Quantitative Analysis of Frozen Section Histology in Mohs Micrographic Surgery.

BACKGROUND: Mohs micrographic surgery (MMS) relies on complete frozen tissue sections for the unique combination of high cure rates and tissue preservation. OBJECTIVE: To quantify and characterize the tissue sectioning process in MMS. MATERIALS AND METHODS: Two hundred eighty-four tissue blocks were analyzed. The histotechnician measured the depth cut into the tissue block for every section placed on the slide. The surgeon identified complete sections. RESULTS: First-stage complete sections were achieved at 285 µm. The ear and hair-bearing cheek required increased depth of sectioning compared with other sites. Small pieces of tissue achieved complete sections at a decreased depth compared with medium or large pieces of tissue. The methodology used in this study was able to identify statistically significant differences between histotechnicians. CONCLUSION: More than 2,000 measurements on 284 tissue blocks provided quantitative data of the tissue sectioning process in MMS, confirming that MMS allows evaluation of both peripheral and deep margins within hundreds of microns of the margin. Results from this study indicate a methodology that is easily implemented providing interpretable data that can be used to assess and improve tissue sectioning ensuring MMS remains the gold standard for removal of challenging cutaneous tumors.

Influence of vascular comorbidities and race on erectile dysfunction after prostate cancer radiotherapy.

INTRODUCTION: Vascular comorbidities (VC) (hypertension, diabetes, and hyperlipidemia) are known factors related to erectile dysfunction (ED) in men. However, no data are yet available for the effects of VC on ED incidence after prostate cancer radiotherapy (XRT). AIM: To investigate the influence of VC on post-XRT ED incidence and to further characterize ED incidence by racial groups. MAIN OUTCOME MEASURES: ED incidence. METHODS: We reviewed 732 charts of patients (267 Caucasian and 465 African American [AA]) who received prostate XRT (external beam radiotherapy and/or brachytherapy) with or without hormone therapy between 1999 and 2010. The number of pre-XRT VC (0, 1, 2, or 3) was determined by medical history and medication list. ED (defined by use of erectile aids or by documentation of moderate or high sexual dysfunction on patient history) was determined pre-XRT as well as 1, 2, and 4 years post-XRT. RESULTS: ED incidence progressively increased from 22% pre-XRT to 58% 4 years post-XRT (P < 0.01). Additionally, ED incidence significantly increased with number of VC-4-year incidence between patients with 1 vs. 0 (P = 0.02), 2 vs. 0 (P < 0.01), 3 vs. 0 (P < 0.01), 3 vs. 1 (P < 0.01), and 3 vs. 2 (P = 0.04) VC (2 vs. 1 VC was nonsignificant). Compared with the Caucasian patients, ED incidences were slightly higher for the AA group with 0, 1, 2, and 3 comorbidities at 4 years follow-up (but statistically nonsignificant). CONCLUSIONS: The number of VCs have a significant effect on development of post-XRT ED. Pre- and post-XRT ED appear to be independent of race when number of VCs are considered. Our results can be used to guide physicians in counseling patients on the incidence of ED by number of VC and as preliminary data for prospective efforts aimed at reducing post-XRT ED.

Impact of 18F-Fluciclovine PET on Target Volume Definition for Postprostatectomy Salvage Radiotherapy: Initial Findings from a Randomized Trial.

The purpose of this study was to evaluate the role of the synthetic amino acid PET radiotracer 18F-fluciclovine in modifying the defined clinical and treatment-planning target volumes in postprostatectomy patients undergoing salvage radiotherapy and to evaluate the resulting dosimetric consequences to surrounding organs at risk. Methods: Ninety-six patients were enrolled in a randomized, prospective intention-to-treat clinical trial for potential salvage radiotherapy for recurrent prostate cancer after prostatectomy. The initial treatment plan was based on the results from conventional abdominopelvic CT and MRI. The 45 patients in the experimental arm also underwent abdominopelvic 18F-fluciclovine PET/CT, and the images were registered with the conventional images to determine whether the results would modify the initial treatment plan. The 51 patients in the control arm did not undergo 18F-fluciclovine PET/CT. For each patient, the clinical and treatment-planning target volumes that would have been treated before 18F-fluciclovine registration were compared with those after registration. For organs at risk (rectum, bladder, and penile bulb), the volumes receiving 40 Gy and 65 Gy before registration were compared with those after registration. Statistical comparisons were made using the paired t test. Acute genitourinary and gastrointestinal toxicity as defined by the Radiation Therapy Oncology Group was compared between the control and experimental arms using the χ2 test. Results: In 24 cases, radiotherapy was planned to a clinical target volume consisting of the prostate bed alone (CTV) (64.8-66.6 Gy). In 21 cases, radiotherapy was planned to a clinical target volume consisting of the pelvis (CTV1) (45.0 Gy) followed by a boost to the prostate bed (CTV2) (19.8-25.2 Gy). In each case, the respective treatment-planning target volume expansion (PTV, PTV1, or PTV2) was 0.8 cm (0.6 cm posterior). With the exception of PTV2, all postregistration volumes were significantly larger than the corresponding preregistration volumes. Analysis of the rectum, bladder, and penile bulb volumes receiving 40 Gy and 60 Gy demonstrated that only the penile bulb volumes were significantly higher after registration. No significant differences in acute genitourinary or gastrointestinal toxicity were observed. Conclusion: Including information from 18F-fluciclovine PET in the treatment-planning process led to significant differences in the defined target volume, with higher doses to the penile bulb but no significant differences in rectal or bladder dose or in acute genitourinary or gastrointestinal toxicity. Longer follow-up is needed to determine the impact of 18F-fluciclovine PET on cancer control and late toxicity endpoints.

Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial.

PURPOSE: (18)F-Fluciclovine (anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of (18)F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. METHODS AND MATERIALS: We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the (18)F-fluciclovine arm. All patients underwent (18)F-fluciclovine PET-CT for the detection of metabolic abnormalities and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each (18)F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. RESULTS: In 21 of 55 abnormalities, a deformable registration was needed to map the (18)F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of (18)F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. CONCLUSIONS: The use of (18)F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.

Impact of magnetic resonance imaging on computed tomography-based treatment planning and acute toxicity for prostate cancer patients treated with intensity modulated radiation therapy.

PURPOSE: To evaluate rectal and bladder dosimetric and clinical acute toxicity endpoints for prostate patients treated with intensity modulated radiation therapy (IMRT) using magnetic resonance images (MRI) registered to computed tomographic (CT) simulation images versus CT alone. MATERIALS AND METHODS: The charts of 155 consecutive prostate cancer patients at our institution from 2004 to 2008 were reviewed. A cohort of 15 IMRT treatment plans was created to compare dosimetric endpoints for CT-MRI vs CT alone. A subsequent clinical comparison involved 81 patients (CT-MRI [n = 28] vs CT alone [n = 53]). Acute genitourinary and rectal toxicity rates for the CT-MRI and CT cohorts were compared; also, univariate and multivariate regression analyses were performed using all major demographic, disease, and treatment factors as covariates. RESULTS: Contoured prostate volumes were 43.0 vs 55.7 cm(3) (P < .001, n = 15) for CT-MRI vs CT definition, with significant reductions in all bladder dose endpoints and rectal V20, V30, and V70. Grades 0, 1, and 2 toxicity rates for CT-MRI (n = 28) vs CT (n = 53) were, respectively, 25%, 25%, and 50% vs 8%, 21%, and 72% (acute genitourinary [GU], P = .024) and 39%, 29%, and 32% vs 32%, 28%, and 40% (acute rectal, P = .495). On univariate regression, only MRI use and International Prostate Symptom Scores reached significance for acute GU toxicity. On multivariate regression, age, prostate volume, and MRI use reached statistical significance for acute GU toxicity. No factor reached significance for rectal toxicity. CONCLUSIONS: This study demonstrates a statistically significant reduction in clinical acute GU toxicity with the clinical implementation of MRI in the treatment planning process.

Reduced acute toxicity associated with the use of volumetric modulated arc therapy for the treatment of adenocarcinoma of the prostate.

PURPOSE: Novel techniques to deliver intensity modulated radiation therapy (IMRT) have resulted in improved treatment efficiency and dosimetric endpoints. We aimed to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated for adenocarcinoma of the prostate (ACP) using volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: A total of 122 (71 IMRT and 51 VMAT) ACP patients treated from 2004 to 2011 with definitive external beam radiation therapy were analyzed. Dose-volume histogram endpoints (V40, V65, V70, and V75 of the bladder and rectum) were collected for each patient. Median follow-up for patients treated with VMAT was 269 days versus IMRT was 1121 days. Acute Common Toxicity Criteria for Adverse Events (CTCAE) GI and GU toxicity scores, obtained during each weekly treatment check, were compared across cohorts. The univariate (UV) association between the covariates and outcomes was assessed and multivariable (MV) cumulative logit models were fit for each outcome. RESULTS: Median patient age was 68 years and median prostate-specific antigen was 8.3. Both bladder and rectal V40, V65, V70, and V75 were all higher in the IMRT group versus the VMAT group (P < .05), which was likely influenced by larger planning target volumes in the IMRT group. The VMAT group had significantly lower rates of acute GU and acute GI CTCAE toxicity on UV association analysis. On MV analysis, VMAT remained independently associated with acute GU (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.07-0.44; P < .001) and GI (OR, 0.16; 95% CI, 0.07-0.41; P < .001) toxicity. CONCLUSIONS: VMAT appears to be independently associated with lower rates of acute GI and GU toxicity when compared with traditional IMRT. Further exploration of toxicity improvements associated with VMAT use in the definitive treatment of ACP is needed.

High-dose radiotherapy with or without androgen deprivation therapy for intermediate-risk prostate cancer: cancer control and toxicity outcomes.

PURPOSE: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). METHODS AND MATERIALS: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as ≥T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: ≥T3, prostate-specific antigen level >20 ng/mL, GS ≥8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. RESULTS: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. CONCLUSIONS: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.