Aaron D. Falchook

Cine-magnetic resonance imaging assessment of intrafraction motion for prostate cancer patients supine or prone with and without a rectal balloon.

Purpose:Determine prostate intrafraction motion with Cine-magnetic resonance imaging (MRI) and deformable registration. Methods:A total of 68 cine-MRI studies were done in 17 different series with 4 scans per series in 7 patients. In without rectal balloon (WORB) scans, 100 mL of water was infused in the rectum. Each series consisted of supine and prone, with a rectal balloon (WRB) and WORB. Each scan was performed over 4 minutes. Automatic deformable registration software developed by View Ray, Inc., Cleveland, Ohio was employed to segment the prostate for each cine-MRI image. A time-based analysis was done for the different positions and the use of the rectal balloon. Results:The variation/standard deviation of the prostate position during 240 seconds was: supine WRB: 0.55 mm, WORB: 1.2 mm, and prone WRB: 1.48 mm, WORB: 2.15 mm (P < 0.001). A strong relationship was observed between time and prostate motion. For the initial 120 s the standard deviation was smaller than for the second 120 s supine WRB 0.54 mm versus 1.37 mm; supine WORB 0.61 mm versus 1.70 mm; prone WRB 0.85 mm versus 1.85 mm; and prone WORB 1.60 mm versus 2.56 mm. The probabilities for prostate staying within ±2 mm to its initial position are: 94.8% supine WRB; 91.5% supine WORB; 92.3% prone WRB; 79.2% prone WORB. Conclusions:Intrafraction prostate motion was found dependent on time, patient position, and the use of a rectal balloon. Relatively stable positions can be obtained for 4 minutes or less especially in the supine position with a rectal balloon.

Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

PURPOSE Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. METHODS AND MATERIALS This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsy Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. RESULTS For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. CONCLUSIONS This is the first population-based study to examine pathologic extent of disease and pathologic Gleason score upgrading based on clinically available information in modern patients. These data inform the selection of radiation therapy strategies and an understanding of whether prostatectomy alone is likely to be curative for patients with early prostate cancers.

Comparison of Patient- and Practitioner-Reported Toxic Effects Associated With Chemoradiotherapy for Head and Neck Cancer.

IMPORTANCE Agreement between patient- and practitioner-reported toxic effects during chemoradiotherapy for head and neck cancer is unknown. OBJECTIVE To compare patient-reported symptom severity and practitioner-reported toxic effects among patients receiving chemoradiotherapy for head and neck cancer. DESIGN, SETTING, AND PARTICIPANTS Forty-four patients participating in a phase 2 trial of deintensified chemoradiotherapy for oropharyngeal carcinoma were included in the present study (conducted from February 8, 2012, to March 2, 2015). Most treatment (radiotherapy, 60 Gy, with concurrent weekly administration of cisplatin, 30 mg/m2) was administered at academic medical centers. Included patients had no prior head and neck cancers, were 18 years or older, and had a smoking history of 10 pack-years or less or more than 10 pack-years but 30 pack-years or less and abstinent for the past 5 years. Cancer status was untreated human papillomavirus or p16-positive squamous cell carcinoma of the oropharynx or unknown head and neck primary site; and cancer staging was category T0 to T3, category N0 to N2c, M0, and Eastern Cooperative Oncology Group performance status 0 to 1. Baseline, weekly, and posttreatment toxic effects were assessed by physicians or nurse practitioners using National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Patient-reported symptom severity was measured using the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE). Descriptive statistics were used to characterize raw agreement between CTCAE grades and PRO-CTCAE severity ratings. INTERVENTIONS Baseline, weekly, and posttreatment toxic effects assessed using CTCAE, version 4.0, and PRO-CTCAE. MAIN OUTCOMES AND MEASURES Raw agreement indices between patient-reported toxic effects, including symptom frequency, severity, and interference with daily activities (score range, 0 [none] to 4 [very severe]), and practitioner-measured toxic effects, including swallowing, oral pain, and hoarseness (score range, 1 [mild] to 5 [death]). RESULTS Of the 44 patients included in the analysis (39 men, 5 women; mean [SD] age, 61 [8.4] years), there were 327 analyzable pairs of CTCAE and PRO-CTCAE symptom surveys and no treatment delays due to toxic effects. Patient-reported and practitioner-reported symptom severity agreement was high at baseline when most symptoms were absent but declined throughout treatment as toxic effects increased. Most disagreement was due to lower severity of toxic effects reported by practitioners (eg, from 45% agreement at baseline to 27% at the final week of treatment for pain). This was particularly noted for domains that are not easily evaluated by physical examination, such as anxiety and fatigue (eg, severity of fatigue decreased from 43% at baseline to 12% in the final week of treatment). CONCLUSIONS AND RELEVANCE Practitioner-reported toxic effects are lower than patient self-reports during head and neck chemoradiotherapy. The inclusion of patient-reported symptomatic toxic effects provides information that can potentially enhance clinical management and improve data quality in clinical trials.

