A Phase I Dose-Escalation Study to Evaluate the Safety and Tolerability of Evofosfamide in Combination with Ipilimumab in Advanced Solid Malignancies.

PURPOSE: As hypoxia can mediate resistance to immunotherapy, we investigated the safety, tolerability, and efficacy of combining evofosfamide, a prodrug that alleviates hypoxia, with ipilimumab, an immune checkpoint inhibitor, in immunologically "cold" cancers, which are intrinsically insensitive to immunotherapy, as well as in "hot/warm" metastatic cancers that are, atypical of such cancers, resistant to immunotherapy. PATIENTS AND METHODS: In a phase I, 3+3 dose-escalation trial (NCT03098160), evofosfamide (400-640 mg/m2) and ipilimumab (3 mg/kg) were administered in four 3-week cycles. The former was administered on days 1 and 8 of cycles 1-2, while the latter was administered on day 8 of cycles 1-4. Response was assessed using immune-related RECIST and retreatment was allowed, if deemed beneficial, after completion of cycle 4 or at progression. RESULTS: Twenty-two patients were enrolled, of whom 21 were evaluable, encompassing castration-resistant prostate cancer (n = 11), pancreatic cancer (n = 7), immunotherapy-resistant melanoma (n = 2), and human papillomavirus-negative head and neck cancer (n = 1). Drug-related hematologic toxicities, rash, fever, nausea, vomiting, and elevation of liver enzymes were observed in > 10% of patients. The most common drug-related grade 3 adverse event was alanine aminotransferase elevation (33.3%). Two patients discontinued ipilimumab and 4 required evofosfamide deescalation due to toxicity. Of 18 patients with measurable disease at baseline, 3 (16.7%) achieved partial response and 12 (66.7%) achieved stable disease. The best responses were observed at 560 mg/m2 evofosfamide. Preexisting immune gene signatures predicted response to therapy, while hypermetabolic tumors predicted progression. Responders also showed improved peripheral T-cell proliferation and increased intratumoral T-cell infiltration into hypoxia. CONCLUSIONS: No new or unexpected safety signals were observed from combining evofosfamide and ipilimumab, and evidence of therapeutic activity was noted.

Dynamics of Erythropoietic Biomarkers in Response to Treatment With Erythropoietin in Belgrade Rats.

Recombinant human erythropoietin (rHuEPO) is used effectively in the treatment of various anemic disorders. Belgrade rat is a useful animal model of anemia caused by defect in iron utilization. The objective of the present study was to investigate the dynamics of erythropoietic biomarkers in Belgrade rats receiving rHuEPO. Pharmacokinetics of rHuEPO was evaluated in Belgrade rats and normal rats after intravenous administration of single doses of the drug (100 and 1350 IU/kg). Pharmacodynamic biomarkers included levels of red blood cells, hemoglobin, and reticulocytes following administration of a single intravenous dose of rHuEPO (100 IU/kg). Red blood cell survival was assessed after treatment with rHuEPO (450 IU/kg), three times a week for 2 weeks. It was found that rHuEPO exhibited non-linear pharmacokinetics in both Belgrade and control rats. At the low dose, plasma concentrations and AUC (area under the curve) were significantly lower while clearance and volume of distribution were higher in Belgrade rats (p < 0.05). At the higher dose, there was no difference in pharmacokinetics between the two groups. Erythropoietic effect of rHuEPO was negligible in Belgrade rats at the dose of 100 IU/kg whereas all studied erythropoietic biomarkers were increased in normal rats. The levels of red blood cells, hemoglobin were significantly lower whereas the percentage of reticulocytes was higher in Belgrade rats compared to that in normal rats (p < 0.05). RHuEPO increased red blood cell survival in both animal groups. In conclusion, rHuEPO effect on erythropoietic biomarkers was stronger in normal rats than Belgrade rats at the studied doses. The findings from this study may provide further insights into understanding of anemic disorders resulting from mutations in the divalent metal transporter.

Oral sex and oropharyngeal cancer: The role of the primary care physicians.

