Faculty Bibliography

Vertebral compression fracture (VCF) occurs after stereotactic body radiation therapy (SBRT) for spine metastasis. Recently, single fraction radiosurgery (sfSRS) is used more frequently. The aim of this study is to determine the clinical outcome of VCF after sfSRS. Spinal instability neoplastic score (SINS) criteria were used to retrospectively score 143 consecutive vertebral segments in 79 patients treated with SRS. Follow-up MRI, pain, and neurologic assessments obtained every 3-6 months. Pain also scored at 7, 14, and 30 days after sfSRS. Follow up was 16 ± 18 months ±SD, range 3-78. Long-term radiographic control occurred in 94 % of cases. Pain improvement resulted within 7 days in 100 % of cases with severe pain and sustained long-term in 95 %. VCF occurred in 21 % of segments: 30 % were de novo VCF. The overall 1 year fracture free probability (1yFFP) was 76 %. Pre-existing VCF resulted in higher probability to progress: 1yFFP 90 versus 60 %. Symptoms presented in 6 % of cases with de novo VCF and 39 % with progressive. The former were treated with vertebral augmentation (VA), the latter with open surgery. Surgery/VA prior to SRS did not change risk of progressive VCF. Univariate but not multivariate analysis identified histology (colorectal), pre-existing VCF, and pain (severe) as significant predictors of VCF. In conclusion, sfSRS compares favourably to SBRT for radiographic and pain control with similar VCF risk. Patients with pre-existing VCF have a higher probability to progress, become symptomatic, and require surgery. These results may help discussing risk and benefits with patients undergoing sfSRS for spinal metastasis and developing new treatment algorithms.

The adrenal gland is a common site of cancer metastasis. Surgery remains a mainstay of treatment for solitary adrenal metastasis. For patients who cannot undergo surgery, radiation is an alternative option. Stereotactic body radiotherapy (SBRT) is an ablative treatment option allowing larger doses to be delivered over a shorter period of time. In this study, we report on our experience with the use of SBRT to treat adrenal metastases using CyberKnife technology. We retrospectively reviewed the Winthrop University radiation oncology data base to identify 14 patients for whom SBRT was administered to treat malignant adrenal disease. Of the factors examined, the biological equivalent dose (BED) of radiation delivered was found to be the most important predictor of local adrenal tumor control. We conclude that CyberKnife-based SBRT is a safe, non-invasive modality that has broadened the therapeutic options for the treatment of isolated adrenal metastases.

Metastatic castrate-resistant prostate cancer (CRPC) refers to the disease state in which metastatic prostate cancer fails to respond to androgen deprivation therapy (ADT). This can be manifest as a rising PSA, increase in radiographically measurable disease, or progression of clinical disease. Roughly 90 % of men with metastatic prostate cancer have bone metastases, which is a predictor of both morbidity and mortality. Historically, treatment has been palliative, consisting of external beam radiation therapy (EBRT) and pharmacological analgesics for pain control and osteoclast inhibitors, such as bisphosphonates and denosumab to mitigate skeletal-related events. Older radiopharmaceuticals, such as Strontium-89 and Samarium-153, are Beta-emitting agents that were found to provide palliation but were without survival benefit and carried high risks of myelosuppression. Radium-223 is an Alpha-emitting radiopharmaceutical that has demonstrated a significant overall survival benefit in men with metastatic CRPC, delay to symptomatic skeletal events (SSEs), and improvement in pain control, with a favorable toxicity profile compared with placebo. Unlike EBRT, Radium-223 has systemic uptake, with the potential to address several bone metastases concurrently and provides overall survival benefit. It is a simple administration with minimal complexity and shielding requirements in experienced hands. EBRT appears to provide a more rapid and dramatic palliative benefit to any given lesion. Because Radium-223 has limited myelosuppression, the two can be thoughtfully integrated, along with multiple agents, for the treatment of men with CRPC with symptomatic bone metastases. Given its excellent safety profile, there is interest and anecdotal safety combining Radium-223 with therapies, such as abiraterone and enzalutamide. Formal recommendations regarding combination therapies will require clinical trials. The use of Alpha-emitting radiopharmaceuticals in castrate-sensitive disease, in metastatic asymptomatic CRPC, the categorical sequencing amongst other treatments for CRPC, as well as the application to other primary pathologies, such as metastatic breast cancer, is currently evolving.

We are reporting a case of a 75-year-old man with multiply recurrent IgA-lambda multiple myeloma status post multiple rounds of chemotherapy, autologous stem cell transplantation, and palliative radiation therapy for diffuse bone lesions. Approximately 15 years after original diagnosis, he developed secondary cutaneous plasmacytomas of the right arm, right chest wall, and right upper back over the course of several months. He underwent palliative involved field 3D conformal photon or en face electron therapy concurrently with various chemotherapy regimens and achieved good to complete response with palliation of pain at the irradiated sites. He died of complications related to his disease approximately 7 months after developing skin lesions. The case presented is unique for dermal involvement of myeloma treated with palliative involved field radiation.

