WE-G-213CD-08: Initial Experience with the Clinical Implementation of a Deep Inspiration Breath Hold for Left Breast Radiotherapy Using Surface Imaging and Visual Aid.

PURPOSE: To evaluate the clinical implementation of a deep inspiration breath hold (DIBH) treatment for left breast radiotherapy using surface imaging and visual aid. METHODS: A CT scan of the patient at DIBH is acquired and used for treatment planning. The plan and skin contour, containing isocenter and surface information are exported from the treatment planning system and imported into the surface imaging system (SIS). The skin contour constitutes the treatment reference surface or target DIBH position. A region of interest (ROI) consisting of the sternum and medial breasts is selected in the SIS. A set of video goggles allows the patient to view their breathing signal within the SIS, aiding in producing a reproducible and stable DIBH similar to simulation. Once the patient is set up at free breathing, she performs a DIBH while being monitored with the SIS. Shifts to minimize displacements from their reference DIBH surface are made. The surface image and patient setup are validated with weekly MV images. The beam is enabled when the two surfaces are within a predetermined tolerance. RESULTS: Data for evaluation of the implementation was acquired for 4 patients throughout treatment. Average treatment time was 16.8 minutes and 14.2 minutes for setup. The average displacement from the reference surface was 0.4 mm during DIBHs. The average reduction of heart mean dose and volume receiving 50% of the prescribed dose between DIBH and FB was 38% and 89% respectively. A total of 15 patients have completed this new treatment. 2 were excluded for inability to achieve reproducible and stable DIBH. CONCLUSION: The workflow we have implemented has proven to be effective and efficient for clinical purposes. Surface imaging provides adequate real time information valuable to the treatment process. Visual aid has helped patients achieve DIBH with high reproducibility and stability.

SU-D-213AB-04: Evaluation of the Dose Calculation in a Commercial Planning System for a Breast Cancer Brachytherapy Technology Using Monte Carlo Simulation.

PURPOSE: To evaluate the dose calculation in a commercial treatment planning system (TPS) for a breast cancer brachytherapy technology using Monte Carlo simulation for 21 patients. METHODS: Plans for 21 patients who received SAVI treatments were modeled using data from the TPS including CT images, structures and source information. The MC code PENELOPE was used, inputting images in voxel format, where density and material (tissue, air, bone and Nitinol) for each voxel were assigned based on its calibrated Hounsfield units and contoured structure sets, respectively. For the source model only gamma-rays and fluorescence X-rays of the NuDat database 192Ir spectrum were used, leaving out photons with emission intensity less than 0.1% and X-rays with energies below 10 keV. Source positions were entered into the plan and run individually. Dose was totaledby individually weighting the dose for each source position using the original TPS plan dwell times and then summing the weighted dose for all positions. RESULTS: Dose from the Monte Carlo plan was compared with dose from the original plan using isodose lines at 50, 100, 150 and 200% of the prescription dose of 34Gy. Dosimetric coverage of the target was compared by evaluating the V100, V150 and V200 (volume of the target covered by 100%, 150 and 200% of the dose respectively). The V200 and V150 had an average increase (and standard deviation) of 9.1% (3.2%) and 3.8% (1.4%) respectively, while the average change in V100 was 1.2% (1.0%). Where variance for the entire simulation was 0.9%. CONCLUSION: We have compared dose distributions of a commercial TPS using Monte Carlo simulation for SAVI breast cancer brachytherapy and found that a dose increase near the air-tissue interface.

Identification of a unique form of p53 in human cord blood associated with the development of maternal autoantibodies.

PROBLEM: The possible link between p53-reactive antibodies in multiparous women and exposure to a unique p53 protein during pregnancy was examined. METHOD OF STUDY: p53-reactive antibodies were evaluated in sera from nulligravid and multiparous women and patients with ovarian cancer by Western immunoblot. Furthermore, the presence of p53 protein was assayed in cord blood by enzyme-linked immunosorbent assay. Cord blood-derived p53 was compared structurally by protein fingerprinting and functionally by gel mobility shift assay to other isolates of p53. RESULTS: Antibodies reactive with wild-type p53 were observed in 92% of multiparous women and 42% were reactive with one tumor-derived p53 protein. p53 protein was detected in 27 of 154 samples of cord blood. Structural analysis indicated that the fetal p53 resembled the UL-1 p53. Functionally, the fetal and UL-1 protein failed to bind DNA. CONCLUSIONS: Fetal p53 protein seems to be distinct from wild-type p53, characterized by enhanced stability, structural differences and inability to bind DNA, analogous to alternatively spliced variants. Exposure to fetal p53 protein may form the basis for immunologic protection against cancer induced by multiparity.

Induction of immune responses to ovarian tumor antigens by multiparity.