BACKGROUND: We aimed to study the prevalence of oral sex and its possible association with human papillomavirus (HPV) 16 infection in the development of oropharyngeal cancer in the US population for possible prevention. METHODS: We conduct a systemic review on the prevalence of oral sex among Americans among different age groups, the prevalence of HPV 16 infection reported in oropharyngeal cancer, and correlation between oral sex and oropharyngeal cancer. RESULTS: Oral sex is prevalent among adolescents and sexually active adults. Sixty percent of oropharyngeal cancer reported in the United States is associated with HPV 16 infections. Individuals who practiced oral sex with multiple partners are at risk for developing oropharyngeal cancer and need to be informed about practicing safe sex or getting vaccination. CONCLUSION: Family physicians will play a key role in prevention and educating the public about the risk of oral sex.

Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With Advanced Cancer.

PURPOSE: The primary objective was to determine safety, toxicity, and a recommended phase II dose regimen of LY2606368, an inhibitor of checkpoint kinase 1, as monotherapy. PATIENTS AND METHODS: This phase I, nonrandomized, open-label, dose-escalation trial used a 3 + 3 dose-escalation scheme and included patients with advanced solid tumors. Intravenous LY2606368 was dose escalated from 10 to 50 mg/m(2) on schedule 1 (days 1 to 3 every 14 days) or from 40 to 130 mg/m(2) on schedule 2 (day 1 every 14 days). Safety measures and pharmacokinetics were assessed, and pharmacodynamics were measured in blood, hair follicles, and circulating tumor cells. RESULTS: Forty-five patients were treated; seven experienced dose-limiting toxicities (all hematologic). The maximum-tolerated doses (MTDs) were 40 mg/m(2) (schedule 1) and 105 mg/m(2) (schedule 2). The most common related grade 3 or 4 treatment-emergent adverse events were neutropenia, leukopenia, anemia, thrombocytopenia, and fatigue. Grade 4 neutropenia occurred in 73.3% of patients and was transient (typically < 5 days). Febrile neutropenia incidence was low (7%). The LY2606368 exposure over the first 72 hours (area under the curve from 0 to 72 hours) at the MTD for each schedule coincided with the exposure in mouse xenografts that resulted in maximal tumor responses. Minor intra- and intercycle accumulation of LY2606368 was observed at the MTDs for both schedules. Two patients (4.4%) had a partial response; one had squamous cell carcinoma (SCC) of the anus and one had SCC of the head and neck. Fifteen patients (33.3%) had a best overall response of stable disease (range, 1.2 to 6.7 months), six of whom had SCC. CONCLUSION: An LY2606368 dose of 105 mg/m(2) once every 14 days is being evaluated as the recommended phase II dose in dose-expansion cohorts for patients with SCC.

Phase 1b study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma.

OBJECTIVE AND METHODS: In this phase 1b study, patients with stage 4 or unresectable stage 3 melanoma were treated with escalating doses of lenvatinib (once daily) and temozolomide (TMZ) (days 1-5) in 28-day cycles, to determine the maximum tolerated dose (MTD) of the combination. Dose Level (DL)1: lenvatinib 20 mg, TMZ 100 mg/m2; DL2: lenvatinib 24 mg, TMZ 100 mg/m2; DL3: lenvatinib 24 mg, TMZ 150 mg/m2. Adverse events (AEs) were recorded and tumor response assessed per RECIST 1.0. RESULTS: Dose-limiting toxicity occurred in 1 of 32 treated patients (DL1); MTD was not reached. The highest dose administered was lenvatinib 24 mg + TMZ 150 mg/m2. Most common treatment-related AEs included fatigue (56.3%), hypertension (53.1%), and proteinuria (46.9%). Overall objective response rate was 18.8% (6 patients), all partial response; (DL1, n = 1; DL3, n = 5). Stable disease (SD) ≥ 16 weeks was observed in 28.1% of patients (DL1 and DL2, n = 1 each; DL3, n = 7); 12.5% of patients had SD ≥ 23 weeks. Single and repeat-dose pharmacokinetics of lenvatinib were comparable across cycles and with concomitant TMZ administration. CONCLUSIONS: Lenvatinib 24 mg/day + TMZ 150 mg/m2/day (days 1-5) demonstrated modest clinical activity, an acceptable safety profile, and was administered without worsening of either lenvatinib- or TMZ-related toxicities in this patient group.

Phase I Dose-Escalation Study of the Multikinase Inhibitor Lenvatinib in Patients with Advanced Solid Tumors and in an Expanded Cohort of Patients with Melanoma.

