Piero Borasio

Stereotactic body radiation therapy for early stage non-small cell lung cancer: Results of a prospective trial

Patients affected with early stage (IA-IB) non-small cell lung cancer (NSCLC), deemed medically inoperable, are usually treated by conventional 3D-CRT, with poor results in terms of local tumour control and survival. Hypofractionated stereotactic body radiation therapy (SBRT) appears to be a valid alternative option, with high rates of local control and promising survival rates according to recent reported series. We herein report the final results of a prospective phase II trial of SBRT in 62 stage I NSCLC patients, homogeneously treated with three fractions of 15Gy each, given every other day during a 1 week time, up to a total dose of 45Gy; dose was prescribed to the 80%-isodose encompassing planning target volume. Patients were immobilized in a dedicated stereotactic body frame; margins around gross tumour volume were 5mm in the axial plane and 10mm in the longitudinal direction. Median age was 73.7 years. A pathologic confirmation of NSCLC was obtained in 64.5% of patients. Forty-three patients had stage IA and 19 stage IB disease. The majority of patients did not experience any toxicity; mild skin reactions, fatigue, dyspnea/cough or transient thoracic pain were recorded in approximately 10% of patients. With a median follow-up time of 28 months, 2 patients experienced an isolated local relapse, 4 an isolated nodal relapse and 15 a systemic failure. At 3 years, local control rate was 87.8%, cancer-specific survival 72.5%, overall survival 57.1%, with 8 out of 20 non-cancer related deaths. In multivariate analysis, tumour volume was associated with a better outcome. In our series, SBRT was well tolerated and confirmed its efficacy, with local control and survival rates globally superior to those reported using conventional radiotherapy. A longer follow-up is needed in order to establish a correct comparison with surgical series, and to fully ascertain a potential negative impact of SBRT on comorbidities of such a fragile patients population.

Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography

OBJECTIVE To evaluate the accuracy of integrated positron emission tomography with 18F-fluoro-2-deoxy-D-glucose (FDG) and computed tomography (PET/CT) in preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer (NSCLC) and to ascertain the role of invasive staging in verifying positron emission tomography (PET)/computed tomography (CT) results. METHODS Retrospective, single institution study of consecutive patients with suspected or pathologically proven, potentially resectable NSCLC undergoing integrated PET/CT scanning in the same PET centre. Lymph node staging was pathologically confirmed on tissue specimens obtained at mediastinoscopy and/or thoracotomy. Statistical evaluation of PET/CT results was performed on a per-patient and per-nodal-station bases. RESULTS A total of 1001 nodal stations (723 mediastinal, 148 hilar and 130 intrapulmonary) were evaluated in 159 patients. Nodes were positive for malignancy in 48 (30.2%) out of 159 patients (N1=17; N2=30; N3=1) and 71 (7.1%) out of 1001 nodal stations (N1=24; N2=46; N3=1). At univariate analysis, lymph node involvement was significantly associated (p<0.05) with the following primary tumour characteristics: increasing diameter, maximum standardised uptake value >9, central location and presence of vascular invasion. PET/CT staged the disease correctly in 128 out of 159 patients (80.5%), overstaging occurred in nine patients (5.7%) and understaging in 22 patients (13.8%). The overall sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT for detecting metastatic lymph nodes were 54.2%, 91.9%, 74.3%, 82.3% and 80.5% on a per-patient basis, and 57.7%, 98.5%, 74.5%, 96.8% and 95.6% on per-nodal-station basis. With regard to N2/N3 disease, PET/CT accuracy was 84.9% and 95.3% on a per-patient basis and on per-nodal-station basis, respectively. Referring to nodal size, PET/CT sensitivity to detect malignant involvement was 32.4% (12/37) in nodes <10mm, and 85.3% (29/34) in nodes > or = 10mm. CONCLUSION Our data show that integrated PET/CT provides high specificity but low sensitivity and accuracy in intrathoracic nodal staging of NSCLC patients and underscore the continued need for surgical staging.

Prognostic significance of Ki67 labelling in resected non small cell lung cancer.

One hundred and eleven tissue samples of primary non small cell lung cancer obtained from patients undergoing radical surgery for resectable disease were investigated for the presence and distribution of Ki67 related antigen using an immunohistochemical technique, as a marker of the proliferative activity of the tumour. No correlation was seen between Ki67 expression and clinico-pathological variables (sex, age, histology, grading and pTNM stage) but disease-free survival was significantly lower in patients with higher Ki67 score (> 25% positive cells) at diagnosis (P < 0.03). Growth fraction evaluated by Ki67 labelling may provide a complementary prognostic parameter in non small cell lung cancer.

