[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to determine the potential role of occupational exposures to chromium (Cr) in the onset of extragonadal germinal embryonal carcinoma. The first two cases of workers in a company with Cr exposure are reported. The published scientific literature regarding the topic in peer-reviewed journals including MEDLINE and CancerLit databases was extensively reviewed. Two young patients who were coworkers in the same company, exposed to Cr, developed extragonadal germinal embryonal carcinomas. One of them also developed angiosarcoma of the mediastinum. To the best of our knowledge these are the first two cases of germinal embryonal carcinoma in patients with occupational exposure to Cr.
Journal of Toxicology and Environmental Health Part A 01/2015; 78(1):1-6. · 1.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.
World journal of gastroenterology : WJG. 12/2014; 20(46):17279-17287.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to compare survival of resected and unresected patients in a large cohort of patients with metastases to the pancreas from renal cell carcinoma (PM-RCC).
Data from 16 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. The Kaplan-Meier and log-rank test methods were used to evaluate overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC, and time to PM-RCC occurrence.
Overall, 103 consecutive patients with radically resected primary tumors were enrolled in the analysis. PM-RCCs were synchronous in only three patients (3 %). In 56 patients (54 %), the pancreas was the only metastatic site, whereas in the other 47 patients, lung (57 %), lymph nodes (28 %), and liver (21 %) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 years (range 0-24 years) after nephrectomy. Surgical resection of PM-RCC was performed in 44 patients (median OS 103 months), while 59 patients were treated with tyrosine kinase inhibitors (TKIs; median OS 86 months) (p = 0.201). At multivariate analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor. None of the other clinical variables, such as age, sex, pancreatic surgery, or the presence of concomitant metastases, were significantly associated with outcome in PM-RCC patients.
The presence of PM-RCC is associated with a long survival, and surgical resection does not improve survival in comparison with TKI therapy. However, surgical resection leads to a percentage of disease-free PM-RCC patients.
Annals of Surgical Oncology 12/2014; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: To assess the predictive role of lactate dehydrogenases (LDH) and fibrinogen (FBG) serum levels in metastatic colorectal cancer (mCRC) patients receiving a first-line bevacizumab-based therapy.Objectives: The aim of the present analysis was to retrospectively evaluate the role of basal and post-treatment LDH and FBG serum levels in predicting the clinical outcome of 139 mCRC patients receiving first-line chemotherapy in combination with bevacizumab.Results: A statistically significant association between high pre-treatment LDH and FBG levels and progressive disease was observed with respect to low basal LDH and FBG patients. Furthermore, median progression-free survival was 7.3 versus 10.8 months and 7.3 versus 9.4 months for high and low LDH and FBG levels, respectively. Within the high LDH group, we observed a statistically significant reduction of LDH mean value compared with pre-treatment values in patients with objective response rate and stable disease.Conclusions: High LDH and FBG levels correlated with prognosis. A significant correlation between bevacizumab-based chemotherapy-induced reduction in LDH serum levels and response to treatment was observed within the high LDH group. These results, if confirmed in larger prospective studies, could be helpful for early identification of patients responsive to bevacizumab-based chemotherapy or candidate to more aggressive treatments.
[Show abstract][Hide abstract] ABSTRACT: Although the extended RAS analysis allows a better identification of patients potentially candidates to anti-EGFR monoclonal antibodies, a significant proportion of tumours may still reveals refractory to such a treatment approach. In these latter cases patients are then exposed to unnecessary toxicities without clinical benefit. Among many further biological factors that may have a role in determining resistance/sensitivity to EGFR-inhibitors, the EGFR itself, other members of the HER family (i.e. HER-2 and HER-3) as well as other surface receptors such as the IGF-1 receptor seem of particular interest. Preclinical models have shown that these receptors are biologically connected to each other and that they are able to directly or indirectly influence each other's downstream molecular pathways. In the presence of abnormal expression of these biological determinants, intracellular pathways may consequently become independent from receptor-targeting pharmacological modulations thus making treatment directed against the receptor ineffective. Clinical observations and translational studies seem to confirm these findings. The Authors have reviewed the literature and have selected recent clinical reports focusing on translational research on EGFR itself or on other molecules that may interfere with its pathway. With the aim to offer an effective tool for research and clinical practice, we also discuss on potential future developments.
Current Drug Targets 11/2014; · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In November 1964, the recently founded American Society of Clinical Oncology (ASCO) held its first national meeting in Chicago (IL, USA). Only 51 members attended the conference. At the 2014 ASCO meeting, more than 30,000 healthcare professionals gathered together in the same city to attend this prime scientific conference. The many passionate attendees not only wanted to celebrate ASCO's 50th anniversary, but they also wanted to share the results of milestone clinical and translational research and, most notably, to consider future avenues of progress against cancer. In this report, the most significant advances in both clinical and translational research presented at the 2014 ASCO plenary session and oral abstract sessions will be discussed, specifically focusing on breast and colorectal carcinomas. Both of these are among the leading causes of cancer-related deaths. Many of the results presented significantly contribute to building a pipeline of novel treatment options. Moreover, these results will soon have an impact on clinical practice and may help medical oncologists move their research forward.
