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Abstract Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal anticancer agents and the role of SAMe in the prevention of this complication. [ABSTRACT FROM AUTHOR]

Background Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. Patients and methods We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. Results Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P = 0.01). Conclusion Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options. [ABSTRACT FROM PUBLISHER]

Background: Hepatotoxicity represents a frequent chemotherapy-related side effect, often associated with course delays, discontinuations, and dose reductions. S-adenosylmethionine (AdoMet) administration is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced damage.Patients and Methods: Seventy-eight patients affected by metastatic colorectal cancer were enrolled. Forty-two patients were treated with bevacizumab and XELOX without administering AdoMet, 32 were treated with the same regimen plus supplementation with AdoMet. Liver enzymes levels were assessed before starting the treatment, and then every therapy cycle, liver toxicity, chemotherapy course delays, discontinuations, and dose reductions due to liver toxicity were recorded.Results: Aspartate aminotransferase (P = 0.02), alanine transaminase (P < 0.001), lactate dehydrogenase (P = 0.008), total bilirubin (P = 0.03), and gamma-glutamyltransferase (P < 0.001) were found to be significantly lower in patients treated with AdoMet than in those who were not. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (P = 0.009) and had a reduced need of course delay (P = 0.042) and dose reduction (P = 0.051).Conclusions: AdoMet supplementation in patients affected by metastatic colorectal cancer treated with oxaliplatin-based regimen seems to be effective in the prevention of chemotherapy-induced liver injury. [ABSTRACT FROM AUTHOR]

Background: KRAS wild-type mutational status is necessary but not sufficient to get benefit from epidermal growth factor receptor inhibition. Predictive markers are currently being evaluated. In this study, we investigated early hypomagnesemia as a predictor of efficacy and outcome in terms of time to progression (TtP) and overall survival (OS) in a cohort of patients affected by advanced colorectal adenocarcinoma KRAS wild-type cetuximab-treated.Patients and methods: One hundred and forty-three patients affected by stage IV colorectal adenocarcinoma KRAS wild type receiving cetuximab + irinotecan (CTX+IRI) as third-line anticancer treatment and resistant to oxaliplatin- and irinotecan-based chemotherapy were retrospectively included. Magnesium plasma levels were measured before the first day and 7, 14, 21 and 28 days after CTX+IRI infusion.Results: The median magnesium basal value showed a statistically significant decrease after the start of CTX+IRI treatment (at 28 days, P < 0.0001). Patients with an early decrease of magnesium levels >50% compared with the basal level had a higher tumor response rate (55.8% versus 16.7%, P < 0.0001), a longer TtP (6.3 versus 3.6, P < 0.0001) and a longer median OS (11.0 versus 8.1, P = 0.002).Conclusions: We have shown that early hypomagnesemia could be a predictor of efficacy and outcome in those patients. Magnesium circulating level is an easy and inexpensive biomarker to routinely be detected in patients treated with cetuximab. [ABSTRACT FROM AUTHOR]

Electrochemotherapy (ECT) couples the administration of anticancer drugs with the delivery of electric pulses that increase the drug uptake through the cell membranes, resulting in an improved efficacy. To evaluate the tolerability and efficacy of cisplatin (CDDP) as an ECT agent to prevent recurrence of incompletely resected mast cell tumors (MCTs). Thirty-seven dogs. Prospective study recruiting dogs with incompletely excised MCTs as confirmed by surgeon and pathology reports. After debulking, the tumor bed and margins were infiltrated with CDDP, and then exposed to trains of biphasic electrical pulses under sedation. Five minutes after the injection of the chemotherapy agent, sequences of 8 biphasic pulses lasting 50 + 50 μs each, were delivered in bursts of 1,300 V/cm for sclerosed and of 800 V/cm for exposed lesions, with caliper or needle array electrodes, respectively. A second session was performed 1 or 2 weeks later based on clinical considerations. The treatment was well tolerated with minimal adverse effects. Twenty-nine dogs had no evidence of recurrence over the 6-year study period, 6 had tumor recurrence, 1 died of multiple cutaneous MCTs, and 1 died of unrelated causes. The estimated median time to recurrence was 1,200 days. Recurrence was not observed among the long-term (>1 year) treated dogs. ECT with CDDP appears effective in the treatment of incompletely resected MCT in dogs and could be a useful addition to the current options based on its low cost, limited toxicity, and ease of administration. [ABSTRACT FROM AUTHOR]