Malignant pleural mesothelioma: clinicopathologic and survival characteristics in a consecutive series of 394 patients

OBJECTIVE Treatment of malignant pleural mesothelioma (MPM) remains disappointing, although recent reports suggest that multimodality therapy including surgery may provide a significant survival benefit. The aims of this single institution study were: to investigate clinicopathologic characteristics and potential prognostic factors in MPM patients, and to ascertain whether surgery followed by adjuvant therapy had an independent prognostic role. METHODS Retrospective review of a prospectively compiled computerized database of all patients with MPM evaluated between 1989 and 2003. Kaplan-Meier method, log-rank test, and Cox model were used in the statistical analysis. RESULTS There were 394 patients: 270 men (68.5%), 124 women, median age 64 (range 28-93). Twenty-seven patients (6.8%) underwent surgical resection (extrapleural pneumonectomy 15, pleurectomy/decortication 12), followed by adjuvant therapy. As of March 2006, 381 patients (96.7%) had died (median survival, 11.7 months; range 0.03-117.9). Median follow-up of 13 surviving patients (3.3%) was 45.2 months (range 28.7-126.5). Overall survival at 2 years was 18.8%. Multimodality therapy including surgery yielded a median survival of 14.5 months and a 2-year survival rate of 29.6%. Using univariate analysis, age (p=0.009), chest pain (p=0.01), weight loss (p=0.001), performance status (p=0.0001), platelet count (p=0.008), histology (p=0.0001), macroscopic appearance of pleural surface (non-specific inflammation, tumor-like thickening, or nodules; p=0.0001), visceral pleura involvement (p=0.0001), degree of involvement of pleural cavity (less than or more than one third of the cavity; p=0.0001), and multimodality therapy (p<0.01) were found to be significant prognostic factors. At multivariate analysis, performance status, platelet count, histology, and degree of involvement of pleural cavity remained independently associated with survival, whereas multimodality therapy failed to enter the model. CONCLUSIONS Significant predictors of survival include performance status, platelet count, histology, and degree of involvement of pleural cavity. Within the confines of this retrospective study and the small number of patients undergoing multimodality therapy, the role of surgery in the treatment of MPM remains unclear. Further investigation is warranted to determine the optimal treatment strategy in this disease.

Bone Sialoprotein Is Predictive of Bone Metastases in Resectable Non–Small-Cell Lung Cancer: A Retrospective Case-Control Study

PURPOSE Bone metastases (BM) in non-small-cell lung cancer (NSCLC) may be detected at diagnosis or during the course of the disease, and are associated with a worse prognosis. Currently, there are no predictive or diagnostic markers to identify high-risk patients for metastatic bone dissemination. PATIENTS AND METHODS Thirty patients with resected NSCLC who subsequently developed BM were matched for clinicopathologic parameters to 30 control patients with resected NSCLC without any metastases and 26 patients with resected NSCLC and non-BM lesions. Primary tumors were investigated by immunohistochemistry for 10 markers involved in bone resorption or development of metastases. Differences among groups were estimated by chi2 test, whereas the prognostic impact of clinicopathologic parameters and marker expression was evaluated by univariate (Wilcoxon and Mantel-Cox tests) and multivariate (Cox proportional hazards regression model) analyses. RESULTS The presence of bone sialoprotein (BSP) was strongly associated with bone dissemination (P < .001) and, independently, with worse outcome (P = .02, Mantel-Cox test), as defined by overall survival. To evaluate BSP protein expression in nonselected NSCLC, a series of 120 consecutive resected lung carcinomas was added to the study, and BSP prevalence reached 40%. No other markers showed a statistically significant difference among the three groups or demonstrated a prognostic impact, in terms of both overall survival and time interval to metastases. CONCLUSION BSP protein expression in the primary resected NSCLC is strongly associated with BM progression and could be useful in identifying high-risk patients who could benefit from novel modalities of surveillance and preventive treatment.

