Search

Lung cancer still remains a high mortality disease in the face of developments in diagnostic and therapeutic methods that occurred in the last 20 years. The analysis of the experiences from the first studies - in which chest X-ray (CXR) was adopted, associated or not with sputum cytology - has failed to show a reduction in lung cancer specific mortality. Subsequent screening studies that have introduced the use of low-dose computed tomography (LDCT) have revealed a large number of early-stage lung cancers, thus potentially curable; however, this has not allowed us to demonstrate a decrease in lung cancer-specific mortality. With the results of the American study National Lung ScreeningTrial (NLST), published in 2011, for the first time a lung cancer-specific mortality reduction by 20% thanks to the use of LDCT compared to RXT, was highlighted. However, a false discovery rate of 96.4% was also described with an overdiagnosis that can be up to 78.9% for bronchioalveolar lung cancer. Due to the high sensitivity of LDCT, able to identify a non-calcified pulmonary nodule in one subject on two, it becomes necessary to avail instruments to more accurately identify suspicious nodules. Until some time ago, the possible use of lung tumour markers was not viable in view of the poor organ specificity. The study and development was, then, pushed to organ- and tissue-specific markers such as microRNA (miRNA), noncoding RNA sequences involved in many processes and expression of oncogenic activity of the microenvironment. The use of biomarkers such as circulating miRNA implemented in LDCT screening has highlighted a reduction of 5 times for the rate of false positives, going from 19.4% to 3.7%, with a sensitivity of 87%, a specificity of 81%, and a negative predictive value of 99%. The need to appropriately use the available resources commensurate with the disease to treat will push more and more towards the implementation of LDCT biomarkers based screenings, stable and easily reproducible, as circulating miRNAs, obviating to problems such as false positives, unnecessary procedures of invasive surgery for benign lesions, and optimizing the cost benefit ratios.The development of new specific biomarkers appears to offer new promising prospects.

Introduction: In planning Yttrium-90 ((90)Y)-radioembolizations, strategy problems arise in tumours with multiple arterial supplies. We aim to demonstrate that tumours can be treated via one main feeding artery achieving flow redistribution by embolizing accessory vessels., Methods: One hundred (90)Y-radioembolizations were performed on 90 patients using glass microspheres. In 19 lesions/17 patients, accessory branches were found feeding a minor tumour portion and embolized. In all 17 patients, the assessment of the complete perfusion was obtained by angiography and single photon emission computerized tomography-computerized tomography (SPECT-CT). Dosimetry, toxicity, and tumor response rate of the patients treated after flow redistribution were compared with the 83 standard-treated patients. Seventeen lesions in 15 patients with flow redistribution were chosen as target lesions and evaluated according to mRECIST criteria., Results: In all patients, the complete tumor perfusion was assessed immediately before radioembolization by angiography in all patients and after the (90)Y-infusion by SPECT-CT in 15 of 17 patients. In the 15 assessable patients, the response rate in their 17 lesions was 3 CR, 8 PR, and 6 SD. Dosimetric and toxicity data, as well tumour response rate, were comparable with the 83 patients with regular vasculature., Conclusions: All embolization procedures were performed successfully with no complications, and the flow redistribution was obtained in all cases. Results in term of toxicity, median dose administered, and radiological response were comparable with standard radioembolizations. Our findings confirmed the intratumoral flow redistribution after embolizing the accessory arteries, which makes it possible to treat the tumour through its single main feeding artery.

