Personal and Occupational Exposure to Organic Solvents and Risk of Non-Hodgkin’s Lymphoma (NHL) in Women (United States)

Objectives: The authors assessed whether home and occupational exposure to organic solvents is associated with risk of NHL in women. Methods: A population-based, incidence case-control study was conducted in upstate New York, involving 376 NHL cases and 463 population controls selected from the Medicare beneficiary files and State driver’s license records. Exposure information was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model, adjusting for a number of risk factors for NHL. Results: Overall, history of exposure to organic solvents was not associated with the risk of NHL. A statistically significant increase in risk associated with occupational exposure was observed only for the subjects whose first exposure occurred before 1970 (OR=1.87, 95% CI 1.03–3.40). When occupational and home exposures to paint thinners/turpentine were combined and analyzed together, the risk of NHL associated with any exposure, compared to no exposure at either job or home, was a statistically significantly increased (OR=1.46, 95% CI: 1.05–2.03). This observation was more pronounced for B-cell lymphoma and for low-grade lymphoma with ORs of 1.52 (95 CI: 1.08–2.14) and 2.20 (95% CI; 1.42–3.41), respectively. Conclusions: The results of this case-control study do support of a major role of organic solvents in the development of NHL among women currently living in the US. However, relatively intensive exposure in past occupations and use of paint thinners/turpentine may deserve further investigation.     

Correlation of toxicity and efficacy with pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD) (Caelyx®)

Purpose

Pegylated liposomal doxorubicin (PLD) is used to treat patients with breast and gynecological cancers. In order to optimize treatment with PLD, we assessed the prognostic and predictive factors for efficacy of PLD.

Methods

Seventeen patients treated with PLD 30 or 40 mg/m² underwent pharmacokinetic sampling during the first cycle of treatment. PLD exposure was calculated. An univariate analysis was performed with the variables: hand–foot syndrome, mucositis, rash, neutropenia, age, tumor type, number of previous therapies, ECOG performance status and progression-free survival (PFS). Candidate variables with p ≤ 0.1 were selected for the multivariate analysis.

Results

Based on the results of the multivariate analysis, the PLD exposure (log AUC) was higher in patients who experienced rash (p = 0.002) and mucositis (p = 0.001) compared to those who did not have these adverse events. The development of hand–foot syndrome was significantly related to a lower risk of disease progression (HR 0.1; 95 % CI 0.02–0.64). Patients with an ECOG status of 0 had a longer PFS than the patients with an ECOG status of 1 (HR 5.4; 95 % CI 1.3–22.8). Moreover, PLD exposure (ln AUC) was also positively related to PFS (HR 0.001; 95 % CI 0.00–0.42).

Conclusions

The extent of the exposure to PLD was correlated with more adverse events and longer PFS. This has important clinical implications, since dose reductions or interruptions might thus negatively affect treatment outcomes. More attention should be paid to preventive and supportive measures of adverse events of PLD to keep the exposure to PLD as high as possible.     

IgM monoclonal gammopathy of undetermined significance (MGUS) and smoldering Waldenström's macroglobulinemia (SWM)

Monoclonal gammopathy of undetermined significance of IgM class (IgM MGUS) was diagnosed in 213 Mayo Clinic patients who were residents of 11 counties in Southeastern Minnesota from 1960 to 1994. During long-term follow-up 29 (14%) developed non-Hodgkin lymphoma (n = 17), Waldenström's macroglobulinemia (n = 6), chronic lymphocytic leukemia (n = 3), and AL amyloidosis (n = 3) with relative risks of 15-, 262-, 6-, and 16-fold, respectively. The cumulative probability of progression to one of these disorders was 10% at 5 years, 18% at 10 years, and 24% at 15 years, approximately 1.5% per year.Forty-eight patients with SWM were identified at Mayo Clinic from 1974 to 1995. During 285 cumulative person-years of follow-up (median, 15.4 years) 34 (71%) progressed to Waldenström's macroglobulinemia (WM), 1 to AL amyloidosis, and 1 to lymphoma (total, 36 [75%]). The cumulative probability of progressing to WM, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, and 59% at 5 years (12% per year).     

