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M Huncharek

Publications and source records attributed to M Huncharek.

At least 19 recordsLinked to original sources
PubMed2001

Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials.

It is currently unclear whether any combination therapy for the treatment of metastatic melanoma is superior to standard single-agent dacarbazine (DTIC) in terms of tumour response and overall survival. The available randomized clinical trial data were combined in a meta-analysis to address this question. Initially a thorough MEDLARS search was conducted covering the time period from January 1970 to January 1999. This literature search was supplemented by manual searches of study bibliographies (including review articles) and review of relevant textbooks. The meta-analysis was performed according to a prospective protocol using strict study eligibility criteria. Data derived from randomized controlled trials comparing single-agent DTIC with combination chemo/immunotherapy were combined using a fixed effects model. Data were stratified into three combination therapy groups: DTIC-containing regimens, non-DTIC-containing therapy, and chemotherapy plus immunotherapy. The primary outcome of interest was the proportion of patients demonstrating a complete or partial response to treatment. A total of 20 randomized trials comprising 3273 patients were initially combined in a meta-analysis. This yielded an odds ratio (OR) of 1.23 (95% confidence interval [CI] 1.02-1.48), demonstrating that combination drug therapies are associated with a 23% increase in response rate compared with single-agent DTIC. The combination of DTIC plus interferon-alpha produced a tumour response rate 53% greater (95% CI 1.10-2.13) than that seen with DTIC alone. This increase was greater than that seen with DTIC-containing multi-drug regimens, which had an OR of 1.33 (95% CI 0.99-1.78). No difference in overall survival was demonstrated. Non-DTIC-containing treatment programmes showed no advantage over DTIC in terms of tumour response rate (OR = 0.77, 95% CI 0.45-1.32). The combination of DTIC and interferon-alpha appears more active than standard single-agent DTIC in metastatic melanoma. Further randomized clinical trials employing a DTIC plus interferon arm are necessary to confirm these results.

Antineoplastic Agents, Alkylating↗
PubMed2001

Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of 6,689 subjects from 8 observational studies.

The etiology of epithelial ovarian cancer is unknown. Prior work suggests that high dietary fat intake is associated with an increased risk of this tumor, although this association remains speculative. A meta-analysis was performed to evaluate this suspected relationship. Using previously described methods, a protocol was developed for a meta-analysis examining the association between high vs. low dietary fat intake and the risk of epithelial ovarian cancer. Literature search techniques, study inclusion criteria, and statistical procedures were prospectively defined. Data from observational studies were pooled using a general variance-based meta-analytic method employing confidence intervals (CI) previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of ovarian cancer associated with high vs. low dietary fat intake. Sensitivity analyses were performed when necessary to evaluate any observed statistical heterogeneity. The literature search yielded 8 observational studies enrolling 6,689 subjects. Data were stratified into three dietary fat intake categories: total fat, animal fat, and saturated fat. Initial tests for statistical homogeneity demonstrated that hospital-based studies accounted for observed heterogeneity possibly because of selection bias. Accounting for this, an RRs was calculated for high vs. low total fat intake, yielding a value of 1.24 (95% CI = 1.07-1.43), a statistically significant result. That is, high total fat intake is associated with a 24% increased risk of ovarian cancer development. The RRs for high saturated fat intake was 1.20 (95% CI = 1.04-1.39), suggesting a 20% increased risk of ovarian cancer among subjects with these dietary habits. High vs. low animal fat diet gave an RRs of 1.70 (95% CI = 1.43-2.03), consistent with a statistically significant 70% increased ovarian cancer risk. High dietary fat intake appears to represent a significant risk factor for the development of ovarian cancer. The magnitude of this risk associated with total fat and saturated fat is rather modest. Ovarian cancer risk associated with high animal fat intake appears significantly greater than that associated with the other types of fat intake studied, although this requires confirmation via larger analyses. Further work is needed to clarify factors that may modify the effects of dietary fat in vivo.

Animals↗
PubMed2000

Use of topical sunscreen and the risk of malignant melanoma. Results of a meta-analysis of 9,067 patients.

