Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT.

BACKGROUND: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors. RESULTS: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV. CONCLUSIONS: [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

Use of transrectal ultrasonography for assessment of the size and location of prostatic carcinoma in dogs.

OBJECTIVE: To evaluate the use of transrectal ultrasonography (TRUS) for the assessment of prostatic tumors in dogs and to compare results for TRUS with results for other imaging modalities. ANIMALS: 10 client-owned male dogs. PROCEDURES: Client-owned dogs identified with prostatic carcinoma were enrolled. Fluoroscopy, transabdominal ultrasonography (TAUS), TRUS, and MRI were performed on all dogs. Tumor measurements, urethral penetration (identification of abnormal tissue within the urethral lumen), and tumor extension into the urinary tract were recorded for all imaging modalities. Agreement between results for MRI (considered the criterion-referenced standard) and results for other modalities were compared. RESULTS: Median body weight of the 10 dogs was 26.3 kg (range, 9.4 to 49.5 kg). No complications were encountered during or after TRUS. Significant moderate to good agreements (intraclass correlation coefficients, 0.60 to 0.86) among TAUS, TRUS, fluoroscopy, and MRI were identified for tumor length and height. Assessments of urethral penetration and tumor extension into the bladder with TRUS did not differ significantly from those made with MRI and were superior in terms of absolute agreement with MRI when compared with those for TAUS. CONCLUSIONS AND CLINICAL RELEVANCE: TRUS was successfully and safely used to evaluate prostatic carcinoma in dogs. There was moderate to good agreement with MRI results for tumor height and length measurements, and TRUS was found to be superior to TAUS for some assessments. Transrectal ultrasonography can be considered an adjunctive imaging modality for the performance of prostatic interventional procedures or assessment of response to treatment.

Assessment of the accuracy and precision of a patient immobilization device for radiation therapy in canine head and neck tumors.

The positioning accuracy and precision of a head and neck immobilization device for radiation therapy of tumors in the canine skull was evaluated. Nineteen dogs with a spontaneous tumor of the head were enrolled including 12 with an intracranial mass and seven with an intranasal or maxillary tumor. Three hundred thirty-three pairs of orthogonal digital portal radiographs were analyzed to assess patient displacement in the cranial-caudal, lateral, and dorso-ventral directions. The mean systematic displacement was 0.8, 1, and 0.9 mm. The mean random displacement was 1.9, 1.6, and 1.5 mm. These values resulted in an overall displacement of 2.1 mm in the cranial-caudal direction, 1.8mm in the lateral direction, and 1.7 mm in the dorsal-ventral direction. The mean displacement value of the three dimensional (3D) vector was 2.4 mm with a standard deviation of 2.1. Ninety-five percent of all vectors were < 6.4 mm. This study quantifies the precision and accuracy of this particular positioning device. Knowing the limitations and setup variability of the system being used to set patients up for daily radiotherapy is paramount to planning and delivering appropriate radiation doses, especially as more complex treatment methods are used.

Standard uptake value predicts survival in non-small cell lung cancer.

BACKGROUND: Integrated [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan is a widely used modality in the evaluation of lung cancer. Our goal was to determine the ability of the standard uptake value (SUV) of the primary tumor (SUV-T) and regional lymph nodes (SUV-N) to predict survival. METHODS: From January 2005 through June 2007, 584 consecutive patients undergoing integrated PET-CT scan for suspected lung cancer were studied. Results of integrated PET-CT scans, including the maximum SUV-T and SUV-N, were recorded. A patient was defined as having a positive PET scan if the maximum SUV (T or N) was greater than 2.5. Overall survival was documented from clinical records and the Social Security Death Index. Cox regression analysis was used to evaluate the correlation between SUV and survival. RESULTS: Among patients with a positive PET scan (n = 329), both SUV-T and SUV-N were predictors of survival. As maximum SUV of the primary mass increased, survival decreased (hazard ratio, 1.05; p < 0.001). As maximum SUV of locoregional lymph nodes increased, survival also decreased (hazard ratio, 1.06; p < 0.001). Furthermore, among patients with no mediastinal disease identified by PET-CT scan, increased SUV-T continued to predict poor survival (hazard ratio, 1.06; p = 0.001). CONCLUSIONS: Local and regional maximum SUVs defined by integrated PET-CT scanning have a strong correlation with survival in patients with non-small cell lung cancer. An elevated SUV is known preoperatively and may assist clinicians in stratifying patients at increased overall risk preoperatively.

Exposure pathway assessment at a copper-beryllium alloy facility.

