ABSTRACT
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers; â¼20% of patients have metastases at diagnosis, and 50%-60% subsequently develop metachronous metastases. Bone involvement, despite being rare, is usually associated with higher disease burden, worse prognosis, impaired quality of life, and significant health-related cost. In the last few years, following the positive results of the TRIBE and TRIBE2 trials, the association of FOLFOXIRI plus bevacizumab has become the new standard of care for metastatic CRC. Despite being highly efficacious in all subgroups, little is known about the activity of this regimen in patients with bone metastases. PATIENTS AND METHODS: We carried out a pooled analysis of TRIBE and TRIBE2 studies focusing on patients with skeletal deposits. RESULTS: Our analyses on the whole population showed that patients with baseline bone involvement reported shorter overall survival [OS; 14.0 versus 26.2 months; hazard ratio (HR) 2.04, 95% confidence interval (CI) 1.46-2.87; P < 0.001] and progression-free survival (PFS; 6.2 versus 11.1 months; HR 1.96, 95% CI 1.42-2.69; P < 0.001) compared with those without bone metastases; no significant interaction with the treatment was reported for PFS (P = 0.094) and OS (P = 0.38). Bone metastases had a negative prognostic implication in the multivariate analysis (HR 2.24, 95% CI 1.54-3.26; P < 0.001). Furthermore, patients with bone lesions at first radiological progression (including those with baseline bone metastases) had a shorter OS compared with those who progressed in other sites (10.4 versus 13.2 months; HR 1.48, 95% CI 1.15-1.91; P = 0.002). A trend toward inferior OS (7.5 versus 11 months, HR 1.50, 95% CI 0.92-2.45; P = 0.10) appeared in patients with basal skeletal deposits compared with those with bone involvement at first radiological progression. CONCLUSIONS: Our study confirmed the negative prognostic impact of bone metastases in CRC. Furthermore, we demonstrated for the first time that the survival advantage of triplet chemotherapy plus bevacizumab is maintained even in this prognostically unfavorable subgroup.
Subject(s)
Bone Neoplasms , Colonic Neoplasms , Colorectal Neoplasms , Humans , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Colorectal Neoplasms/pathology , Quality of Life , Camptothecin/therapeutic use , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Prognosis , Colonic Neoplasms/drug therapy , Bone Neoplasms/drug therapyABSTRACT
BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Sorafenib/pharmacology , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Propensity Score , Retrospective Studies , Liver Neoplasms/drug therapyABSTRACT
BACKGROUND: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. PATIENTS AND METHODS: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. RESULTS: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). CONCLUSION: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Humans , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Irinotecan/pharmacology , Irinotecan/therapeutic use , Retrospective Studies , Fluorouracil/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment Outcome , Colonic Neoplasms/drug therapyABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Carcinoma, Hepatocellular/drug therapy , Humans , Liver Neoplasms/drug therapy , Phenylurea Compounds , Prognosis , Quinolines , Retrospective StudiesABSTRACT
BACKGROUND: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting. PATIENTS AND METHODS: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed. RESULTS: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS. CONCLUSIONS: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , BRCA1 Protein/genetics , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Cisplatin/therapeutic use , Germ Cells , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/geneticsABSTRACT
BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/drug therapy , Humans , Liver Neoplasms/drug therapy , Phenylurea Compounds , Prognosis , QuinolinesABSTRACT
INTRODUCTION: The consensus molecular subtypes (CMS) demonstrated prognostic value in metastatic colorectal cancer (mCRC). Similarly, a prognostic impact was suggested for the pre-consensus CRCAssigner (CRCA) classifier in early stages. The potential predictive role of these classifiers with regard to the choice of the first-line therapy has not been established. We investigated the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study. METHODS: Among 679 randomized patients, 426 and 428 (63%) samples were profiled according to CMS and CRCA classifications, respectively. The prognostic and predictive impact of both CMS and CRCA subtypes was investigated with univariate and multivariate analyses for progression-free survival (PFS), PFS 2 (PFS2), and overall survival (OS). RESULTS: Significant associations of CMS and CRCA subtypes with PFS, PFS2, and OS were demonstrated; the CMS classifier confirmed its independent prognostic value in the multivariable model (P value for PFS/PFS2/OS = 0.01/0.07/0.08). The effect of treatment intensification was independent of CMS subtypes (P value for interaction for PFS/PFS2/OS = 0.88/0.75/0.55). A significant interaction effect between CRCA subtypes and treatment arm was demonstrated in PFS (P = 0.02), PFS2 (P = 0.01), and OS (P = 0.008). The benefit of FOLFOXIRI seemed more relevant in the stem-like (PFS, hazard ratio = 0.60; P = 0.03) and mixed subtypes (hazard ratio = 0.44; P = 0.002). These findings were confirmed in a subgroup of patients of the previous TRIBE study. CONCLUSIONS: We confirmed the independent prognostic role of CMS classification in mCRC independently of RAS/BRAF status. CRCA classification may help identifying subgroups of patients who may derive more benefit from FOLFOXIRI/bevacizumab.