OBJECTIVE: Because epidemiologic data indicate a reduction in ovarian cancer risk with increased parity, the occurrence of maternal immunization against ovarian tumor-associated antigens during pregnancy was investigated. METHODS: Sera were obtained from nulligravid and multiparous women and from men. Cellular proteins were isolated from four ovarian tumor cell lines as well as from normal ovaries. These proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the presence of cellular proteins reactive with each individual's serum was assessed by Western immunoblot. Tumor-reactive antibodies from two multiparous women were used to prepare immunoaffinity columns for the isolation of reactive proteins from ovarian tumor cells. These immunoaffinity-purified antigens were transferred electrophoretically to nitrocellulose membranes, stained with Ponceau S, and identified by amino acid sequencing. RESULTS: Western immunoblot analysis of the cellular proteins from four established ovarian tumor cell lines using sera from multiparous women as the primary antibody indicated that these samples recognized multiple bands on ovarian tumors, ranging from 30 to 150 kD. Two commonly recognized proteins were isolated and subjected to microsequencing, which identified the 56-kD band protein as elongation factor-1 alpha and the 38-kD protein as nucleophosmin/B23 protein. Both of these proteins play integral roles in cell growth. CONCLUSION: These findings suggest that certain antigens expressed by the fetus immunize women during pregnancy. This immune response may protect these women from the subsequent development of cancer.

Lymphokine-activated killer (LAK)-mediated lysis of sequentially isolated ovarian cancer cell lines.

PROBLEM: Understanding immunologic eradication of cancer is hampered by failure to explore tumor evolution. Cell surface molecules may alter with therapy and disease progression. These alterations can translate into variable susceptibility to immune-mediated cell lysis. METHOD OF STUDY: Cell lines from a patient with ovarian carcinoma isolated at surgical debulking (UL-3A), during chemotherapy (UL-3B), and after progression (UL-3C) were used to study changes in cell lysis by natural killer (NK) and lymphokine-activated killer (LAK) cells. The role of adhesion molecules ICAM-1, LFA-3, and glycoproteins in the demonstrated differential killing was also examined. RESULTS: An inverse relationship between attachment and lysis was demonstrated. UL-3C, the most sensitive to lysis (50%), attached the least lymphocytes (40%), whereas UL-3A, the least sensitive (33%), attached the most lymphocytes (71%). A correlation with ICAM-1 and LFA-3 expression was not demonstrated. CONCLUSION: Ovarian cancer cells evolve throughout the disease course, and this may manifest as differential sensitivity to immune-mediated cell lysis.

An incremental dosing protocol for women with severe vaginal trichomoniasis and adverse reaction to metronidazole.

OBJECTIVE: Our purpose was to develop and test an incremental dosing protocol for women with adverse reaction to metronidazole and severe symptomatic Trichomonas vaginitis. STUDY DESIGN: Two women with documented Trichomonas infection and presumed metronidazole allergy were initially treated with a number of alternative methods without success. With persistent severe symptoms associated with their infection, these women were admitted to the hospital and underwent an intravenous incremental metronidazole dosing protocol. RESULTS: Both patients were successfully treated without adverse event. They are both symptom-free and apparently cured several months after treatment. CONCLUSION: This protocol offers a new therapeutic option to women with adverse metronidazole reactions and severe symptomatic Trichomonas vaginitis resistant to treatment with nonmetronidazole therapy.

Exponential regression of CA 125 during salvage treatment of ovarian cancer with taxol.

The role of serum CA 125 in monitoring the response of epithelial ovarian cancer to treatment has been extensively investigated. The exponential regression curve [1n(CA 125) = i+s (days after initiation of treatment)] has been reported to describe the rate of change of serum CA 125 during treatment. In this model, the y-axis intercept (i) represents the initial CA 125-secreting tumor burden, while the slope (s) is determined by the response to treatment. The exponential regression curve was calculated for 66 patients undergoing salvage chemotherapy with taxol. At a mean follow-up of 121 days, 50 (75%) patients had progressed and 35 (53%) had died. Stratification of the patients by stage, grade, or histology did not reveal any significant differences in the regression rate. When the patients were stratified by response, the mean regression rate was 0.0157 +/- 0.011 for patients with progressive disease (N = 19) vs -0.0250 +/- 0.031 for those with stable disease (N = 25) and -0.0250 +/- 0.015 for those with a partial response (N = 22) (P < 0.0001). The regression rate did not correlate with progression-free interval or survival (P > 0.05). We conclude that changes in serum CA 125 levels follow an exponential regression curve in patients undergoing salvage chemotherapy with taxol for progressive or recurrent ovarian cancer. A positive regression rate may predict which patients will progress prior to the time progression becomes clinically evident. However, a negative rate fails to provide discriminatory utility in predicting progression-free interval or survival.