Controlling beryllium inhalation exposures to comply with regulatory levels (2 micro g m(-3) of air) does not appear to prevent beryllium sensitization and chronic beryllium disease (CBD). Additionally, it has proven difficult to establish a clear inhalation exposure-response relationship for beryllium sensitization and CBD. Thus, skin may be an important route of exposure that leads to beryllium sensitization. A 2000 survey had identified prevalence of sensitization (7%) and CBD (4%) in a beryllium alloy facility. An improved particulate migration control program, including dermal protection in production areas, was completed in 2002 at the facility. The purpose of this study was to evaluate levels of beryllium in workplace air, on work surfaces, on cotton gloves worn by employees over nitrile gloves, and on necks and faces of employees subsequent to implementation of the program. Over a 6 day period, we collected general area air samples (n = 10), wipes from routinely handled work surfaces (n = 252), thin cotton glove samples (n = 113) worn by employees, and neck wipes (n = 109) and face wipes (n = 109) from the same employees. In production, production support and office areas geometric mean (GM) levels of beryllium were 0.95, 0.59 and 0.05 micro g per 100 cm(2) on work surfaces; 42.8, 73.8 and 0.07 micro g per sample on cotton gloves; 0.07, 0.09 and 0.003 micro g on necks; and 0.07, 0.12 and 0.003 micro g on faces, respectively. Correlations were strong between beryllium in air and on work surfaces (r = 0.79), and between beryllium on cotton gloves and on work surfaces (0.86), necks (0.87) and faces (0.86). This study demonstrates that, even with the implementation of control measures to reduce skin contact with beryllium as part of a comprehensive workplace protection program, measurable levels of beryllium continue to reach the skin of workers in production and production support areas. Based on our current understanding of the multiple exposure pathways that may lead to sensitization, we support prudent control practices such as use of protective gloves to minimize skin exposure to beryllium salts and fine particles.

Cost effectiveness of chest computed tomography after lung cancer resection: a decision analysis model.

BACKGROUND: Postoperative surveillance with chest computed tomography (CT) is often performed in patients who have undergone resection of non-small cell lung cancer (NSCLC), despite lack of supporting data. This study involves the creation of a decision analysis model to predict the cost effectiveness of postoperative surveillance CT. METHODS: A decision analysis model was created in which a hypothetical cohort of patients underwent annual chest CT after resection of a stage IA NSCLC. The incidence of second primary lung cancer (SPLC), sensitivity and specificity of CT, as well as survival after resection of initial primary and SPLC were derived from published literature. The cost of CT and other procedures prompted by a positive finding on CT was calculated from Medicare reimbursement schedules. Cost effectiveness was defined as a cost of less than 60,000 dollars per quality-adjusted life-year gained in the cohort under surveillance compared with controls under no surveillance. RESULTS: In the initial (base case) analysis, the cost of surveillance CT was 47,676 dollars per quality-adjusted life-year gained, implying cost effectiveness. However, factors that rendered surveillance CT cost ineffective were (1) age at entry into the surveillance program greater than 65 years, (2) cost of CT greater than 700 dollars, (3) incidence of SPLC of less than 1.6% per patient per year of follow-up, and (4) a false positive rate of surveillance CT greater than 14%. CONCLUSIONS: Surveillance with postoperative CT may be a cost-effective intervention to detect SPLC in selected patients with previously resected stage IA NSCLC.

Surveillance computed tomography after complete resection for non-small cell lung cancer: results and costs.

OBJECTIVE: We sought to determine the prevalence of defined abnormalities on surveillance computed tomography after complete resection for non-small cell lung cancer, as well as the nature and cost of further testing prompted by these abnormalities. We also sought to determine whether resectable metachronous lung cancer can be detected with surveillance scans. METHODS: A retrospective analysis was performed of all patients who presented for follow-up in 2002 after complete resection for non-small cell lung cancer. Data collected included demographics, clinicopathologic features of the initial lung cancer, the number and results of surveillance computed tomographic scans performed in 2002, the attending surgeons' impressions of the surveillance scans, the nature of any abnormalities and further diagnostic testing prompted by these abnormalities, and the nature of any lung cancer detected on surveillance scans, as well as the treatment rendered. The cost of surveillance scanning and associated diagnostics was computed by using Medicare fee schedules. RESULTS: Two hundred thirteen patients met the criteria for inclusion in the study cohort. One hundred sixty-eight surveillance scans were performed in 140 of these patients. One hundred five scans were interpreted as abnormal by the radiologist with regard to pulmonary nodules, adenopathy, or pleural fluid, but the surgeon was suspicious for recurrent or new primary lung cancer in only 32 of 105 scans. Further workup revealed recurrent or new primary lung cancer in 16 of 32 patients, with 6 undergoing resection for localized disease. The cost of the surveillance scans and associated care in the study cohort were 16.6% higher than the cost of care in a hypothetically identical cohort not subjected to surveillance scanning. CONCLUSIONS: Surveillance computed tomography is frequently abnormal after complete resection for non-small cell lung cancer; however, the majority of these abnormalities are not clinically suspicious. Resectable metachronous lung cancer is detected by using surveillance scanning; however, the use of this modality can be associated with increased cost.

Surface area of respirable beryllium metal, oxide, and copper alloy aerosols and implications for assessment of exposure risk of chronic beryllium disease.

The continued occurrence of chronic beryllium disease (CBD) suggests the current occupational exposure limit of 2 microg beryllium per cubic meter of air does not adequately protect workers. This study examined the morphology and measured the particle surface area of aerodynamically size-separated powders and process-sampled particles of beryllium metal, beryllium oxide, and copper-beryllium alloy. The beryllium metal powder consisted of compact particles, whereas the beryllium oxide powder and particles were clusters of smaller primary particles. Specific surface area (SSA) results for all samples (N=30) varied by a factor of 37, from 0.56 +/- 0.07 m(2)/g (for the 0.4-0.7 microm size fraction of the process-sampled reduction furnace particles) to 20.8 +/- 0.4 m(2)/g (for the 6 microm) to 20.8 +/- 0.44 m(2)/g (for the particle size fraction