Josh Yamada

Risk of Fracture After Single Fraction Image-Guided Intensity-Modulated Radiation Therapy to Spinal Metastases

PURPOSE Single-fraction image-guided intensity-modulated radiation therapy (IG-IMRT) allows for tumoricidal treatment of traditionally radioresistant cancers while sparing critical adjacent structures. Risk of vertebral fracture after IG-IMRT for spinal metastases has not been defined. PATIENTS AND METHODS We evaluated 62 consecutive patients undergoing single fraction IG-IMRT at 71 sites for solid organ metastases. A neuroradiologist and three spine surgeons evaluated prospectively obtained magnetic resonance/computed tomography (CT) imaging studies for post-treatment fracture development and tumor recurrence. RESULTS Fracture progression was noted in 27 vertebrae (39%). Multivariate logistic regression analysis showed that CT appearance, lesion location, and percent vertebral body involvement independently predicted fracture progression. Lesions located between T10 and the sacrum were 4.6 times more likely to fracture than were lesions above T10 (95% CI, 1.1 to 19.7). Lytic lesions were 6.8 times more likely to fracture than were sclerotic and mixed lesions (95% CI, 1.4 to 33.3). As percent vertebral body involvement increased, odds of fracture also increased. Patients with fracture progression had significantly higher narcotic use, change in Karnofsky performance score, and a strong trend toward higher pain scores. Local tumor progression occurred in seven patients and contributed to one fracture. Obesity, posterior element involvement, bisphosphonate use, and local kyphosis did not confer increased risk. CONCLUSION Vertebral fracture is common after single fraction IG-IMRT for metastatic spine lesions. Lytic disease involving more than 40% of the vertebral body and location at or below T10 confer a high risk of fracture, the presence of which yields significantly poorer clinical outcomes. These results may help clinicians identify high-risk patients who would benefit from prophylactic vertebro- or kyphoplasty.

Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer.

PURPOSE To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. METHODS AND MATERIALS Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). RESULTS For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. CONCLUSIONS This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes with acceptable toxicity.

Timing of surgery and radiotherapy in the management of metastatic spine disease: A systematic review

The last decade has witnessed a dramatic change in management of metastatic spine disease, with an increased role for surgery and emerging use of stereotactic radiotherapy, often in combination. Patients may be treated with radiotherapy followed by surgery, or have surgery and then adjuvant radiotherapy. In both cases, the surgeon and oncologist need to select the optimal timing for surgery and radiotherapy to minimize wound complications while obtaining maximum oncolytic effects. The purpose of this review was to determine the optimal timing of surgery and radiotherapy in patients surgically treated for spinal metastases. A systematic review utilizing Medline, Embase, Paper First, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews was performed. References were screened to further identify relevant studies and basic science literature reviewed. A total of 46 reports discussing the timing of surgery after radiotherapy, describing experience in 5836 patients, were identified. Only one retrospective study addressed the research question and suggested that surgery within seven days of radiation increases the rate of postoperative wound complications. Timing of adjuvant radiotherapy following surgery was addressed in 51 reports describing 7090 patients. None of the studies specifically answered the research question. The time interval between radiotherapy and surgery was reported as 5-21 days in nine studies. Based on this systematic review together with the understanding of general principles of wound healing and effects of radiation on wound healing, the optimal radiotherapy-surgery/surgery-radiotherapy time interval should be at least one week to minimize wound complications.

Real-time Intraoperative Computed Tomography Assessment of Quality of Permanent Interstitial Seed Implantation for Prostate Cancer

OBJECTIVES To evaluate the use of real-time kilovoltage cone-beam computed tomography (CBCT) during prostate brachytherapy for intraoperative dosimetric assessment and correcting deficient dose regions. METHODS A total of 20 patients were evaluated intraoperatively with a mobile CBCT unit immediately after implantation while still anesthetized. The source detector system was enclosed in a circular CT-like geometry with a bore that accommodates patients in the lithotomy position. After seed deposition, the CBCT scans were obtained. The dosimetry was evaluated and compared with the standard postimplantation CT-based assessment. In 8 patients, the deposited seeds were localized in the intraoperative CBCT frame of reference and registered to the intraoperative transrectal ultrasound images. With this information, a second intraoperative plan was generated to ascertain whether additional seeds were needed to achieve the planned prescription dose. The final dosimetry was compared with the postimplantation scan assessment. RESULTS The mean differences between the dosimetric parameters from the intraoperative CBCT and postimplant CT scans were < .5% for percentage of volume receiving 100% of the prescription dose, minimal dose received by 90% of the prostate, and percentage of volume receiving 150% of the prescription dose. The minimal dose received by 5% (maximal dose) of the urethra differed by 8% on average and for the rectum an average difference of approximately 18% was observed. After fusion of the implanted seed coordinates from the intraoperative CBCT scans to the intraoperative transrectal ultrasound images, the dosimetric outcomes were not significantly different from the postimplantation CT dosimetric results. CONCLUSIONS Intraoperative CT-based dosimetric evaluation of prostate permanent seed implantation before anesthesia reversal is feasible and might avert misadministration of dose delivery. The dosimetric measurements using the intraoperative CBCT scans were dependable and correlated well with the postimplant diagnostic CT findings.