Objective: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) should be considered in sudden onset, prepubertal Anorexia Nervosa (AN), arising shortly after an apparent streptococcal infection. However, the absence of a specific biological marker of PANDAS renders the diagnosis difficult. This paper critically reviews available tests for PANDAS and recommends a standardized approach to its investigation. Method: Medline database review between 1990 and 2008. Results: Existing tests may be categorized as: (i) Non-specific markers of inflammation or immune response (Erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; Neopterin), (ii) specific markers of streptococcal infection (throat swab and anti-streptococcal antibodies, Anti-streptolysin, ASO; Antideoxyribonuclease B, antiDNaseB), (iii) non-specific markers of auto-immune reaction (Antineuronal antibodies, AnAb; D8/17). No one test reliably identifies PANDAS. The lack of specificity and methodological problems may lead to errors of diagnosis. Discussion: When PANDAS-Anorexia Nervosa (PANDAS-AN) is suspected clinically we recommend conducting all the above investigations. The more positive results there are the more likely is the diagnosis, but particular weighting should be given to AnAb and D8/17. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR), which participates in signalling pathways that are deregulated in cancer cells, is frequently mutated in colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan. We included 55 heavily pretreated patients (colon/rectum: 34/11, M/F: 16/29, median age 63 years, range: 27–79) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen. Patients were followed for tumour response and were also evaluated for the time to tumour progression, and safety of treatment. Cetuximab was given at an initial dose of 400 mg m−2, followed by weekly infusions of 250 mg m−2. Irinotecan was administered weekly at the dose of 90 mg m−2. All patients were assessable for treatment efficacy and safety response rate was 25.4% (95% CI: 21.7–39.6%); 38.2% (95 CI: 18.6–39.8%) of patients showed a disease stability as the best response. As a consequence, the overall tumour control rate was 63.6% (95% CI: 46.4–70.6%). The median time to progression was 4.7 months (95% CI: 2.5–7.1 months) and the median survival time was 9.8 months (95% CI: 3.9–10.1 months). The most common G3-4 noncutaneous side toxicities were: diarrhoea (16.4%), fatigue (12.7%) and stomatitis (7.3%). 89.1% of patients developed skin toxicity and 32.6% of cases was of grade 3–4. No allergic reactions were identified at any courses in any patients. Fever was documented in 27.3% of patients and was most commonly recorded after the first administration. Cetuximab has clinically significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens.British Journal of Cancer (2006) 94, 792–797. doi:10.1038/sj.bjc.6603018 www.bjcancer.com Published online 28 February 2006 [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of apoptosis and apoptosis-involved proteins in a series of surgically resected pancreatic cancer patients. All patients affected by pancreatic adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. Patients' clinical data and pathological tumour features were recorded. Survivin and Cox-2 expression were evaluated by immunohistochemical staining. Apoptotic cells were identified using the TUNEL method. Tumour specimen of 67 resected patients was included in the study. By univariate analysis, survival was influenced by Survivin overexpression. The nuclear Survivin overexpression was associated with better prognosis (P = 0.0009), while its cytoplasmic overexpression resulted a negative prognostic factor (P = 0.0127). Also, the apoptotic index was a statistically significant prognostic factor in a univariate model (P = 0.0142). By a multivariate Cox regression analysis, both the nuclear (P = 0.002) and cytoplasmic (P = 0.040) Survivin overexpression maintained the prognostic statistical value. This is the first study reporting a statistical significant prognostic relevance of nuclear and cytoplasmic Survivin overexpression in pancreatic cancer. In particular, patients with high nuclear Survivin staining showed a longer survival, whereas patients with high cytoplasmic Survivin staining had a shorter overall survival. [ABSTRACT FROM AUTHOR]