Subject(s)
Camptothecin , Colorectal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/therapeutic use , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Consensus , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , PrognosisABSTRACT
BACKGROUND: The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS: Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates. RESULTS: Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%). CONCLUSIONS: The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Age Factors , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Nausea/chemically induced , Nausea/pathology , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Progression-Free Survival , Sex Characteristics , Treatment Outcome , Vomiting/chemically induced , Vomiting/pathologyABSTRACT
BACKGROUND: Refining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies. PATIENTS AND METHODS: We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations. Hypothesizing a prevalence of candidate alterations of 15% and 0% in resistant and sensitive RAS and BRAF wild-type patients, respectively, with two-sided α and ß errors of 0.05 and 0.20, 47 patients per group were needed. RESULTS: Forty-seven patients per group were included. PRESSING panel alterations were significantly more frequent in resistant (24 out of 47, 51.1%) than in sensitive (1 out of 47, 2.1%) patients (P < 0.001) and in right- (12 out of 29, 41.4%) than left-sided (13 out of 65, 20.0%) tumours (P = 0.03). The predictive accuracy of PRESSING panel and sidedness was 75.3% and 70.2%, respectively. Among hyper-selected patients, right-sidedness was still associated with resistance (P = 0.002). The predictive accuracy of the combined evaluation of PRESSING panel and sidedness was 80.4%. As a secondary analysis, 8 (17.0%) resistant and 0 sensitive patients showed microsatellite instability (P < 0.001). CONCLUSION: The investigated panel of genomic alterations allows refining the selection of RAS and BRAF wild-type metastatic colorectal cancer patients candidates for anti-EGFRs, partially explaining and further corroborating the predictive ability of primary tumour sidedness.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , ErbB Receptors/antagonists & inhibitors , Antibodies, Monoclonal/immunology , Case-Control Studies , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/immunology , Disease-Free Survival , ErbB Receptors/immunology , Humans , Microsatellite Instability , Patient Selection , Prospective Studies , Survival RateABSTRACT
Background: Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC. Patients and methods: Four hundred eleven refractory mCRC patients with ECOG performance status (PS) ≤2 receiving regorafenib, TAS-102 or other treatments were used as developing set. Putative prognostic variables were selected using a random forest model and included in a binary logistic model from which the nomogram was developed. The nomogram was externally validated and its performance was evaluated by examining calibration (how close predictions were to the actual outcome) and discriminative ability (Harrell C index) both on developing (internal validation) and validating (external validation) sets. Results: Four variables were selected and included in the nomogram: PS (P < 0.0001), primary tumor resection (P = 0.027), LDH value (P = 0.0001) and peritoneal involvement (P = 0.081). In the developing set, the nomogram discriminative ability was high (C = 0.778), and was confirmed in the validating set (C = 0.778), where the overall outcome was better as a consequence of the enrichment in patients receiving regorafenib or TAS-102 (46% versus 34%; P < 0.0001). Conclusions: Our nomogram may be a useful tool to predict the probability of death within 12 weeks in patients with refractory mCRC. Based on four easy-to-collect variables, the 'Colon Life' nomogram and free app for smartphones may improve mCRC patients' selection for later-line therapies and assist researchers for the enrollment in clinical trials in this setting.
