Faculty Bibliography

PURPOSE: Ionizing radiation can reduce tumor growth outside the field of radiation, known as the abscopal effect. Although it has been reported in multiple malignancies, the abscopal effect remains a rare and poorly understood event. Ionizing radiation generates inflammatory signals and, in principle, could provide both tumor-specific antigens from dying cells and maturation stimuli that are necessary for dendritic cells' activation of tumor-specific T cells. We therefore tested the hypothesis that the abscopal effect elicited by radiation is immune mediated. This was directly tested by enhancing the number of available dendritic cells using the growth factor Flt3-Ligand (Flt3-L). METHODS AND MATERIALS: Mice bearing a syngeneic mammary carcinoma, 67NR, in both flanks were treated with Flt3-L daily for 10 days after local radiation therapy (RT) to only 1 of the 2 tumors at a single dose of 2 or 6 Gy. The second nonirradiated tumor was used as indicator of the abscopal effect. Data were analyzed using repeated measures regression. RESULTS: RT alone led to growth delay exclusively of the irradiated 67NR tumor, as expected. Surprisingly, growth of the nonirradiated tumor was also impaired by the combination of RT and Flt3-L. As control, Flt3-L had no effect without RT. Importantly, the abscopal effect was shown to be tumor specific, because growth of a nonirradiated A20 lymphoma in the same mice containing a treated 67NR tumor was not affected. Moreover, no growth delay of nonirradiated 67NR tumors was observed when T cell deficient (nude) mice were treated with RT plus Flt3-L. CONCLUSIONS: These results demonstrate that the abscopal effect is in part immune mediated and that T cells are required to mediate distant tumor inhibition induced by radiation

PURPOSE: To compare thin-section multi-detector row computed tomographic (CT) colonography with conventional colonoscopy in the evaluation of colorectal polyps and cancer in asymptomatic average-risk patients. MATERIALS AND METHODS: Sixty-eight asymptomatic men (age > 50 years) scheduled to undergo screening colonoscopy were enrolled in this study. CT colonography was followed by conventional colonoscopy, performed on the same day. Supine and prone CT colonography were performed after colonic insufflation with room air. A gastroenterologist measured all polyps, which were categorized as 1-5, 6-9, or over 10 mm. Biopsy and histologic evaluation were performed of all polyps. CT colonography and colonoscopy results were compared for location, size, and morphology of detected lesions. Point estimates and 95% CIs were provided for specificity and sensitivity of CT by using results at conventional colonoscopy as the reference standard. RESULTS: At colonoscopy, 98 polyps were identified in 39 patients; 21 (21.4%) of 98 were detected at CT colonography. Sensitivity was 11.5% (nine of 78) for polyps 1-5 mm, 52.9% (nine of 17) for polyps 6-9 mm, and 100% (three of three) for polyps over 10 mm. Results at colonoscopy were normal in 29 (42.6%) of 68 patients; at CT colonography, results were correctly identified as normal in 26 of these 29 patients. In one of these patients, a lesion larger than 10 mm was detected at CT colonography. The per-patient specificity of CT was 89.7% (26 of 29; 95% CI: 72.7%, 97.8%). The mean time for CT image interpretation was 9 minutes. CONCLUSION: In patients at average risk for colorectal cancer, CT colonography is a sensitive and specific screening test for detecting polyps 10 mm or larger; the sensitivity for detecting smaller polyps is decreased. Examination findings can be interpreted in a clinically feasible amount of time

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity)

PURPOSE: A patient-specific dose-escalation scheme using a Bayesian model of Escalation with Overdose Control (EWOC) was conducted to establish the maximum tolerated dose (MTD) of PNU-214936 in advanced non-small-cell lung cancer (NSCLC). PNU-214936 is a murine Fab fragment of the monoclonal antibody 5T4 fused to a mutated superantigen staphylococcal enterotoxin A (SEA). PATIENTS AND METHODS: Seventy-eight patients with NSCLC were treated with an individualized dose of PNU-214936 calculated using EWOC, based on their anti-SEA antibody level, and given as a 3-hour infusion on 4 consecutive days. RESULTS: Fever (82%; grade 3 to 4, 2.6%) and hypotension (57%; grade 3 to 4, 9%) were the most common toxicities. Eight dose-limiting toxicities occurred, as defined as any grade 4 toxicity occurring within the first 5 days. The MTD was defined as a function of pretreatment anti-SEA antibody level. MTD ranged from 103 ng/kg for patients with anti-SEA concentrations < or = 10 pmol/mL, to 601 ng/kg for patients with anti-SEA concentrations of 91 to 150 pmol/mL. A minor tumor response was demonstrated in five of 66 assessable patients. CONCLUSION: EWOC determined phase I doses of PNU-214936 that were adjusted for patient anti-SEA antibody level, while safeguarding against overdose. Furthermore, the method permitted the construction of a dosing algorithm that would allow patients in subsequent clinical investigations to be treated with a dose of PNU-214936 that is tailored to their specific tolerance for the agent, as reflected by their pretreatment anti-SEA