PURPOSE: Prior epidemiological studies suggest that the use of sunscreen preparations is associated with increased risk of cutaneous malignant melanoma (CMM) although the data are conflicting. A meta-analysis was performed to evaluate this suspected association.METHODS: A protocol was developed for a meta-analysis examining the association between frequent sunscreen use versus non-use and the development of CMM. Data from observational studies were pooled using a general variance based meta-analytic method employing confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of melanoma associated with sunscreen use versus non-use. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity.RESULTS: Eleven case-control studies enrolling 9,067 patients were combined in a meta-analysis. This yielded a RRs of 1.11 (CI = 0.37-3.32), a non-statistically significant result, (i.e. no association between sunscreen use and melanoma risk). Since the data were found to be heterogeneous, i.e. Q = 42.0 (p < 0.001), a series of sensitivity analyses were performed to explore possible sources of heterogeneity. Stratifying studies based on study design, i.e. hospital based versus population based, showed that hospital derived data were highly heterogeneous (Q = 36.9, p < 0.001) while the population registry data were not (Q = 4.9, p = 0.18). Combining those studies using population based data gave a RRs of 1.01 (95% CI = 0.46-2.28) indicating no association between sunscreen use and the development of CMM.CONCLUSIONS: The available epidemiological data do not support the existence of a relationship between topical sunscreen use and an increased risk of CMM.

Journal Article↗
PubMed2000

Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight published studies.

Mutation of the p53 tumor suppressor gene is considered a possible marker of poor survival among patients with non-small cell lung cancer (NSCLC). This report presents the results of a meta-analysis of the available data addressing this issue. Using previously described methods, a protocol was developed for a meta-analysis examining the prognostic significance of p53 mutations in NSCLC. Two-year survival data derived from 829 patients in eight published studies were analyzed using a general variance-based method employing confidence intervals described by Greenland (Epidemiol. Rev. 9 (1986) 1-30). The outcome of interest was a summary relative risk (RRs) reflecting the risk of death at 2 years associated with p53 mutation positive versus p53 negative disease. Prior to calculation of a RRs, an analysis for homogeneity (Q) showed Q to equal 22.3. With 8 degrees of freedom, this yielded a P value corresponding to P<0.005. This indicated substantial heterogeneity across studies in terms of their estimate of effect. Although a RRs of 1.52 was found when all eight studies were combined (favoring a negative prognostic role for p53 mutation), the validity of this estimate is questionable since the existing heterogeneity indicates that factors other than p53 mutation account for the variability in RRs across studies. Sensitivity analyses suggested that selection bias might represent an important source of variability in that p53 mutations may differ in their effects on biological behavior of NSCL tumors. Other possible confounders include smoking history, race, geographic location of study and socio-economic status. The available data do not support a clear role for p53 mutation as a prognostic marker in NSCLC. It appears that multiple sources of bias may contribute to spurious association of p53 mutation status and survival. Future analyses must control for possible confounders in order to determine whether certain p53 mutations are truly associated with poor clinical outcome.

Biomarkers, Tumor↗
PubMed2000

Intravesical chemotherapy prophylaxis in primary superficial bladder cancer: a meta-analysis of 3703 patients from 11 randomized trials.

The impact of intravesical chemotherapy prophylaxis on recurrence of superficial transitional cell carcinoma of the bladder is poorly defined. The objective of this report is to present a meta-analysis of the available clinical trial data to quantify the effect of intravesical chemotherapy on tumor recurrence following complete transurethral resection (TURB) in patients with newly diagnosed superficial bladder cancer. A prospective protocol outlining the above meta-analysis was initially developed followed by a thorough search of the existing published literature using strict eligibility criteria. Eleven randomized trials were found that met protocol specifications. These studies contained data on 3703 patients that were statistically combined using a fixed effects model (Peto). The outcome of interest was the proportion of patients recurring at 1, 2, and 3 years post-TURB. Combining all 11 studies using 1-year recurrence as the outcome measure yielded a Peto odds ratio (ORp) of 0.56, demonstrating a 44% reduction in 1-year recurrence among patients treated with intravesical chemotherapy versus those treated with TURB alone. A statistical test for heterogeneity (Q) showed these data to be heterogenous (the studies are not measuring an effect of the same size). Sensitivity analyses were performed to determine sources of heterogeneity. These tests suggest that chemotherapy treatment schedule may account for the wide variation in tumor recurrence rates across studies. When the available clinical trial data were stratified by duration of treatment, the meta-analysis showed that intravesical chemotherapy decreased tumor recurrence from 30% to 80% depending on the outcome of interest (i.e., recurrence at 1, 2, or 3 years post-TURB). Intravesical chemotherapy appears to have a major impact on decreasing the chance of recurrence of superficial transitional cell carcinoma of the bladder. This is in contrast to prior analyses suggesting only modest efficacy in this clinical setting (i.e., on the order of a 14% reduction in recurrence).

Administration, Intravesical↗
PubMed2000

Epidermal growth factor receptor gene amplification as a prognostic marker in glioblastoma multiforme: results of a meta-analysis.