This study was designed to elucidate the possible relationship between tumour related genes and angiogenesis in colon cancer. The protein expression of p53, bcl-2, Von Willebrand factor and vascular endothelial growth factor (VEGF) were analysed by immunohistochemistry in 57 paraffin-embedded colon cancer. The results showed that microvessel density (MVD) was lower in VEGF negative tumours than in VEGF positive ones (P<0.0001). MVD and VEGF in p53 negative tumours were significantly lower than in p53 positive tumours (respectively, P=0.003 and P<0.0001). Moreover, positive correlations were recorded between VEGF expression and MVD, and bcl-2 expression (respectively, P<0.0001 and P=0.009). Our data confirm the central role of VEGF in angiogenesis and suggest direct correlations among p53, bcl-2 and VEGF expression in colon cancer. [Copyright &y& Elsevier]

The article reports on the use of electrochemotherapy (ECT) and surgery in an 11-year-old male castrated Belgian malinois dog to cure a soft tissue sarcoma. The dog underwent a complete blood cell count, urinalysis and abdominal ultrasonography before ECT. The dog's soft tissue sarcoma had been reduced with 5.5 x 5 x 2 cm. after ECT.

Comments on the article 'Enoxaparin Effect Depends on Body-weight and Current Doses May Be Inadequate in Obese Patients,' published in volume 90, 2003 issue of the 'British Journal of Surgery.' Relationship between low molecular weight heparin (LMWH) pharmacodynamic or pharmacokinetic parameters and patients' weight; Correlation between doses of LMWH and surgery-related thromboembolic events.

BACKGROUND Desmoid tumorS are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments. METHODS We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral y-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival. RESULTS From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (4196 vs. 896; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 096, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P50.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54°/o), fatigue On 51%), hypophosphatemia On 42°6), and maculopapular rash (in 3296); 95% adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (7496). CONCLUSIONS Nirogacestat was associated with significant benefits with respect to progressionfree survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFiCIinica]Trials.gov number, NCT03785964.). [ABSTRACT FROM AUTHOR]

Presents a correction to the article "Nuclear and Cytoplasmic Expression of Survivin in 67 Surgically Resected Pancreatic Cancer Patients," previously published in the "British Journal of Cancer."

In localized prostate cancer (PCa), Grade Group (GG) and Gleason Score (GS) have a well-established prognostic role. In metastatic castration resistant prostate cancer (mCRPC), the prognostic role of GS and GG is less defined. In first-line treatment of mCRPC, androgen receptor (AR)-directed drugs (abiraterone acetate, enzalutamide) and docetaxel represent the referring options. There is no evidence that the GS/GG systems can add information to guide the choice between AR-directed drugs and docetaxel in the first-line setting of mCRPC. Nowadays there are no validated biomarkers, which define patients who may benefit or not from hormonal treatments or chemotherapy. Androgen receptor (AR) copy number variations (CNV) are predictive factors of poor response to abiraterone and enzalutamide. There are no available data about the association between AR CNV and GG. In this retrospective study, we analysed the association of the highest GG score with AR CNV and their impact on the clinical outcome of AR-directed drugs and docetaxel as first-line therapy for mCRPC patients. Patients benefit from docetaxel, abiraterone or enzalutamide regardless the GG. However, the presence of GG5 and AR CNV gain identifies a subgroup of patients with poor prognosis, which could benefit from front-line docetaxel instead of AR-directed drugs. [ABSTRACT FROM AUTHOR]