Purpose: To evaluate the short-term safety and efficacy of the new generation of 70-150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT)., Methods: Forty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response., Results: All patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1-6) and 43 mm (range 10-190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2-4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures)., Conclusion: DEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data., Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n=119) and controls (n=989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk., Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1s (FEV1) independently of MLD (OR 5.37, 95% CI: 2.63-10.97 for FEV1<60% vs. FEV1≥90%), and with increasing MLD independently of FEV1 (OR 3.00, 95% CI: 1.60-5.63 for MLD>-823 vs. MLD<-857 Hounsfield units)., Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV1 was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The purpose of this study was to evaluate the natural evolution of ground-glass nodules (GGNs) in the Multicentric Italian Lung Detection (MILD) trial, which adopted a nonsurgical approach to this subset of lesions., Methods: From September 2005 to August 2007, 56 consecutive MILD participants with 76 GGNs were identified from 1866 individuals who underwent baseline low-dose computed tomography. The features of GGNs were assessed and compared with the corresponding repeat low-dose computed tomographies after a mean time of 50.26 ± 7.3 months. The GGNs were classified as pure (pGGN) or part-solid (psGGN) GGNs. The average of the maximum and the minimum diameters for both pGGNs and psGGNs and the maximum diameter of the solid portion of psGGNs were manually measured. At follow-up, GGNs were classified as follows: resolved, decreased, stable, or progressed (according to three defined growth patterns)., Results: A total of 15 of 48 pGGNs (31.3%) resolved, 4 of 48 (8.3%) decreased in size, 21 of 48 (43.8%) remained stable, and 8 of 48 (16.7%) progressed. Among the psGGNs with a solid component smaller than 5 mm, 3 of 26 (11.5%) resolved, 11 of 26 (42.3%) remained stable, and 12 of 26 (46.2%) progressed. One of the two psGGNs with a solid component larger than 5 mm remained stable, and the other decreased in size. Four lung cancers were detected among the GGN subjects, but only one arose from a psGGN, and was resected in stage Ia., Conclusions: The progression rate of the GGNs toward clinically relevant disease was extremely low in the MILD trial and supports an active surveillance attitude.

The efficacy and cost-effectiveness of low-dose spiral computed tomography (LDCT) screening in heavy smokers is currently under evaluation worldwide. Our screening program started with a pilot study on 1035 volunteers in Milan in 2000 and was followed up in 2005 by a randomized trial comparing annual or biennial LDCT with observation, named Multicentric Italian Lung Detection. This included 4099 participants, 1723 randomized to the control group, 1186 to biennial LDCT screening, and 1190 to annual LDCT screening. Follow-up was stopped in November 2011, with 9901 person-years for the pilot study and 17 621 person-years for Multicentric Italian Lung Detection. Forty-nine lung cancers were detected by LDCT (20 in biennial and 29 in the annual arm), of which 17 were identified at baseline examination; 63% were of stage I and 84% were surgically resectable. Stage distribution and resection rates were similar in the two LDCT arms. The cumulative 5-year lung cancer incidence rate was 311/100 000 in the control group, 457 in the biennial, and 620 in the annual LDCT group (P=0.036); lung cancer mortality rates were 109, 109, and 216/100 000 (P=0.21), and total mortality rates were 310, 363, and 558/100 000, respectively (P=0.13). Total mortality in the pilot study was similar to that observed in the annual LDCT arm at 5 years. There was no evidence of a protective effect of annual or biennial LDCT screening. Furthermore, a meta-analysis of the four published randomized trials showed similar overall mortality in the LDCT arms compared with the control arm.

