Radiation Oncology at Thomas Jefferson University: A Specialty Emerges as a Department Evolves

Jefferson Radiation Oncology has maintained over fifty years of excellence led by only four chairmen. Dr Kramer after receiving his medical training inLondonled the department into the modern megavoltage era while creating the first independent academic radiation oncology department in the country. He was well-respected nationally as a leader and advocate for the specialty and he mastered the execution of progressive ideas that have raised the standard for the profession. The creation of the Radiation Therapy Oncology Group (RTOG) was critical in developing trials to expand the management and treatment of malignancy. The Patterns of Care Study (PCS) educated the masses on providing optimal care to patients by comparing strategies for the management and treatment of carcinoma through surveys across theUnited States. Dr Mansfield expanded his mentor’s vision and together they developed the Bodine Centre for Cancer Treatment, a new state-of-the-art building for cancer treatment. He helped to dispel common misconceptions, thus raising the social consciousness for managing and treating the underserved community. Dr Curran grew the RTOG to new levels in trial development, funding, and respect both domestically and internationally. He helped develop new technology in the department and markedly expanded the Jefferson Cancer Network. Finally, Dr Dicker set a new course for the department with biologically-driven radiation therapy keepingJeffersonat the forefront of new technology for the diagnosis and treatment of malignancy

Neurostimulatory and ablative treatment options in major depressive disorder: a systematic review

Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5-10% of the general population and up to 20-25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods. © The Author(s) 2010.Link_to_subscribed_fulltex

Risk-Reducing Mastectomy and Reconstruction Following Prophylactic Breast Irradiation: Hope Sustained

Risk-reducing mastectomy (RRM) is often advocated for BRCA1/2 mutation carriers who face a heightened lifetime risk of breast cancer. However, many carrier patients seek alternative risk-reducing measures. In a phase II nonrandomized trial, we previously reported that prophylactic irradiation to the contralateral breast among BRCA carriers undergoing breast-conserving treatment significantly reduced subsequent contralateral breast cancer. Herein, we report the outcome of salvage mastectomy and reconstruction in 11 patients that suffered reoccurrences of breast cancer in either the ipsilateral or contralateral breast or elected to have the procedure for risk reduction during the eight-year follow-up period. Patients’ satisfaction with the procedure and physicians’ assessment of the cosmetic outcome were not inferior for previously irradiated compared to non-irradiated breasts. Although the numbers are small, the results are encouraging and sustain hope in a challenging population. Our findings support continuing research as well as a discussion of risk-reduction alternatives besides mastectomy, including prophylactic breast irradiation, in BRCA1/2 mutation carriers

Hemodynamic response imaging: a potential tool for the assessment of angiogenesis in brain tumors.

Blood oxygenation level dependence (BOLD) imaging under either hypercapnia or hyperoxia has been used to study neuronal activation and for assessment of various brain pathologies. We evaluated the benefit of a combined protocol of BOLD imaging during both hyperoxic and hypercapnic challenges (termed hemodynamic response imaging (HRI)). Nineteen healthy controls and seven patients with primary brain tumors were included: six with glioblastoma (two newly diagnosed and four with recurrent tumors) and one with atypical-meningioma. Maps of percent signal intensity changes (ΔS) during hyperoxia (carbogen; 95%O2+5%CO2) and hypercapnia (95%air+5%CO2) challenges and vascular reactivity mismatch maps (VRM; voxels that responded to carbogen with reduced/absent response to CO2) were calculated. VRM values were measured in white matter (WM) and gray matter (GM) areas of healthy subjects and used as threshold values in patients. Significantly higher response to carbogen was detected in healthy subjects, compared to hypercapnia, with a GM/WM ratio of 3.8 during both challenges. In patients with newly diagnosed/treatment-naive tumors (n = 3), increased response to carbogen was detected with substantially increased VRM response (compared to threshold values) within and around the tumors. In patients with recurrent tumors, reduced/absent response during both challenges was demonstrated. An additional finding in 2 of 4 patients with recurrent glioblastoma was a negative response during carbogen, distant from tumor location, which may indicate steal effect. In conclusion, the HRI method enables the assessment of blood vessel functionality and reactivity. Reference values from healthy subjects are presented and preliminary results demonstrate the potential of this method to complement perfusion imaging for the detection and follow up of angiogenesis in patients with brain tumors

Predictive value of tumor recurrence using urinary vascular endothelial factor levels in patients receiving radiation therapy for Glioblastoma Multiforme (GBM).