Subject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Cost-Benefit Analysis , Nomograms , Aged , Colon/drug effects , Colon/pathology , Colorectal Neoplasms/mortality , Disease-Free Survival , Drug Combinations , Female , Humans , Logistic Models , Male , Middle Aged , Neoplasm Metastasis , Phenylurea Compounds/administration & dosage , Prognosis , Proportional Hazards Models , Pyridines/administration & dosage , Pyrrolidines , Thymine , Trifluridine/administration & dosage , Uracil/administration & dosage , Uracil/analogs & derivativesABSTRACT
Bioaugmentation-assisted phytoremediation implies the administration of selected plant growth promoting bacteria, which significantly improve plant growth and sequestration of heavy metals. In this work, 184 bacterial strains associated with roots of Pistacia lentiscus were isolated from plants spontaneously growing in the abandoned Sardinian mining areas (SW Sardinia, Italy) and phylogenetically characterised. Twenty-one bacterial isolates were assayed for properties relevant for plant growth promotion and metal tolerance. Five different strains, belonging to the genera Novosphingobium, Variovorax, Streptomyces, Amycolatopsis, Pseudomonas, were selected based on their properties for the greenhouse phytoremediation tests. Among the tested inocula, the strain Variovorax sp. RA128A, able to produce ACC deaminase and siderophore, was able to significantly enhance germination and increase length and weight of shoots and roots. Irrespective of the applied treatment, mastic shrub was able to accumulate Cd, Pb and Zn especially in roots.
Subject(s)
Biodegradation, Environmental , Metals, Heavy/analysis , Metals, Heavy/metabolism , Mining , Pistacia/growth & development , Pistacia/microbiology , Plant Roots/metabolism , Italy , Pistacia/metabolism , Plant Roots/microbiology , Soil Microbiology , Soil Pollutants/analysis , Soil Pollutants/metabolismABSTRACT
The nitrogen and moisture of manure are highly variable parameters and depend on animal type, husbandry techniques, environmental conditions and storage time. The precision in manure dose estimation for crops fertilization depends on the total nitrogen and moisture content just before its incorporation in the field. The aim of the study is to develop a Fourier Transform Near Infrared (FT-NIR) spectroscopy method to determine the total Kjeldhal nitrogen (TKN%) and moisture (M%) of different types of poultry manure prior to land application. Samples covering a wide range of poultry types and different husbandry conditions were obtained from farms of North-Eastern Italy in order to develop the method. The method was calibrated (R(2) = 0.94 for TKN%, R(2) = 0.99 for M%) and validated (R(2) = 0.82 for TKN%, R(2) = 0.95 for M%) in the laboratory. An external validation was also performed in situ with independent samples, of similar origin to the previous data set, which were collected just before application in the field. Spectra acquisitions for these samples were carried out using the same instrumentation which was placed in a special vehicle for monitoring campaigns. The results showed satisfactory prediction accuracy (R(2) = 0.82 for TKN%, R(2) = 0.93 for M%). Finally, an additional analysis was performed to discriminate the different types of poultry effluents. The TKN and M measurements in the disposal areas indicated that current agronomic practices lead to more than double poultry manure oversupply. The proposed FT-NIR methodology aims to improve the current fertilization management and environmental protection by providing fast and precise estimations of poultry manure doses prior to land application.
Subject(s)
Fertilizers/analysis , Manure/analysis , Nitrogen/analysis , Spectroscopy, Near-Infrared/methods , Animals , Conservation of Natural Resources , Poultry , Water/analysisABSTRACT
Abandoned tailing dumps from mining industry represent important sources of metal contamination in the surrounding environments. This study evaluates the potential of two Mediterranean native plants, Pistacia lentiscus and Phragmites australis, for phytoremediation of two Sardinian contaminated mine sites. A 6 months study has been conducted at greenhouse-controlled conditions with the aim of investigating the plant capability to tolerate high metal concentrations and to extract or immobilize them within the roots. The possibility to mitigate stress on the plants and improve treatment efficiency by adding compost as amendment was also evaluated. Both species were able to restrict accumulation of Cd, Pb and Zn to the root tissues exhibiting a metal concentration ratio of plant roots to soil bioavailable fraction higher than two (four in the case of Zn). However, the two species showed different adaptation responses, being the survival of P. australis after 6 months in contaminated soil lower (25 %-58 %) than that observed for P. lentiscus (77 %-100 %). Compost addition resulted in a lower metal uptake in tissues of both plants and a higher survival of P. australis, whilst almost no effect was observed as regard the growth of both species. The two tested species appear to be promising candidates for phytostabilization, P. lentiscus exhibiting a greater adaptability to heavy metal contaminated matrices than P. australis.
