SU-E-T-572: A Plan Quality Metric for Evaluating Knowledge-Based Treatment Plans.

PURPOSE: In prostate IMRT treatment planning, the variation in patient anatomy makes it difficult to estimate a priori the potentially achievable extent of dose reduction possible to the rectum and bladder. We developed a mutual information-based framework to estimate the achievable plan quality for a new patient, prior to any treatment planning or optimization. METHODS: The knowledge-base consists of 250 retrospective prostate IMRT plans. Using these prior plans, twenty query cases were each matched with five cases from the database. We propose a simple DVH plan quality metric (PQ) based on the weighted-sum of the areas under the curve (AUC) of the PTV, rectum and bladder. We evaluate the plan quality of knowledge-based generated plans, and established a correlation between the plan quality and case similarity. RESULTS: The introduced plan quality metric correlates well (r2 = 0.8) with the mutual similarity between cases. A matched case with high anatomical similarity can be used to produce a new high quality plan. Not surprisingly, a poorly matched case with low degree of anatomical similarity tends to produce a low quality plan, since the adapted fluences from a dissimilar case cannot be modified sufficiently to yield acceptable PTV coverage. CONCLUSIONS: The plan quality metric is well-correlated to the degree of anatomical similarity between a new query case and matched cases. Further work will investigate how to apply this metric to further stratify and select cases for knowledge-based planning.

SU-E-T-415: Evaluation of the Effect of the Dose Buildup Region for Flattening Filter Free Beams in IMRT Plans of Lung and Sinuses.

PURPOSE: The surface and buildup dose is known to be greater for flattening-filter-free (FFF) beams as compared to flattened beams. We compare the effect of this difference in the dose buildup region between the two beam modes, in the context of IMRT plans for the lung and sinuses. METHODS: IMRT plans are delivered using both the standard flattened beam mode (6X) and flattening-filter-free mode (6XFFF). We compare the dosimetric differences of these two modes, for IMRT treatments for the lung and sinuses. Radiochromic films and parallel-plate ionization chamber measurements were taken, and evaluated for the following field sizes: 2×2 cm2 , 3×3 cm2 , 5×5 cm2 , 8×8 cm2 , 10×10 cm2 , and 20×20 cm2 . We evaluated the area under the PDD curve (AUC) for the buildup region for both 6X and 6XFFF beams. Ten SBRT lung and five IMRT sinuses plans were generated using the EclipseTM planning system, commissioned with AAA. Plan evaluation involved the comparison of the isodose distributions between plans of the two delivery modes. RESULTS: For small field sizes, the dose in the buildup region is greater for FFF beam than for flattened beam. The percentage differences between 6XFFF and 6X flattened beams for the following field sizes (2×2 cm2 , 3×3 cm2 , 5×5 cm2 , 8×8 cm2 , 10×10 cm2 , and 20×20 cm2 ) are 3.4%,2.2%, 7.2%, 4.9%, 0.9%, and -0.5%, respectively. Plan evaluation of the IMRT sinus cases found approximately 3% higher maximum dose within the PTV for FFF plans. No observable differences were found between two types of SBRT lung plans. CONCLUSIONS: For small fields, the dose buildup region of FFF beam is slightly greater than that of flattened beams. This effect is more pronounced in IMRT sinus cases, leading to higher dose within the PTV. There was no difference in the SBRT lung plans between the two beam modes.

Detection of a novel point mutation in the p53 gene in grade II astrocytomas by PCR-SSCP analysis with additional Klenow treatment.

Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) with additional Klenow treatment and direct sequencing mutations in the p53 tumor suppressor gene were analyzed from 21 cases of human astrocytomas. Three cases had p53 gene mutations: two of them were glioblastomas showing a point mutation, one in exon 5 and the other in 6. The last one was a gemistocytic astrocytoma showing a point mutation in exon 5. The frequency of p53 gene mutations in the astrocytomas examined was 14.3% (3 out of 21). No SSCP alterations were observed in any of the p53 fragments amplified from WHO grade I pilocytic astrocytomas and WHO grade III anaplastic astrocytomas. Further examination by direct sequencing showed that two mutations of glioblastomas had single-base substitutions resulting in silent and missense mutations, whereas one of the gemistocytic astrocytomas had a double-base substitution resulting in a missense mutation. The present studies revealed that all mutations were located outside the hot spots and, interestingly, one of them disclosed a missense mutation in exon 5 at codon 166, which was first detected in a grade II astrocytoma (gemistocytic type). It is possible that the missense mutation at this codon may be associated with special risk factors for the development of astrocytic tumors in Thai patients.

The observation of immunosuppressor(s) derived from cultured tumor cells and its partial neutralization with OK-432.

Malignant tumors such as brain tumors have been reported to be associated with immunosuppression caused by certain tumor-secreted cytokines. The reversion of tumor-derived immunosuppression has not been described. The use of OK-432, an immunomodulatory agent prepared from Su-strain of Streptococcus pyogenes A3, to activate peripheral blood mononuclear cells from a patient with glioblastoma multiforme has demonstrated a sharp rise in proliferative response. This proliferative response was compromised in the presence of living and irradiated autogeneic cancer cells. The conditioned media from cultured cells of glioblastoma multiforme, astrocytoma, and cholangiocarcinoma were tested for immunosuppressive ability. We found that conditioned media from 3 of 4 cases of glioblastoma, all 3 cases of astrocytoma, and 1 case of cholangiocarcinoma exhibited immunosuppressive activity toward the proliferative response of allogeneic peripheral blood mononuclear cells to phytohemagglutinin. This is the first report that cholangiocarcinoma produces soluble immunosuppressor(s). Our finding suggested that soluble substance(s) as well as direct cell-cell contact between tumor cells and mononuclear cells play roles in the observed tumor-derived immunosuppression.

The analysis of peri-tumor necrosis following the subcutaneous implantation of autologous tumor cells transfected with an episome transcribing an antisense insulin-like growth factor 1 RNA in a glioblastoma multiforme subject.

A subject inflicted with glioblastoma multiforme who received partial tumor resection and radiotherapy was recruited for an ex vivo gene therapy protocol using irradiated autologous tumor cells that had been engineered to suppress the expression of insulin-like growth factor I as the tumor vaccine. After subcutaneous injection for 8 weeks, the subject developed peri-tumor necrosis with mass effect. The authors wondered whether this event could have resulted from the tumor vaccine. The tissue section bordering the necrotic tumor tissue to the viable normal tissue was examined for nature of any infiltrated cells and their activities. Lymphocytes, macrophages, and a small number of neutrophils diffused into the necrotic tumor tissue were found. The infiltrated lymphocytes consisted of both CD4+ and CD8+ T cells. The functional activity of these lymphocytes was demonstrated by the active production of interferon y and tumor necrosis factor alpha based on the respective immunofluorescent staining localized to these cells. This finding is compatible with the proposed mechanism underlying the tumor vaccination. However, the contribution of radiation treatment to this event cannot be clearly ruled out.

Osteoblastoma of the ethmoid sinus in a nine-year-old child--an unusual occurrence.

Osteoblastoma is a benign bone tumor which is common in the vertebral column and long bone of the extremities. The paranasal sinus involvement is rare. We reported a case of benign osteoblastoma of the ethmoid sinus in a nine-year-old boy who presented with exophthalmos. The tumor had aggressive growth with cranial base involvement. Radiologic finding was a mottled soft tissue mass with sclerotic margin. Histologic features were the presence of osteoblast, small trabeculae of woven bone and rich vascular fibrous stroma. Differential diagnoses consist of various kinds of fibro osseous lesions; the closest one is osteoid osteoma. Surgery is the treatment of choice, external ethmoidectomy with lateral rhinotomy was performed in this case. Recurrence is common according to previous reports. Previous literature were reviewed and discussed.