Non-surgical organ preservation strategies for locally advanced laryngeal tumors: what is the Italian attitude? Results of a national survey on behalf of AIRO and AIOM

Abstract

Chemoradiotherapy is the treatment mostly used as organ preservation (OP) strategy worldwide in advanced laryngo-hypopharyngeal cancer. Due to the not homogeneous results of the literature data regarding the pre-treatment assessment and treatment schedule in this setting of patients, the Italian societies of radiation oncology and medical oncology surveyed (by an online survey) their memberships regarding the Italian attitude on larynx preservation in clinical practice. The survey outline addressed different items such as: demographics (11 items), pre-treatment evaluation (12 items), treatment schedules (10 items) and outcomes (3 items). The survey was filled in by 116 clinical oncologists (64 % radiation and 36 % medical oncologists). Results highlighted that pretreatment evaluation was not homogeneous among the respondents. The treatment of choice for the OP program resulted the concurrent chemoradiotherapy (66 %). Induction chemotherapy was proposed mostly in case of aggressive tumors such as advanced stage (T4 or N3) and/or unfavorable primary sites (hypopharynx). Moreover, after induction chemotherapy, for responders patients most participants (46 %) proposed concurrent chemoradiotherapy, while 18 and 19 % proposed radiotherapy alone or radiotherapy and cetuximab, respectively. For patients with stable disease after induction chemotherapy, the respondents declared to suggest surgery, radiotherapy and cetuximab or radiotherapy alone in 38, 32 and 15 % of cases, respectively. Results of the present survey highlighted the variability of therapeutic approaches offered in clinical practice for patients candidate to a larynx OP program. Analysis of abovementioned results may give the chance to modify some clinical attitudes and create the background for future clinical investigation in this field.

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Effects of first-line chemotherapy on natural killer cells in adult T-cell leukemia–lymphoma and peripheral T-cell lymphoma

Abstract

Purpose

Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine–cyclophosphamide–doxorubicin–prednisone (VCAP), doxorubicin–ranimustine–prednisone (AMP), and vindesine–etoposide–carboplatin–prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia–lymphoma (ATL), or the cyclophosphamide–doxorubicin–vincristine–prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL).

Methods

The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a ⁵¹Cr release assay, respectively.

Results

A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15–17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment.

Conclusions

These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.

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Effects of first-line chemotherapy on natural killer cells in adult T-cell leukemia–lymphoma and peripheral T-cell lymphoma

Abstract

Purpose

Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine–cyclophosphamide–doxorubicin–prednisone (VCAP), doxorubicin–ranimustine–prednisone (AMP), and vindesine–etoposide–carboplatin–prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia–lymphoma (ATL), or the cyclophosphamide–doxorubicin–vincristine–prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL).

Methods

The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a ⁵¹Cr release assay, respectively.

Results

A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15–17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment.

Conclusions

These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.

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Adjuvant chemotherapy and relative survival of patients with stage II colon cancer – A EURECCA international comparison between the Netherlands, Denmark, Sweden, England, Ireland, Belgium, and Lithuania

Publication date: August 2016
Source:European Journal of Cancer, Volume 63
Author(s): A.J. Breugom, E. Bastiaannet, P.G. Boelens, L.H. Iversen, A. Martling, R. Johansson, T. Evans, S. Lawton, K.M. O'Brien, E. Van Eycken, R. Janciauskiene, G.J. Liefers, A. Cervantes, V.E.P.P. Lemmens, C.J.H. van de Velde
BackgroundThe aim of the present EURECCA international comparison is to compare adjuvant chemotherapy and relative survival of patients with stage II colon cancer between European countries.MethodsPopulation-based national cohort data (2004–2009) from the Netherlands (NL), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), and Belgium (BE) were obtained, as well as single-centre data from Lithuania. All surgically treated patients with stage II colon cancer were included. The proportion of patients receiving adjuvant chemotherapy was calculated and compared between countries. Besides, relative survival was calculated and compared between countries.ResultsOverall, 59,154 patients were included. The proportion of patients receiving adjuvant chemotherapy ranged from 7.1% to 29.0% (p < 0.001). Compared with NL, a better adjusted relative survival was observed in SE (stage II: relative excess risks (RER) 0.53, 95% confidence interval (CI) 0.44–0.64; p < 0.001), and BE (stage II: RER 0.84, 95% CI 0.76–0.92; p < 0.001), and in IE for patients with stage IIA disease (RER 0.80, 95% CI 0.65–0.98; p = 0.03).ConclusionThe proportion of patients with stage II colon cancer receiving adjuvant chemotherapy varied largely between seven European countries. No clear linear pattern between adjuvant chemotherapy and adjusted relative survival was observed. Compared with NL, SE and BE showed an improved adjusted relative survival for stage II disease, and IE for patients with stage IIA disease only. Further research into selection criteria for adjuvant chemotherapy could eventually lead to individually tailored, optimal treatment of patients with stage II colon cancer.