Subject(s)
Metals, Heavy/pharmacokinetics , Pistacia/metabolism , Poaceae/metabolism , Soil Pollutants/pharmacokinetics , Waste Products/analysis , Analysis of Variance , Biodegradation, Environmental , Italy , Metals, Heavy/analysis , Mining , Pistacia/growth & development , Plant Roots/metabolism , Poaceae/growth & development , Soil Pollutants/analysisABSTRACT
A novel biopolymer was described in the form of an extracellular polysaccharide (EPS) by Pedobacter sp. strain MCC-Z, a member of a bacterial genus not previously described as an emulsifier producer. The new biomolecule was extracted, purified and characterized, and its surface and emulsifying properties were evaluated. The purified bioemulsifier, named Pdb-Z, showed high emulsifying activity (E24% = 64%) and reduced the surface tension of water up to 41 mN/m with a critical micelle concentration value of 2.6 mg/mL. The chemical characterization of Pdb-Z was performed using (1)H NMR, FT-IR, HPLC/MS/MS and GC/MS. Pdb-Z was found to contain 67% of carbohydrates, consisting mainly of galactose and minor quantities of talose, 30% of lipids, being pentadecanoic acid the major lipidic constituent, and 3% of proteins. The bioemulsifier was a glycolipids-protein complex with an estimated molecular mass of 10(6)Da. Furthermore, Pdb-Z emulsified pure aliphatic and aromatic hydrocarbons as well as diesel more efficiently than commercial synthetic surfactants, used for comparison. Our results suggest Pdb-Z has interesting properties for applications in remediation of hydrocarbon-contaminated environments and bioremediation processes.
Subject(s)
Emulsifying Agents/chemistry , Pedobacter/chemistry , Diffusion , Emulsifying Agents/isolation & purification , Fatty Acids/analysis , Hydrodynamics , Hydrophobic and Hydrophilic Interactions , Monosaccharides/analysis , Proton Magnetic Resonance Spectroscopy , Spectroscopy, Fourier Transform Infrared , Surface TensionABSTRACT
BACKGROUND: Although Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive validation to be included in the standard approach to finding sentinel nodes in breast cancer. MATERIALS AND METHODS: To validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches. RESULTS: At the end of the enrollment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%-99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects. CONCLUSIONS: The index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC.
Subject(s)
Breast Neoplasms/pathology , Carcinoma/pathology , Fluorescent Dyes , Indocyanine Green , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy/methods , Adult , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Carcinoma/surgery , Cohort Studies , Female , Humans , Mastectomy/methods , Mastectomy, Segmental/methods , Middle Aged , Prospective Studies , Radiopharmaceuticals , Technetium Tc 99m Aggregated AlbuminABSTRACT
Corsica and Sardinia represent major hotspots of plant diversity in the Mediterranean area and are priority regions for conservation due to their high number of endemic plant species. However, information supporting human decision-making on the conservation of these species is still scarce, especially at the genetic level. In this work, the first assessment is reported of the species-wide spatial genetic structure and diversity of Ferula arrigonii Bocchieri, a Corso-Sardinian endemic located in a few coastal sites and on small islands. Nine populations covering the entire natural range of the species were investigated by means of AFLP (amplified fragment length polymorphism) markers. Results indicate that this species is characterised by high levels of genetic polymorphism (92% polymorphic fragments) and of genetic diversity (H(w) = 0.317) and by relatively low differentiation among populations (F(st) = 0.057). PCoA, Bayesian analysis and neighbour-joining clustering were also employed to investigate the genetic structure of this species. Three genetically distinct groups were detected, although with considerable overlap between populations.