Predictors of castration-resistant prostate cancer after dose-escalated external beam radiotherapy.

Castration‐resistant prostate cancer (CRPC) is a near uniformly fatal form of prostate cancer; however, information on time to development and predictors for progression to CRPC is limited. We report a detailed longitudinal study for development of CRPC in men initially treated with external beam radiotherapy (EBRT).

Urethral alarm probe for permanent prostate implants

We have developed a urethral dosimetry system for real time dose verification along the urethra during permanent implant prostate brachytherapy. The urethral alarm probe uses “spectroscopic dosimetry” to calculate the dose rate along the urethra in real time. The application of spectroscopic dosimetry for the urethral alarm probe was verified using Monte Carlo calculations. In phantom depth dose measurements as well as isotropy measurements were performed to verify the usefulness of the urethra alarm probe as an in vivo real time dosimeter.

History of International Workshop on Mini-Micro- and Nano- Dosimetry (MMND) and Innovation Technologies in Radiation Oncology (ITRO)

The biannual MMND (former MMD) - IPCT workshops was founded in collaboration between the Centre for Medical Radiation Physics, University of Wollongong and the Memorial Sloan Kettering Cancer Center (MSKCC) in 2001 and has become an important international multidisciplinary forum for the discussion of advanced quality assurance (QA) dosimetry technology for radiation therapy and space science, as well as advanced technologies for clinical cancer treatment.

Sequence of Surgery, Radiotherapy, and Stereotactic Radiosurgery in the Treatment of Metastatic Spine Disease: Effects on Wound Healing

Treatment for patients with epidural cord compression from spinal metastases continues more than a decade of evolution. The standard of care is shifting to surgery and external beam radiation therapy (EBRT) in combination, rather than EBRT alone. New surgical techniques are enabling effective cord decompression, more extensive tumor excision, and spine stabilization, even in patients who present with significant pain and reduced ambulation. Excellent preliminary results have been shown from stereotactic radiosurgery (SRS) as adjuvant or even primary treatment in these patients. A change in the interval between radiation-based treatment and surgery, or between surgery and subsequent EBRT or SRS has the potential to significantly impact wound healing. We reviewed the literature to present the available evidence on wound complications and on the timing of surgery and radiation in these patients. Based on animal studies and the few patient series bringing specific evidence in humans, it would appear that an interval of at least 1 week is indicated between EBRT or SRS and surgery, and between surgery and radiation-based treatment. An interval of 2–4 weeks or longer reduces the risk of wound healing complications, facilitates increased tensile strength in surgical wounds, and allows better bone fusion. Consistent reporting of wound healing complications and additional research is needed.

Insufficiency Fractures of the Sacrum following Stereotactic Body Radiotherapy for Sacral Tumors

Introduction There is little data on sacral insufficiency fracture(SIF) incidence following pelvic radiotherapy, with existing studies based on conventional fractionation. Stereotactic body radiotherapy (SBRT), characterized by dose escalation with hypofractionation, may pose even greater risks to sacral integrity. This study aims to define SIF incidence and risk factors following SBRT. Methods Records of 43 consecutive patients who underwent sacral SBRT from September 2005-May 2009 were reviewed. Baseline patient information (age, gender, menopausal status, body mass index, use of bone-thinning agents, presence of osteoporosis), tumor characteristics (histology, lesion appearance and extent) and treatment parameters (dose/fractionation, prior radiation/surgery) were documented. Primary end-point was development of new fractures or progression of pre-existing fractures. Secondary end-points included pain scores, analgesic use, functional ability, and local tumor control. Results Median follow-up was 17months. Common histologies included sarcoma, renal cell, and prostate carcinoma; 47% of lesions were lytic, 37% sclerotic and the remainder mixed. Doses ranged from 18-24Gy/1fraction to 30Gy/5fractions with 45% receiving single fractions.14% had prior radiation (median dose: 30Gy/10fractions).Five patients developed SIF. In four, fractures occurred in the context of controlled local disease. Median time to SIF was 8.2months. Symptoms varied from minimal pain requiring no intervention to severe pain impacting on function. Two patients underwent sacroplasty due to intractable pain, with both obtaining good analgesia. Low event numbers precluded meaningful univariate/multivariate analyses. One-year local tumor control rates were excellent (91.7%). Conclusion In this study, actuarial SIF incidence at one year was 8.2%, suggesting that SIF risk from sacral SBRT is low. However, larger prospective studies with longer follow-up are needed. In addition, novel therapies such as sacroplasty need further study to determine safety, efficacy and indications for use.