Jaden D. Evans

Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease

BACKGROUND Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. OBJECTIVE To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. INTERVENTION C-11 choline positron emission tomography/computed tomography (CholPET). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. RESULTS AND LIMITATIONS Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. CONCLUSIONS CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. PATIENT SUMMARY We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

Prostate cancer–specific PET radiotracers: A review on the clinical utility in recurrent disease

Prostate cancer-specific positron emission tomography (pcPET) has been shown to detect sites of disease recurrence at serum prostate-specific antigen (PSA) levels that are lower than those levels detected by conventional imaging. Commonly used pcPET radiotracers in the setting of biochemical recurrence are reviewed including carbon 11/fludeoxyglucose 18 (F-18) choline, gallium 68/F-18 prostate-specific membrane antigen (PSMA), and F-18 fluciclovine. Review of the literature generally favors PSMA-based agents for the detection of recurrence as a function of low PSA levels. Positive gallium 68/F-18 PSMA positron emission tomography/computed tomography scans detected potential sites of recurrence in a median 51.5% of patients when PSA level is <1.0 ng/mL, 74% of patients when PSA level is 1.0 to 2.0 ng/mL, and 90.5% of patients when PSA level is >2.0 ng/mL. Review of carbon 11/fludeoxyglucose 18 (F-18) choline and F-18 fluciclovine data commonly demonstrated lower detection rates for each respective PSA cohort, although with some important caveats, despite having similar operational characteristics to PSMA-based imaging. Sensitive pcPET imaging has provided new insight into the early patterns of disease spread, which has prompted judicious reconsideration of additional local therapy after either prostatectomy, definitive radiation therapy, or postprostatectomy radiation therapy. This review discusses the literature, clinical utility, availability, and fundamental understanding of pcPET imaging needed to improve clinical practice.

A Prospective Pilot Study of Single 19 Gy Fraction High-Dose-Rate Brachytherapy for Favorable-Risk Adenocarcinoma of the Prostate

Objective: To evaluate the acute genitourinary (GU) and gastrointestinal (GI) toxicities, health-related quality of life (HRQOL) factors, biochemical control rates, and technical feasibility of high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer delivered in a single fraction. Methods: A single-institution, prospective pilot study evaluating 6 patients with low- and intermediate-risk prostate cancer treated in 2013. Patients received a single 19 Gy fraction as HDR monotherapy. Patients were assessed according to the Common Terminology Criteria for Adverse Events version 4.0, the International Index of Erectile Function (IIEF-5), the International Prostate Symptom Score (IPSS), the Expanded Prostate Cancer Index Composite–Bowel Assessment (EPIC-Bowel), a Quality of Life (QOL) Assessment, and an institutionally designed quality of care (QOC) questionnaire. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Patients tolerated the implant well and were all discharged home the same day by approximately 4 pm. Median follow-up was 9 months. No grade 3, 4 or 5 toxicities were observed. Two of the 6 patients (33%) experienced grade 2 GU toxicity. One patient (17%) experienced grade 2 GI toxicity. HRQOL bowel and urinary assessments revealed a majority of complaints at 3 months, which returned to baseline at 6 months. Conclusion: HDR brachytherapy as monotherapy for favorable-risk prostate cancer using one implant delivered in a single 19 Gy dose has acceptable acute toxicities and HRQOL reports similar to alternative treatment options.

Clinical application of lying-on-the-floor total skin electron irradiation for frail patients with cutaneous lymphoma: An emphasis on the importance of in vivo dosimetry

Total skin electron irradiation (TSEI) is an effective option for cutaneous T-cell lymphoma (CTCL). Two conventional methods used to deliver TSEI are the Stanford multiple dual field technique and the McGill rotational technique; however, both techniques require patients to stand for 10 to 30 minutes and cannot be used in nonambulatory patients. Our group has previously described technical parameters for “lying-on-the-floor” total skin electron beam therapy for nonambulatory patients.Wenow report clinical implementation of this technique in a nonambulatory patient with progressive CTCL with particular emphasis on the critical importance of in vivo dosimetry.

Stereotactic body radiation therapy for medically-inoperable, clinically-localized urothelial carcinoma of the renal pelvis: a case report

Abstract Background Upper urinary tract urothelial carcinoma (UUTUC) is rare, accounting for less than 5% of urothelial malignancies. Standard treatment is radical nephroureterectomy (RNU) with systematic excision of bladder cuff. While commonly used for bladder urothelial carcinoma, the role of primary or adjuvant radiotherapy for UUTUC is unclear. Furthermore, there are no guidelines for management of inoperable patients, whether due to extensive disease burden, solitary kidney, poor performance status, or patient refusal. Stereotactic body radiation therapy (SBRT) may be a treatment option for this unique patient population. Case presentation A 93-year old male presented with a one year of intermittent gross hematuria. CT imaging showed a 4.5 cm soft tissue mass in the upper left intra-renal collecting system without evidence for regional lymphadenopathy or distant metastatic disease. Urine cytology confirmed urothelial carcinoma. He was staged clinical T2, N0, M0. Following urology and cardiology evaluation, the patient was deemed medically-inoperable for RNU due to cardiac comorbidities. He was not a candidate for percutaneous ablation due to tumor location in renal pelvis and anesthesia risk. He was treated using SBRT with 50 Gy in 4 fractions over 4 consecutive days. His hematuria resolved approximately 10 days after completion of SBRT. The patient showed no clinical signs of acute or late adverse events. He underwent routine evaluation and at his most recent 31-month post-SBRT evaluation, imaging showed a complete response (RECIST criteria v1.1) without evidence of locoregional recurrence or distant metastasis. He expired 33 months after SBRT due to decompensated systolic heart failure. Conclusion The role for radiotherapy in the management of UUTUC is unclear. Utilizing conventionally fractionated radiotherapy, the outcomes of all retrospective data are marginal with weak grade recommendations. SBRT is a promising technique for medically-inoperable UUTUC. Limited reported outcomes are favorable and warrant further investigation of the role of SBRT in the treatment of UUTUC.

