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Summary We explored activity and safety of a dose-dense/dose-intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVDDD-DI) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two-stage Bryant-Day Phase II study to receive six cycles of ABVDDD-DI without consolidation radiotherapy. Cycles were supported with granulocyte colony-stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m2; first four cycles only). Co-primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event-free (EFS) and disease-free survival (DFS). All patients received the four doxorubicin-intensified courses and 96% concluded all six cycles (82·3% within the intended 18 weeks). This translated into a 66·9% increase of received dose-intensity for doxorubicin and 31·8% for the other agents over standard ABVD. The CR rate was 95·1% (78/82) and 87·8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14·6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five-year EFS and DFS was 88·3% and 93·7%, respectively. ABVDDD-DI regimen was well-tolerated and ensured substantial CR and EFS rates without radiotherapy.

Objective: FEV1 measured on the first postoperative day has shown to be a better predictor of complications than traditional ppoFEV1. Therefore, its estimation before operation may enhance risk stratification. The objective of this study was to develop and validate a model to predict FEV1 on the first postoperative day after major lung resection. Methods: FEV1 was prospectively measured on the first postoperative day in 272 patients submitted for lobectomy or pneumonectomy at two centers. A random sample of 136 patients was used to develop a model estimating the first day FEV1 by using multiple regression analysis including several preoperative and operative factors. The model was then validated by bootstrap analysis and tested on the other sample of 136 patients. Results: Factors reliably associated with postoperative first day FEV1 were age (p = 0.002), preoperative FEV1 (p < 0.0001), the presence of epidural analgesia (p < 0.0001), and the percentage of nonobstructed segments removed during operation (p = 0.001). The following model estimating the first day postoperative FEV1 was derived: 2.648 + 0.295 age + 0.371 FEV1 + 8.216 epidural analgesia 0.338 percentage of non-obstructed segments removed during operation. In the validation set, the mean predictedfirst day postoperative FEV1 value did not differ from the observed one (42.6 vs 42.0, respectively; p = 0.3) and the plot of the observed versus the predicted first day FEV1 showed a satisfactory calibration. Conclusions: We developed a model predicting the first day postoperative FEV1. If future analyses will prove its role in stratifying the early postoperative risk, it may be integrated in preoperative evaluation algorithms to refine risk stratification. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Recently published papers have shown that lobectomy improves lung function in selected patients with chronic obstructive pulmonary disease (COPD) months after surgery, but little information can be found discussing the effect of lobectomy on pulmonary function in the immediate period after surgery in these cases. The aim of this multicenter prospective study is to evaluate whether preoperative COPD influences the decrease of forced expiratory volume in 1 second the day after surgery.One hundred eighty-five patients undergoing nonextensive lobectomy were included. Selection criteria and perioperative management were homogeneous; all procedures were performed by muscle-sparing or video-assisted thoracoscopic surgical approach. Multivariate regression analysis was performed to identify whether COPD index (calculated by adding the percent preoperative forced expiratory volume in 1 second to the preoperative ratio of forced expiratory volume in 1 second to forced vital capacity, both values taken in decimal form) had an independent and reliable association with the decrease in forced expiratory volume in 1 second observed on the first postoperative day corrected for the effect of other preoperative and operative factors. The regression analysis was then validated by bootstrap analysis.Thirty-day mortality of the series was 1.1% (2 patients) and cardio-respiratory morbidity 20% (37 patients). Patients with lower preoperative pulmonary volumes had lower postoperative decrease of the pulmonary function (Pearson correlation coefficient, 0.28; p0.001). At linear regression, COPD index (p = 0.008), modality of analgesia (p0.0001), pain score (p = 0.01), the percentage of functioning parenchyma removed during operation (p = 0.006), and the presence of coronary artery disease (p = 0.03) had independent and reliable influence on the dependent variable (p0.001 and 0.003, respectively).Preoperative COPD degree (measured as COPD index) has a direct independent correlation with the decrease in postoperative forced expiratory volume in 1 second the day after surgery.