Guideline-Discordant Use of Imaging During Work-Up of Newly Diagnosed Prostate Cancer

PURPOSE Overuse of radiographic imaging in patients with prostate cancer (CaP) who are unlikely to have metastatic disease is costly and can lead to patient harm from unnecessary procedures. However, underuse of imaging can lead to undiagnosed metastatic disease, resulting in aggressive treatments in patients with incurable disease. The National Comprehensive Cancer Network (NCCN) recommends bone scans and computed tomography (CT) or magnetic resonance imaging (MRI) during initial work-up of select patients with intermediate- or high-risk CaP. We quantify the proportion of patients who received work-up discordant with NCCN guidelines. METHODS Patients in the SEER-Medicare database diagnosed from 2004 to 2007 were included. We report bone scan and CT/MRI from date of diagnosis to the earlier of first treatment or 6 months. RESULTS Sixty-five percent of patients for whom bone scan was recommended received it, and 49% received recommended CT/MRI. Further, 43% of patients for whom bone scan was not recommended received it, and 38% received CT/MRI when not recommended. Age and race were significantly associated with discordance on multivariable models. There was significant regional variation. Underuse of recommended bone and CT/MRI scans decreased in more recent years, but overuse of unnecessary CT/MRI increased. CONCLUSION There is a high prevalence of both overuse and underuse of guideline-recommended imaging in CaP. Additional research is required to examine contributing factors to guideline nonadherence in the imaging work-up of CaP.

Stage at presentation and survival outcomes of patients with Gleason 8–10 prostate cancer and low prostate-specific antigen

OBJECTIVE To evaluate outcomes for men with high Gleason score and low prostate-specific antigen (PSA) prostate cancer. Low PSA levels among men with Gleason 8-10 prostate cancer may be owing to cellular dedifferentiation rather than low disease burden. We hypothesized that men with Gleason 8-10 prostate cancer and low PSA levels have increased risk for advanced disease and worse survival. MATERIALS AND METHODS Men diagnosed from 2004 to 2007 with Gleason 8-10 prostate adenocarcinoma in the National Cancer Data Base were included. Patients were stratified by PSA levels at diagnosis: 0.1 to 3.9, 4.0 to 9.9, 10.0 to 19.9, and≥20.0ng/ml. Outcomes were clinical TNM category, pathologic stage (for prostatectomy patients), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazards models were used. RESULTS A total of 37,283 patients were included. Men with PSA levels of<4.0ng/ml were more likely than those with PSA levels of 4 to 9.9ng/ml to present with clinical T3-4 disease (15% vs. 10%, P<0.001), nodal (4% vs. 2%, P<0.001) and distant (5% vs. 3%, P<0.001) metastasis. However, among patients treated with prostatectomy, lower PSA levels were not associated with increased likelihood of pathologic T3-4 disease or nodal metastasis. Six-year OS was 89.1% (PSA: 0.1-3.9ng/ml) vs. 91.0% (PSA: 4.0-9.9ng/ml) for prostatectomy (log-rank P<0.001), and 75.8% vs. 81.0% for radiotherapy (P<0.001). Multivariable analyses showed OS of patients with PSA levels of 0.1 to 3.9ng/ml to be similar to those with PSA levels of 10 to 19.9ng/ml. CONCLUSIONS Patients with Gleason 8-10 cancer and PSA levels of<4.0ng/ml have more aggressive disease than those with PSA levels of 4 to 9.9ng/ml; these low PSA cancers behave more like those with PSA levels of 10 to 19.9ng/ml. Further study is needed to evaluate potential biological differences in these patients with low PSA-producing cancers.