PURPOSE: This "3+3" phase I study evaluated the safety, biologic, and clinical activity of lenvatinib, an oral multikinase inhibitor, in patients with solid tumors. EXPERIMENTAL DESIGN: Ascending doses of lenvatinib were administered per os twice daily in 28-day cycles. Safety and response were assessed for all patients. Angiogenic and apoptotic factors were tested as possible biomarkers in an expanded melanoma cohort. RESULTS: Seventy-seven patients were treated in 3 cohorts: 18 with intermittent twice-daily dosing (7 days on, 7 days off) of 0.1-3.2 mg; 33 with twice-daily dosing of 3.2-12 mg; and 26 with twice-daily dosing of 10 mg (expanded melanoma cohort). Maximum tolerated dose was established at 10 mg per os twice daily. Prominent drug-related toxicities included hypertension (43%), fatigue (42%), proteinuria (39%), and nausea (25%); dose-limiting toxicities included hypertension, fatigue, and proteinuria. Twelve patients (15.6%) achieved partial response (PR, n = 9) or unconfirmed PR (uPR, n = 3), and 19 (24.7%) achieved stable disease (SD) ≥23 weeks. Total PR/uPR/SD ≥23 weeks was 40.3% (n = 31). Responses (PR/uPR) by disease were as follows: melanoma, 5 of 29 patients (includes 1 patient with NRAS mutation); thyroid, 3 of 6 patients; pancreatic, 1 of 2 patients; lung, 1 of 1 patients; renal, 1 of 1 patients; endometrial, 1 of 4 patients; and ovarian, 1 of 5 patients. AUC(0-24) and C(max) increased dose proportionally. In multivariate Cox proportional hazard model analyses, increased baseline systolic blood pressure and decreased angiopoietin-1 ratio (2 hours:baseline) were associated with longer progression-free survival (PFS) in the expanded melanoma cohort (P = 0.041 and P = 0.03, respectively). CONCLUSIONS: The toxicity profile, pharmacokinetics, and antitumor activity of lenvatinib are encouraging. Decreases in the angiopoietin-1 ratio correlated with longer PFS in melanoma patients.

KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors.

PURPOSE: To evaluate clinicopathologic and molecular features of patients with metastatic colorectal cancer (mCRC) and their outcomes in early-phase trials using pathway-targeting agents. PATIENTS AND METHODS: We analyzed characteristics of 238 patients with mCRC referred to the phase 1 trials unit at MD Anderson Cancer Center. KRAS, PIK3CA and BRAF status were tested using PCR-based DNA sequencing. RESULTS: Fifty-one percent of patients harbored KRAS mutations; 15% had PIK3CA mutations. In the multivariate regression model for clinical characteristics KRAS mutations were associated with an increased incidence of lung and bone metastases and decreased incidence of adrenal metastases; PIK3CA mutations were marginally correlated with mucinous tumors (p = 0.05). In the univariate analysis, KRAS and PIK3CA mutations were strongly associated. Advanced Duke's stage (p<0.0001) and KRAS mutations (p = 0.01) were the only significant independent predictors of poor survival (Cox proportional hazards model). Patients with PIK3CA mutations had a trend toward shorter progression-free survival when treated with anti-EGFR therapies (p = 0.07). Eighteen of 78 assessable patients (23%) treated with PI3K/Akt/mTOR axis inhibitors achieved stable disease [SD] ≥6 months or complete response/partial response (CR/PR), only one of whom were in the subgroup (N = 15) with PIK3CA mutations, perhaps because 10 of these 15 patients (67%) had coexisting KRAS mutations. No SD ≥6 months/CR/PR was observed in the 10 patients treated with mitogen-activating protein kinase (MAPK) pathway targeting drugs. CONCLUSIONS: KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome. Overcoming resistance may require targeting both pathways.

Geographic region of residence and blood lead levels in US children: results of the National Health and Nutrition Examination Survey.