Introduction and objective: There is a low correlation between predicted postoperative FEV1 (ppoFEV1) and FEV1 measured the days after pulmonaryresection,whenmostcomplicationsaredeveloped.ThehypothesisofthisinvestigationisthatppoFEV1doesnotpredictpostoperative morbidity in patients undergoing lung resection when immediate postoperative FEV1 is considered in the predictive model. Methods: One hundred ninety-eight consecutive patients undergoing lobectomy or pneumonectomy were included in a prospective, multiinstitutional study. Independent variables: age, body mass index, ppoFEV1, surgical approach (VATS or muscle-sparing thoracotomy), type of analgesia (epidural or intraveous), postoperative visual analogue pain score and FEV1 measured the day after the operation. Target variable: occurrence of postoperative cardio-respiratory complications. Method of analysis: classification tree (CART) dividing the population at random in two subsets anddevelopinga bootstrapset of100treesresamplingtrainingdata.Therelativeimportanceofeach variableandtheaccuracyofbothinitial and committee trees to predict the outcome were presented. Results: One hundred seventy-seven lobectomies and 21 pneumonectomies were included.Overallcardio-respiratorymorbiditywas 22%.Accordingto CARTresults,firstdayFEV1was themostimportantvariable to classifycases as primary splitter and as a surrogate of each primary splitter (100% importance). Patient age followed (51%) and ppoFEV1 was third (43%) with a scoresimilartopostoperativepainscore(42%)andtypeofanalgesia(36%).Sensitivityandspecificityoftheinitialtreewere,respectively,0.5and 0.7; values for committee tree were 0.5 sensitivity and 0.7 specificity. Conclusion: Postoperative cardio-respiratory complications are more related to FEV1 measured in the first postoperative day than to ppoFEV1 value. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Objective: Scanty information can be found regarding ppoFEV1% correlation with true FEV1% in the immediate days after surgery, when most cardio-respiratory complications are developed. This prospective multicentric investigation aims to describe the evolution of FEV1 in a series of uneventful lobectomy cases before hospital discharge, and to identify factors associated with the variation of postoperative residual FEV1, with the ratio between the actual and the predicted postoperative FEV1 measured during the first 6 postoperative days. Methods: One hundred and sixty-one patients submitted to lobectomy were prospectively enrolled in the study. Patients with chest wall resections and postoperative complications were excluded. Data from a total of 125 patients were thus used for the analysis. The following clinical variables were recorded: age, preoperative FEV1, ppoFEV1, presence of chronic obstructive pulmonary disease (COPD), surgical approach (VATS or muscle-sparing thoracotomy), side (right or left) and site (upper or lower) of resection, type of analgesia (epidural or intravenous), and daily visual analogue pain score (VAS). FEV1 was measured in every patient at hospital admission and daily until discharge or up to postoperative day 6. Random effects time-series cross-sectional regression analyses were performed to identify factors associated with variation of postoperative residual function (100 (preoperative FEV1 postoperative FEV1/preoperative FEV1 100)), and of FEV1 ratio ((actual postoperative FEV1 100)/ppoFEV1). For these analyses, the dependent variables (postoperative residual function and FEV1 ratio) and the pain score were analysed as panel longitudinal data. The regression analyses were subsequently validated by bootstrap procedure. Results: FEV1% was lower at first postoperative day and increased gradually up to day 6 but mean values never reached ppoFEV1%. Pain scores decreased from day 1 to day 6. Preoperative FEV1 (p < 0.0001) and postoperative pain score (p < 0.0001) resulted independently and reliably inversely associated with postoperative residual FEV1 (model R 2 ,0 .16). Preoperative FEV1 (p = 0.001), postoperative pain score (p < 0.0001), and epidural analgesia (p = 0.04) resulted independently and reliably associated with postoperative FEV1 ratio (model R 2 , 0.13). Conclusion: Current methods of prediction of postoperative FEV1 greatly underestimated the real functional loss in the immediate postoperative period. Therefore, for the purpose of a more accurate risk stratification we need to correct the traditional prediction of postoperative FEV1.