Dietary phytoestrogen intake—lignans and isoflavones—and breast cancer risk (Canada)

Objective To evaluate whether phytoestrogen intake is associated with reduced breast cancer risk, using a novel phytoestrogen database. Methods Population-based breast cancer cases aged 25–74 years (diagnosed 2002–2003) were identified using Ontario Cancer Registry (n = 3,063) and controls (n = 3,430) were an age-stratified random sample of women identified through random digit dialing. An epidemiologic and Block food frequency questionnaire—expanded to include phytoestrogen-containing foods—was mailed to all subjects. The recently published Ontario phytoestrogen database was applied to FFQ responses to estimate intake. Multivariate logistic regression provided odds ratio (OR) estimates, while controlling for confounders. Results Among all women, lignan intake was associated with a reduced breast cancer risk (Q5 vs. Q1 MVOR: 0.81, 95% CI: 0.65, 0.99); however, following stratification by BMI, this reduction in risk was statistically significant only among overweight (BMI > 25) women. Total phytoestrogen intake was also associated with a risk reduction among overweight women only. Among pre-menopausal women, total phytoestrogen intake was associated with a significant reduction in breast cancer risk among overweight women only (Q5 vs. Q1 MVOR: 0.51, 95% CI: 0.30, 0.87). Among post-menopausal women, no statistically significant association was observed between breast cancer risk and isoflavones or lignans. Conclusion Lignan intake may be associated with reduced breast cancer risk among pre-menopausal women, and our data suggest BMI modifies this association.     

Body size and ovarian cancer: case–control study and systematic review (Australia)

Objective: Although increased body mass is an established risk factor for a variety of cancers, its relation with cancer of the ovary is unclear. We therefore investigated the association between measures of body mass index (BMI) and ovarian cancer risk. Methods: Data from an Australian case–control study of 775 ovarian cancer cases and 846 controls were used to examine the association with BMI. We have also summarized the results from a number of other studies that have examined this association. Results: There was a significant increased risk of ovarian cancer with increasing BMI, with women in the top 15% of the BMI range having an odds ratio (OR) of 1.9 (95% confidence interval (CI), 1.3–2.6) compared with those in the middle 30%. Stratifying by physical activity showed a stronger effect among inactive women (OR = 3.0, 95% CI 1.3–6.9). The overall effect was consistent with the findings of most prior population-based case–control studies, while cohort studies reported positive effects closer to the null. Hospital-based studies gave variable results. Conclusions: Taken together, the evidence is in favor of a small to moderate positive relation between high BMI and occurrence of ovarian cancer.     

University Students’ Knowledge about the Relation between Human Papillomavirus (HPV) and Head and Neck and Oral Cancers

Introduction: Human papillomavirus (HPV) causes the most common sexually transmitted infection (STI) in the world. It affects people regardless of gender and age, causing genital warts and cancer. Objective: To evaluate university students’ knowledge of HPV and its relationship with head and neck and oral cancers. Methods: This is a cross-sectional study using an online questionnaire administered to undergraduate students at a public university (n=335). Results: In total, 69.3% of the participants were unaware of the relationship between HPV and head and neck cancers and 34.6% claimed that HPV may not cause oral cancer.  The chances of knowing about the relationship of HPV with head and neck cancers were significant for participants who knew that HPV could be asymptomatic (OR = 9.9; p = 0.029), that might cause genital warts in men (OR = 4.0; p = 0.015), and those aged 24 years or older (OR = 1.9; p = 0.021). However, undergraduate students in the field of health and medicine (OR = 0.419; p = 0.002), who had sex at least twice a week (OR = 0.471; p = 0.017), and were unaware of the target public for the HPV vaccine (OR: 0.222, p<0.001) were less likely to know about the relationship. Students who knew of the relationship between HPV and female (OR = 3.6; p = 0.010) and male genital warts (OR = 3.0; p = 0.005) or were immunized (OR = 1.8; p = 0.020) were more likely to understand the viral interaction with oral cancer. Those who were unaware of the population eligible for HPV vaccine (OR = 0.493; p = 0.017) also showed gaps in their knowledge of this relationship. Conclusion: Our findings showed that there were limitations in the knowledge about HPV, its vaccine, and its relationship with head and neck and oral cancers.     

Patterns and trends in esophageal cancer mortality and incidence in Europe (1980–2011) and predictions to 2015

BackgroundOver the last few decades, esophageal cancer incidence and mortality trends varied substantially across Europe, with important differences between sexes and the two main histological subtypes, squamous cell carcinoma (ESCC) and adenocarcinoma (EAC).Patients and methodsTo monitor recent esophageal cancer mortality trends and to compute short-term predictions in the European Union (EU) and selected European countries, we analyzed data provided by the World Health Organization (WHO) for 1980–2011. We also analyzed incidence trends and relative weights of ESCC and EAC across Europe using data from Cancer Incidence in Five Continents.ResultsLong-term decreasing trends were observed for male esophageal cancer mortality in several southern and western European countries, whereas in central Europe mortality increased until the mid-1990s and started to stabilize or decline over the last years. In some eastern and northern countries, the rates were still increasing. Mortality among European women remained comparatively low and showed stable or decreasing trends in most countries. Between 2000–2004 and 2005–2009, esophageal cancer mortality declined by 7% (from 5.34 to 4.99/100 000) in EU men, and by 3% (from 1.12 to 1.09/100 000) in EU women. Predictions to 2015 show persistent declines in mortality rates for men in the EU overall, and stable rates for EU women, with rates for 2015 of 4.5/100 000 men (about 22 300 deaths) and 1.1/100 000 women (about 7400 deaths). In northern Europe, EAC is now the predominant histological type among men, while for European women ESCC is more common and corresponding rates are still increasing in several countries.Conclusion(s)The observed trends reflect the variations in alcohol drinking, tobacco smoking and overweight across European countries.     