PURPOSE: This study investigated the association between geographic region and blood lead levels (BLLs) in US children, as well as trends in this relationship, using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: SAS® and SUDAAN® software programs were utilized to develop linear regression models adjusted for several factors associated with BLLs. RESULTS: The largest decline in BLLs was observed in Northeastern children, while the percentage of children with elevated blood lead levels decreased the most for the West and Northeast. Lead levels of Northeastern children were still higher than those of children living in the West. However, levels were not different among children residing in the Northeast, Midwest, and South, and the blood lead concentrations were less than 5 µg/dL for all but one subgroup of children and less than 2 µg/dL for >70% of the subgroups. More importantly, the effects of different risk factors for higher blood lead levels varied by region even after adjusting for all other covariates. CONCLUSIONS: The results of this study not only provide relevant and current blood lead levels for US children that can be used as reference values to evaluate biomonitoring data, but can also be used to help direct prevention and surveillance strategies to reduce lead in the environment of at-risk children.

Pattern of failure following chemoradiation for locally advanced non-small cell lung cancer: potential role for stereotactic body radiotherapy.

Standard of care for locally advanced non-small cell lung cancer has been concurrent chemoradiation. However, optimal chemotherapy regimen, radiation therapy dose and treatment volume have not been clearly defined despite 30 years of controlled clinical trials. This review analyzes survival and failure pattern reported from randomized studies of chemoradiation for non-small cell lung cancer. Despite introduction of new chemotherapy agents, survival remained poor; rates of both locoregional failures and distant metastasis remained high. The current radiation dose appears insufficient to reliably establish local control. Stereotactic body radiotherapy may allow radiation dose escalation and should be tested in future clinical trials.

Molecular biology of breast cancer stem cells: potential clinical applications.

Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy.

Altered glucose metabolism during chemoradiation for head and neck cancer.

UNLABELLED: Platinum-based chemotherapy has been reported to induce diabetes and hyperosmolar coma in nondiabetic patients. The aim of the present study was to determine whether the administration of chemoradiation for head and neck carcinoma alters glucose metabolism during and after treatment. PATIENTS AND METHODS: Weekly nonfasting serum glucose level was obtained during treatment of one hundred and six patients with locally advanced head and neck cancer who underwent chemoradiationt. RESULTS: For the 91 non-diabetic patients, mean serum glucose level measured 97.75 before and 102.1, 102, 104.1, 109.1, 109.7, 110.3, 109.8, 113.2, 107.7 and 104.3 mg/dl during weeks 1-10 of treatment respectively. Serum glucose level elevation reached statistical significance for weeks 5-8. CONCLUSION: Chemoradiation for head and neck cancer may produce severe glucose metabolism alteration during treatment.

Epidemiologic features and clinical subgroups of anotia/microtia in Texas.

BACKGROUND: Few studies have investigated the epidemiologic features of clinically defined subgroups of anotia/microtia. METHODS: Data on cases of anotia and/or microtia among 1999-2005 deliveries were obtained from the Texas Birth Defects Registry, a population-based active surveillance system. We determined crude and adjusted associations between selected factors and seven clinical subgroups of anotia/microtia. RESULTS: In total, 742 cases were diagnosed with anotia and/or microtia, corresponding to a prevalence of 2.86 per 10,000 live births. Of those, 45% had no other major birth defect ("isolated"), 77% were unilateral, and 22% bilateral. Anotia alone made up 6%, whereas microtia made up 94%. Birth prevalence was higher with increasing maternal age and among Mexico-born Hispanics. Compared to white mothers, Hispanic mothers were two-to-three times more likely to have infants with all but the syndromic and bilateral groups (adjusted prevalence ratios [aPRs] = 2.05-2.61). Non-Hispanic blacks had significantly lower risk for total anotia/microtia, and for the isolated, unilateral, and microtia subgroups (aPRs = 0.42-0.64). Less educated mothers were three-to-four times more likely to have children with anotia (aPRs = 2.98 for less than high school, 3.97 for high school graduates). Males were more likely to be born with total anotia/microtia and with syndromic, unilateral, and microtia subtypes (aPRs = 1.27-1.41). CONCLUSIONS: In Texas, most anotia/microtia cases were in the unilateral and microtia groups, and 45% were isolated. Several clinical subgroups exhibited higher prevalence in males and among older mothers. Relative to whites, blacks were at lower risk and Hispanics (especially Mexico-born mothers) were at higher risk for selected types of anotia/microtia.

Analysis of factors influencing Dysphagia severity following treatment of head and neck cancer.

