Oncology Specialist (cancer), Radiologist
10 years of experience
Video profile
Accepting new patients
West End
Massachusetts General Hospital
100 Blossom St
Boston, MA 02114
617-726-8650
Locations and availability (3)

Education ?

Medical School Score Rankings
University of Pennsylvania (2000)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Associations
American Society of Clinical Oncology
American Board of Radiology

Affiliations ?

Dr. Shih is affiliated with 5 hospitals.

Hospital Affilations

Score

Rankings

  • Boston Medical Center
    Medical Oncology
    1 Boston Medical Ctr Pl, Boston, MA 02118
    • Currently 4 of 4 crosses
    Top 25%
  • Massachusetts General Hospital
    Medical Oncology
    55 Fruit St, Boston, MA 02114
    • Currently 4 of 4 crosses
    Top 25%
  • Newton-Wellesley Hospital
    Medical Oncology
    2014 Washington St, Newton Lower Falls, MA 02462
    • Currently 4 of 4 crosses
    Top 25%
  • Boston: Massachusetts General Hospital
  • Mass General Hospital
  • Publications & Research

    Dr. Shih has contributed to 22 publications.
    Title Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients with Breast Cancer and Brain Metastases.
    Date May 2012
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype.

    Title Late Effects of Cns Radiation Therapy.
    Date September 2010
    Journal Cancer Treatment and Research
    Title Radiation Therapy in Acromegaly.
    Date April 2008
    Journal Reviews in Endocrine & Metabolic Disorders
    Excerpt

    Radiation therapy is generally not a primary treatment modality for growth hormone-secreting pituitary adenomas. However, in patients with acromegaly refractory to medical and/or surgical interventions, radiation can offer durable tumor control and often biochemical remission. Technique of radiation therapy delivery and dose vary by adenoma size and extrasellar extension. Radiation can be delivered in a single sitting by stereotactic radiosurgery or in fractionated form of smaller doses delivered over typically 5-6 weeks in 25-30 treatments. A brief overview of forms of radiation modalities is reviewed followed by discussion of the role for radiation therapy, rationale of delivery method, and potential adverse effects.

    Title Fractionated Radiotherapy Versus Stereotactic Radiosurgery for Pituitary Adenomas.
    Date April 2008
    Journal Nature Clinical Practice. Neurology
    Title An Approach for Practical Multiobjective Imrt Treatment Planning.
    Date January 2008
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To introduce and demonstrate a practical multiobjective treatment planning procedure for intensity-modulated radiation therapy (IMRT) planning. METHODS AND MATERIALS: The creation of a database of Pareto optimal treatment plans proceeds in two steps. The first step solves an optimization problem that finds a single treatment plan which is close to a set of clinical aspirations. This plan provides an example of what is feasible, and is then used to determine mutually satisfiable hard constraints for the subsequent generation of the plan database. All optimizations are done using linear programming. RESULTS: The two-step procedure is applied to a brain, a prostate, and a lung case. The plan databases created allow for the selection of a final treatment plan based on the observed tradeoffs between the various organs involved. CONCLUSIONS: The proposed method reduces the human iteration time common in IMRT treatment planning. Additionally, the database of plans, when properly viewed, allows the decision maker to make an informed final plan selection.

    Title Stereotactic Radiation Treatment for Benign Meningiomas.
    Date December 2007
    Journal Neurosurgical Focus
    Excerpt

