Siavash Jabbari

Stereotactic Body Radiotherapy as Monotherapy or Post–External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response

PURPOSE High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. PATIENTS AND METHODS To date, 38 patients have been treated with SBRT at the University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy × 4 fractions), and 18 were treated with SBRT boost (9.5 Gy × 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. RESULTS SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). CONCLUSIONS Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.

Nanotechnology in cancer prevention, detection and treatment: bright future lies ahead

This paper is an overview of advances and prospects in applications of nanotechnology for cancer prevention, detection and treatment. We begin with a brief description of the underlying causes of cancer. Then we address preventive treatment, disease-time treatment, and diagnosis in the context of some of the most recent advances in nanotechnology. Nanoparticle science is also briefly addressed as the foundation upon which most nanotechnology cancer therapy is based. It is demonstrated how nanotechnology can help solve one of the most challenging and longstanding problems in medicine, which is how to eliminate cancer without harming normal body tissue.

Equivalent Biochemical Control and Improved Prostate-Specific Antigen Nadir After Permanent Prostate Seed Implant Brachytherapy Versus High-Dose Three-Dimensional Conformal Radiotherapy and High-Dose Conformal Proton Beam Radiotherapy Boost

PURPOSE Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. PATIENTS AND METHODS A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. RESULTS With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir < or =0.5 ng/mL, 91% vs. 59%, respectively). CONCLUSION We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or CPBRTB.

Results of the 2005-2008 association of residents in radiation oncology survey of chief residents in the United States: Clinical training and resident working conditions

PURPOSE To document clinical training and resident working conditions reported by chief residents during their residency. METHODS AND MATERIALS During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistics were used to assess changes in clinical training and resident working conditions over time. RESULTS Surveys were completed by representatives from 55 programs (response rate, 71.4%) in 2005 to 2006, 60 programs (75.9%) in 2006 to 2007, and 74 programs (93.7%) in 2007 to 2008. Nearly all chief residents reported receiving adequate clinical experience in commonly treated disease sites, such as breast and genitourinary malignancies; and commonly performed procedures, such as three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Clinical experience in extracranial stereotactic radiotherapy increased over time (p < 0.001), whereas clinical experience in endovascular brachytherapy (p <0.001) decreased over time. The distribution of gynecologic and prostate brachytherapy cases remained stable, while clinical case load in breast brachytherapy increased (p = 0.006). A small but significant percentage of residents reported receiving inadequate clinical experience in pediatrics, seeing 10 or fewer pediatric cases during the course of residency. Procedures involving higher capital costs, such as particle beam therapy and intraoperative radiotherapy, and infrequent clinical use, such as head and neck brachytherapy, were limited to a minority of institutions. Most residency programs associated with at least one satellite facility have incorporated resident rotations into their clinical training, and the majority of residents at these programs find them valuable experiences. The majority of residents reported working 60 or fewer hours per week on required clinical duties. CONCLUSIONS Trends in clinical training and resident working conditions over 3 years are documented to allow residents and program directors to assess their residency training.

Successful Treatment of High Risk and Recurrent Pediatric Desmoids Using Radiation as a Component of Multimodality Therapy

PURPOSE To evaluate the role of radiation therapy (RT) as a component of multimodality therapy for pediatric desmoids. METHODS AND MATERIALS Twenty-one children diagnosed between 1987 and 2005 were identified. Median age at start of treatment was 13 years (range, 2-21). Primary therapy consisted of resection alone (10), resection + external beam radiation therapy (EBRT) (5), resection + chemotherapy (CT; 3), EBRT alone (1), and CT alone (2). RESULTS The median follow-up from start of treatment is 75.7 months (range, 16-162). Examining patients with gross total resections (GTRs) (-) margins and those who had GTRs (+) margins followed by EBRT, only 2 of 7 failed primary treatment. Conversely, 13 of 14 patients with other primary treatments failed locally. Of the 15 patients who recurred, only 1 patient had a GTR (-) margins. Seven of these patients had salvage therapy that did not include RT, and of these only 2 have no evidence of disease (NED) at last follow-up. In contrast, the remaining 8 patients received RT as a component of their final salvage therapy and 7 of these are NED at last follow-up. At last follow-up, no patient has died, although toxicities of therapy have occurred. CONCLUSIONS Local control is difficult to achieve in pediatric patients with desmoids. In the setting in which negative surgical margins cannot be achieved, RT plays a key role in achieving NED status. Even after multiple recurrences, successful salvage is achievable, particularly when high-dose focal therapy is incorporated.