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Rethinking end-points for bone-targeted therapy in advanced cancer

Publication date: August 2016
Source:European Journal of Cancer, Volume 63
Author(s): Susana Gómez García, Mark Clemons, Eitan Amir
The principal objective for any medical therapy is to improve either the duration of life and/or its quality. Metastases in bone can lead to clinically defined events termed skeletal-related events (SREs) which are a quantifiable measure of skeletal morbidity. Avoidance and/or delay of SREs have become the principal objective in trials exploring the efficacy of bone-targeted therapy in patients with skeletal metastases. Despite reductions in the frequency or rate of SRE occurrence, trials of bone-targeted therapy have failed to show any effect on either progression-free or overall survival when compared with placebo or other bone-targeting agents. Similarly, trials of bone-targeted therapy have not shown consistent effects on quality of life. The validity of SRE-based primary outcome measures in cancer clinical trials is therefore, questionable. More novel end-point selection for trials of bone-targeted therapy seems warranted. Composite measures comprising occurrence of symptomatic skeletal events and patient reported outcomes may be an effective solution and warrants further investigation.



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Concordance of the HER2 protein and gene status between primary and corresponding lymph node metastatic sites of extramammary Paget disease

Abstract

Recent studies have reported the overexpression of human epidermal growth factor receptor 2 (HER2) in primary extramammary Paget disease (EMPD). These results indicate that therapies that target HER2 may be useful in treating metastatic EMPD, for which the prognosis is poor. However, there is limited information on the expression and gene amplification of HER2 in metastatic EMPD. Twenty-six corresponding lymph node metastatic sites of primary EMPD underwent immunohistochemical evaluation of HER2 protein overexpression. In cases of HER2 protein overexpression, further analysis into the amplification of the HER2 gene was undertaken using dual colored in situ hybridization. In the corresponding lymph node metastasis of EMPD, HER2 protein overexpression and gene amplification were detected in 38 % and 19 % of cases, respectively. In 22 out of 26 cases (85 %), there were no differences in HER2 protein overexpression between the primary tumors and the corresponding lymph node metastasis (kappa coefficient 0.65). Likewise, HER2 gene amplification status was concordant in 92 % of cases (kappa coefficient 0.75). HER2 status is in good overall concordance between primary tumors and the corresponding metastatic sites. As there was a discrepancy in a minority of cases, HER2 status should be evaluated at both the primary and the metastatic sites, whenever possible.

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Integrinβ1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies because of its broad resistance to chemotherapy. Numerous evidence indicates that integrinβ1 is upregulated in some human cancers, and it is correlated with resistance to various therapies. However, the role of integrinβ1 in chemotherapy is not clear in pancreatic cancer. The present study evaluates the potential of integrinβ1 to predict chemoresistance and prognosis in patients and to modulate resistance to gemcitabine in PDAC cells. Primary drug-resistance (DR) cancer cells were isolated, and DR cells from MiaPaCa-2 and AsPC-1 parent cell lines (PCL) were selected. Integrinβ1 expression was determined using immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and Western blotting. Changes in drug response after knockdown of integrinβ1 via RNA interference (RNAi) were evaluated using the viability of cancer cells as colon formation, proliferation using Western blot of Ki-67 and apoptosis using cleaved caspase-3 immunofluorescence. qRT-PCR and Western blot also detected variations in the activities of cdc42 and AKT after integrinβ1 suppression. Patient survival and relative factors were assessed using Kaplan-Meier and Cox regression analyses. Integrinβ1 expression was upregulated in PDAC, which was significantly associated with intrinsic and acquired gemcitabine resistance and worse outcomes. The downregulation of integrinβ1 attenuated PDAC chemoresistance, and this attenuation partially correlated with reduced Cdc42 and AKT activity, which are target molecules of integrinβ1 in some human cancers. These findings identified integrinβ1 as a special marker of drug resistance and a serious prognosis, and they furthermore support the use of integrinβ1 as a novel potential therapeutic target to overcome chemotherapy resistance. The results also suggest a possible drug-resistant signalling pathway of integrinβ1 in PDAC.