Background Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC. Patients and methods This retrospective, multicenter, observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes. Results Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P = 0.009) and produced a trend toward improved overall survival versus no zoledronic acid. Conclusion This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting. [ABSTRACT FROM AUTHOR]

Perrone G, Santini D, Vincenzi B, Zagami M, La Cesa A, Bianchi A, Altomare V, Primavera A, Battista C, Vetrani A, Tonini G&Rabitti C(2005)Histopathology46,561–568COX-2 expression in DCIS: correlation with VEGF, HER-2/ neu, prognostic molecular markers and clinicopathological features: There is considerable evidence that links COX-2 to the development of cancer. The aim of our study was to assess, by immunohistochemistry, COX-2 expression in ductal carcinomain situ(DCIS) and its possible correlation with HER-2/ neu, vascular endothelial growth factor (VEGF) expression and other common immunohistochemical parameters (p53, ER, PGR, Ki67).: Tissue samples of 49 archival cases of DCIS without any invasive component were analysed for COX-2, HER-2/ neu, VEGF, oestrogen and progesterone receptors, Ki67 and p53 by immunohistochemistry using specific antibodies. COX-2 expression was detected in 43 (87.8%) tissue samples, of which 12 (24.5%) were graded as weak, 22 (44.9%) as moderate and nine (8.4%) as high expression. Only six (12.2%) lesions were negative for COX-2 expression. VEGF expression was detected in 93.8% of samples; 66.7% of lesions were found to be positive for HER-2/ neuexpression. Furthermore, COX-2 expression was significantly correlated with VEGF expression (P = 0.003). A significant positive correlation was also observed between COX-2 and HER-2/ neuexpression (P < 0.0001).: Our results suggest that COX-2 is highly expressed in DCIS and takes part in the molecular pathway implicated in progression of breast cancer and may provide a rationale for targeting COX-2 in preinvasive breast cancer therapy. [ABSTRACT FROM AUTHOR]

Background Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. Material and methods Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. Results Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. Conclusion Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding evaluation of vitamin D plasma levels in patients during the treatment of breast cancer by chemotherapy.

A review on the articles "Epidemiology of Biliary Tract Cancers: An Update," by G. Randi, M. Malvezzi, and F. Levi, which appeared in an issue of "Annals of Oncology," and "Difference in Biological Characteristics and Sensitivity to Chemotherapy and Radiotherapy Between Intrahepatic and Extrahepatic Cholangiocarcinoma Cells in Vitro," by X.R. He and X.P. Wu, which appeared in an issue of "Chinese Medical Sciences Journal," is presented.

The article presents a case study which investigates the potential role of mucin 2 (MUC2) and mucin 5 (MUC5) glycoprotein expression in patients with radically resected ampullary carcinoma. Under normal conditions, such proteins are known to play a protective role for epithelial tissues. Patients were stratified according to the dichotomized variables into MUC2 and MUC5 negative versus MUC2 and MUC5 positive groups to determine the prognostic effect of MUC2 and MUC5 protein expression by univariate survival analysis.

Presents the case of a 61-year-old man with eruptive, exanthematous psoriasis, who showed a complete and long-lasting regression of skin lesions following therapy with gemcitabine as a single anticancer agent for an advanced pancreatic adenocarcinoma. Pathogenesis; Mechanism of action of gemcitabine.

Presents a case of patients with severe liver dysfunction after raltitrexed administration in an hepatitis C positive colorectal cancer patient. Case history of the patient; Impact of chemotherapy-induced immunosuppression on viral replication; Amplification of the intrinsic hepatotoxicity of ratitrexed.