    Meningiomas are the second most common primary tumor of the brain. Gross-total resection remains the preferred treatment if achievable with minimal morbidity. For incompletely resected or inoperable benign meningiomas, 3D conformal external-beam radiation therapy can provide durable local tumor control in 90 to 95% of cases. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) are highly conformal techniques, using steep dose gradients and stereotactic patient immobilization. Stereotactic radiosurgery has been used as an alternative or adjuvant therapy to surgery for meningiomas in locations, such as the skull base, where operative manipulation may be particularly difficult. Stereotactic radiotherapy is useful for larger meningiomas (> 3-3.5 cm) and those closely approximating critical structures, such as the optic chiasm and brainstem. Although SRS has longer follow-up than SRT, both techniques have excellent 5-year tumor control rates of greater than 90% for benign meningiomas. Stereotactic radiotherapy has toxicity equivalent to that of radiosurgery, despite its biased use for larger meningiomas with more complicated volumes. Reported rates of imaging-documented regression are higher for radiosurgery, but neurological recovery is relatively good with both techniques. Stereotactic radiosurgery and fractionated SRT are complementary techniques appropriate for different clinical scenarios.

    Title Patient Study of in Vivo Verification of Beam Delivery and Range, Using Positron Emission Tomography and Computed Tomography Imaging After Proton Therapy.
    Date July 2007
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To investigate the feasibility and value of positron emission tomography and computed tomography (PET/CT) for treatment verification after proton radiotherapy. METHODS AND MATERIALS: This study included 9 patients with tumors in the cranial base, spine, orbit, and eye. Total doses of 1.8-3 GyE and 10 GyE (for an ocular melanoma) per fraction were delivered in 1 or 2 fields. Imaging was performed with a commercial PET/CT scanner for 30 min, starting within 20 min after treatment. The same treatment immobilization device was used during imaging for all but 2 patients. Measured PET/CT images were coregistered to the planning CT and compared with the corresponding PET expectation, obtained from CT-based Monte Carlo calculations complemented by functional information. For the ocular case, treatment position was approximately replicated, and spatial correlation was deduced from reference clips visible in both the planning radiographs and imaging CT. Here, the expected PET image was obtained from an analytical model. RESULTS: Good spatial correlation and quantitative agreement within 30% were found between the measured and expected activity. For head-and-neck patients, the beam range could be verified with an accuracy of 1-2 mm in well-coregistered bony structures. Low spine and eye sites indicated the need for better fixation and coregistration methods. An analysis of activity decay revealed as tissue-effective half-lives of 800-1,150 s. CONCLUSIONS: This study demonstrates the feasibility of postradiation PET/CT for in vivo treatment verification. It also indicates some technological and methodological improvements needed for optimal clinical application.

    Title Approximating Convex Pareto Surfaces in Multiobjective Radiotherapy Planning.
    Date November 2006
    Journal Medical Physics
    Excerpt

    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.

    Title Planar Fluorescence Imaging Using Normalized Data.
    Date March 2006
    Journal Journal of Biomedical Optics
    Excerpt

    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.

    Title 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.
    Date December 2005
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    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.

    Title Genetic Analyses for Predictors of Radiation Response in Glioblastoma.
    Date December 2005
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    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.

    Title Long-term Results of Intraoperative Electron Beam Irradiation (ioert) for Patients with Unresectable Pancreatic Cancer.
    Date February 2005
    Journal Annals of Surgery
    Excerpt

    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.

    Title Internal Target Volume Determined with Expansion Margins Beyond Composite Gross Tumor Volume in Three-dimensional Conformal Radiotherapy for Lung Cancer.
    Date November 2004
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    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.

    Title Advances in Combined Radiation Therapy for the Management of Rectal Cancer.
    Date October 2003
    Journal Expert Review of Anticancer Therapy
    Excerpt

    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.

    Title Germline Tp53 Mutations in Breast Cancer Families with Multiple Primary Cancers: is Tp53 a Modifier of Brca1?
    Date April 2003
    Journal Journal of Medical Genetics
    Title Brca1 and Brca2 Mutation Frequency in Women Evaluated in a Breast Cancer Risk Evaluation Clinic.
    Date March 2002
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    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.