Stereotactic spinal radiosurgery and delayed vertebral fracture risk

The spine is one of the most common sites for tumor metastasis. It is estimated that approximately 30% of all patients with cancer develop spinal metastasis at some point in their cancer course. Spinal metastatic disease can cause significant morbidity in patients, including pain, hypercalcemia, pathologic fractures, spinal instability, and compression of the spinal cord or cauda equina. Management of spinal metastases can be complex and may benefit from multimodal therapeutic strategies to achieve optimal outcomes. Stereotactic spinal radiosurgery (SSRS) is an emerging technique that has been developed to deliver highly conformal ionizing radiation doses, designed to control gross disease while simultaneously minimizing dose to surrounding critical structures such as the spinal cord. Current data on SSRS suggest favorable local control rates of approximately 90% at 1 year, complete pain response of approximately 50%, and low rates of highgrade toxicity. However, as with all emerging technologies, understanding the potential complications of novel therapies such as SSRS is fundamental to safely implementing this technology throughout the wider oncology community. The focus of this case and review is the risk of vertebral fracture after SSRS.

Percutaneous image guided nodal biopsy after C-11 Choline PET/CT for Biochemically Recurrent Prostate Cancer: Imaging Predictors of Disease and Clinical Implications

Purpose Management of recurrent prostate cancer necessitates timely diagnosis and accurate localization of the sites of recurrent disease. The purpose of this study was to assess predictors of histologic outcomes after 11C-choline positron emission tomography/computed tomography (CholPET) to increase the positive predictive value and specificity of CholPET in identifying imaging predictors of malignant and benign nodal disease to better inform clinical decision making regarding local therapy planning. Materials and Methods Retrospective review of patients undergoing CholPET followed by percutaneous core needle biopsy between January 1, 2010 and January 1, 2016. A total of 153 patients were identified who underwent 166 biopsy procedures. Patient, CholPET, procedural, and pathologic characteristics were recorded. Results A total of 157 biopsies were technically successful, and 110 (70.1%; 95% confidence interval, 62.2-77.1) yielded histologic results abnormal for metastatic prostate cancer. Lesion location, lesion maximum standardized uptake value (SUVmax), SUV ratio (calculated as the ratio of SUVmax to SUV mean in the right atrium), prostate-specific antigen, lesion short axis length, total Gleason score, and castration resistance were all associated with abnormal biopsy results (P values <.001, <.001, <.001, .02, .02, .02, and .015, respectively). External iliac, common iliac, and inguinal sites were associated with much lower rates of histologic positivity (mean [95% confidence interval], 51.2% [35.1-67.1], 46.2% [19.2-74.9], and 33.3% [7.5-70.1]), respectively. Conclusions In a cohort of patients in whom core needle biopsy was performed after CholPET, characteristics of choline localization including node location, SUVmax, lesion–to–blood pool SUV ratio, prostate-specific antigen, total Gleason score, and castration resistance were significantly associated with abnormal biopsy results for metastatic disease on CholPET. Relatively high false positive rates were found in common iliac, external iliac, and inguinal lymph node locations. Histologic confirmation of these sites should be strongly considered in the appropriate clinical scenario before designing additional local therapy plans.

Abstract 3440: High-dose-rate brachytherapy as monotherapy for favorable-risk adenocarcinoma of the prostate delivered in a single 19 Gy fraction: Preliminary results of a prospective pilot study

INTRODUCTION: We evaluated the acute genitourinary (GU) and gastrointestinal (GI) toxicities, health-related quality of life (HRQOL) factors, biochemical control rates, and technical feasibility of high-dose-rate (HDR) brachytherapy as monotherapy for favorable-risk prostate cancer delivered in a single 19 Gy fraction. METHODS: A single-institution, prospective pilot study was performed by evaluating 6 patients with low- and intermediate-risk prostate cancer treated with high-dose-rate (HDR) brachytherapy as monotherapy. Patients received a single 19 Gy fraction as HDR monotherapy without the use of a transperineal hyaluronic acid injection. Patients were assessed according to the Common Terminology Criteria for Adverse Events version 4.0 and Health-Related Quality of Life (HRQOL) questionnaires. Additionally, prostate specific antigen levels have been followed for evidence of biochemical failure. RESULTS: All 6 patients tolerated the implant well and were all discharged home the same day. Median follow-up was 15 months with all subjects followed for at least 12 months. No grade 3, 4, or 5 toxicities were observed. Two of the 6 patients experienced grade 2 GU toxicity. One patient experienced grade 2 GI toxicity. HRQOL bowel and urinary assessments revealed peak complaints at 3 months which returned to baseline at 6 months. There have been no biochemical relapses. CONCLUSION: This is the first study using HDR brachytherapy as monotherapy for favorable-risk prostate cancer using one implant delivered in a single 19 Gy dose in the United States. All patients demonstrated acceptable acute toxicities and were pleased with their cost-effective treatment choice. Citation Format: Scott Dahlbeck, Chase C. Hansen, Werner deRiese, A. Robert Kagan, Carlos Torres, Maurizio Chiriva-Internati, Everardo Cobos, Jose A. Figueroa, Diane Nguyen, Lukman Tijani, Jaden D. Evans. High-dose-rate brachytherapy as monotherapy for favorable-risk adenocarcinoma of the prostate delivered in a single 19 Gy fraction: Preliminary results of a prospective pilot study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3440. doi:10.1158/1538-7445.AM2015-3440