Experimental studies have shown that vinorelbine is a powerful radiosensitizer in vitro. To date, no reports on clinical activity of the single agent vinorelbine as radiosensitizer have been published. The aim of the present phase I study was to determine the maximum tolerated dose (MTD) of vinorelbine administered daily concurrently with thoracic radiotherapy, with or without amifostine support, in the treatment of locally advanced non small cell lung cancer. In vitro studies have shown that vinorelbine can potentiate the antitumor effects of radiation therapy. Amifostine is a sulphydril compound that has shown to protect normal tissues from chemotherapy and radiotherapy-induced toxicities. Radiotherapy lasted 6 weeks and the total dose was 55 Gy. The daily fraction was 1.8 Gy, administered 5 days a week for 5 weeks and increased to 2.0 Gy during the sixth and last week. Concurrent vinorelbine was administered daily with a planned escalation of the dose from 4, to 5 and 6 mg/m 2 . Fourteen patients were enrolled in the study. The first dose of vinorelbine was 4 mg/m 2 and it showed to be feasible without dose-limiting toxicity (DLT). Instead, the second dose level of 5 mg/m 2 was unfeasible because three out of six patients had DLT (grade 4 neutropenia, treatment interruption longer than 2 weeks for prolonged grade 2 neutropenia and treatment interruption longer than 2 weeks for prolonged grade 3 esophagitis together with grade 4 dyspnea). At that time, the study continued adding amifostine to vinorelbine in order to increase its MTD. Amifostine was administered by means of subcutaneous injection 15 min before each radiotherapy fraction at the fixed dose of 300 mg/m 2 . However, 5 mg/m 2 of vinorelbine were considered unfeasible even with amifostine support because three out of five patients showed DLT (grade 4 neutropenia, febrile grade 4 neutropenia and grade 3 liver toxicity). Among 14 patients enrolled in the study, eight completed the planned treatment because six patients experienced DLT, which determined treatment interruption. Overall, four partial and two complete responses were observed. Two partial and one complete response were observed in those three patients who had been treated with the first dose of vinorelbine. In conclusion, our data show that the MTD of daily vinorelbine is 4 mg/m 2 . Therefore, this is the recommended dose of daily vinorelbine to be administered with concurrent thoracic radiotherapy in a phase II trial. Finally, amifostine administered subcutaneously failed to increase the MTD of daily vinorelbine.

Background Intrapulmonary percussive ventilation (IPV) aims at clearing retained secretions through oscillary vibrations generated by high frequency bursts of gas delivered into the airways at rates between 200 and 300 breaths per minute and at a delivery pressure of 10 to 20 cm water. In addition, IPV can improve recruitment of alveolar units and deliver aerosolized medications. The use of IPV to resolve challenging postlobectomy localized pneumothoraces is hereafter described. Methods Between January 2005 and March 2009, four patients with long-term complicated postresectional residual air spaces persisting 6 months (mean, 187 days) after primary surgery were treated by IPV. The type of operation was upper lobectomy and lower lobectomy-wedge resection in 1 and 3 patients, respectively. Mean preoperative and immediate postsurgical forced expiratory volume in the first second of expiration were 2.31 L and 1.49 L, respectively. Mean preoperative and immediate postsurgical forced vital capacity were 3.13 L and 2.1 L, respectively. Patients were subjected to 12-minute-long IPV sessions up to a total of 8 to 12 sessions administered every other day in an outpatient setting. Results Complete resolution of the spaces within a mean of 22 days of beginning of treatment was noted. The post-IPV forced expiratory volume in the first second of expiration and forced vital capacity were 1.72 and 2.4 liters, respectively. No treatment-related morbidity was observed. Conclusions Intrapulmonary percussive ventilation can be expected to decisively contribute to resolving long-term localized pneumothoraces after subtotal pulmonary resections in an outpatient setting.

Lung cancer is the first cause of cancer death for males agedor =35 years, and the second for females aged between 35 and 70 years. Elderly patients seem to have the worst performance status (PS) and earlier stage of disease at diagnosis. We analyzed data concerning 1,035 patients with lung cancer referred to the National Cancer Institute of Naples. The variables considered in the analysis were: gender; type of cancer [small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC)]; ECOG (Eastern Cooperative Oncology Group) PS, the stage of disease at diagnosis, the histological type, age at diagnosis. In order to better assess the relevance of age at diagnosis in lung cancer patients we categorized the age into two groups (youngor =70; old70 years). The statistical analyses were performed using chi2 trend test with corresponding p-value and odds ratios (OR) for the examined variables, with a corresponding 95% confidence interval. These were derived using multiple logistic regression, fitted by the maximum likelihood method. For all the 1035 patients the risk between the age at diagnosis and the performance status was not statistically significant (OR=1.1, 95%CI 0.8-1.5). We repeated the same risk distinguishing the histological type and we analyzed the performance status for the SCLC (OR=1.0, 95%CI 0.4-2.5) and the stage at diagnosis (OR=1.0, 95%CI 0.4-3.0), without any significant difference. Our study showed that elderly patients with lung cancer do not seem to have different characteristics at presentation, particularly related to stage of disease, PS and histology, as compared to their younger counterpart. Other characteristics such as type and number of co-morbidities and organ function differ in the two groups of populations.