Massimo Bellomi

Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results

BACKGROUND Low-dose spiral CT of the chest effectively detects early-stage lung cancer in high-risk individuals. The high rate of benign nodules and issues of making a differential diagnosis are critical factors that currently hamper introduction of large-scale screening programmes. We investigated the efficacy of repeated yearly spiral CT and selective use of positron emission tomography (PET) in a large cohort of high-risk volunteers. METHODS We enrolled 1035 individuals aged 50 years or older who had smoked for 20 pack-years or more. All patients underwent annual low-dose CT, with or without PET, for 5 years. Lesions up to 5 mm were deemed non-suspicious and low-dose CT was repeated after 12 months (year 2). FINDINGS By year 2, 22 cases of lung cancer had been diagnosed (11 at baseline, 11 at year 2). 440 lung lesions were identified in 298 (29%) participants, and 95 were recalled for high-resolution contrast CT. PET scans were positive in 18 of 20 of the identified cancer cases. Six patients underwent surgical biopsy for benign disease because of false-positive results (6% of recalls, 22% of invasive procedures). Complete resection was achieved in 21 (95%) lung cancers, 17 (77%) were pathological stage I (100% at year 2), and the mean tumour size was 18 mm. There were no interval lung cancers in the 2.5 years of follow-up (average time on study from randomisation to last contact), although 19 individuals were diagnosed with another form of cancer (two deaths and 17 non-fatal admissions). INTERPRETATION Combined use of low-dose spiral CT and selective PET effectively detects early lung cancer. Lesions up to 5 mm can be checked again at 12 months without major risks of progression.

Quantification of Free Circulating DNA As a Diagnostic Marker in Lung Cancer

Purpose: Analysis of circulating DNA in plasma can provide a useful marker for earlier lung cancer detection. This study was designed to assess the sensitivity and specificity of a quantitative molecular assay of circulating DNA to identify patients with lung cancer and monitor their disease. Materials and Methods: The amount of plasma DNA was determined through the use of real-time quantitative polymerase chain reaction (PCR) amplification of the human telomerase reverse transcriptase gene (hTERT) in 100 non–small-cell lung cancer patients and 100 age-, sex-, and smoking-matched controls. Screening performance of the assay was calculated through the receiver operating characteristic (ROC) curve. Odds ratios were calculated using conditional logistic regression analysis. Results: Median concentration of circulating plasma DNA in patients was almost eight times the value detected incontrols (24.3 v 3.1 ng/mL). The area under the ROC curve was 0.94 (95% CI, 0.907 to 0.973). Plasma DNA was a strong risk fact...

A randomized, prospective trial of central venous ports connected to standard open-ended or Groshong catheters in adult oncology patients.

Implanted central venous access is practiced extensively in oncology; however, information on the relevance of using the device with a valved catheter (Groshong), compared with an open‐ended catheter, is scarce. The authors investigated the two types of catheters in a randomized trial using the same type of subcutaneous port and evaluated efficacy as well as early and late complications.

Lung cancer screening with low-dose computed tomography: A non-invasive diagnostic protocol for baseline lung nodules

BACKGROUND Indeterminate non-calcified lung nodules are frequent when low-dose spiral computed tomography (LD-CT) is used for lung cancer screening. We assessed the diagnostic utility of a non-invasive work-up protocol for nodules detected at baseline in volunteers enrolled in our single-centre screening trial, and followed for at least 1 year. METHODS 5201 high-risk volunteers, recruited over 1 year from October 2004, underwent baseline LD-CT; 4821 (93%) returned for the first repeat LD-CT. Nodules <or=5mm underwent repeat LD-CT at 1 year; nodules 5.1-8mm underwent LD-CT 3 months later; lesions >8mm received combined CT-positron emission tomography (CT-PET). A subset of nodules >8mm was studied by CT with contrast. Protocol failures were delayed diagnosis with disease progression beyond stage I, and negative surgical biopsy. RESULTS 2754 (53%) volunteers presented one or more non-calcified nodules. Ninety-two lung cancers were diagnosed: 55 at baseline and 37 at annual screening (66% stage I). Among the 37 incident cancers, 17 had a baseline nodule that remained stage I, 7 had a baseline nodule that progressed beyond stage I, and 13 presented a new malignant nodule. Baseline and annual cancers were 79 (1.5%) and 13 (0.2%), respectively. In 15 of 104 (14%) invasive diagnostic procedures, the lesion was benign. Sensitivity, and specificity were 91 and 99.7%, respectively, for the entire protocol; 88 and 93% for CT-PET; and 100 and 59% for CT with contrast. CONCLUSIONS The protocol limits invasive diagnostic procedures while few patients have diagnosis delay, supporting the feasibility of lung cancer screening in high-risk subjects by LD-CT. Nevertheless further optimization of the clinical management of screening-detected nodules is necessary.