The aim was to assess the influence of treatment, tumor stages and sites on the severity of dysphagia following treatment. Sequential modified barium swallow (MBS) examinations were performed in patients who complained of chronic dysphagia following treatment of their head and neck cancer. Patients were selected if they were cancer free at their last MBS and had 2 or more MBS studies. Dysphagia severity was graded on a scale of 1 to 7. Dysphagia grade was compared between the first and last MBS to assess its evolution. Between 1996 and 2005, 63 patients with chronic dysphagia underwent MBS to assess dysphagia severity for nutritional support. Twenty-one patients (33%) had improvement of their dysphagia. Two of these patients (3%) achieved normalization of the swallowing. Twenty-five patients (40%) had no change of the dysphagia severity. Dysphagia grade increased in 17 patients (27%). Analysis of patient characteristics did not show any significant difference between these three groups of patients. MBS is a useful tool to monitor dysphagia severity and to identify aspiration risk. Stages of disease and treatment modality do not seem to impact on the course of dysphagia.

Aspiration risk and postoperative radiation for head and neck cancer.

The aim of the study was to assess the aspiration risk following postoperative radiation for head and neck cancer. Thirty-seven patients had Modified Barium Swallow before and following treatment. Dysphagia severity was graded from 1 to 7. Before treatment there were sixteen grade 1, seventeen grade 2, three grade 3 and one grade 5. Following postoperative radiation, two patients had grade 1, eleven patients had grade 2, thirteen patients had grade 3, four patients had grade 4, four patients had grade 5, one patients had grade 6, and two patients had grade 7. Nineteen percent (7/37) of the patients developed aspiration (grade 5-7). Aspiration is life-threatening and may develop for all tumor sites and stages.

Levels of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in southern Mississippi catfish and estimation of potential health risks.

Fish consumption has been classified as one of the primary pathways of exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls (PCBs). In this study, we evaluated tissue levels of the 17 laterally substituted PCDD/Fs, 12 dioxin-like PCBs, and 97 non-dioxin-like PCBs in a number of wild-caught and farm-raised catfish collected throughout southern Mississippi. Total lipid-adjusted TEQ and non-dioxin-like PCB concentrations in wild-caught catfish fillets were significantly higher than concentrations in farm-raised fillet samples. The percent contribution of PCDDs, PCDFs, and dioxin-like PCBs to mean total TEQ varied between wild-caught and farm-raised samples as well as by collection site for wild-caught catfish. The non-dioxin-like PCBs that contributed the most to total PCB concentrations also differed between wild-caught and farm-raised samples. Regardless of whether samples were farm-raised or wild-caught, estimated cancer risks associated with consumption of these catfish were less than 27.0E-06. Overall, results of this study indicate that levels of dioxin-like compounds and PCBs in Mississippi catfish are similar to those measured in more recent studies in the US and that levels of these compounds appear to be decreasing in this food source.

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 treatment 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.

Long-term aspiration following treatment for head and neck cancer.

BACKGROUND: Dysphagia and aspiration are long-term complications with life-threatening consequences following treatment of head and neck cancer. We would like to assess the prevalence of aspiration in patients with long-term persistence of dysphagia (1 year or more) following treatment for head and neck cancer and to identify potential risk factors of aspiration. METHODS: Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. RESULTS: Between 1992 and 2004, 74 patients with dysphagia underwent MBS 12-152 months following treatment (median 29 months). There were 2 grade 1, 22 grade 3, 21 grade 4, 11 grade 5, 7 grade 6, and 11 grade 7 cases. Twenty-nine patients (39%) had long-term aspiration at a median follow-up of 25 months (range 12-82). Eighteen patients (24%) required permanent gastrostomy because of severe aspiration. Type of treatment and disease stage did not seem to influence long-term aspiration risk. CONCLUSION: Patients with long-term dysphagia after treatment for head and neck cancer are at risk of aspiration. MBS should be performed to identify these patients.

Dysphagia severity and aspiration following postoperative radiation for locally advanced oropharyngeal cancer.