Purpose: We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems., Methods and Materials: Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT)., Results: Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% ± 4% and 92% ± 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% ± 7%, as opposed to 98% ± 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% ± 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate., Conclusions: This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The mature results from trials comparing ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) and BEACOPP (bleomycin, etoposide, Adriamycin [doxorubicin], cyclophosphamide, Oncovin [vincristine], procarbazine, prednisone) chemotherapies in advanced Hodgkin lymphoma will be available in some years. An early comparison of their curative potential can however be obtained from an assessment of initial tumor burden and chemoresistance., Patients and Methods: Less than a complete remission after treatment and relapse occurring within 12 months thereafter were assumed to be clinical expressions of chemoresistance. The tumor burden was calculated from the measurements of all the lesions documented by staging computed tomography (CT) and was normalized to body surface area to give the relative tumor burden (rTB). Using logistic regression analysis, the relationship between initial rTB, chemoresistance, and chemotherapy regimen administered was retrospectively studied in 222 patients selected from those enrolled in 2 similar randomized trials., Results: The median rTB volumes were 157.9 cm(3)/m(2) in the 115 patients treated with ABVD vs. 154.6 cm(3)/m(2) in the 107 patients treated with BEACOPP, and the distribution of the volumes was identical in the 2 groups. The rTB was confirmed as the best predictor of early treatment failures (22 less than complete responses plus 21 early relapses). For the same rTB, the risk of chemoresistance to BEACOPP was about half that of the chemoresistance to ABVD or, for a given risk of chemoresistance, BEACOPP cured patients with an rTB 89.1 cm(3)/m(2) greater than that cured by ABVD (ie, more than 50% of the median tumor load of patients with advanced-stage disease)., Conclusion: This account of rTB allows an early comparative evaluation of the curative ability of different chemotherapy regimens., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Heat shock proteins (HSP) from tumor cells contain the gp96 polypeptide associated with cancer-specific antigenic peptides. Mice that are immunized with HSP/peptide-complex (HSPPC) derived from cancer tissue reject tumor from which HSPs are purified. We tested in humans whether vaccination with HSPPC-gp96 (Oncophage) from autologous liver metastases of colorectal carcinoma induces cancer-specific T-cell responses in patients rendered disease free by surgery., Experimental Design: Twenty-nine consecutive patients underwent radical resection of liver metastases [Memorial Sloan-Kettering Cancer Center (MSKCC) score 1-3 (good prognosis), 18 patients; score 4-5 (bad prognosis), 11 patients] and received autologous tumor-derived HSPPC-96. Two vaccine cycles were administered (four weekly injections followed by four biweekly injections after 8 weeks). Class-I HLA-restricted, anti-colon cancer lines T-cell response was measured by ELISPOT assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Feasibility, safety, and possible clinical benefits were also evaluated., Results: Either a de novo induced or a significant increase of preexisting class I HLA-restricted T-cell-mediated anti-colon cancer response was observed in 15 (52%) of 29 patients. Frequency of CD3+, CD45RA+, and CCR7- T lymphocytes increased in immune responders. No relevant toxicity was observed. As expected, patients with good prognosis had a significantly better clinical outcome than those with poor prognosis [2-year overall survival (OS), 89 versus 64%, P = 0.001; disease-free survival (DFS), 46 versus 18%, P = 0.001]. Patients with immune response had a statistically significant clinical advantage over nonresponding subjects (2-year OS, 100% versus 50%, P = 0.001; DFS, 51% versus 8%, P = 0.0001). Occurrence of immune response led to better tumor-free survival, whatever the predicted prognosis was (hazard ratio, 0.11-0.12 with/without stratification; P = 0.0012-0.0003)., Conclusions: HSPPC-96 vaccination after resection of colorectal liver metastases is safe and elicits a significant increase in CD8+ T-cell response against colon cancer. In this limited number of patients, two-year OS and DFS were significantly improved in subjects with postvaccination antitumor immune response, independently from other clinical prognostic factors.

Objective: The purpose of our study was to evaluate the effectiveness of intraarterial infusion of paclitaxel incorporated into human albumin nanoparticles for use as induction chemotherapy before definitive treatment of advanced squamous cell carcinoma of the tongue., Subjects and Methods: Twenty-three previously untreated patients (age range, 27-75 years) who had carcinoma of the tongue (stage T3-T4, any N) received intraarterial therapy with paclitaxel incorporated into albumin nanoparticles delivered by transfemoral catheterization into the external carotid artery (10 patients), selectively into the lingual artery (12 patients), or into a faciolingual trunk (1 patient). Each patient received two to four infusions, with a 3-week interval between infusions. The dose administered was 230 mg/m(2) in eight patients, 180 mg/m(2) in six patients, and 150 mg/m(2) in nine patients. Sixteen patients underwent surgery. Of these 16 patients, eight subsequently received radiotherapy, and three received a combination of chemotherapy and radiotherapy. Of the remaining seven patients, one received chemotherapy alone, four received radiotherapy alone, one received chemotherapy plus radiotherapy, and one refused any further treatment., Results: Sixty-seven infusions were performed successfully. Eighteen patients (78%) had a clinical and radiologic objective response (complete, 26%; partial, 52%). Three patients (13%) showed stable disease, and two (9%) showed disease progression. The four patients with complete clinical response who underwent surgery showed microscopic residual carcinoma measuring less than 1 mm in two patients, less than 5 mm in one patient, and less than 1 cm in one patient. The toxicities encountered were hematologic (grade 3) in two patients (8.6%) and neurologic (grade 4) in two patients (reversible paralysis of the facial nerve, 8.6%). Two catheter-related complications occurred: one reversible brachiofacial paralysis and one asymptomatic occlusion of the external carotid artery., Conclusion: Intraarterial infusion of paclitaxel in albumin nanoparticles proved reproducible and effective and deserves further investigation as induction chemotherapy before definitive treatment of advanced tumors of the tongue, with a view to organ preservation.