgery, while the remaining 28 patients received nonoperative therapy. The 5-year, 10-year, and 20-year survival rates of the surgical group were 85.00%, 63.40%, and 47.00%, while the 5-year and 10-year survival rates of the nonoperative group were 63.70% and 46.40%, respectively. The multivariate analysis showed that the complaint duration (<7 months or ≥7 months) and treatment methods (R0 resection, R1 resection with radiotherapy, R1 resection without radiotherapy) were independent prognostic factors for disease-free survival of the R0/1 (resection with no residual tumor or microscopic residual tumor) resected patients, while the tumor size (≤3 cm or >3 cm) and treatment methods were independent prognostic factors for the overall survival. Sixty-four (45.1%) patients in the R0/1 group experienced recurrence/progression, and compared with chemotherapy or supportive treatment, local treatment significantly improved the prognosis of these patients (P < .050). CONCLUSIONS: The complaint duration and tumor size are independent prognostic factors for disease-free survival and overall survival in TACC, respectively. Complete resection of the primary tumor, postoperative adjuvant radiotherapy for patients with positive margins, and local treatment after postoperative recurrence or progression may contribute to better survival.

Primary Pulmonary Acinic Cell Carcinoma: A Clinicopathological Study of 6 Cases and Literature Review.

Primary pulmonary acinic cell carcinoma (ACC) is rare. The clinicopathological features are not identical to that of classic ACC that leads to misdiagnosis. In this article, we summarized the clinicopathological features of 25 such cases, including 6 cases in this series and additional 19 cases in the literature. Pulmonary ACCs showed an overwhelming solid growth pattern. The neoplastic cells had eosinophilic granular and clear cytoplasm in most cases and displayed basophilic cytoplasm in only 4 cases. Intratumoral fibrous septa, mitotic figure, necrosis, and psammoma bodies were observed in some cases. Prominent nuclear atypia and perineural invasion might suggest high-grade transformation, metastasis, and recurrence. The tumor cells were strongly positive for CK8/18 and negative for TTF-1, p63, S-100, mammaglobin, MUC5b, MUC5ac, and DOG1. CK7 was exclusively positive for neoplastic cells with ductal differentiation. Of the 25 included cases, 10 cases were initially misdiagnosed. The tumor was prone to involve the right bronchus. The patient outcome was favorable. The accurate diagnosis of primary pulmonary ACC relies on comprehensive evaluation of histological and immunohistochemical features and realization of the difference from classic ACC.

Evaluation of the Prognostic Significance of TNM Staging Guidelines in Lung Carcinoid Tumors.

INTRODUCTION: The TNM classification for lung cancer, originally designed for NSCLC, is applied to staging of bronchopulmonary carcinoid tumors. The validity of the eighth edition of the staging system for carcinoid tumors has not been assessed. In this study, we evaluated its prognostic accuracy by using data from a large national population-based cancer registry. METHODS: Patients with typical and atypical bronchopulmonary carcinoids diagnosed between 2000 and 2013 were identified from the National Cancer Institute's Surveillance, Epidemiology and End Results registry. We used competing risks analysis to compare 10-year disease-specific survival (DSS) across stages. RESULTS: Overall, 4645 patients with bronchopulmonary carcinoid tumors were identified. Worsening DSS with increasing TNM status and stage was demonstrated across both typical and atypical carcinoids, with overlaps between adjacent subcategories. The combined stages (I versus II, II versus III, and III versus IV) showed greater separation in DSS despite persistent overlaps between groups. For typical carcinoids, we found decreased DSS for stages II, III, and IV, with hazard ratios of 3.8 (95% confidence interval [CI]: 2.6-5.6), 4.3 (95% CI: 3.0-6.1), and 9.0 (95% CI: 6.1-13.1), respectively, compared with stage I. CONCLUSION: The combined stage categories of the eighth edition of the TNM staging system provide useful information on outcomes for typical and atypical carcinoids. However, persistent overlaps in combined stage and subcategories of the staging system limit the usefulness of the TNM staging system, particularly in intermediate stages. These limitations suggest the need for future further study and refinement.

Regional variation in lung and bronchus cancer survival in the US using mortality-to-incidence ratios.