Population-based incidence and survival of central nervous system (CNS) malignancies in Girona (Spain) 1994–2005

The purpose of this study was to describe the incidence and survival of primary Central Nervous System (CNS) malignancies using data from the population-based cancer registry for Girona province (north-east Spain).     

Serous tubal intraepithelial carcinoma (STIC) – clinical impact and management

Introduction: Serous tubal intraepithelial carcinoma (STIC) is most likely precursor lesion of the most part of high-grade serous pelvis carcinomas, carcinosarcoma and undifferentiated carcinoma with incidence of 0.6% to 7% in BRCA carriers or women with strong family history of breast or ovarian carcinoma. STIC is a pathomorphologically and immunohistochemically detectable lesion which biological significance and clinical relevance is unknown.

Areas covered: We investigate methods of STIC diagnostics and we present an overview of recent studies and available knowledge on surgical management, adjuvant chemotherapy and subsequent follow-up procedure in women with an isolated STIC.

Expert commentary: Patients found to have an incidental STIC lesion should be referred for screening of BRCA1/2 mutation. In absence of an invasive disease, follow-up of patient remains a reasonable choice. A rational scheme should include check-ups every 6 months consisting of gynecological examinations, CA 125 and/or HE4 and pelvic ultrasound examination by an expert sonographer.     

Predictors of mortality and tumor recurrence in desmoplastic infantile ganglioglioma and astrocytoma—and individual participant data meta-analysis (IPDMA)

Journal of Neuro-Oncology - Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the...     

Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours?

Purpose The aim of this trial was to evaluate the safety and efficacy of oxaliplatin and capecitabine (XELOX) in neuroendocrine tumours’ (NETs) treatment. Methods Forty patients (pts) with advanced NETs were treated. Of these, 13 had untreated poorly differentiated NETs, 27 had well-differentiated NETs in progression after somatostatin analogues. Patients received oxaliplatin e.v. 130 mg/mq i.v. and capecitabine 2,000 mg/mq/die. The primary sites of the disease were: lung (10 pts), pancreas (15 pts), small bowel (8 pts), unknown (1 pt), others (6 pts). Results In 13 pts with poorly differentiated NETs objective responses (OR) were: 3 PR (23%), 1 SD (7%), 9 PD (70%). Biochemical responses were 11%. In 27 patients with well-differentiated NETs the OR were: 8 PR (30%), 13 SD (48%) and 6 PD (22%). Biochemical and symptomatic responses were 20 and 50%, respectively. Conclusions The XELOX regimen is effective and tolerated in well-differentiated NETs after progression following somatostatin analogues.     

Estrogen Receptor β lpar;ESR2) Polymorphisms and Endometrial Cancer (United States)

OBJECTIVE: We hypothesized that variations in the ESR2 gene may influence estrogen exposure in the uterus and thus influence endometrial cancer risk. We validated and screened for variants in the ESR2 gene and examined whether they are associated with endometrial cancer risk. METHODS: We resequenced the promoter and coding regions of the ESR2 gene in 24 endometrial cancer cases, and genotyped the validated/discovered SNPs and intronic dinucleotide CA repeat in a nested case-control study of endometrial cancer (cases = 222, controls = 666) in the Nurses' Health Study (NHS). We also explored statistical interaction between ESR2 genotypes and body mass index (BMI) or hormone replacement therapy (HRT) use among postmenopausal women and cancer risk. RESULTS: Two SNPs were validated [rs1256049 in exon 5 (allelic frequencies = 98% G, 2% A) and rs1271572 in the promoter region (allelic frequencies = 60% G, 40% T)]. After adjusting for potential confounders, we observed no association between ESR2 gene polymorphisms and endometrial cancer risk [rs1256049 (OR = 1.2; 95%CI: 0.7-2.3), rs1271572 (OR = 0.8; 95%CI: 0.5-1.1) and CA repeat (22 repeat allele versus > or = 22 repeat allele, OR = 1.1; 95%CI: 0.7-1.7)]. We also did not observe any significant effect modification of the ESR2 polymorphisms by BMI or HRT use among postmenopausal women. CONCLUSION: Our results indicate that ESR2 polymorphisms may not be associated with endometrial cancer risk.     