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Antidepressant use and risk of central nervous system metastasis

Abstract

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, were found to increase central nervous system (CNS) metastasis in mice. Our study investigated in humans whether antidepressants, and specifically SSRIs, increased the relative odds of CNS metastasis. We identified 189 cases of CNS metastasis amongst breast cancer, melanoma, and non-Hodgkin lymphoma subjects who were diagnosed with CNS metastasis or infiltration between January 1, 2005 and September 30, 2013 and 756 controls (patients without CNS metastasis or infiltration). Using logistic regression, we estimated the relative odds of CNS metastasis associated with antidepressant use adjusting for relevant covariates. The prevalence of antidepressants was 28.6 % in cases and 27.5 % in controls, whereas SSRIs were used in 16.9 % of cases and 17.3 % of controls. Among all patients, antidepressants were not associated with CNS metastasis or infiltration. No consistent patterns of association were observed in the analyses of other cancer subsets or exposure measures, with the possible exception of an increased risk of CNS metastasis associated with 'any SSRI use' among breast cancer patients (OR = 1.73, 95 % CI = 0.75, 4.04). We did not observe clear patterns of association, which may be due in part to the small sample size in many of our analyses.

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Antidepressant use and risk of central nervous system metastasis

Abstract

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, were found to increase central nervous system (CNS) metastasis in mice. Our study investigated in humans whether antidepressants, and specifically SSRIs, increased the relative odds of CNS metastasis. We identified 189 cases of CNS metastasis amongst breast cancer, melanoma, and non-Hodgkin lymphoma subjects who were diagnosed with CNS metastasis or infiltration between January 1, 2005 and September 30, 2013 and 756 controls (patients without CNS metastasis or infiltration). Using logistic regression, we estimated the relative odds of CNS metastasis associated with antidepressant use adjusting for relevant covariates. The prevalence of antidepressants was 28.6 % in cases and 27.5 % in controls, whereas SSRIs were used in 16.9 % of cases and 17.3 % of controls. Among all patients, antidepressants were not associated with CNS metastasis or infiltration. No consistent patterns of association were observed in the analyses of other cancer subsets or exposure measures, with the possible exception of an increased risk of CNS metastasis associated with 'any SSRI use' among breast cancer patients (OR = 1.73, 95 % CI = 0.75, 4.04). We did not observe clear patterns of association, which may be due in part to the small sample size in many of our analyses.

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Integrinβ1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies because of its broad resistance to chemotherapy. Numerous evidence indicates that integrinβ1 is upregulated in some human cancers, and it is correlated with resistance to various therapies. However, the role of integrinβ1 in chemotherapy is not clear in pancreatic cancer. The present study evaluates the potential of integrinβ1 to predict chemoresistance and prognosis in patients and to modulate resistance to gemcitabine in PDAC cells. Primary drug-resistance (DR) cancer cells were isolated, and DR cells from MiaPaCa-2 and AsPC-1 parent cell lines (PCL) were selected. Integrinβ1 expression was determined using immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and Western blotting. Changes in drug response after knockdown of integrinβ1 via RNA interference (RNAi) were evaluated using the viability of cancer cells as colon formation, proliferation using Western blot of Ki-67 and apoptosis using cleaved caspase-3 immunofluorescence. qRT-PCR and Western blot also detected variations in the activities of cdc42 and AKT after integrinβ1 suppression. Patient survival and relative factors were assessed using Kaplan-Meier and Cox regression analyses. Integrinβ1 expression was upregulated in PDAC, which was significantly associated with intrinsic and acquired gemcitabine resistance and worse outcomes. The downregulation of integrinβ1 attenuated PDAC chemoresistance, and this attenuation partially correlated with reduced Cdc42 and AKT activity, which are target molecules of integrinβ1 in some human cancers. These findings identified integrinβ1 as a special marker of drug resistance and a serious prognosis, and they furthermore support the use of integrinβ1 as a novel potential therapeutic target to overcome chemotherapy resistance. The results also suggest a possible drug-resistant signalling pathway of integrinβ1 in PDAC.