Despite major achievements aimed at reducing smoking over the last 50 years in the U.S., lung cancer remains the leading cause of cancer death. This study used mortality-to-incidence rate ratios (MIR) calculated from 2008 to 2012 National Cancer Institute data to highlight state-level variations in relative lung and bronchus cancer survival. In an ad hoc sensitivity analysis, we calculated a correlation between our state-level MIRs and five-year 1-survival rates for states reporting incident lung and bronchus cancer cases (2004-2008) to the Surveillance, Epidemiology, and End Results (SEER) Program database. Differences were observed in state lung and bronchus cancer MIRs, with the highest MIR values (poor relative survival) in southern states and the lowest MIRs primarily in northeastern states. In our sensitivity analysis, state-level MIRs were highly correlated with 1-survival rates. Examining regional variation in survival using MIRs can be a useful tool for identifying areas of health disparities and conducting surveillance activities.

Long-Term Outcome of Definitive Chemoradiotherapy and Induction Chemoradiotherapy Followed by Surgery for T4 Esophageal Cancer with Tracheobronchial Invasion.

BACKGROUND: T4 esophageal cancer (EC) that invades the trachea or bronchus often has poorer prognosis than other T4 ECs. We investigated the long-term results of definitive chemoradiotherapy (dCRT) or induction chemoradiotherapy followed by surgery (iCRT-S) in patients with T4 EC with tracheobronchial invasion (TBI). PATIENTS AND METHODS: From 2003 to 2013, 71 patients with T4 EC with TBI were treated in our institution; 58 underwent dCRT, and 13 underwent iCRT-S. The long-term results associated with survival were retrospectively analyzed, and prognostic factors were examined by univariable and multivariable analysis. RESULTS: The 1-, 2-, and 5-year overall survival for all patients with T4 EC with TBI treated by dCRT or iCRT-S was 57, 29, and 19%, respectively. Multivariable analysis revealed that clinical lymph node (LN) metastasis and the treatment period were significant prognostic factors. Clinical LN positivity had significantly poorer prognosis than LN negativity. The treatment outcome in the later period was significantly better than that in the earlier period. In particular, the outcome after dCRT revealed significantly better prognosis in the later compared with the earlier period, whereas the outcome after iCRT-S did not show such a difference. With respect to treatment modality, no significant difference in survival was observed between dCRT and iCRT-S. CONCLUSIONS: Clinical LN negativity and later treatment period were significantly good prognostic factors for T4 EC with TBI. The recent improvements in dCRT outcomes may help to achieve survival comparable to that of iCRT-S.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of administering radiotherapy for the treatment of malignant tumours while breathing HBO. SEARCH METHODS: In September 2017 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library Issue 8, 2017, MEDLINE, Embase, and the Database of Randomised Trials in Hyperbaric Medicine using the same strategies used in 2011 and 2015, and examined the reference lists of included articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air or an alternative sensitising agent. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of and extracted data from the included trials. MAIN RESULTS: We included 19 trials in this review (2286 participants: 1103 allocated to HBOT and 1153 to control).For head and neck cancer, there was an overall reduction in the risk of dying at both one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and some evidence of improved local tumour control immediately following irradiation (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to imprecision). There was a lower incidence of local recurrence of tumour when using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78, high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate-quality evidence due to inconsistency between trials). There was also some evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45 95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No trials reported a quality of life assessment. Any benefits come at the cost of an increased risk of severe local radiation reactions with HBOT (severe radiation reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the available evidence failed to clearly demonstrate an increased risk of seizures from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality evidence).For carcinoma of the uterine cervix, there was no clear benefit in terms of mortality at either one year or five years (RR with HBOT at one year 0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI 0.80 to 1.14, moderate-quality evidence due to inconsistency between trials). Similarly, there was no clear evidence of a benefit of HBOT in the reported rate of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high-quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality evidence due to inconsistency between trials). We also found no clear evidence for any effect of HBOT on the rate of development of metastases at both two years and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due to inconsistency). There were, however, increased adverse effects with HBOT. The risk of a severe radiation injury at the time of treatment with HBOT was 2.05, 95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of local tumour control, quality of life assessments, or the risk of seizures during treatment.With regard to the treatment of urinary bladder cancer, there was no clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97, 95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality evidence due to imprecision). No trial reported on failure of local control, local recurrence, quality of life, or adverse effects.When all cancer types were combined, there was evidence for an increased risk of severe radiation tissue injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33, high-quality evidence) and of oxygen toxic seizures during treatment (RR with HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision). AUTHORS' CONCLUSIONS: We found evidence that HBOT improves local tumour control, mortality, and local tumour recurrence for cancers of the head and neck. These benefits may only occur with unusual fractionation schemes. Hyperbaric oxygenation therapy is associated with severe tissue radiation injury. Given the methodological and reporting inadequacies of the included studies, our results demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for uterine cervical or bladder cancer. There is little evidence available concerning malignancies at other anatomical sites.