UNLABELLED: The aim of the present study was to assess dysphagia severity following postoperative radiation for locally advanced oropharyngeal cancer. PATIENTS AND METHODS: Eighteen patients with oropharyngeal carcinoma had undergone postoperative radiation. There were eight base of tongue, eight tonsils, and two soft palate carcinomas. All the patients had undergone modified barium swallow (MBS) to assess the persistence of dysphagia (more than one month) post-treatment. All the patients were cancer-free at the time of the swallowing study. Dysphagia severity was graded as 1-7. RESULTS: At a median follow-up of 12 months, there were three grade 2, four grade 3, two grade 4, five grade 5, two grade 6, and two grade 7. Only three patients (17%) had normal swallow post-treatment. Six patients (33%) had mild to moderate dysphagia (grade 3-4). Nine patients (50%) developed aspiration (grade 5-7). Among the patients who developed aspiration, four (22%) required tube feeding for severe aspiration. CONCLUSION: Long-term (more than one year) dysphagia following postoperative radiation for oropharyngeal cancer may be symptomatic of permanent damage to the swallowing mechanism. Evaluation of patients who complain of persistence of dysphagia a year or more following treatment should include MBS, because of the increased risk of aspiration.

Addendum to: Evaluation of PCDD/F and dioxin-like PCB serum concentration data from the 2001-2002 National Health and Nutrition Examination Survey of the United States population.

In 2007, we published a paper in the Journal of Exposure Science and Environmental Epidemiology describing PCDD/F and dioxin-like PCB serum concentration data collected for the 2001-2002 National Health and Nutrition Examination Survey. Since publication of this paper, several of the 1998 World Health Organization Toxic Equivalency Factors (TEFs), which were used to calculate the summary statistics we presented, have been changed. In this addendum, we publish new reference statistics using the WHO(2006) TEFs in addition to assessing the effect of these new TEFs on total TEQ concentrations for the general US population. We also examined the effect of the limits of detection (LODs) on the calculated TEQ summary statistics for the top seven contributing congeners and completed a missing data analysis to determine whether our estimates were biased by excluding individuals without complete congener profiles. Similar to our previous results, 2, 3, 7, 8-TCDD; 1, 2, 3, 7, 8-PeCDD; 1, 2, 3, 6, 7, 8-HxCDD; 2, 3, 4, 7, 8-PeCDF; and PCB 126 contributed the most to total TEQ. However, both PCB 156 and 157 were no longer significant contributors, instead being displaced by 1, 2, 3, 4, 7, 8-HxCDF, and PCB 169. In general, the decrease in TEFs for the mono-ortho-substituted PCBs decreased their contribution to total TEQ appreciably, causing TEQ(17-9) to approximately equal TEQ(17-3). The effect of LODs for five of the top seven contributing congeners was negligible; however, the LODs for 2, 3, 7, 8-TCDD and 1, 2, 3, 7, 8-PeCDD were noticeably higher and may impact TEQ estimates primarily for individuals aged 20-29 years. Results from the missing data analysis provide compelling evidence that the summary statistics we reported previously, as well as those described here, were not greatly influenced due to censoring data.

Prevalence of pharyngeal and esophageal stenosis following radiation for head and neck cancer.

OBJECTIVE: To evaluate the risk and outcome of pharyngoesophageal stenosis in patients who complained of dysphagia following radiation for head and neck cancer. DESIGN: Retrospective study. SETTING: Veterans Administration hospital. PATIENTS: Patients who complained of persistent dysphagia following radiation alone or combined with surgery or chemotherapy for head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. All patients had modified barium swallow (MBS) and an endoscopic examination for initial evaluation of their dysphagia. Traditional barium swallow was requested when there was a suspicion of pharyngoesophageal stenosis on MBS. RESULTS: Two hundred twenty-two patients underwent MBS for evaluation of dysphagia posttreatment. Traditional barium swallow confirmed the diagnosis of pharyngeal (n = 2) or esophageal (n = 14) stenosis in 16 patients. Eight patients had esophageal stenosis on endoscopic examination. All patients underwent dilatation for relief of their dysphagia. The number of dilatations performed was, respectively, one in 12 patients, two in 4 patients, three in 3 patients, four in 3 patients, five in one patient, and six in one patient. CONCLUSION: Pharyngeal and/or cervical esophageal stenosis may be the cause of dysphagia following radiation for head and neck cancer. Esophageal dilatations often offer temporary relief of the dysphagia.