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Hypocholesterolemic and Anticarcinogenic Effect of Vicia faba Protein Hydrolyzates.

Hypocholesterolemic and Anticarcinogenic Effect of Vicia faba Protein Hydrolyzates.

Nutr Cancer. 2016 Jun 9;:1-9

Authors: León-Espinosa EB, Sánchez-Chino X, Garduño-Siciliano L, Álvarez-González RI, Dávila-Ortiz G, Madrigal-Bujaidar E, Téllez-Medina DI, Jiménez-Martínez C

Abstract
In recent years, the consumption of vegetal-source proteins has been studied to determine their preventing effect on the development of several chronic diseases. The initial purpose of this report was to determine the effect of a hypercholesterolemic diet (HCD) given to mice, alone or with azoxymethane (AOM), on various obesity biochemical biomarkers, as well as on the induction of colon aberrant crypts (aberrant crypt foci; ACF). At the end of the 5-week assay, animals fed the HCD showed alterations in the level of total cholesterol, high- and low-density lipoproteins, and in the Atherogenic Index; besides, a significant elevation was observed in the number of ACF. Our second aim was to examine the effect of a Faba Protein Hydrolyzate (FPH) on mice fed the HCD. We first obtained protein hydrolyzates from the seeds of Vicia faba, determined the in vitro antioxidant potential with two tests, and, subsequently, evaluated the effect on obesity biomarkers and on the number of ACF. In the first case, we found that, generally, the best protective effect was obtained with the low dose of FPH (10 mg/kg) administered to animals fed the HCD, and injected AOM. With respect to the number of ACF, we observed that this dose was more effective, inhibiting such lesions to almost the level determined for the normocholesterolemic diet (NCD). Therefore, our results demonstrated the relevance of a HCD to develop anomalies in obesity biomarkers in mouse, as well as to increase the number of precarcinogenic lesions. Our results also showed a protective response with the administration of FPH, particularly with a specific dose, suggesting the need for extending research on the matter by widening the spectra of doses, in order to clearly define its potential to counteract the damage induced by the HCD, as well as to confirm if antioxidation in mice was involved in such an effect.

PMID: 27282923 [PubMed - as supplied by publisher]

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Prognostic Role of Body Mass Index in Advanced Small Bowel Adenocarcinoma Patients Receiving Palliative Chemotherapy.

Prognostic Role of Body Mass Index in Advanced Small Bowel Adenocarcinoma Patients Receiving Palliative Chemotherapy.

Nutr Cancer. 2016 Jun 9;:1-6

Authors: Lee DW, Lee KH, Kim TY, Han SW, Oh DY, Im SA, Kim TY, Bang YJ

Abstract
As small bowel adenocarcinoma (SBA) is a rare cancer worldwide, prognostic factors have not been clearly defined. The purpose of this study is to assess the prognostic role of clinicopathologic features, including body mass index (BMI), in patients with advanced SBA. A total of 28 consecutive patients with advanced SBA treated with palliative chemotherapy were retrospectively enrolled and analyzed. Clinicopathologic features, progression-free survival (PFS), and overall survival (OS) were compared according to BMI level. Eighteen patients had BMI < 25 kg/m(2) (overweight/normal/underweight in Asian) and ten patients had BMI ≥ 25 kg/m(2) (obese in Asian). Baseline characteristics were similar regardless of patient's BMI. Compared to patients with BMI < 25 kg/m(2), patients with BMI ≥ 25 kg/m(2) had higher response rate to chemotherapy (40.0% vs. 0%, P = 0.010), longer OS (11.2 vs. 7.0 months, P = 0.018) and a tendency toward prolonged PFS (2.1 vs. 1.9 months, P = 0.085). Multivariate analysis revealed that BMI ≥ 25 kg/m(2) is an independent positive prognostic factor of OS (adjusted hazard ratio 0.35, P = 0.024). In conclusion, baseline BMI ≥ 25 kg/m(2) has a positive prognostic role in patients with advanced SBA.

PMID: 27282771 [PubMed - as supplied by publisher]

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Table of Content Volume 55, Number 8, August 2016

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