CT features of solitary fibrous tumour of the pleura: experience in 26 patients

Purpose.The purpose of this study was to identify the typical computed tomography (CT) features of solitary fibrous tumours of the pleura (SFTP) and determine which findings would allow confirmation of the pleural origin or benign behaviour of the tumour.Materials and methods.Twenty–six preoperative CT studies of the chest (23 enhanced and 14 unenhanced) were retrospectively reviewed.Results.Up to 50% of SFTP were larger than 10 cm. At unenhanced CT, they showed homogeneous attenuation in 5 cases (35.7%) and inhomogeneous attenuation in 9 (64.3%). At contrastenhanced CT, they were inhomogeneous in 21 cases (91.3%), with geographic pattern (61.9% of cases), serpiginous linear areas of enhancement (intralesional vessels) (23.8%), rounded (52.4%) or linear (33.3%) areas of low attenuation (necrosis).Conclusions.Depending on location, size and histological features, SFTP may produce a large spectrum of findings. Typical CT features of small SFTP were well–defined margins and smooth contours, homogeneous attenuation and right or obtuse angles with the pleura. Larger lesions were characterised by well–defined margins and lobulated contours, geographic pattern in enhanced CT scans, acute angles or smooth tapering margins with the pleura.

Epidermal growth factor ligand/receptor loop and downstream signaling activation pattern in completely resected nonsmall cell lung cancer.

In recent years, molecular insights shed light on the role of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer (NSCLC), and new therapeutic agents, such as the EGFR tyrosine kinase inhibitors, were tested successfully, with responsiveness to those agents more likely in those patients with specific EGFR gene alterations. The objective of the current study was to investigate the protein profiles of EGFR, c‐erb‐B2, transforming growth factor α (TGF‐α) (one of the EGFR ligands commonly expressed in NSCLC), and some downstream molecules, potentially to detect a subset of tumors with an activated autocrine loop that is responsible for higher intracellular signaling.

Air leaks following pulmonary resection for malignancy: risk factors, qualitative and quantitative analysis

Air leaks are a common complication of pulmonary resection. The aims of this study were to analyze risk factors for postoperative air leak and to evaluate the role of air leak measurement in identifying patients at increased risk for cardiorespiratory morbidity and prolonged air leak. From March to December 2009, 142 consecutive patients underwent pulmonary resection for malignancy and were prospectively followed up. Preoperative and intraoperative risk factors for air leak were evaluated. Air leaks were qualitatively and quantitatively labeled twice daily. There were 52 (36.6%) patients who had an air leak on day 1, and 32 (22.5%) who had an air leak on day 2. Air leak was ≥180 ml/min in 12 (37.5%) of these patients. Independent predictors of air leak on day 2 included type of pulmonary resection, presence of adhesions, and incomplete fissures. Cardiorespiratory morbidity was significantly higher (34.4%) in patients who experienced air leak on day 2 than in those who did not (10.9%) (P=0.002). Nine (75%) out of 12 patients with air leak ≥180 ml/min on day 2 had prolonged air leak (greater than five days) (P=0.0001).

A suitable system of reconstruction with titanium rib prosthesis after chest wall resection for Ewing sarcoma

The recent improvements in chemotherapy and surgical resection in Ewing sarcoma (ES) increased the overall survival as well as the importance of chest wall reconstruction. These improvements are in order to avoid asymmetrical growth, functional and cosmetic compromise after surgery. Chest wall reconstruction still remains a big issue in young patients with ES. We present a case of ES of the left chest wall, arising from a rib, in a 14-year-old patient. He was admitted after neoadjuvant chemotherapy and radiotherapy. The patient underwent a chest wall resection of three ribs and a wedge lung resection of the upper lobe followed by chest wall reconstruction with Stratos™ rib titanium prostheses. This new device is suitable for reconstruction after major chest wall resection with good cosmetic and functional results. During the follow-up, there was no evidence of local and distant recurrence, the pain was under control and there were no functional alterations in the chest wall.

Lung cancer stage is an independent risk factor for surgical mortality.

Aims and Background To study surgical mortality and evaluate major risk factors, with specific focus on the role of pathological stage in patients undergoing lung cancer resection. Methods and Study Design Age, gender, comorbidity, resection volume, experience of the hospital and surgical team have been reported as variables related to postoperative morbidity and mortality in lung cancer. The role of pathological tumor stage on postoperative mortality has never been fully evaluated. The study included 1418 consecutive lung cancer resections performed from 1998 to 2002 in two institutions. The effect of age, gender, comorbidity, resection volume, pathological stage and induction therapies on postoperative mortality was assessed by univariable and multivariable logistic regression analysis. Results Postoperative mortality was 1.8% overall, 3.7% (9/243) for pneumonectomy, 1.7% (17/1016) for lobectomy, and null (0/159) for sublobar resections (P = 0.020). At multivariable analysis, cardiovascular comorbidity (P = 0.008), resection volume (P = 0.036) and pathological stage (P = 0.027) emerged as significant predictors of surgical mortality. Conclusions Early stage lung cancer resection has a favorable effect on surgical mortality, not only by preventing the need for pneumonectomy, but also by reducing mortality after lobectomy.