Emanuele Voulaz

A Randomized Study of Lung Cancer Screening with Spiral Computed Tomography: Three-year Results from the DANTE Trial

RATIONALE Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies. OBJECTIVES To explore the effect of screening with low-dose spiral computed tomography (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage at diagnosis, and resectability. METHODS Male subjects, aged 60 to 75 years, smokers of 20 or more pack-years, were randomized to screening with LDCT or control groups. All participants underwent a baseline, once-only chest X-ray and sputum cytology examination. Screening-arm subjects had LDCT upon accrual to be repeated every year for 4 years, whereas controls had a yearly medical examination only. MEASUREMENTS AND MAIN RESULTS A total of 2,811 subjects were randomized and 2,472 were enrolled (LDCT, 1,276; control, 1,196). After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) patients receiving LDCT and 34 (2.8%) control subjects (P = 0.016). Resectability rates were similar in both groups. More patients with stage I disease were detected by LDCT (54 vs. 34%; P = 0.06) and fewer cases were detected in the screening arm due to intercurrent symptoms. However, the number of advanced lung cancer cases was the same as in the control arm. Twenty patients in the LDCT group (1.6%) and 20 controls (1.7%) died of lung cancer, whereas 26 and 25 died of other causes, respectively. CONCLUSIONS The mortality benefit from lung cancer screening by LDCT might be far smaller than anticipated.

Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography

RATIONALE Screening for lung cancer with low-dose spiral computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20% compared with screening with chest X-ray (CXR) in the National Lung Screening Trial, but uncertainty remains concerning the efficacy of LDCT screening in a community setting. OBJECTIVES To explore the effect of LDCT screening on lung cancer mortality compared with no screening. Secondary endpoints included incidence, stage, and resectability rates. METHODS Male smokers of 20+ pack-years, aged 60 to 74 years, underwent a baseline CXR and sputum cytology examination and received five screening rounds with LDCT or a yearly clinical review only in a randomized fashion. MEASUREMENTS AND MAIN RESULTS A total of 1,264 subjects were enrolled in the LDCT arm and 1,186 in the control arm. Their median age was 64.0 years (interquartile range, 5), and median smoking exposure was 45.0 pack-years. The median follow-up was 8.35 years. One hundred four patients (8.23%) were diagnosed with lung cancer in the screening arm (66 by CT), 47 of whom (3.71%) had stage I disease; 72 control patients (6.07%) were diagnosed with lung cancer, with 16 (1.35%) being stage I cases. Lung cancer mortality was 543 per 100,000 person-years (95% confidence interval, 413-700) in the LDCT arm versus 544 per 100,000 person-years (95% CI, 410-709) in the control arm (hazard ratio, 0.993; 95% confidence interval, 0.688-1.433). CONCLUSIONS Because of its limited statistical power, the results of the DANTE (Detection And screening of early lung cancer with Novel imaging TEchnology) trial do not allow us to make a definitive statement about the efficacy of LDCT screening. However, they underline the importance of obtaining additional data from randomized trials with intervention-free reference arms before the implementation of population screening.

Surgical Procedures in the DANTE Trial, A Randomized Study of Lung Cancer Early Detection with Spiral Computed Tomography: Comparative Analysis in the Screening and Control Arm

Background: The patient population derived from lung cancer screening programs with low-dose spiral computed tomography (LDCT) is different from the general population accessing thoracic surgical services. Methods: Retrospective review of all surgical cases in the DANTE trial, a randomized study of lung cancer screening with LDCT. Patient characteristics, workup, procedures, resections for benign disease, complications, tumor features, and final outcomes have been analyzed in the LDCT and in the control arm. Results: In the LDCT arm, 77 suspicious lesions were surgically managed in 72 patients. A benign lesion was diagnosed in 17 cases (22%). Major video-assisted thoracoscopic surgery resection was carried out in five lung cancer cases (7%) and segmentectomy in 11 (19%). Complete resection was achieved in 93%, and stage I rate was 73%. Two patients had a local recurrence after open lobectomy, and three had a resectable new primary. In the control group, 28 patients underwent 31 surgical procedures, in five cases (16%) for benign lesions. No major video-assisted thoracoscopic surgery resections were carried out. Resectability rate was 88%, and stage I rate was 52%. Five patients had a local recurrence and two had a second primary. Conclusions: Surgery for benign lesions is a relevant issue in screening-derived patients. Local control may be achieved by minimally invasive techniques or segmentectomy; however, developing the necessary skills requires an effort by the surgical team. Long-term survivors have a noticeable chance of developing second primary cancers or resectable recurrences and may benefit from a second resection.

Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients

There is a well‐established link between inflammation and cancer of various organs, but little data are available on inflammation‐associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high‐risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high‐sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high‐risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer‐free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high‐risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.

Huge malignant phyllodes breast tumor: a real entity in a new era of early breast cancer

Phyllodes tumor is an extremely rare tumor of the breast. It occurs in females in the third and fourth decades. The difficulty in distinguishing between phyllodes tumors and benign fibroadenoma may lead to misdiagnosis. Lymph node involvement is rarely described in phyllodes tumors; for this reason, sentinel node biopsy may be warranted. We present a case of a 33-year-old woman affected by huge tumor of the right breast with ulceration in the skin with a rapid tumor growth and with omolateral axillary metastasis.

Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery

PurposeRadiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery.MethodsA cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built.ResultsThe Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65–0.85), 0.68 (95%CI: 0.57–0.80), and 0.68 (95%CI: 0.58–0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51–0.69), 0.64 (95%CI: 0.53–0.75), and 0.65 (95%CI: 0.50–0.72) for the CT, the PET, and the PET+CT images, respectively.ConclusionsA radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery.

Comorbidity, postoperative morbidity and survival in patients undergoing radical surgery for malignant pleural mesothelioma.

OBJECTIVES We examined a series of malignant pleural mesothelioma (MPM) patients who underwent radical surgery to explore relationships among comorbidity, postoperative morbidity and survival. METHODS A retrospective analysis was carried out of all MPM patients operated on in a single centre from 2000 to 2015. The Charlson Comorbidity Index (CCI) was used to classify patients according to their underlying condition. Postoperative complications were scored according to WHO-derived criteria. Survival comparisons were performed by Cox analysis. RESULTS Ninety-one patients underwent extrapleural pneumonectomy (EPP), 47 underwent pleurectomy decortication (PD) and 25 underwent palliative pleurectomy. The mean CCI of PD patients was significantly higher compared with that of EPP patients (P= 0.044). The frequency of grade 3+ complications was similar between EPP and PD (27 vs 26%). However, EPP patients had a 6-fold higher frequency of pleural sepsis (24 vs 4%, P= 0.002) occurring up to 695 days postoperatively. Median overall survival was 19 months (95% CI 13-25) after EPP, 30 months (95% CI 20-35) after PD and 13 months (95% CI 5-32) after palliative pleurectomy. At multivariate analysis, CCI (P< 0.001), histology (P= 0.014) and pleural sepsis (P= 0.001), but not complete resection, were significantly associated with survival. There was a trend in favour of PD over palliative resection after adjusting for histology and CCI. CONCLUSIONS The CCI is an independent predictor of survival in MPM patients undergoing radical surgery. Owing to its significant frequency and adverse impact, pleural sepsis may contribute to a reduced life expectancy after EPP. Surgical treatment of MPM remains debatable.

Evaluating interest in narrative therapy for decision making about pectus excavatum treatment

OBJECTIVES The decision to proceed with surgical treatment for pectus excavatum (PE) is rarely clear-cut. Patients interested in treatment are referred for evaluation by numerous different specialists, but psychosocial counselling is currently not included in this process. Our objective was to assess whether PE patients would be interested in formal assistance with the decision-making process surrounding PE surgery using narrative therapy principles. METHODS Ninety-seven untreated PE patients at 5 different institutions in 4 countries completed a questionnaire consisting of 13 questions, with 3 questions specifically evaluating interest in narrative therapy. RESULTS Eighty-two percent of participants were interested in narrative therapy to assist with the decision-making process surrounding PE surgery. Individuals most interested in narrative therapy tend to be more interested in correction (P < 0.05) to improve the way they feel about their body (P < 0.05). CONCLUSIONS The majority of PE patients are interested in narrative therapy to aid the decision-making process about treatment. We propose that narrative therapy should be offered to PE patients during the treatment evaluation process to address the psychosocial difficulties associated with PE and the surgical decision-making process overall. Future studies should assess the effectiveness of this interdisciplinary model.