Subject(s)
Ferula/genetics , Polymorphism, Genetic , Amplified Fragment Length Polymorphism Analysis , Bayes Theorem , Cluster Analysis , Conservation of Natural Resources , France , Geography , Italy , Mediterranean RegionABSTRACT
The aim was to evaluate the cost of capecitabine vs conventional combination chemotherapics such as 5-fluorouracil (5-FU) for the treatment of metastatic colorectal cancer (mCRC) in Italy. The study was a multicenter, retrospective longitudinal treatment-cost analysis. Patients older than 18 years, diagnosis of mCRC and at least 3 completed cycles of chemotherapy with oral capecitabine or 5-FU also in association with other chemotherapic agents were enrolled. Direct healthcare resources attributable to mCRC treatment were quantified using 2007 prices and tariffs. The analysis was conducted from the National Health Service perspective with a 6-month time horizon. A total of 231 patients affected by mCRC (55% males; mean age 63.7+/-10.31 yrs) were studied. Total direct costs per patient per month in capecitabine and 5-FU groups were euro1,001.66 +/- euro434.93 and euro3,172.81 +/- euro1,232.37 respectively (p<0.0001). Oral capecitabine therapy cost the health service less than intravenous therapies.
Subject(s)
Antimetabolites, Antineoplastic/economics , Colorectal Neoplasms/pathology , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Fluorouracil/economics , Age Factors , Antimetabolites, Antineoplastic/therapeutic use , Capecitabine , Colorectal Neoplasms/drug therapy , Cost-Benefit Analysis , Deoxycytidine/economics , Deoxycytidine/therapeutic use , Female , Fluorouracil/therapeutic use , Health Expenditures , Humans , Longitudinal Studies , Male , Middle Aged , Neoplasm Metastasis , Retrospective Studies , Sex FactorsABSTRACT
AIMS: To study the effect of selected bacterial strains on hemp water-retting and properties of retted fibre. METHODS AND RESULTS: The trials were performed in laboratory tanks. The traditional water-retting process, without inoculum addition, was compared to a process modified by inoculating water tanks with two selected pectinolytic bacteria: the anaerobic strain Clostridium sp. L1/6 and the aerobic strain Bacillus sp. ROO40B. Six different incubation times were compared. Half the fibre obtained from each tank was combed. Micromorphological analyses were performed by scanning electron microscopy on uncombed and combed fibres. Moreover, organoleptic and chemical analyses of uncombed fibres were performed. CONCLUSIONS: The inoculum, besides speeding up the process, significantly improved the fibre quality. The fibre was not damaged by mechanical hackling, thanks to the good retting level obtained by the addition of selected strains, differently to what happened with the traditionally retted fibre. The best fibre quality was obtained after 3-4 days of retting with the addition of the bacterial inoculum. SIGNIFICANCE AND IMPACT OF THE STUDY: Retting is the major limitation to an efficient production of high-quality hemp fibres. The water-retting process and fibre quality were substantially improved by simultaneously inoculating water tanks with two selected pectinolytic strains.
Subject(s)
Bacillus/growth & development , Cannabis , Clostridium/growth & development , Industrial Microbiology/methods , Pectins/metabolism , Textiles , Aerobiosis , Anaerobiosis , FlaxSubject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Hepatectomy , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Chemotherapy, Adjuvant , Colorectal Neoplasms/pathology , Evidence-Based Medicine , Humans , Liver Neoplasms/secondary , Practice Patterns, Physicians' , Treatment OutcomeABSTRACT
Lipoplatin is a liposome encapsulated form of cisplatin. phase i studies on lipoplatin have demonstrated that the compound has an excellent toxicity profile. therefore we performed a phase ii trial in heavily pre-treated patients with advanced non-small-cell lung cancer (NSClC), performance status 0-2 in which the primary endpoint was response rate and secondary endpoints were safety and overall survival.Nineteen patients, average age 64 years old, with stage iV NSClC, were treated with lipoplatin 100 mg/m(2) every two weeks, as second line chemotherapy.We observed 1 partial remission (5.2%) and 3 stable diseases (15.9%). Time to progression (ttp) was 16 weeks and median overall survival (OS) was 31 weeks (7.2 months). We observed G1-G2 toxicity during chemotherapy, mainly gastrointestinal with nausea and vomiting (4 patients), asthenia (3 patients), mucositis (2 patients) and anemia (4 patients).Our phase ii study does not support a more extensive use of lipoplatin in phase III studies. An increase of dosage and a better selection of patients are mandatory to understand the real therapeutic activity of lipoplatin.