BACKGROUND: Glioblastoma Multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Standard of care includes maximal resection followed by chemoradiotherapy. Tumors need adequate perfusion and neovascularization to maintain oxygenation and for removal of wastes. Vascular endothelial growth factor (VEGF) is a well characterized pro-angiogenic factor. We hypothesized that the increases in urinary VEGF levels would occur early in the course of tumor recurrence or progression. We examine the feasibility of collecting and analyzing urinary VEGF levels in a prospective, multi-institutional trial (Radiation Therapy Oncology Group, RTOG, 0611) as well as the role of VEGF as a marker of tumor recurrence. METHOD: We evaluated VEGF levels in urine specimens collected post-operatively, at the conclusion of radiation therapy (RT) and one month following RT. Urinary VEGF levels were correlated with tumor progression at one year. VEGF levels were measured by enzyme-linked immunosorbant assay in urine specimens and normalized to urinary creatinine levels. Sample size was determined based on a 50% 1-year recurrence rate. With a sensitivity and specificity of 80%, the expected 95% confidence interval was (0.69, 0.91) with 100 patients. A failure was defined as documented disease progression, recurrence or death before one year. RESULTS: 202 patients were enrolled between February-2006 and October-2007. Four patients were ineligible as they did not receive RT. Of the remaining 198 patients, 128 had all three samples collected. In this group, 35 patients (27.3%) did not progress, 89 (69.5%) had progression and 4 (3.1%) died without evidence of progression. Median VEGF levels at baseline were 52.9 pg/mg Cr (range 0.2- 15,034.4); on the last day of RT, 56.6 (range 0-2,377.1); and at one month follow-up, 70.0 (range 0.1-1813.2). In patients without progression at 1-year, both baseline VEGF level and end of RT VEGF level were lower than those of patients who progressed: 40.3 (range 0.2-350.8) vs. 59.7 (range 1.3-15,034.4) and 41.8 (range 0-356.8) vs. 69.7 (range 0-2,377.1), respectively. This did not reach statistical significance. Comparison of the change in VEGF levels between the end of RT and one month following RT, demonstrated no significant difference in the proportions of progressors or non-progressors at 1-year for either the VEGF increased or VEGF decreased groups. CONCLUSION: Urine can be collected and analyzed in a prospective, multi-institutional trial. In this study of patients with GBM a change in urinary VEGF levels between the last day of RT and the one month following RT did not predict for tumor progression by one year

Interstitial biodegradable balloon for reduced rectal dose during prostate radiotherapy: Results of a virtual planning investigation based on the pre- and post-implant imaging data of an international multicenter study

PURPOSE: To evaluate dose reduction caused by the implantation of an interstitial inflatable and biodegradable balloon device aiming to achieve lower rectal doses with virtual 3D conformal external beam radiation treatment. MATERIALS AND METHODS: An inflatable balloon device was placed, interstitially and under transrectal ultrasound guidance, into the rectal-prostate interspace prior treatment initiation of 26 patients with localized prostate cancer, who elected to be treated with radiotherapy (3D CRT or IMRT). The pre- and post-implant CT imaging data of twenty two patients were collected (44 images) for the purpose of the 3D conformal virtual planning presented herein. RESULTS: The dorsal prostate-ventral rectal wall separation resulted in an average reduction of the rectal V70% by 55.3% (\ub116.8%), V80% by 64.0% (\ub117.7%), V90% by 72.0% (\ub117.1%), and V100% by 82.3% (\ub124.1%). In parallel, rectal D2ml and D0.1ml were reduced by 15.8% (\ub111.4%) and 3.9% (\ub16.4%), respectively. CONCLUSIONS: Insertion of the biodegradable balloon into the prostate-rectum interspace is similar to other published invasive procedures. In this virtual dose distribution analysis, the balloon insertion resulted in a remarkable reduction of rectal volume exposed to high radiation doses. This effect has the potential to keep the rectal dose lower especially when higher than usual prostate dose escalation protocols or hypo-fractionated regimes are used. Further prospective clinical investigations on larger cohorts and more conformal radiation techniques will be necessary to define the clinical advantage of the biodegradable interstitial tissue separation device

Hemodynamic Response Imaging in the healthy brain.

<p>Representative HRI results obtained from a 29 year old healthy subject. (A) ΔS-O₂ map; (B) ΔS-CO₂ map; (C) the corresponding T₁-weighted (anatomical) image; (D) the gray and white matter masks (GM and WM, respectively); the mean time courses of the signal intensity change (%) during hyperoxic challenge (E) and hypecapnic (F) challenges, calculated from the GM VOI of this subject.</p