An opportune time for targeted brain arteriovenous malformation therapy.
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Journal Article↗
Biomedical subjects
Helen A Shih
Publications and source records attributed to Helen A Shih.
Approximating convex pareto surfaces in multiobjective radiotherapy planning.
Radiotherapy planning involves inherent tradeoffs: the primary mission, to treat the tumor with a high, uniform dose, is in conflict with normal tissue sparing. We seek to understand these tradeoffs on a case-to-case basis, by computing for each patient a database of Pareto optimal plans. A treatment plan is Pareto optimal if there does not exist another plan which is better in every measurable dimension. The set of all such plans is called the Pareto optimal surface. This article presents an algorithm for computing well distributed points on the (convex) Pareto optimal surface of a multiobjective programming problem. The algorithm is applied to intensity-modulated radiation therapy inverse planning problems, and results of a prostate case and a skull base case are presented, in three and four dimensions, investigating tradeoffs between tumor coverage and critical organ sparing.
Algorithms↗
Mapping of nodal disease in locally advanced prostate cancer: rethinking the clinical target volume for pelvic nodal irradiation based on vascular rather than bony anatomy.
PURPOSE: Toxicity from pelvic irradiation could be reduced if fields were limited to likely areas of nodal involvement rather than using the standard "four-field box." We employed a novel magnetic resonance lymphangiographic technique to highlight the likely sites of occult nodal metastasis from prostate cancer. METHODS AND MATERIALS: Eighteen prostate cancer patients with pathologically confirmed node-positive disease had a total of 69 pathologic nodes identifiable by lymphotropic nanoparticle-enhanced MRI and semiquantitative nodal analysis. Fourteen of these nodes were in the para-aortic region, and 55 were in the pelvis. The position of each of these malignant nodes was mapped to a common template based on its relation to skeletal or vascular anatomy. RESULTS: Relative to skeletal anatomy, nodes covered a diffuse volume from the mid lumbar spine to the superior pubic ramus and along the sacrum and pelvic side walls. In contrast, the nodal metastases mapped much more tightly relative to the large pelvic vessels. A proposed pelvic clinical target volume to encompass the region at greatest risk of containing occult nodal metastases would include a 2.0-cm radial expansion volume around the distal common iliac and proximal external and internal iliac vessels that would encompass 94.5% of the pelvic nodes at risk as defined by our node-positive prostate cancer patient cohort. CONCLUSIONS: Nodal metastases from prostate cancer are largely localized along the major pelvic vasculature. Defining nodal radiation treatment portals based on vascular rather than bony anatomy may allow for a significant decrease in normal pelvic tissue irradiation and its associated toxicities.
Aged↗
Genetic analyses for predictors of radiation response in glioblastoma.
PURPOSE: Radiotherapy (RT) for patients with glioblastoma improves survival and is recommended for nearly all patients with this diagnosis. However, the response to RT is variable in this patient population. Prior studies have suggested that underlying genetic alterations in the tumor may account for some of this treatment-related heterogeneity. It has been previously reported that epidermal growth factor receptor (EGFR) gene amplification and TP53 mutation correlate with the response to RT in patients with glioblastoma. METHODS AND MATERIALS: We sought to identify molecular markers that could predict the response to RT, progression-free survival after RT, and overall survival among 75 glioblastoma patients treated with RT at a single institution. Genetic analyses assessed EGFR amplification, TP53 mutations, CDKN2A/p16 deletion, and losses of chromosomes 1p, 10q, and 19q. RESULTS: Unlike previous reports, no association of EGFR amplification with response to RT, progression-free survival, or overall survival was found. Moreover, no association was found between these endpoints and the other genetic alterations assayed (TP53 mutation, CDKN2A/p16 deletion, loss of heterozygosity 1p, loss of heterozygosity 10q, and loss of heterozygosity 19q). However, in accordance with recent observations that the prognostic effects of genetic alterations in glioblastoma may depend on patient age, we observed age-dependent prognostic effects of TP53 and CDKN2A/p16 alterations in our patient population. For patients > or = 57 years old, those harboring TP53 mutations had a decreased overall survival compared with patients without TP53 mutations. Similarly, deletion of CDKN2A/p16 in patients > or = 57 years was associated with decreased progression-free survival after RT and a trend toward a shorter time to progression after RT compared with similar patients without the deletion. CONCLUSION: These data contrast with previous studies regarding the significant prognostic effect of EGFR with respect to RT response. Although our observations regarding the age-dependent prognostic effects of TP53 and CDKN2A/p16 are consistent with a prior report regarding these alterations, the present results should be considered preliminary, given the small sample size.