Comparison of Dosimetric and Biologic Effective Dose Parameters for Prostate and Urethra Using 131Cs and 125I for Prostate Permanent Implant Brachytherapy

PURPOSE To compare the urethral and prostate absolute and biologic effective doses (BEDs) for 131 Cs and 125 I prostate permanent implant brachytherapy (PPI). METHODS AND MATERIALS Eight previously implanted manually planned 125 I PPI patients were replanned manually with 131 Cs, and re-planned using Inverse Planning Simulated Annealing. 131 Cs activity and the prescribed dose (115 Gy) were determined from that recommended by IsoRay. The BED was calculated for the prostate and urethra using an alpha/beta ratio of 2 and was also calculated for the prostate using an alpha/beta ratio of 6 and a urethral alpha/beta ratio of 2. The primary endpoints of this study were the prostate D90 BED (pD90BED) and urethral D30 BED normalized to the maximal potential prostate D90 BED (nuD30BED). RESULTS The manual plan comparison (alpha/beta = 2) yielded no significant difference in the prostate D90 BED (median, 192 Gy2 for both isotopes). No significant difference was observed for the nuD30BED (median, 199 Gy2 and 202 Gy2 for 125 I and 131 Cs, respectively). For the inverse planning simulated annealing plan comparisons (alpha/beta = 2), the prostate D90 BED was significantly lower with 131 Cs than with 125 I (median, 177 Gy2 vs. 187 Gy2, respectively; p = 0.01). However, the nuD30BED was significantly greater with 131 Cs than with 125 I (median, 192 Gy2 vs. 189 Gy2, respectively; p = 0.01). Both the manual and the inverse planning simulated annealing plans resulted in a significantly lower prostate D90 BED (p = 0.01) and significantly greater nuD30BED for 131 Cs (p = 0.01), compared with 125 I, when the prostate alpha/beta ratio was 6 and the urethral alpha/beta ratio was 2. CONCLUSION This report highlights the controversy in comparing the dose to both the prostate and the organs at risk with different radionuclides.

Stereotactic Body Radiotherapy for Spinal Metastases: Practice Guidelines, Outcomes, and Risks.

AbstractSpine metastases can be a debilitating and difficult therapeutic challenge for a significant number of cancer patients. Surgical management of spine metastases is often limited because of the complexity, risks, and recovery delays associated with open invasive surgical procedures. Conventional palliative external beam radiation therapy is the most common treatment modality. However, it is associated with limited palliative efficacy and local tumor control, including in the postoperative setting. In the era of improving systemic disease control, spine stereotactic body radiotherapy is fast emerging as the therapeutic modality of choice for selected de novo, postoperative, and salvage reirradiation spine metastases patients. Considerable expertise, multidisciplinary collaboration, and rigid adherence to quality metrics are required for the safe application of this highly conformal ablative therapy. This review highlights the current state of the evidence, understanding of the late effects, and technological requirements for spine stereotactic body radiotherapy specific to spinal metastases.

High-dose-rate brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience.

PURPOSE Treatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT. PATIENTS AND METHODS Six men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound-guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30Gy, received 24Gy in four fractions. RESULTS Median age was 67.5 (56-74) years. At a median followup of 26 (14-60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3-5 toxicity. CONCLUSION Transperineal ultrasound-guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.

Results of the 2005 to 2008 association of residents in radiation oncology surveys of chief residents in the United States: Didactics and research experience

ObjectivesTo analyze the didactics and research experience reported by chief residents during their residency training. MethodsDuring the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology (ARRO) conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistic was used to assess for changes in didactics and research experience over time. ResultsDuring the years surveyed, an increasing percentage of programs offered curriculum-based didactics in clinical oncology (P=0.042), with a similar trend of borderline significance observed in biostatistics (P = 0.056). Each year, the majority of programs offered >40 hours of curriculum-based training in clinical oncology and physics, >20 hours in radiobiology, and 10 hours or fewer in biostatistics. 11% to 13% of residents reported having no full-time equivalent radiation biologists affiliated with their training program. Less than 64% of programs incorporated mock oral boards into their training. An increasing percentage of programs evaluated residents in a “360 degree” manner, with a trend to significance (P=0.073). Over 80% of programs required resident participation in research activities and allocated dedicated elective research time, typically 4 months or longer. Though the vast majority of programs make clinical research activities available to interested residents, borderline significance (P = 0.051) was observed for a decreasing percentage of such programs during the years analyzed. ConclusionsTrends in didactics and research experience over three years are documented to allow residents and program directors to assess their residency training.

Non-small Cell Lung Cancer

Most common noncutaneous cancer in the world. Second most common cancer in the US, behind prostate in men and breast in women. No. 1 cause of cancer death in the US and worldwide. >90% of cases are associated with smoking or involuntary smoking. Second most common cause in the US is radon. Asbestos exposure is associated with 3–4% of cases. Risk of tobacco-induced second primary is ∼2–3% per year. The surgical lymph node levels 1–9 correspond to N2 nodes, and levels 10–14 correspond to N1 nodes. 1 = high mediastinal, 2 = upper paratracheal, 3 = pre and retrotracheal, 4 = lower paratracheal, 5 = AP window, 6 = paraaortic, 7 = subcarinal, 8 = paraesophageal below carina, 9 = pulmonary ligament, 10 = hilar, 11 = interlobar, 12 = lobar, 13 = segmental, and 14 = subsegmental. Adenocarcinoma comprises 40–50% of cases. It tends to be peripherally located; it has a high propensity to metastasize (frequently to the brain).