Binding kinetics of tetrachloro-1,2-diaminocyclohexaneplatinum (IV) (tetraplatin) and cis-diamminedichloroplatinum (II) at 37 degrees C with human plasma proteins and with bovine serum albumin. Does aquation precede protein binding?

Experiments were conducted at 37 degrees C to study the kinetics of (a) binding of cis-diamminedichloroplatinum (II) (CDDP) and of a racemic mixture of d- and l-isomers of trans-tetrachloro-1,2-diaminocyclohexaneplatinum (IV) [or tetraplatin (TP)] to protein [human plasma proteins or bovine serum albumin (BSA)]; (b) aquation (acid hydrolysis) of CDDP and of TP; and (c) binding of charged (aquated) CDDP species to BSA. The experiments were performed at clinically relevant concentrations for CDDP, so that the proportional concentrations of platinum complexes relative to the concentrations of other chemical species in blood plasma were similar to those obtaining in the clinical use of the drug. "Free" (unbound) platinum complexes were separated from the protein-bound complexes were separated from the protein-bound complexes by gel filtration chromatography. By use of ion-exchange chromatography, charged platinum species were separated from the uncharged species and free charged platinum species of CDDP were separated from those bound to BSA. Platinum in various fractions was quantitated by atomic absorption spectrophotometry with electrothermal atomization; proteins were quantitated by te Bradford method with Coomassie blue dye. The kinetic data obtained by the application of these methods for CDDP are in good agreement with those obtained by other methods, e.g., binding rates based on separations by centrigugal ultrafiltration. The overall protein-binding reaction of CDDP was consistent with a binding process comprising two consecutive first-order reaction steps: the rate-controlling aquation reaction [half-life (t 1/2), approximately 2 hr] followed by a more rapid binding reaction of the charged (aquated) CDDP species to the protein (t 1/2, approximately 23 min). However, the results for TP indicated that prior aquation was not required for protein binding, and we could surmise that binding of TP to protein proceeds via a direct nucleophilic attack. An unexpected finding was the marked, reproducible difference in rates of aquation between the two lots of TP that we used; this finding suggests the need for cautions evaluation of pharmacokinetic data describing the behavior of TP.     

Intraperitoneal 5-fluoro-2′-deoxyuridine (FUDR) and (S)-leucovorin for disease predominantly confined to the peritoneal cavity: a pharmacokinetic and toxicity study

Intraperitoneal (IP) administration of fluorinated pyrimidines has been evaluated for ovarian and gastrointestinal malignancies in phase I, II, and III trials. The tolerance and pharmacokinetic profile of IP 5-fluoro-2-deoxyuridine (FUDR) alone and with (R,S)-leucovorin ((R,S)-LV) have each been evaluated in previous phase I studies. FUDR doses of 3 g per day with and without (R,S)-LV doses up to 640 mg per day given IP are well tolerated. The current phase I study was designed to determine the pharmacokinetic profiles and clinical tolerance of escalating doses of the pure biologically activeS-isomer of leucovorin ((S)-LV) given IP with the same dosing schedule of FUDR. A group of 16 patients with disease confined to the abdominal cavity were treated in this study. Pharmacokinetic studies of blood and peritoneal fluid, toxicity profiles, and clinical response for the first three cycles are reported here. The toxicity profile did not significantly differ from the prior two studies. All nonhematologic toxicities, such as fatigue, nausea, vomiting, diarrhea, and abdominal discomfort were less than grade 4, and most were less than grade 3. Neutropenia and thrombocytopenia were uncommon and observed only in patients with compromised bone marrow reserve. The pharmacokinetic profiles were also congruent with the previous studies and indicate a three-log advantage for FUDR. The (S)-LV profiles in the peritoneal cavity paralleled those of FUDR. Antitumor effects or absence of progression until after cessation of therapy were documented in 11 patients. At a median follow-up of 18 months 44% of patients were alive. IP administration of 3-g of FUDR and up to 640 mg (S)-LV daily for three days was well tolerated. The tolerance and antitumor effects observed during IP FUDR and LV in these studies encourage further exploration of this regimen against ovarian and gastrointestinal malignancies. The actual role and optimal dose of LV as an enhancer of the antitumor actions of FUDR administered by this route remain unknown.Supported in part by RO1 CA-50412, Cancer Center Core Grant, and NIH National Center for Research Resources of the General Clinical Research Center Grant MO1RR-43