PROTON THERAPY COVERAGE FOR PROSTATE CANCER TREATMENT

PURPOSE To determine the impact of prostate motion on dose coverage in proton therapy. METHODS AND MATERIALS A total of 120 prostate positions were analyzed on 10 treatment plans for 10 prostate patients treated using our low-risk proton therapy prostate protocol (University of Florida Proton Therapy Institute 001). Computed tomography and magnetic resonance imaging T(2)-weighted turbo spin-echo scans were registered for all cases. The planning target volume included the prostate with a 5-mm axial and 8-mm superoinferior expansion. The prostate was repositioned using 5- and 10-mm one-dimensional vectors and 10-mm multidimensional vectors (Points A-D). The beam was realigned for the 5- and 10-mm displacements. The prescription dose was 78 Gy equivalent (GE). RESULTS The mean percentage of rectum receiving 70 Gy (V(70)) was 7.9%, the bladder V(70) was 14.0%, and the femoral head/neck V(50) was 0.1%, and the mean pelvic dose was 4.6 GE. The percentage of prostate receiving 78 Gy (V(78)) with the 5-mm movements changed by -0.2% (range, 0.006-0.5%, p > 0.7). However, the prostate V(78) after a 10-mm displacement changed significantly (p < 0.003) with different movements: 3.4% (superior), -5.6% (inferior), and -10.2% (posterior). The corresponding minimal doses were also reduced: 4.5 GE, -4.7 GE, and -11.7 GE (p < or = 0.003). For displacement points A-D, the clinical target volume V(78) coverage had a large and significant reduction of 17.4% (range, 13.5-17.4%, p < 0.001) in V(78) coverage of the clinical target volume. The minimal prostate dose was reduced 33% (25.8 GE), on average, for Points A-D. The prostate minimal dose improved from 69.3 GE to 78.2 GE (p < 0.001) with realignment for 10-mm movements. CONCLUSION The good dose coverage and low normal doses achieved for the initial plan was maintained with movements of < or = 5 mm. Beam realignment improved coverage for 10-mm displacements.

Use of mobile device technology to continuously collect patient-reported symptoms during radiation therapy for head and neck cancer: A prospective feasibility study

Purpose Accurate assessment of toxicity allows for timely delivery of supportive measures during radiation therapy for head and neck cancer. The current paradigm requires weekly evaluation of patients by a provider. The purpose of this study is to evaluate the feasibility of monitoring patient reported symptoms via mobile devices. Methods and materials We developed a mobile application for patients to report symptoms in 5 domains using validated questions. Patients were asked to report symptoms using a mobile device once daily during treatment or more often as needed. Clinicians reviewed patient-reported symptoms during weekly symptom management visits and patients completed surveys regarding perceptions of the utility of the mobile application. The primary outcome measure was patient compliance with mobile device reporting. Compliance is defined as number of days with a symptom report divided by number of days on study. Results There were 921 symptom reports collected from 22 patients during treatment. Median reporting compliance was 71% (interquartile range, 45%-80%). Median number of reports submitted per patient was 34 (interquartile range, 21-53). Median number of reports submitted by patients per week was similar throughout radiation therapy and there was significant reporting during nonclinic hours. Patients reported high satisfaction with the use of mobile devices to report symptoms. Conclusions A substantial percentage of patients used mobile devices to continuously report symptoms throughout a course of radiation therapy for head and neck cancer. Future studies should evaluate the impact of mobile device symptom reporting on improving patient outcomes.

Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer.

Randomized trials have shown that androgen‐deprivation therapy (ADT) improves survival for men with intermediate‐risk prostate cancer treated with radiotherapy (RT). The benefit of ADT to patients with favorable intermediate‐risk prostate cancer treated with modern dose‐escalated RT is unknown. This study evaluated the effectiveness of ADT on survival of men with favorable intermediate‐risk prostate cancer treated with dose‐escalated RT.

Effect of race and histology on patterns of failure in women with early stage endometrial cancer treated with high dose rate brachytherapy.

BACKGROUND Clinical trials have helped refine management of early stage endometrial cancer (EC). For patients with intermediate risk features, adjuvant radiation is considered, primarily vaginal cuff brachytherapy. For higher risk patients, there may be a role for chemotherapy and radiation. The purpose of this study is to examine patterns of failure for early stage EC patients treated with postoperative high dose rate brachytherapy. METHODS In this single institution retrospective cohort study, 208 women with early stage endometrial cancer who received definitive therapy between January 1, 2000 and January 1, 2013 were identified. RESULTS Median follow-up was 46.4 (range, 6.2-137.3) months. Thirteen (6.3%) patients developed with locoregional recurrent disease and 15 (7.2%) patients developed distant metastasis. Freedom from recurrence at 5 years was 88.6% for white patients and 60.5% for black patients (p=0.0093). Five year recurrence free survival (RFS) for white vs. black patients was 82.9% vs. 48.9% (p=0.0007). Five year overall survival (OS) was 86.8% for white patients and 59.5% for black patients (p=0.0023). Black patients with unfavorable histology treated with chemotherapy and vaginal brachytherapy had a 15% locoregional recurrence rate, more than double the rate of local recurrence compared to AA patients with endometrioid histology and white patients with any histology (6% locoregional recurrence rate). CONCLUSIONS Black women with unfavorable histology early stage EC experience increased rates of recurrence and worse survival compared to white patients. Patterns of failure in this group also indicate a high locoregional failure rate for the black patients with unfavorable histology (type II).

Elective neck dissection for second primary after previous definitive radiotherapy.

PURPOSE The aim of this study was to define the role of neck dissection during surgery for patients who have received elective nodal irradiation in the course of treatment for a prior squamous cell carcinoma of the head and neck (SCCHN) and are subsequently diagnosed with a second primary SCCHN. MATERIALS AND METHODS We reviewed the medical records of 13 patients who received both definitive radiotherapy and elective nodal irradiation for T1-4 N0 M0 SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx who then subsequently developed a metachronous T1-4 N0 M0 SCCHN primary at a new site. All second primary tumors were treated with surgery. Ten of the 13 patients also received an elective neck dissection (END) at that time: 7 unilateral and 3 bilateral. We report the outcomes for the patients in this series. RESULTS One (8%) of 13 neck dissection specimens was positive in 1 (10%) of 10 patients. The 5-year outcomes were the following: local-regional control, 67%; local control, 77%; disease-free survival, 62%; overall survival, 38%; and cause-specific survival rate, 77%. Six patients experienced treatment-related complications of grade 2 or higher (per Common Terminology Criteria for Adverse Events, version 4). Complications occurred exclusively in patients who received an END. CONCLUSIONS The risk of occult nodal disease may be low enough to justify omitting an END for a second primary SCCHN in selected patients while maintaining treatment efficacy and reducing patient morbidity. Larger studies on this subject are needed to further address this question.