[Show abstract][Hide abstract] ABSTRACT: 2014 Genitourinary Cancers Symposium San Francisco, CA, USA, 30 January-1 February 2014 The American Society of Clinical Oncology symposium dedicated to genitourinary tumors represents an unmissable opportunity for the whole oncology community with a special interest in the diagnosis and treatment of genitorurinary tract malignancies, in particular kidney and prostate tumors. The 2014 Genitourinary Cancers Symposium focused attention on the need to find a personalized therapy for metastatic renal cell carcinoma and castration-resistant prostate cancer patients. The development of biomarkers for tumor response and/or resistance will represent a major step in this context and has been the focus of several researches at the symposium.
[Show abstract][Hide abstract] ABSTRACT: Measures of prognosis for cancer patients are typically evaluated at the time of diagnosis. However, this study assessed the changes in 2-year CS rates after first-line chemotherapy for metastatic UC.Patients and Methods
Conditional overall survival and CPFS probability were estimated using the Kaplan–Meier method. Adjusted survival functions were stratified according to age groups (< 70 years vs. ≥ 70 years), sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS; ECOG PS ≤ 2 vs. ECOG PS > 2), pretreatment Hb levels (< 12 mg/dL vs. ≥ 12 mg/dL) and pretreatment NLR (< 3 vs. ≥ 3). Pairs of CS curves were compared using the Mantel–Haenszel log-rank test.ResultsTwo hundred ninety-eight patients were included in this analysis, 233 were male, and their median age was 69 years. First-line median overall survival and progression-free survival were 10.7 months (95% confidence interval [CI], 9.6-12.6) and 6.0 months (95% CI, 5.5-7.1), respectively. CPFS and COS showed an increasing trend in the population considered (b = 0.35; P < .001 and b = 0.79; P < .001, respectively). A significant increase in terms of COS and CPFS trends was identified in patients with age < 70 years (P = .02 and P = .005, respectively) and pretreatment NLR ≤ 3 (P = .05 and P < .001, respectively). Patients with Hb levels < 12 g/dL showed a significantly poorer 2-year COS.Conclusion
The conditional probability of survival at 2 years from the start of first-line chemotherapy for advanced UC changes over time according to clinical characteristics.
Clinical Genitourinary Cancer 10/2014; · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Totally implantable central venous accesses (port-a-cath) are often used for chemotherapy administration or prolonged intravenous infusions in cancer patients. Local and systemic complications may occur both during and after placement of port-a-cath despite the well-established techniques for its placement and care. Out of other catheter-related local complications, thrombosis and infections represent the most common. Complications related to central venous catheter may be associated with infusion of both conventional chemotherapy and molecularly targeted therapy. Incidence and nature of complications of central venous catheter have been well established for long-term chemotherapy. However, very sparse data exists on the incidence of complications of molecularly targeted therapies administered through a central venous catheter. Hence, we decided to retrospectively analyze the local complications of a central venous catheter in patients receiving molecularly targeted therapy and conventional chemotherapy, respectively.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: Aim: SIADH may be related to several causes (pulmonary disorders, CNS disturbances, drugs and chemotherapeutic agents), but in the majority of cases it is caused by malignancies. This observational study aimed to analyze treatments and outcome of SIADH in cancer pts. Methods: This study includes 69 consecutive cancer pts who experienced SIADH between 2010 and 2014 in 22 Italian Cancer Centers. Data on clinico-pathology, anticancer and SIADH treatments were recorded and statistically analized. Results: M/F ratio was 47/22, median age was 67 years (range 37-83). Primary tumor was lung cancer in 50 pts (SCLC in 39), while it was GI cancer in 8 pts. Fifty-eight pts were hospitalized due to SIADH, HN at admission was ≤130 mEq/l in 94.3%. Median duration of hospitalization was 13 days (range 3-90). 31 pts received tolvaptan for SIADH treatment (group A); other treatments included hypertonic saline solutions, diuretics, fluids restriction (group B). Group A included a significant higher N° of lung cancer pts (77.4% vs 68.4%) with metastatic disease (80.6% vs 76.3%). Moreover pts in group A had more severe HN at admission: serum sodium was ≤130 mEq/l in 96.7% pts and <120 mEq/l in 48% of pts, while in group B it was ≤130 mEq/l in 66.6% of pts and <120 mEq/l in 42.9%. Median sodium at the beginning of tolvaptan was 120 mEq/l (range 110-130), in group B it was 117 mEq/l (range 109-132). In group A 13 pts started tolvaptan 15 mg/daily, 4 started with 30 mg and 14 with 7.5 mg. No toxicity due to tolvaptan was observed in 25 pts, 6 experienced dry mouth. In 19 pts a dose change was required: in 4 it was increased to 30 mg/daily, while in the remaining 15 it was decreased to 7.5 mg every other day. HN improvement with tolvaptan was observed in all cases. Lenght of hospitalization was significantly longer in pts not receiving tolvaptan (15 days, range 4-100, vs 12 days, range 3-53 in pts receiving tolvaptan vs 8 days, range 1-41 in pts receiving tolvaptan since start of tolvaptan, p = 0.002). Severity of HN and not obtaining its correction correlated with lenght of stay and with overall survival (p < 0.05). Conclusions: To our knowledge this is the largest study analyzing SIADH in cancer pts to demonstrate that HN due to SIADH may result in a prolongation of hospitalization and in a worse overall survival when not adequately corrected and that tolvaptan represents an effective treatment potentially improving both. Disclosure: All authors have declared no conflicts of interest.