Long-term, totally implantable central venous access ports connected to a Groshong atheter for chemotherapy of solid tumours: Experience from 178 cases using a single type of device

The aim of this study was to examine the early and late complications rate of central venous access ports connected to the Groshong catheter for long-term chemotherapy delivering. All patients suffering from a neoplastic disease, who required long-term chemotherapy and underwent insertion of implantable ports during a 21-month period (1 October 1994-30 June 1996) were prospectively studied. A single type of port was used, constructed of titanium and silicone rubber (Dome Port, Bard Inc., Salt Lake City, U.S.A), connected to an 8 F silastic Groshong catheter tubing (Bard Inc.). A team of different operators (two general surgeons, one interventional radiologist and four anaesthesiologists) was involved in inserting the port. All devices were placed in the operating room under fluoroscopic control. A central venous access form was filled in by the operator after the procedure and all ports were followed prospectively for device-related and overall complications. Data from the follow-up of these patients were entered in the form and collected in a database. Follow-up continued until the device was removed, the patient died or the study was closed. 178 devices, comprising a total of 32,089 days in situ, were placed in 175 patients. Three patients received a second device after removal of the first. Adequate follow-up was obtained in all cases (median 180 days, range 4-559). 138 devices (77.5%) were still in situ when the study was closed. Early complications included six pneumothoraxes, three arterial punctures and two revisions for port and/or catheter malfunction (overall early complications in 8 patients). Late complications included 3 cases (1.68% of devices) of catheter rupture and embolisation (0.093 episodes/1000 days of use), 2 cases (1.12% of devices) of venous thrombosis (0.062 episodes/1000 days of use), 1 case (0.56% of devices) of pocket infection (0.031 episodes/1000 days of use), and 4 cases (2.24% of devices) of port-related bacteraemias (0.124 episodes/1000 days of use). Infections were caused by coagulase-negative Staphylococcus aureus (4 cases) and Bacillus subtilis (1 case); they required port removal in 3 out of 5 cases. This study represents the largest published series of patients with totally implantable access ports connected to Groshong catheters; this device is a good option for long-term access to central veins and delivery of chemotherapeutic regimens, including continuous intravenous infusions. The low incidence of major complications related to implantation and management of these devices support increased use in oncology patients.

Estimating overdiagnosis in low-dose computed tomography screening for lung cancer: a cohort study.

BACKGROUND Lung cancer screening may detect cancer that will never become symptomatic (overdiagnosis), leading to overtreatment. Changes in size on sequential low-dose computed tomography (LDCT) screening, expressed as volume-doubling time (VDT), may help to distinguish aggressive cancer from cases that are unlikely to become symptomatic. OBJECTIVE To assess VDT for screening-detected lung cancer as an indicator of overdiagnosis. DESIGN Retrospective estimation of the VDT of cancer detected in a prospective LDCT screening cohort. SETTING Nonrandomized, single-center screening study involving persons at high risk for lung cancer enrolled between 2004 and 2005 who received LDCT annually for 5 years. PATIENTS 175 study patients diagnosed with primary lung cancer. MEASUREMENTS VDT was measured on LDCT and classified as fast-growing (<400 days), slow-growing (between 400 and 599 days), or indolent (≥600 days). RESULTS Fifty-five cases of cancer were diagnosed at baseline, and 120 were diagnosed subsequently. Of the latter group, 19 cases (15.8%) were new (not visible on previous scans) and fast-growing (median VDT, 52 days); 101 (84.2%) were progressive, including 70 (58.3%) fast-growing and 31 (25.8%) slow-growing (15.0%) or indolent (10.8%) cases. Lung cancer-specific mortality was significantly higher (9.2% per year) in patients with new compared with slow-growing or indolent (0.9% per year) cancer. Sixty percent of fast-growing progressive cancer and 45% of new cancer were stage I, for which survival was good. LIMITATIONS This is a retrospective study. Volume-doubling time can only indicate overdiagnosis and was estimated for new cancer from 1 measurement (a diameter of 2 mm assumed the previous year). CONCLUSION Slow-growing or indolent cancer comprised approximately 25% of incident cases, many of which may have been overdiagnosed. To limit overtreatment in these cases, minimally invasive limited resection and nonsurgical treatments should be investigated. PRIMARY FUNDING SOURCE Italian Association for Cancer Research.