Background Advanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival. Objectives Evaluate the capability of electrochemotherapy ( ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head. Animals Twenty-one cats with periocular carcinoma (17 squamous cell carcinoma [ SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head. Methods Nonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m2 IV) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m2 IV) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2-8) were performed every other week until complete remission ( CR) or tumor progression occurred. Results Toxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [ CR] and 2 Partial Response [ PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months ( P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively. Conclusions Electrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco-regional strategies for cancer therapy in sensitive body regions such as periocular region. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: Over a 2-year period, 459 devices were placed in two academic Italian institutions. Patients' characteristics, catheter-related complications, and their relationship with targeted therapy administration were retrospectively assessed. Results: Catheter-related complications occurred in 30 out of the 459 analyzed cancer patients (7 %). Local complications occurred in 12 (40 %) and 18 (60 %) patients receiving standard chemotherapy and biological drugs, respectively. Eighteen (72 %) out of 25 patients developing biological complications (BC) were receiving biological drugs. Infusion of a biological drug through a central venous catheter has been shown to increase the risk of central venous catheter complications ( p = 0.02). No difference between the incidence of complication between anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents was observed in our study despite the statistically significant early development of port-a-cath complication in the anti-EGFR group. Treatment with a biological drug and the stage of disease, in univariate analysis, had independent effect on the duration for development of catheter-related complications. Conclusions: Molecularly targeted therapy may influence the occurrence of BCs, i.e., infection and dehiscence. Onset of BCs occurred earlier in patients receiving biological drugs (more frequently with bevacizumab than with anti-EGFR therapy) than those undergoing traditional chemotherapy. Further studies are needed to ascertain the findings of our study and to elucidate the reason for the higher incidence of catheter-related complications. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prognostic and predictive value of circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) irrespective of detection level. Materials and methods: We evaluated the prognostic and predictive significance of CTC count at baseline and under treatment in 119 mCRC subjects and compared the standard cutoff (≥3 CTCs/7.5 mL to ≥1 CTCs/7.5 mL). Results: An overall comparison was made between patients with 0, 1-2 and ≥3 CTC (median PFS 8, 4 and 5 months, respectively). Two poor prognostic groups were found, including patients with ≥1 CTCs before and during treatment and patients with 0 CTC at baseline who converted to ≥1 CTCs ( p = 0.014). Conclusions: The presence of at least 1 CTC at baseline count is predictive for poor prognosis in mCRC patients. Patients with 1-2 CTC should be switched from the favorable prognostic group-conventionally defined by the presence of <3 CTC-to the unfavorable, deserving a more careful monitoring. [ABSTRACT FROM AUTHOR]

Abstract: Background: To report on anthracycline-based chemotherapy in a retrospective case-series analysis of solitary fibrous tumour (SFT) patients treated within the Italian Rare Cancer Network. Patients and methods: We reviewed a set of SFT treated with chemotherapy since 2002, focusing on anthracycline, administered alone or in combination with ifosfamide. Responses to ifosfamide as a single agent were also evaluated. Pathologic diagnosis was centrally reviewed, distinguishing typical, malignant (MSFT) and dedifferentiated (DSFT) subtypes. Results: Among 42 SFT patients treated with chemotherapy, we selected 31 cases (mean age: 62years; locally advanced/metastatic: 13/18; front-line/further line: 25/6; typical/MSFT/DSFT/not assessable: 1/17/12/1) who received anthracycline-based chemotherapy (anthracycline monotherapy: eight; anthracycline+ifosfamide: 23). 30 patients are evaluable for response. Best response by Response Evaluation Criteria in Solid Tumours (RECIST) was: partial response (PR): 6 (20%), stable disease (SD): eight (27%), progressive disease (PD): 16 (53%) cases. Responses were confirmed after 3months. Median progression-free survival (PFS) was 4 (range 2–15) months, with 20% of patients being progression-free at 6months. PR was found in 2/18 (11%) MSFT and 4/12 (30%) DSFT, with a median PFS of 3.5 and 5months in MSFT and DSFT, respectively. 19 patients received high-dose prolonged-infusion ifosfamide (front-line/further line: 11/8; typical/MSFT/DSFT: 0/15/4) with two (10%) PR, five (26%) SD, 12 (63%) PD. Conclusions: This retrospective series suggests that in SFT anthracyclines have a degree of antitumour activity in the range of soft tissue sarcoma chemotherapy. Ifosfamide monotherapy seemed to have lower activity. A higher response rate was observed in DSFT in comparison to MSFT. Studies on targeted therapies are ongoing. [ABSTRACT FROM AUTHOR]

