Systemic administration of vascular endothelial growth factor monoclonal antibody reduces the growth of papillary thyroid carcinoma in a nude mouse model

Papillary thyroid carcinomas (PTC) are the most common thyroid cancers in children. Most are successfully treated with surgery and radioactive iodine, but some persist. PTC express high levels of vascular endothelial growth factor (VEGF) and VEGF receptor (Flt-1). PTC with the most intense expression of VEGF have the greatest recurrence risk. We hypothesized that blockade of VEGF would inhibit PTC growth. To test this, we used systemic VEGF monoclonal antibody (VEGF-MAb) to treat PTC xenografts in nude mice. Treated animals (n = 9) received 200 microg VEGF-MAb by daily i.p. injection for 10 wk, while control animals (n = 9) received vehicle alone. Tumor size was significantly reduced in the treatment group (0.28 +/- 0.06 vs 1.05 +/- 0.25 g, p = 0.008). VEGF immunostaining was more intense (2.57 +/- 0.30 vs 1.75 +/- 0.25, p = 0.06) and the number of p53 positive cells was increased (1.66 +/- 0.24 vs 0.83 +/- 0.31, p = 0.048) in treated tumors. Animal weight was similar in both groups (29.1 +/- 1.1 vs 27.4 +/- 1.1 g, p = 0.30). In conclusion, systemic VEGF-MAb significantly reduced the growth of PTC, suggesting that VEGF-MAb might be useful for treatment of resistant PTC.     

Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.     

Functional results and quality of life after tracheal resection for locally invasive thyroid cancer

BACKGROUND: Local invasion of the upper aerodigestive tract by thyroid cancer, although uncommon, is a serious cause of morbidity and mortality. The impact of aerodigestive tract resection on the functional status and quality of life of the patient has not previously been investigated. METHODS: Patients with locally invasive thyroid cancer were included in a prospective surgical protocol. Swallowing function was assessed with barium swallow at 7 days and 1 month postoperatively. Postoperative quality of life (QOL) was measured using a validated head and neck QOL instrument. RESULTS: Seven patients underwent airway resection for locally invasive recurrent thyroid cancer in the period 1999 to 2001. At 1 week postoperative 3 of 7 (43%) had no evidence of aspiration on barium swallow. At 4 weeks 6 of 7 (86%) had no aspiration. Postoperative QOL scores in the domains of eating function (85.2) and emotional status (78.6) were significantly better than those of a comparison group undergoing treatment for cancers of the oropharynx, P = 0.012 and P = 0.0077, respectively. CONCLUSIONS: Tracheal resection for locally invasive thyroid cancer is associated with a return to full dietary intake within 4 weeks of surgery in most cases. Function and QOL after this type of surgery are acceptable.     

Illnesses related to shank application of metam-sodium, Arvin, California, July 2002

OBJECTIVES: To evaluate the health effects of methyl isothiocyanate (MITC) and other byproducts resulting from the soil-incorporated (shank) application of 25,000 pounds of metam-sodium on July 8, 2002, near the community of Arvin, California. METHODS: Residents in a four-block area were interviewed regarding eye and upper respiratory irritation, non-specific systemic symptoms, and lower respiratory complaints. The distribution of cases was compared to results of Industrial Source Complex (ISC3) air dispersion modeling for the metam-sodium byproduct, methyl isothiocyanate (MITC). The 1-hour 200 ppb no-observed-effect- level (NOEL) and 800 ppb lowest-observed-effect level (LOEL) from a previous human eye irritation study were used to interpret the results of the air modeling estimates. Peak concentrations were compared to the 4-minute NOEL of 600 ppb and the LOEL of 1.9 ppm. RESULTS: Two-hundred-fifty-two cases of irritant, non-specific systemic, and respiratory symptoms were associated with the metam-sodium application. These included 178 community residents or visitors and 74 employees of a carrot packing operation located in the affected neighborhood of Arvin. The most severe reported illness occurred in a community visitor with a history of pre-existing pulmonary disease, who was hospitalized for a week with respiratory distress. ISC3 Modeling indicated 1-hour MITC concentrations in the affected community ranged from 0.8-1.0 ppm, in the range of the LOEL, with peak concentrations between 2.4 and 3.2 ppm. CONCLUSION: Estimated MITC concentrations during the episode exceeded both the 4-minute NOEL and 1-hourNOELby approximately four fold. The high concentrations of MITC present in the affected neighborhood may have been partially attributable to failure to immediately complete a required post-application water-treatment on 15 of the 100 treated acres. However, because of the limited area involved, the violation was unlikely to have accounted for the entire incident. Similar episodes may occur when metam-sodium fumigants are used adjacent to other rural communities.