    Title Brca1 and Brca2 Mutations in Breast Cancer Families with Multiple Primary Cancers.
    Date May 2001
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Ninety-eight women ascertained from high-risk breast/ovarian cancer clinics with breast cancer reporting at least one other primary cancer in themselves or in a relative with breast cancer were compared with 99 women with breast cancer who reported a family history of breast cancer only. All DNA was screened for coding region mutations in BRCA1 and BRCA2 using heteroduplex analysis, followed by direct sequencing. Our data indicate that 42.9% of families reporting breast and any second nonbreast type of primary cancer in the same individual had a BRCA1 or BRCA2 mutation, as compared with the 12.1% of families reporting breast cancer only (P < 0.001). Among the 66 women reporting breast cancer and a nonovarian second primary cancer, 15 (22.7%) had mutations in BRCA1 or BRCA2 (P = 0.04). Among the 32 families where ovarian cancer was the second primary cancer, 27 (84.4%) had a mutation in BRCA1 or BRCA2 (P < 0.001). BRCA1 and BRCA2 mutations were twice as common in the presence of a reported second nonovarian cancer. These data suggest that the presence of multiple primary cancer of any kind may predict for an increased likelihood of finding a BRCA1 or BRCA2 mutation and supports previous studies suggesting that BRCA1 and BRCA2 mutations may be associated with an increased susceptibility to cancers other than breast and ovarian cancer.

    Title Germline Mutations in Brca1 and Brca2 in Breast-ovarian Families from a Breast Cancer Risk Evaluation Clinic.
    Date May 2001
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: Data from the Breast Cancer Linkage Consortium suggest that the proportion of familial breast and ovarian cancers linked to BRCA1 or BRCA2 may be as high as 98% depending on the characteristics of the families, suggesting that mutations in BRCA1 or BRCA2 may entirely account for hereditary breast and ovarian cancer families. We sought to determine what proportion of families with both breast and ovarian cancers seen in a breast cancer risk evaluation clinic are accounted for by coding region germline mutations in BRCA1 and BRCA2 as compared to a linkage study group. We also evaluated what clinical parameters were predictive of mutation status. PATIENTS AND METHODS: Affected women from 100 families with at least one case of breast cancer and at least one case of ovarian cancer in the same lineage were screened for germline mutations in the entire coding regions of BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis, a polymerase chain reaction-based heteroduplex analysis, or direct sequencing. RESULTS: Unequivocal deleterious mutations were found in 55% (55 of 100) of the families studied. Mutations in BRCA1 and BRCA2 accounted for 80% and 20% of the mutations overall, respectively. Using multivariate analysis, the strongest predictors of detecting a mutation in BRCA1 or BRCA2 in this study group were the presence of a single family member with both breast and ovarian cancer (P <.0009; odds ratio [OR], 5.68; 95% confidence interval [CI], 2.04 to 15.76) and a young average age at breast cancer diagnosis in the family (P <.0016; OR, 1.69; 95% CI, 1.23 to 2.38). CONCLUSION: These results suggest that at least half of breast/ovarian families evaluated in a high-risk cancer evaluation clinic may have germline mutations in BRCA1 or BRCA2. Whether the remaining families have mutations in noncoding regions in BRCA1, mutations in other, as-yet-unidentified, low-penetrance susceptibility genes, or represent chance clustering remains to be determined.

    Title Livedo Reticularis, Ulcers, and Peripheral Gangrene: Cutaneous Manifestations of Primary Hyperoxaluria.
    Date October 2000
    Journal Archives of Dermatology
    Title Screening for Genomic Rearrangements in Families with Breast and Ovarian Cancer Identifies Brca1 Mutations Previously Missed by Conformation-sensitive Gel Electrophoresis or Sequencing.
    Date October 2000
    Journal American Journal of Human Genetics
    Excerpt