Amplification of the epidermal growth factor receptor (EGFR) gene occurs in approximately 40% of cases of glioblastoma multiforme (GBM) and is considered a possible marker of poor prognosis. This report presents the results of a meta-analysis of the available data addressing this issue. Using a prospective protocol, a meta-analysis was designed to assess the possible prognostic importance of EGFR gene amplification in GBM. One-year survival data derived from seven published studies were analyzed using a general variance based method employing confidence intervals described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of death at 1 year from diagnosis associated with EGFR amplification-positive versus -negative disease. Prior to calculation of a RRs, an analysis for homogeneity (Q) showed Q to equal 9.21. With 6 df this yielded a P value of 0.12, indicating that the data were homogenous and could be combined in a meta-analysis. Pooling all available studies gave a RRs of 1.13 with a 95% confidence interval of 0.71-1.80, a nonstatistically significant result. The data suggest that the available studies are insufficient for determining whether EGFR gene amplification is of prognostic value in GBM. Important potential confounding factors are the influence of underlying EFGR gene mutation on patient survival and lack of control for important known clinical prognostic indicators in many studies. Future work must incorporate these parameters in multivariate analyses to determine whether EGFR gene alterations are truly associated with poor clinical outcome.

Adult↗
PubMed1999

K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer: a combined analysis of 881 cases.

The treatment of non-small cell lung cancer (NSCLC) remains unsatisfactory, with most patients succumbing to metastatic disease within 5 years of diagnosis. Improved selection of patients for aggressive adjuvant therapy may contribute to improved survival. Mutation of the k-ras oncogene is considered a potentially clinically useful prognostic biomarker for this purpose. This report presents the results of a meta-analysis performed to determine whether the existing data support such a role for k-ras mutations in NSCLC. Two year survival data derived from 881 NSCLC patients in eight published studies were analyzed using a general variance-based meta-analytical method employing confidence intervals. The outcome of interest was a summary relative risk (RR(s)) reflecting the risk of death at 2 years associated with k-ras mutation-positive versus k-ras mutation-negative disease. Prior to calculation of RR(s), analysis for heterogeneity showed Q to equal 15.52 (7 df, P = 0.03). This indicated heterogeneity across the analyzed studies in terms of their estimate of effect. Possible sources of heterogeneity were identified and included selection bias and various other sources of uncontrolled confounding. Although a RR(s) of 2.35 (95% CI = 1.61-3. 22) was found when all eight studies were combined (favoring a negative prognostic role for k-ras mutation), it is unclear whether the magnitude of the RR(s) would persist after adjusting for other well-established prognostic indicators (e.g. stage). The existing data suggest that k-ras mutation may be associated with shortened survival in NSCLC, although this finding awaits confirmation in well-designed multivariate analyses which adjust for the effect of known prognostic indicators.

Adenocarcinoma↗
PubMed1996

Parental cancer and genetic predisposition in malignant pleural mesothelioma: a case-control study.

Familial clustering of pleural mesothelioma (PM) has been previously reported suggesting that genetic factors (predisposition) may be involved in PM. We studied parental cancer history in a cohort of 39 cases of PM and 259 age matched controls to assess the possible influence of family history on PM risk. Cases consisted of 39 patients with PM treated at our institution between 1978 and 1993. An age frequency matched control group (by 5-year age groups) consisted of 259 subjects who were spouses or friends of patients undergoing resection of primary lung cancer. Data were obtained by interview of controls and interview of the patient or next of kin (usually spouse) for cases. The following data were obtained using a standard questionnaire and medical record review; age, sex, date of diagnosis, history of asbestos exposure, smoking history, method of diagnosis, histologic subtype, type of treatment, parental cancer history and tumor type. Cases and control frequency of parental cancer and site specific tumor frequency were compared using chi-square analysis. Twenty-eight (71%) cases reported a parental history of cancer versus 114 (44%) in the control group (P<0.01). Gastrointestinal malignancies were the predominant tumor type among parents of cases, i.e. 11 cases (40%) versus 25% of controls (P<0.01). No other tumor site showed an increased frequency among cases. These data suggest a possible role for family history in the development of PM. Genetic predisposition may be important in the etiology of this tumor.

Asbestos↗
PubMed1996

Dietary intake and the risk of malignant mesothelioma.