OBJECTIVE: The effects of a 6-week psychoeducational group intervention on the distress, coping, personal growth, and marital communication of wives of men diagnosed with prostate cancer were evaluated using a randomized clinical trial. METHODS: Sixty wives completed measures prior to random assignment to either the psychoeducational group intervention or a no-treatment control group, and 1 month after completion of the group. RESULTS: No differences with regard to wives' general distress or cancer-specific distress were noted. In comparison with the control group, participants receiving the intervention perceived that having a spouse with prostate cancer had made positive contributions to their lives, reported gains in the use of positive reappraisal coping and reductions in denial coping. CONCLUSION: Although the psychoeducational intervention did not result in changes in psychological distress, improvements in adaptive coping and indicators of psychological growth were found. The utility of group interventions for spouses of men with prostate cancer is discussed

The ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal cells covering the ovary. Ninety percent of all human ovarian malignancies arise from this layer of cells. Incessant ovulation, hyperovulation induced by infertility treatment, and hormone replacement therapy have been suggested as risk factors for ovarian cancer. In this study, two groups of rats, with and without surgically induced injury to the ovary, were treated with 17beta-estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response of the OSE cells was measured using bromodeoxyuridne (BrdU) and (3)H-thymidine. All hormones, alone or in combination with ovarian surgery, were found to increase significantly the rate of proliferation of the rat OSE. These data demonstrate that hormones associated with infertility treatments and hormone replacement therapy, as well as injury- or ovulation-induced rupture of the ovarian surface, stimulate the rat OSE, and hence could have a role in the development of ovarian cancer via proliferation-associated mutagenesis, or alternatively, by promoting the rapid selection of OSE cells with accumulated mutations

PURPOSE: To evaluate if differences exist in the interpretation of thin- and thick-section reconstructions at computed tomographic (CT) colonography. MATERIALS AND METHODS: Twenty-five patients underwent multi-detector row CT colonography prior to colonoscopy. CT images were reconstructed with two methods: 1.25-mm sections reconstructed every 1 mm (thin) and 5-mm sections reconstructed every 2 mm (thick). Two independent readers interpreted thin sections, then waited a minimum of 15 days before interpreting thick sections. With colonoscopy as the reference standard, comparisons were made between interpretation of thin and thick sections, including sensitivity, specificity, and number of false-positive observations. Interpretation times were recorded, and comparisons were made by using repeated measures analysis of variance. For all tests, P <.05 indicated a statistically significant difference. RESULTS: At colonoscopy, 10 patients had 12 polyps (</=5 mm, n = 7; 6-9 mm, n = 2; >/=10 mm, n = 3). Sensitivity for polyp detection was statistically indistinguishable for thin and thick sections. Reader 1 had three false-positive findings with thin sections and six with thick sections. Reader 2 had six false-positive findings with thin sections and 11 with thick sections. For both readers, the number of false-positive findings was significantly lower for thin sections than for thick sections (P =.035). Specificity was 93.3% with thin sections and 80.0% with thick sections for reader 1 and 80.0% with thin sections and 73.3% with thick sections for reader 2. Mean interpretation time for reader 1 was significantly longer with thin sections (P <.001). Mean interpretation time for reader 2 was 13.0 minutes for both thin and thick sections. CONCLUSION: Specificity improved for both readers with thin sections, with no difference in sensitivity.

BACKGROUND: The purpose of this study was to examine sociodemographic and psychosocial correlates of intention to undergo prophylactic oophorectomy among women with a family history of ovarian cancer. METHODS: Participants were 76 women enrolled in a familial cancer risk assessment program. Psychosocial assessments were collected upon entry into the program and included measures of perceived risk of developing ovarian cancer, perceived benefits and limitations of prophylactic oophorectomy, and psychological distress. In addition, respondents were asked whether they intended to undergo prophylactic oophorectomy in the following 12 months. RESULTS: Thirty-four percent reported intention to have surgery within 12 months. Logistic regression analyses indicated that intention to undergo surgery was associated with several psychosocial factors including greater perceived risk of developing ovarian cancer and greater perceived benefits of surgery. CONCLUSIONS: Women who have heightened risk perceptions and who perceive there to be many benefits of surgery may be more inclined to undergo the procedure, possibly without fully considering the potential limitations and consequences of surgery. These findings suggest the need for education and risk counseling designed to facilitate informed decision making among not only high-risk women, but also women who perceive themselves to be at increased risk.