Adolescent↗
Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer.
SUMMARY BACKGROUND DATA: To analyze the effects of a treatment program of intraoperative electron beam radiation therapy (IOERT) and external beam radiation therapy and chemotherapy on the outcome of patients with unresectable or locally advanced pancreatic cancer. METHODS: From 1978 to 2001, 150 patients with unresectable and nonmetastatic pancreatic cancer received IOERT combined with external beam radiation therapy and 5-fluorouracil-based chemotherapy for definitive treatment. RESULTS: The 1-, 2-, and 3-year actuarial survival rates of all 150 patients were 54%, 15%, and 7%, respectively. Median and mean survival rates were 13 and 17 months, respectively. Long-term survival has been observed in 8 patients. Five patients have survived beyond 5 years and 3 more between 3 and 4 years. There was a statistically significant correlation of survival to the diameter of treatment applicator (a surrogate for tumor size) used during IOERT. For 26 patients treated with a small-diameter applicator (5 cm or 6 cm), the 2- and 3-year actuarial survival rates were 27% and 17%, respectively. In contrast, none of the 11 patients treated with a 9-cm-diameter applicator survived beyond 18 months. Intermediate survival rates were seen for patients treated with a 7- or 8-cm-diameter applicator. Operative mortality was 0.6%, and postoperative and late complications were 20% and 15%, respectively. CONCLUSIONS: A treatment strategy employing IOERT has resulted in long-term survival in 8 of 150 patients with unresectable pancreatic cancer. Survival benefit was limited to patients with small tumors. Enrollment of selected patients with small tumors into innovative protocols employing this treatment approach is appropriate.
Adult↗
Internal target volume determined with expansion margins beyond composite gross tumor volume in three-dimensional conformal radiotherapy for lung cancer.
PURPOSE: Gross tumor volume (GTV) of lung cancer defined by fast helical CT scan represents an image of moving tumor captured at a point in active respiratory movement. However, the method for defining internal margins beyond GTV to account for its expected physiologic movement and all variations in size and shape during the administration of radiation has not been established. The goal of this study was to determine the internal margins with expansion margins beyond individual GTVs defined with (1) fast scan at shallow free breathing, (2) breath-hold scans at the end of tidal volume inspiration and expiration, and (3) 4-s slow scan to approximate the composite GTV of all scans. METHODS AND MATERIALS: A series of sequential CT scans were acquired with (1) a fast helical scan at shallow free breathing and (2) breath-hold scans at the end of tidal volume expiration and inspiration for the first 6 patients, and (3) a 4-s slow scan at quiet free breathing, which was added for the latter 7 patients. We fused breath-hold scans and the 4-s slow scan to the fast scan at shallow free breathing to generate the composite GTV. Margins necessary to encompass the composite GTV beyond individual GTVs defined by either fast scan at quiet free breathing, breath-hold scans, or the 4-s slow scan at quiet free breathing were defined as expansion or internal margins and termed the internal target volumes. The centroid of the tumor volume was also used as another reference for tumor movement. RESULTS: Thirteen patients with 14 tumors were enrolled into the study. Substantial tumor movement was noted by either the extent of internal margins beyond each GTV or the movement of the centroid. Internal margins varied significantly according to the method of CT scanning for determination of GTV. Even for tumors in the same lobe of the lung, a wide range of internal margins and significant variation in the centroid movement in all directions (x, y, and z) were observed. The GTV of a single fast helical scan at free breathing (n = 14) required the largest internal margin (mean, 3.5 mm; maximum, 18 mm; standard deviation [SD], 4.2 mm) to match the composite GTV, compared with those of the 4-s slow scan (mean 2.7 mm, maximum 14 mm, SD 3.5 mm) or combined breath-hold scans (mean 1.1 mm, maximum 9 mm, SD 1.9 mm). Internal margins (expansion margins) required to approximate the composite GTV in 95% of cases were 13 mm, 10 mm, and 5 mm for the GTVs of a single fast scan, 4-s slow scan, and breath-hold scans at the end of tidal volume inspiration and expiration, respectively. CONCLUSIONS: The internal margins required to account for the internal tumor motion in three-dimensional conformal radiotherapy are substantial. For the use of symmetric and population-based margins to account for internal tumor motion, GTV defined with breath-hold scans at the end of tidal volume inspiration and expiration has a narrower range of internal margins in all directions than that of either a single fast scan or 4-s slow scan.