Should liver metastases of breast cancer be biopsied to improve treatment choice

BACKGROUND Currently, the acquisition of tissue from metastatic deposits is not recommended as a routine practice. Our aim was to evaluate the discordance rate of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) receptor status between primary tumor and liver metastases and its potential impact on treatment choice. PATIENTS AND METHODS We retrospectively analyzed a database including 1250 ultrasound-guided liver biopsies carried out at the European Institute of Oncology from August 1999 to March 2009. ER, PgR, and HER2 status were determined by immunohistochemistry and/or FISH. Differences between proportions were evaluated using Fishers exact test. RESULTS We identified 255 consecutive patients with matched primary and liver tissue samples. Changes in ER status were observed in 37 of 255 patients (14.5%). Changes in PgR status were observed in 124 of 255 patients (48.6%). Changes in HER2 status were observed in 24 of 172 assessable patients (13.9%). We observed a discordance in receptor status (ER, PgR, and HER2) between primary tumor and liver metastases, which led to change in therapy for 31 of 255 of patients (12.1%). CONCLUSIONS Biopsy of metastases for reassessment of biological features should be considered in all patients, when safe and easy to carry out, since it is likely to impact treatment choice.

Ultrasound-guided vacuum-assisted core breast biopsy: experience with 406 cases

PurposeThe aim of this study was to determine the indications, accuracy and complications of vacuum-assisted breast biopsy (VABB) performed using ultrasonographic (US) guidance for non-palpable lesions.Materials and methodsThis was a prospective study in which results from consecutive US-guided VABB performed between January 1999 and April 2003 were subsequently compared to those from excisional biopsy or to long-term follow-up imaging.ResultsFour hundred and six lesions were submitted to VABB procedures. Out of those, 78.9% were benign, 18.8% were malignant, 1.7% was lobular neoplasia, and 0.4% was atypical duct hyperplasia. Underestimation occurred in 2.6% of the cases and false negative results in 0.6%. Sensitivity to VABB was 97%, specificity went up to 100%, negative predictive value was 99%, positive predictive value was 100%, and accuracy was 99%. Complications occurred in 9% of the patients.ConclusionUS-guided VABB is an accurate and safe procedure. The main indication is the non-palpable suspicious breast lesions (category 4). This new technique could be a good alternative for percutaneous and surgery biopsy.

Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

BackgroundThis study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.MethodsA consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.ResultsOf the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).ConclusionA prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.

Lung Cancer Risk Prediction to Select Smokers for Screening CT—a Model Based on the Italian COSMOS Trial

Screening with low-dose helical computed tomography (CT) has been shown to significantly reduce lung cancer mortality but the optimal target population and time interval to subsequent screening are yet to be defined. We developed two models to stratify individual smokers according to risk of developing lung cancer. We first used the number of lung cancers detected at baseline screening CT in the 5,203 asymptomatic participants of the COSMOS trial to recalibrate the Bach model, which we propose using to select smokers for screening. Next, we incorporated lung nodule characteristics and presence of emphysema identified at baseline CT into the Bach model and proposed the resulting multivariable model to predict lung cancer risk in screened smokers after baseline CT. Age and smoking exposure were the main determinants of lung cancer risk. The recalibrated Bach model accurately predicted lung cancers detected during the first year of screening. Presence of nonsolid nodules (RR = 10.1, 95% CI = 5.57–18.5), nodule size more than 8 mm (RR = 9.89, 95% CI = 5.84–16.8), and emphysema (RR = 2.36, 95% CI = 1.59–3.49) at baseline CT were all significant predictors of subsequent lung cancers. Incorporation of these variables into the Bach model increased the predictive value of the multivariable model (c-index = 0.759, internal validation). The recalibrated Bach model seems suitable for selecting the higher risk population for recruitment for large-scale CT screening. The Bach model incorporating CT findings at baseline screening could help defining the time interval to subsequent screening in individual participants. Further studies are necessary to validate these models. Cancer Prev Res; 4(11); 1778–89. ©2011 AACR.