Impact of tumor board recommendations on treatment outcome for locally advanced head and neck cancer

Background/Aims: To identify physician selection factors in the treatment of locally advanced head and neck cancer and how treatment outcome is affected by Tumor Board recommendations. Methods: A retrospective analysis of 213 patients treated for locally advanced head and neck cancer in a single institution was performed. All treatments followed Tumor Board recommendations: 115 patients had chemotherapy and radiation, and 98 patients received postoperative radiation. Patient characteristics, treatment toxicity, locoregional control and survival between these two treat- ment groups were compared. Patient survival was compared with survival data reported in randomized studies of locally advanced head and neck cancer. Results: There were no differences in comorbidity factors, and T or N stages between the two groups. A statistically significant number of patients with oropharyngeal and oral cavity tumors had chemoradiation and postoperative radiation, respectively (p < 0.0001). Grade 3-4 toxicities during treatment were 48 and 87% for the postoperative radiation and chemoradiation groups, respectively (p = 0.0001). There were no differences in survival, locoregional recurrences and distant metastases between the two groups. Patient survival was comparable to survival rates reported by randomized studies of locally advanced head and neck cancer. Conclusion: Disease sites remained the key determining factor for treatment selection. Multidisciplinary approaches provided optimal treatment outcome for locally advanced head and neck cancer, with overall survival in these patients being comparable to that reported in randomized clinical trials. Copyright © 2008 S. Karger AG.

Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.

Promising results with exemestane in the first-line treatment of metastatic breast cancer: a randomized phase II EORTC trial with a tamoxifen control.

Because tamoxifen (TAM), a nonsteroidal antiestrogen, is routinely used in the adjuvant setting, other hormone therapies are needed as alternatives for first-line treatment of metastatic breast cancer (MBC). Currently, exemestane (EXE) and other antiaromatase agents are indicated for use in patients who experience failure of TAM. In this multicenter, randomized, open-label, TAM-controlled (20 mg/day), phase II trial, we examined the activity and tolerability of EXE 25 mg/day for the first-line treatment of MBC in postmenopausal women. Exemestane was well tolerated and demonstrated substantial first-line antitumor activity based on intent-to-treat analysis of peer-reviewed responses. In the EXE arm, values for complete, partial, and objective response, clinical benefit, and time to tumor progression (TTP) exceeded those reported for TAM although no statistical comparison was made. Based on these encouraging results, a phase III trial will compare EXE and TAM.

Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

PURPOSE: Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer. PATIENTS AND METHODS: Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline). Surrogacy was assessed through the correlation between the end points as well as through the correlation between the treatment effects on the end points. RESULTS: Tumor response (survival odds ratio [OR], 6.2; 95% CI, 5.3 to 7.0) and disease control (survival OR, 5.5; 95% CI, 4.8 to 6.3) were strongly associated with OS. PFS (rank correlation coefficient, 0.688; 95% CI, 0.686 to 0.690) and TTP (rank correlation coefficient, 0.682; 95% CI, 0.680 to 0.684) were moderately associated with OS. Response log ORs were strongly correlated with PFS log hazard ratios (linear coefficient [rho], 0.96; 95% CI, 0.73 to 1.19). Response and disease control log ORs and PFS and TTP log hazard ratios were poorly correlated with log hazard ratios for OS, but the confidence limits of rho were too wide to be informative. CONCLUSION: No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.

Polymeric and monomeric IgA response in serum and milk after parenteral cholera and oral typhoid vaccination

SCOPUS: ar.j

Significant variations of Anti-Müllerian hormone serum levels during pregnancy and during oral contraception

info:eu-repo/semantics/nonPublished

Gene therapy for glioblastoma [correction of gliobestome] multiform: in vivo tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir.

Clinical Trial

Study of gene expression in thyrotropin-stimulated thyroid cells by cDNA expression array: ID3 transcription modulating factor as an early response protein and tumor marker in thyroid carcinomas.