Ability of FDG PET and CT radiomics features to differentiate between primary and metastatic lung lesions

PurposeTo evaluate the ability of CT and PET radiomics features to classify lung lesions as primary or metastatic, and secondly to differentiate histological subtypes of primary lung cancers.MethodsA cohort of 534 patients with lung lesions were retrospectively studied. Radiomics texture features were extracted using the LIFEx package from semiautomatically segmented PET and CT images. Histology data were recorded in all patients. The patient cohort was divided into a training and a validation group and linear discriminant analysis (LDA) was performed to classify the lesions using both direct and backward stepwise methods. The robustness of the procedure was tested by repeating the entire process 100 times with different assignments to the training and validation groups. Scoring metrics included analysis of the receiver operating characteristic curves in terms of area under the curve (AUC), sensitivity, specificity and accuracy.ResultsRadiomics features extracted from CT and PET datasets were able to differentiate primary tumours from metastases in both the training and the validation group (AUCs 0.79 ± 0.03 and 0.70 ± 0.04, respectively, from the CT dataset; AUCs 0.92 ± 0.01 and 0.91 ± 0.03, respectively, from the PET dataset). The AUC cut-off thresholds identified by LDA using direct and backward elimination strategies were −0.79 ± 0.06 and −0.81 ± 0.08, respectively (CT dataset) and −0.69 ± 0.05 and −0.68 ± 0.04, respectively (PET dataset). For differentiation between primary subgroups based on CT features, the AUCs in the training and validation groups were 0.81 ± 0.02 and 0.69 ± 0.04 for adenocarcinoma (Adc) vs. squamous cell carcinoma (Sqc) or “Other”, 0.85 ± 0.02 and 0.70 ± 0.05 for Sqc vs. Adc or Other, and 0.77 ± 0.03 and 0.57 ± 0.05 for Other vs. Adc or Sqc. The same analyses for the PET data revealed AUCs of 0.90 ± 0.10 and 0.80 ± 0.04, 0.80 ± 0.02 and 0.61 ± 0.06, and 0.97 ± 0.01 and 0.88 ± 0.04, respectively.ConclusionPET radiomics features were able to differentiate between primary and metastatic lung lesions and showed the potential to identify primary lung cancer subtypes.

Robot-assisted surgery for lung cancer: State of the art and perspectives.

The robotic surgical system is the result of a long process of development aimed at producing a natural extension of the surgeons eyes and hands via the intermediation of a computer. In this way, the ease of movement obtained with open surgery is summated with the advantages of the minimally invasive technique. Since 2000, when the first robotic system for surgery was introduced, robot-assisted thoracic surgery (RATS) has been adopted by an increasing number of centres around the world, and today is used in ∼10% of lobectomies in the US. Here, we review the characteristics and function of the robotic system available today (namely, Intuitive Surgical Inc.s da Vinci Surgical System), outline the different techniques for major lung resection via RATS, compare RATS with video-assisted thoracoscopic surgery (VATS) and thoracotomy, and speculate on future developments. To date, no randomized trials have reported comparative data on RATS vs. VATS/thoracotomy for lung cancer. Retrospective analysis comparing RATS vs. thoracotomy have revealed advantages for the former, especially shorter hospital stays and a lower complication rate, but RATS produces similar or only slightly better results to VATS, the two being minimally invasive techniques with no need for rib separation. A few studies have reported RATS to be safer than VATS, with less conversions for bleeding, less complications; in others, it was associated with lower postoperative consumption of pain killers and quicker return of patients to normal activity. In addition, lymphnode upstaging has been shown to be higher with RATS than with VATS, with a similar rate as thoracotomy. The main disadvantage of RATS is the higher costs of instrumentation. Nevertheless, the future will probably see reductions in the costs and improvements in the instrumentation, integration with 3D imaging to improve virtual reality, and more patients benefitting from minimally invasive procedures for lung malignancies.