A high consumption of fruit and vegetables reduces the risk of several types of cancer. There is little information on the association between dietary intake and mesothelioma. A hospital-based case-control study of 94 men and women with malignant mesothelioma and 64 control patients without cancer was conducted to determine the odds associated with consumption of carotenoid-containing fruits and vegetables. After statistical adjustment for occupational asbestos exposure, the odds ratio was 0.2 [95% confidence interval (CI) 0.1-0.8] for carrot consumption and 0.5 (95% CI 0.2-1.4) for tomato consumption. However, the frequency of consuming other foods that have a high vitamin A or carotenoid content was not associated with a decreased risk of cancer. These results provide some justification for the hypothesis that provitamin A or beta-carotene may decrease the risk of mesothelioma. The body mass index was unrelated to the risk of mesothelioma.

Adult↗
PubMed1995

Small cell carcinoma of the esophagus. The Massachusetts General Hospital experience, 1978 to 1993.

Thirteen patients with small cell carcinoma of the esophagus were treated at the Massachusetts General Hospital between 1978 and 1993. These patients accounted for 1.6% of all patients with esophageal neoplasms seen at our institution during this period. Five patients presented with extensive disease while eight were noted to have limited disease at diagnosis. Seven patients were treated with primary chemotherapy while four patients received radiation therapy alone. No patient in this series underwent surgical resection. Four complete responses to treatment were observed although overall survival was only 7 months. One patient receiving chemotherapy, external beam radiation therapy, and endoesophageal brachytherapy is alive and well without evidence of disease 24 months from diagnosis.

Aged↗
PubMed1995

Serum prostate-specific antigen as a predictor of radiographic staging studies in newly diagnosed prostate cancer.

The standard staging evaluation of prostate cancer includes digital rectal examination, measurement of serum tumor markers, radionuclide bone scan, and abdominal pelvic computed tomography (CT) or nuclear magnetic resonance imaging (MRI). We retrospectively reviewed 300 cases of newly diagnosed, untreated adenocarcinoma of the prostate to evaluate the ability of serum prostate-specific antigen (PSA) to predict results of staging radiographic studies (bone scan, CT/MRI). The medical records of 300 newly diagnosed, untreated prostate cancer patients were reviewed. The following information was collected on a standard data form: age, clinical stage based on digital rectal examination, method of diagnosis, histological grade, serum PSA level, results of radionuclide bone scan and additional radiographic studies to confirm bone scan results, results of abdominal pelvic CT/MRI, and presence or absence of bone pain. The results of this review were tabulated and analyzed with regard to the ability of serum PSA level to predict positive results of radiographic staging studies. The mean PSA level of the study group was 24.6 ng/ml. Ten patients (3.6%) presented with positive bone scan results with 5 of these having serum PSA levels greater than 20 ng/ml (range 27.6 ng/ml-144 ng/ml, mean 66.3 ng/ml). The 5 remaining patients all had elevated PSA levels ranging between 4.1 and 20.0 ng/ml. No patient with a positive staging bone scan presented with a normal serum PSA. Ten patients (4.0%) presented with a positive abdominal/pelvic CT/MRI (adenopathy only; no patients had radiographic evidence of abnormalities of the upper urinary tract). Eight had serum PSA levels greater than 20 ng/ml, ranging from 30.0 to 234 ng/ml. No patient with a positive study presented with a normal serum PSA level. No patient with either positive bone scan or abdominal pelvic CT/MRI presented with bone pain. We conclude that in asymptomatic patients with newly diagnosed, untreated prostate cancer and serum PSA levels of less than 10 ng/ml, a staging radionuclide bone scan may not be necessary. Likewise, in patients with serum PSA levels of less than 20 ng/ml the likelihood of positive findings on abdominal/pelvic CT/MRI is extremely low. Abdominal/pelvic CT/MRI does not appear necessary in this setting. With over 130,000 cases of newly diagnosed prostate cancer each year in the United States, elimination of staging radiographic studies in the patients outlined above could result in economic savings on the order of 30-80 million dollars per year.

Abdomen↗
PubMed1995

Genetic characteristics of prostate cancer.

Prostate cancer is the most commonly diagnosed malignancy in united States males. Unfortunately, numerous controversies surround clinical management for early stage disease and the utility of population screening. Much of this controversy stems from the lack of knowledge about the biology of prostate cancer, including the lack of clearly defined risk factors, absence of markers indicative of aggressive clinical behavior, as well as a lack of a clear understanding of its underlying genetic features. This paper reviews currently available evidence regarding the genetic characteristics of adenocarcinoma of the prostate, including the impact of family history of disease risk, the nature of structural genetic aberrations, and the possible role of oncogenes and tumor suppressor genes in its pathogenesis. A clearer understanding of these issues will hopefully lead to more effective and rational treatment policies in addition to the development of effective disease prevention strategies.

Adenocarcinoma↗