Induction of cell proliferation by mitogen or growth factor stimulation leads to the specific induction or repression of a large number of genes. To identify genes differentially regulated by the cAMP-dependent transduction pathway, which is poorly characterized so far, we used the cDNA expression array technology. Hybridizations of Atlas human cDNA expression arrays with (32)P-labeled cDNA probes derived from control or thyrotropin (TSH)-stimulated dog thyrocytes in primary culture generated expression profiles of hundreds of genes simultaneously. Among the genes that displayed modified expression, we selected the transcription factor ID3, whose expression was increased by a cAMP-dependent stimulus. ID3 overexpression after TSH stimulation was first verified by Northern blotting analysis, and its mRNA regulation was then investigated in response to a variety of agents acting on thyrocyte proliferation and/or differentiation. We show that: (1) ID3 mRNA induction was stronger after stimulation of the cAMP cascade, but was not restricted to this signaling pathway, as phorbol myristate ester (TPA) and insulin also stimulated mRNA accumulation; (2) in contrast, powerful mitogens for thyroid cells, epidermal growth factor and hepatocyte growth factor, did not significantly modify ID3 mRNA levels; (3) ID3 protein levels closely parallelled mRNA levels, as revealed by immunofluorescence experiments showing a nuclear signal regulated by TSH; (4) in papillary thyroid carcinomas, ID3 mRNA was downregulated. Our results suggest that ID3 expression might be more related to the differentiating process induced by TSH than to the proliferative action of this hormone.

Expression of galectin-3 in the tumor immune response in colon cancer.

The role of tumor-associated macrophages (TAMs) is controversial. Although most studies on different cancer types associate them with a poorer prognosis, interestingly in colon cancer, most articles indicate that TAMs prevent tumor development; patients with high TAMs have better prognosis and survival rate. M1-polarized macrophages produce high level of tumor necrosis factor-alpha, interleukin-1 beta or reactive oxygen species, which can effectively kill susceptible tumor cells. In contrast, M2-polarized macrophages can secrete different factors that promote tumor cell growth and survival or favor angiogenesis and tissue invasion. Considering the beneficial role of TAMs in colon cancer, we speculated that they may not display the M2 polarization commonly observed in tumor microenvironment, but rather develop M1 properties. Therefore, we used an in vitro model to analyze the effects of supernatants from M1-polarized macrophages on DLD-1 colon cancer cells. Our data indicate that the conditioned medium from LPS-activated macrophages (CM-LAM) contains a high level of granulocyte-macrophage colony-stimulating factor, interleukins-1 beta, -6, -8 and tumor necrosis factor-alpha, and that it exerts a marked growth inhibitory activity on DLD-1 cells. Prolonged exposure to CM-LAM results in cell death by apoptosis. Such exposure to CM-LAM leads to the modulation of gal-3 expression: we observed a marked downregulation of gal-3 mRNA and protein expression following CM-LAM treatment. We also describe that the knockdown of gal-3 sensitizes DLD-1 cells to CM-LAM. These data suggest an involvement of gal-3 in the response of colon cancer cells to proinflammatory stimuli, such as the conditioned medium from activated macrophages.

A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir.

This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies.

Doxifluridine and leucovorin: an oral treatment combination in advanced colorectal cancer

Purpose: This study was designed to test the activity and feasibility of an all-oral regimen of levo-leucovorin and doxifluridine (dFUR) in the treatment of advanced colorectal cancer and to establish whether the pharmacokinetics of dFUR and fluorouracil (FU) are affected by demographic and/or biologic parameters. Materials and Methods: One hundred eight patients with histologically proven colorectal cancer received orally administered levo-leucovorin 25 mg followed 2 hours later by dFUR 1,200 mg/m2 on days 1 to 5, with the cycle being repeated every 10 days. Results: Among 62 previously untreated patients, two complete responses (CRs) and 18 partial responses (PRs) were observed (overall response rate, 32%; 95% confidence interval, 21% to 45%). The median response duration was 4 months (range, 2 to 13) and the median survival time, 14 months. Among 46 pretreated patients, there were three CRs and three PRs (response rate, 13%; 95% confidence interval, 5% to 26%). In this group of patients, the median response duration was 4 months (range, 1 to 12) and the median survival time, 12 months. No toxic deaths were observed. The only World Health Organization (WHO) grade 3 to 4 side effect was diarrhea (32 patients). Conclusion: This regimen is active in previously untreated colorectal cancer patients and combines good compliance with safety. Limited but definite efficacy was also detected in the patients previously treated with FU, which suggests incomplete cross- resistance between the two drugs. The pharmacokinetic results suggest that the conversion rate of dFUR to FU increases between days 1 and 5, but that FU levels remain low in comparison to those measured after classical FU therapy. Under the experimental conditions used in this study, the interpatient variability of pharmacokinetic parameters remains largely unexplained by the tested variables.