[Show abstract][Hide abstract] ABSTRACT: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer.
Annals of Surgical Oncology 09/2014; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The number of anti-angiogenic drugs who demonstrated activity in metastatic colorectal cancer patients is arising but there is still much debate on which is the optimal use of this class of agents, with particular emphasis given on when (meant as in which line of treatment) and how (meant as in duration of treatment). We sampled the data of randomised phase II-III trials employing this type of drugs, with particular emphasis on trying to “highlight” situations where anti-angiogenetic treatment could provide most benefit. The review displays all relevant clinical data regarding the use of anti-angiogenic drugs in metastatic colorectal cancer and comments on potential implications of these trials in everyday clinical practice.
Cancer Treatment Reviews 09/2014; · 6.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:
Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC.
PATIENTS AND METHODS:
Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed.
The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001).
This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life
[Show abstract][Hide abstract] ABSTRACT: Hyponatraemia is one of the most common tumour-related electrolyte disorders. Several clinical, histological and serum factors have been found to influence prognosis, but, to date, there are no studies focusing on the prognostic role of hyponatraemia in mesothelioma. The aim of this study was to assess the prognostic role of hyponatraemia in malignant pleural mesothelioma.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.
[Show abstract][Hide abstract] ABSTRACT: Sunitinib malate (Sutent; Pfizer, Inc, New York, NY) is an oral multitargeted tyrosine kinase inhibitor that inhibits VEGF receptors (VEGFR-1, VEGFR-2, and VEGFR-3) among a family of kinase targets and have a central role in first-line treatment of metastatic renal cell carcinoma (mRCC). The approved schedule for sunitinib is 50 mg/day oid in the so called “4 weeks on and two weeks off” (4/2 schedule). Since treatment with sunitinib can be maintained for years, adequate treatment of adverse events (AEs) and care for quality of life is essential. For this reason, several alternative schedules have been proposed in order to personalize sunitinib administration and reduce related toxicity. This review discuss the efficacy and tolerability of alternative regimens to the standard 4/2 schedule that have been investigated in RCC patients including schedule of 50 mg/day 2-weeks on/1-week off, continuous schedule of 37.5 mg daily and the “Stop and Go strategy”.
Critical Reviews in Oncology/Hematology 08/2014; · 4.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Historically, the cornerstone of treatment of advanced gastric cancer (GC) is 5-fluorouracil (5-FU)-based chemotherapy that increases median overall survival (OS) compared to best supportive care by some months. The addition of cisplatin (CDDP) to chemotherapy doublets showed a limited but significant benefit in term of OS according to a Cochrane meta-analysis. However, the recent individual patient-data GASTRIC meta-analysis, confirms this benefit in term of progression-free survival (PFS) but not OS, in randomized eight trials that include or not CDDP. The substitution of CDDP with a modern agent (oxaliplatin, irinotecan or taxanes) has been poorly evaluated in the literature. The REAL-2 phase III trial confirmed the equivalence of oxaliplatin and CDDP-based triplets, and a meta-analysis of three oxaliplatin-based randomized trials demonstrated that these combinations are better that CDDP-based doublets or triplets, improving both PFS (HR =0.88) and OS (HR =0.88). In particular, oxaliplatin-based chemotherapy was associated with less neutropenia and thromboembolic events, but with worse neurotoxicity. Given that the role of chemotherapy in advanced GC is palliative, CDDP-free regimens, and in particular oxaliplatin-based chemotherapy, may be considered for both CDDP-fit and unfit patients (that are those with poor renal function, older age, bad performance status or who cannot tolerate forced hydration for example). The limited absolute survival benefit of chemotherapy in advanced GC (few weeks at best), the cumbersome vascular toxicity of CDDP and the activity of several new drugs such irinotecan, oxaliplatin, taxanes and oral fluoropyrimidines make nowadays possible to consider CDDP-free regimens for the treatment of this incurable disease.
Journal of gastrointestinal oncology 08/2014; 5(4):318-22.