    The frequency of genomic rearrangements in BRCA1 was assessed in 42 American families with breast and ovarian cancer who were seeking genetic testing and who were subsequently found to be negative for BRCA1 and BRCA2 coding-region mutations. An affected individual from each family was tested by PCR for the exon 13 duplication (Puget et al. 1999a) and by Southern blot analysis for novel genomic rearrangements. The exon 13 duplication was detected in one family, and four families had other genomic rearrangements. A total of 5 (11. 9%) of the 42 families with breast/ovarian cancer who did not have BRCA1 and BRCA2 coding-region mutations had mutations in BRCA1 that were missed by conformation-sensitive gel electrophoresis or sequencing. Four of five families with BRCA1 genomic rearrangements included at least one individual with both breast and ovarian cancer; therefore, 4 (30.8%) of 13 families with a case of multiple primary breast and ovarian cancer had a genomic rearrangement in BRCA1. Families with genomic rearrangements had prior probabilities of having a BRCA1 mutation, ranging from 33% to 97% (mean 70%) (Couch et al. 1997). In contrast, in families without rearrangements, prior probabilities of having a BRCA1 mutation ranged from 7% to 92% (mean 37%). Thus, the prior probability of detecting a BRCA1 mutation may be a useful predictor when considering the use of Southern blot analysis for families with breast/ovarian cancer who do not have detectable coding-region mutations.

    Title Molecular Analysis of Episomal Human Papillomavirus Type 16 Dna in a Cervical Carcinoma Cell Line.
    Date April 1998
    Journal Virus Research
    Excerpt

    Integration of human papillomavirus type 16 DNA sequences into host DNA is a frequent event in cervical carcinogenesis. However, recent studies showing that HPV16 is present exclusively in an episomal form in many primary cervical cancers suggest that HPV16 can transform target cells by mechanisms that do not require viral integration. We have established a cervical carcinoma cell line that harbors episomal copies of HPV16 DNA of approximately 10 kb. Restriction enzyme and two-dimensional gel analysis confirmed that HPV16 DNA was extrachromosomal with both monomeric and multimeric forms present. HPV16 was maintained as episomes with passage both in culture and after subcutaneous growth in nude mice. The 10 kb viral genome, consisting of a full-length copy of HPV16 and a partial duplication of the long control region and the L1 open reading frame, exhibited transforming activity comparable to prototype HPV16. This cell line should provide a useful model system for studying the biological significance of the physical state of the HPV16 genome in cervical carcinoma cells.

    Title Proton Stereotactic Radiosurgery for the Treatment of Benign Meningiomas.
    Date
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: Given the excellent prognosis for patients with benign meningiomas, treatment strategies to minimize late effects are important. One strategy is proton radiation therapy (RT), which allows less integral dose to normal tissue and greater homogeneity than photon RT. Here, we report the first series of proton stereotactic radiosurgery (SRS) used for the treatment of meningiomas. METHODS AND MATERIALS: We identified 50 patients with 51 histologically proven or image- defined, presumed-benign meningiomas treated at our institution between 1996 and 2007. Tumors of <4 cm in diameter and located ≥2 mm from the optic apparatus were eligible for treatment. Indications included primary treatment (n = 32), residual tumor following surgery (n = 8), and recurrent tumor following surgery (n = 10). The median dose delivered was 13 Gray radiobiologic equivalent (Gy[RBE]) (range, 10.0-15.5 Gy[RBE]) prescribed to the 90% isodose line. RESULTS: Median follow-up was 32 months (range, 6-133 months). Magnetic resonance imaging at the most recent follow-up or time of progression revealed 33 meningiomas with stable sizes, 13 meningiomas with decreased size, and 5 meningiomas with increased size. The 3-year actuarial tumor control rate was 94% (95% confidence interval, 77%-98%). Symptoms were improved in 47% (16/ 34) of patients, unchanged in 44% (15/34) of patients, and worse in 9% (3/34) of patients. The rate of potential permanent adverse effects after SRS was 5.9% (3/51 patients). CONCLUSIONS: Proton SRS is an effective therapy for small benign meningiomas, with a potentially lower rate of long-term treatment-related morbidity. Longer follow-up is needed to assess durability of tumor control and late effects.


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