BACKGROUND AND PURPOSE: Rectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding, and genetic factors may be important. MATERIALS AND METHODS: A genome-wide association study (GWAS) was performed to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites. RESULTS: rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined p-values 5.4x10(-8) and 6.9x10(-7) respectively). Several other SNPs had p-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers' d=5.0x10(-12) in the replication cohort). CONCLUSIONS: This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified.

UNLABELLED:What's known on the subject? and What does the study add? There appears to be a clear difference in cancer control outcomes for patients with Gleason scores of 3+4 and those with scores of 4+3 after radical prostatectomy. It has been documented that patients with Gleason 4+3 prostate cancer have higher incidences of non-organ-confined disease than those with primary pattern 3. Higher rates of extracapsular extension, seminal vesicle invasion and positive margins have been found to be associated with primary pattern 4 over 3. These higher rates of non-organ-confined disease can lead to increased biochemical failure, which, in turn, can lead to higher mortality rates. This study provides information on the prognostic significance of primary Gleason pattern in the brachytherapy management of prostate cancer. Study Type - Prognosis (case series) Level of Evidence 4. OBJECTIVES/OBJECTIVE:• To report the biochemical outcomes for Gleason 7 prostate cancer treated with brachytherapy. • To analyse the impact of the primary Gleason pattern as well as other disease- and treatment-related factors on outcome. PATIENTS AND METHODS/METHODS:• A total of 560 patients with Gleason 7 prostate cancer were treated between 1990 and 2008 with brachytherapy, alone or in combination with hormonal therapy and/or external beam radiation therapy. • There were 352 patients with Gleason pattern 3+4 and 208 with Gleason pattern 4+3. • The mean (range) presenting PSA level was 11.2 (1-300) ng/mL, and the median was 7.8 ng/mL. • The presenting clinical stages were T1b in 1%, T1c in 33%, T2a in 16%, T2b in 32%, T2c in 16% and T3 in 2% of patients. RESULTS:• The actuarial freedom from biochemical failure rate at 10 years was 82%. • There was no significant difference between 10-year freedom from biochemical failure rates for patients with Gleason scores of 3+4 (79%) and those with scores of 4+3 (82%). • Biologically effective dose and presenting PSA level were both significant predictors of biochemical failure in multivariate analysis. CONCLUSIONS:• The primary Gleason pattern in Gleason 7 prostate cancer shows no significant effect on biochemical failure when treated with brachytherapy. • These results are different from those found after radical prostatectomy and are probably attributable to the enhanced local control afforded by a brachytherapy approach to this disease subset.

PURPOSE/OBJECTIVE:To measure the benefits of intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) when used in combination with brachytherapy for the treatment of prostate cancer. METHODS AND MATERIALS/METHODS:We conducted a retrospective review of all patients with localized prostate cancer who received external-beam radiotherapy (EBRT) in combination with brachytherapy with at least 1 year follow-up (n = 812). Combination therapy consisted of (103)Pd or (125)I implant, followed by a course of EBRT. From 1993 to March 2003 521 patients were treated with 3D-CRT, and from April 2003 to March 2009 291 patients were treated with IMRT. Urinary symptoms were prospectively measured with the International Prostate Symptom Score questionnaire with a single quality of life (QOL) question; rectal bleeding was assessed per the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. The Pearson χ(2) test was used to compare toxicities experienced by patients who were treated with either IMRT or 3D-CRT. Logistic regression analyses were also performed to rule out possible confounding factors. RESULTS:Within the first 3 months after treatment, patients treated with 3D-CRT scored their urinary symptoms as follows: 19% mild, 44% moderate, and 37% severe; patients treated with IMRT scored their urinary symptoms as follows: 36% mild, 47% moderate, and 17% severe (p < 0.001). The 3D-CRT patients rated their QOL as follows: 35% positive, 20% neutral, and 45% negative; IMRT patients rated their QOL as follows: 51% positive, 18% neutral, and 31% negative (p < 0.001). After 1 year of follow-up there was no longer any difference in urinary morbidity between the two groups. Logistic regression confirmed the differences in International Prostate Symptom Score and QOL in the acute setting (p < 0.001 for both). Grade ≥ 2 rectal bleeding was reported by 11% of 3D-CRT patients and 7% of IMRT patients (p = 0.046); logistic regression analysis also confirmed this observation (p = 0.040). CONCLUSIONS:When used in combination with brachytherapy, IMRT offers less Grade ≥ 2 rectal bleeding, less acute urinary toxicities, and is associated with a higher QOL compared with 3D-CRT.