Aged↗
Advances in combined radiation therapy for the management of rectal cancer.
Significant advances have been made in the use of adjuvant radiation for patients with localized rectal cancer. Recent progress in adjuvant postoperative radiation regimens relates to the integration of systemic therapy into radiation, as well as redefining the techniques and sequences for both modalities. The adjuvant radiation management approach in both North America and Europe has been shifting towards preoperative adjuvant therapy to promote sphincter-preserving surgery and to decrease acute and late toxicity. Although 5-fluorouracil-based chemotherapy in combination with radiation remains the standard adjuvant therapy for rectal cancer, the integration of novel chemotherapeutic agents and biologic modulators remains an active area of investigation.
Combined Modality Therapy↗
BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic.
PURPOSE: To determine the prevalence of BRCA1 and BRCA2 mutations in families identified in a breast cancer risk evaluation clinic. PATIENTS AND METHODS: One hundred sixty-four families seeking breast cancer risk evaluation were screened for coding region mutations in BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis and DNA sequencing. RESULTS: Mutations were identified in 37 families (22.6%); 28 (17.1%) had BRCA1 mutations and nine (5.5%) had BRCA2 mutations. The Ashkenazi Jewish founder mutations 185delAG and 5382insC (BRCA1) were found in 10 families (6.1%). However, 6174delT (BRCA2) was found in only one family (0.6%) despite estimates of equal frequency in the Ashkenazi population. In contrast to other series, the average age of breast cancer diagnosis was earlier in BRCA2 mutation carriers (32.1 years) than in women with BRCA1 mutations (37.6 years, P =.028). BRCA1 mutations were detected in 20 (45.5%) of 44 families with ovarian cancer and 12 (75%) of 16 families with both breast and ovarian cancer in a single individual. Significantly fewer BRCA2 mutations (two [4.5%] of 44) were detected in families with ovarian cancer (P =.01). Eight families had male breast cancer; one had a BRCA1 mutation and three had BRCA2 mutations. CONCLUSION: BRCA1 mutations were three times more prevalent than BRCA2 mutations. Breast cancer diagnosis before 50 years of age, ovarian cancer, breast and ovarian cancer in a single individual, and male breast cancer were all significantly more common in families with BRCA1 and BRCA2 mutations, but none of these factors distinguished between BRCA1 and BRCA2 mutations. Evidence for reduced breast cancer penetrance associated with the BRCA2 mutation 6174delT was noted.
Adolescent↗
Planar fluorescence imaging using normalized data.
Fluorescence imaging of tissues has gained significant attention in recent years due to the emergence of appropriate reporter technologies that enable noninvasive sensing of molecular function in vivo. Two major approaches have been used so far for fluorescence molecular imaging, i.e., epi-illumination (reflectance) imaging and fluorescence molecular tomography. Transillumination is an alternative approach that has been employed for imaging tissues in the past and could be similarly beneficial for fluorescence molecular imaging. We investigate data normalization schemes in reflectance and transillumination mode and experimentally demonstrate that normalized transillumination offers significant advantages over planar reflectance imaging and over nonnormalized methods. Our observations, based on phantoms and on postmortem and in vivo mouse measurements display image quality improvement, superior depth sensitivity, and improved imaging accuracy over the nonnormalized methods examined. Normalized planar imaging retains implementation simplicity and could be used to improve on standard fluorescence reflectance imaging and as a simplified alternative to the more integrated and accurate tomographic methods.
Algorithms↗