Abstract: Background: To report on anthracycline-based chemotherapy in a retrospective case-series analysis of solitary fibrous tumour (SFT) patients treated within the Italian Rare Cancer Network. Patients and methods: We reviewed a set of SFT treated with chemotherapy since 2002, focusing on anthracycline, administered alone or in combination with ifosfamide. Responses to ifosfamide as a single agent were also evaluated. Pathologic diagnosis was centrally reviewed, distinguishing typical, malignant (MSFT) and dedifferentiated (DSFT) subtypes. Results: Among 42 SFT patients treated with chemotherapy, we selected 31 cases (mean age: 62years; locally advanced/metastatic: 13/18; front-line/further line: 25/6; typical/MSFT/DSFT/not assessable: 1/17/12/1) who received anthracycline-based chemotherapy (anthracycline monotherapy: eight; anthracycline+ifosfamide: 23). 30 patients are evaluable for response. Best response by Response Evaluation Criteria in Solid Tumours (RECIST) was: partial response (PR): 6 (20%), stable disease (SD): eight (27%), progressive disease (PD): 16 (53%) cases. Responses were confirmed after 3months. Median progression-free survival (PFS) was 4 (range 2–15) months, with 20% of patients being progression-free at 6months. PR was found in 2/18 (11%) MSFT and 4/12 (30%) DSFT, with a median PFS of 3.5 and 5months in MSFT and DSFT, respectively. 19 patients received high-dose prolonged-infusion ifosfamide (front-line/further line: 11/8; typical/MSFT/DSFT: 0/15/4) with two (10%) PR, five (26%) SD, 12 (63%) PD. Conclusions: This retrospective series suggests that in SFT anthracyclines have a degree of antitumour activity in the range of soft tissue sarcoma chemotherapy. Ifosfamide monotherapy seemed to have lower activity. A higher response rate was observed in DSFT in comparison to MSFT. Studies on targeted therapies are ongoing. [Copyright &y& Elsevier]

Purpose: The management of brain metastases (BM) from breast cancer (BC) needs to be improved, and new therapeutic strategies are urgently requested. In this view, we have evaluated the efficacy, tolerability, and safety of concurrent low protracted dose of temozolomide (TMZ), metronomic oral vinorelbine (VNB), and radiotherapy in BC women with previously untreated BM.Methods: Thirty-six patients with newly diagnosed BM were treated with TMZ orally administered at a dose of 75 mg/m(2) during whole-brain radiotherapy, followed by 4 weeks off-therapy and a subsequent administration of oral 70 mg/m(2) VNB fractionated in days 1, 3, and 5, weekly for three consecutive weeks plus TMZ at 75 mg/m(2) on days 1-21, all every 4 weeks for up to 12 additional cycles. The primary end point was the evaluation of the objective response rate (ORR).Results: Three complete responses and 16 partial responses have been achieved with an ORR of 52 % (95 % CI 38-67 %) that exceeded the target activity per study design. The median progression-free survival and overall survival were 8 and 11 months, respectively. The schedule appeared to be well tolerated, and side effects were generally mild. The functional assessment of cancer therapy-breast (FACT-B) analysis showed a significant positive change during the study.Conclusions: In conclusion, the treatment was safe and a significant number of objective responses were observed with a significant improvement in quality of life demonstrated by FACT-B. On the basis of the present results, a large randomized trial is warranted in BC patients with previously untreated BM. [ABSTRACT FROM AUTHOR]

Background Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC). Patients and methods Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration. Results CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P < 0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category. Conclusion The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment. [ABSTRACT FROM PUBLISHER]