Endobronchial Treatment for Bronchial Carcinoid: Patient Selection and Predictors of Outcome.

BACKGROUND: Traditionally, surgical resection is the preferred treatment for typical carcinoids and atypical carcinoids located in the lungs. Recently however, several studies have shown excellent long-term outcome after endobronchial treatment of carcinoid tumors located in the central airways. This study investigates clinical and radiological features as predictors of successful endobronchial treatment in patients with a bronchial carcinoid tumor. OBJECTIVES: To identify clinical and radiological features predictive of successful endobronchial treatment in patients with bronchial carcinoid. METHODS: This analysis was performed in a cohort of patients with typical and atypical bronchial carcinoid referred for endobronchial treatment. Several patient characteristics, radiological features, and histological grade (typical or atypical carcinoid) were tested as predictors of successful endobronchial treatment. RESULTS: One hundred and twenty-five patients with a diagnosis of bronchial carcinoid underwent endobronchial treatment. On multivariate analysis, a tumor diameter <15 mm (odds ratio 0.09; 95% confidence interval 0.02-0.5; p = <0.01) and purely intraluminal growth on computer tomography (CT scan) (odds ratio, 9.1; 95% confidence interval 1.8-45.8; p = <0.01) were predictive of radical endobronchial treatment. The success rate for intraluminal tumors with a diameter <20 mm was 72%. CONCLUSIONS: Purely intraluminal disease and tumor diameter on CT scan seem to be independent predictors for successful endobronchial treatment in patients with bronchial carcinoid. Based on these data, patients with purely intraluminal carcinoid tumors with a diameter <20 mm on CT scan are good candidates for endobronchial treatment, regardless of histological grade. In contrast, all patients with a tumor diameter ≥20 mm should be directly referred for surgery.

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Two-Stage Surgery Without Parenchyma Resection for Endobronchial Carcinoid Tumor.

BACKGROUND: The aim of the study was to evaluate the efficacy of a combined approach of endoscopic resection followed by pure bronchoplasty without any pulmonary resection in patients with endobronchial carcinoids. METHODS: We applied a two-stage technique, endoscopic resection first followed by pure bronchoplasty, to 25 patients (10 men, 15 women) with endobronchial carcinoid tumors. The median age was 32.4 years (range, 19 to 64). The indications for this technique were pure endobronchial carcinoid without lymph node involvement. Tumor was located on the right side in 18 patients (72%), and on the left in 7 patients (28%). Flexible bronchoscopy was carried out in all patients as the first-stage procedure for debulking and searching for a true pedicle of the tumor. Different types of pure bronchoplasty were performed as the second-stage surgery with systematic mediastinal lymph node dissection. RESULTS: The resection was complete (R0) in all cases. Tumors were pathologically staged as pT1aN0 in 18 patients, pT2N0 in 5, and pT3N0 in 2 patients; 23 tumors were typical and only two were atypical carcinoids. Morbidity was 28.0% (only minor complications), with no mortality. Overall 5-year and 10-year survival was 100.0% and 91.8%, respectively. No recurrence of the primary tumor was observed in any case. CONCLUSIONS: Two-stage surgery consisting of endoscopic resection and pure bronchoplasty without lung parenchyma resection is an effective technique for the treatment of endobronchial carcinoid, with an excellent oncologic outcome.