Proton therapy toxicity outcomes for localized prostate cancer: Long-term results at a comprehensive cancer center.

Background: Proton therapy (PT) has unique biologic properties with excellent clinical outcomes for the management of localized prostate cancer. Here, we aim to characterize the toxicity of PT for patients with localized prostate cancer and propose mitigation strategies using a large institutional database. Methods: We reviewed medical records of 2772 patients with localized prostate cancer treated with definitive PT between May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 849]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 117]. Descriptive statistics and Kaplan-Meier estimates assessed toxicity and freedom from biochemical relapse (FFBR). Results: Median follow-up was 7.0 years. The median dose was 78 Gy(RBE)(range: 72-79.2 Gy) in 2.0 Gy(RBE) fractions; 63 % of patients received 78 Gy(RBE) in 39 fractions, and 29 % received 76 Gy(RBE) in 38 fractions. Overall rates of late grade ≥3 GU and GI toxicity were 0.87 % and 1.01 %, respectively. Two patients developed grade 4 late GU toxicity and seven patients with grade 4 late GI toxicity. All patients experiencing severe late grade 4 toxicities were treated to 78 Gy(RBE) in 39 fractions with 80 Gy(RBE) dose to the anterior rectal wall and/or bladder neck. The 10-year FFBR rates for patients with LR to U-IR disease were compared between those treated with 76 and 78 Gy(RBE); the rates were 94.5 % (95 % confidence interval [CI] 92.4-96.0 %) and 93.2 % (95 % CI 91.3-95.7 %), respectively (log-rank p = 0.22). Conclusions: Proton therapy is associated with low rates of late grade ≥3 GU and GI toxicity. While rare, late grade 4 toxicities occurred in nine (0.3 %) patients. De-escalation to a total dose of 76 Gy(RBE) yields excellent clinical outcomes for patients with LR to U-IR disease with the potential for significant reductions in grade ≥3 late toxicity.

PSA: Declining utilization of prostate brachytherapy.

PURPOSE: To analyze rates of brachytherapy use for prostate cancer over time and evaluate patient characteristics, demographics and factors predictive for its utilization. METHODS: Data was retrospectively analyzed from the National Cancer Database (NCDB) for patients with localized prostate cancer treated between 2010 and 2015. Patients were included if they had biopsy confirmed localized adenocarcinoma of the prostate, were treated with radiation as definitive local therapy, and were at least 18 years old. Utilization rates of external beam radiation (EBRT), brachytherapy (BT) and combination (EBRT + BT) were evaluated over time. Univariable (UVA) and backwards elimination multivariable (MVA) analysis were performed to determine characteristics predictive for brachytherapy use. RESULTS: We analyzed 178,837 patients with localized adenocarcinoma of the prostate treated between 2010 and 2015 with radiation therapy. During this period, the use of EBRT increased from 67% to 78%, BT (both monotherapy and combination with EBRT) decreased from 33% to 22%, BT monotherapy decreased from 25% to 16% and EBRT + BT decreased from 8% to 6%. Age >70, government funded insurance or lack of insurance, intermediate or high-risk disease and treatment at an academic center were associated with significantly lower utilization of brachytherapy (all p <0.001), while higher median zip code income was associated with increased use (p = 0.02). On multivariable analysis patients who were younger, had private insurance, were lower NCCN risk category and treated in non-academic cancer centers, had a higher rate of brachytherapy utilization. Notably, on both UVA and MVA brachytherapy practice decreased with increasing year of diagnosis (OR 0.881, 95% CI 0.853-0.910, p <0.001). CONCLUSION: Rates of brachytherapy utilization for the treatment of prostate cancer continue to decrease over time. Treatment at an academic center was associated with reduced likelihood of brachytherapy use. This has significant implications for the training of future radiation oncology residents/fellows and direct consequences for both our patients and healthcare expenditure.

A Sandwich Metal-Insulation-Metal Composite for Magnetoelectric Memory: Experiment and Modeling.

Driven by the development of internet technology, higher requirements on information materials and data storage devices were demanded. To improve the work efficiency and performance of the new generation of information materials and data storage devices, the magnetoelectric (ME) coupling and storage mechanism of magnetoelectric composites deserve more attention. Here, we explored the influence of applied magnetic fields on the output voltage on a metal-insulation-metal (MIM) sandwich composite for realizing the magnetoelectric memory by experiments and modeling. It is found that the DC magnetic field (H dc) and the output voltage of the polyvinylidene fluoride film are linearly correlated. At a frequency of 1 kHz, the magnetoelectric voltage coefficient is 60.71 mV cm-1 Oe-1, which is evidently larger than that of other film materials. From this work, we can conclude that the MIM sandwich composite could generate higher magnetoelectric voltage under the AC magnetic field (H ac) with higher frequency, which could be used as the magnetoelectric memory device, and provides significant support for improving the performance of magnetoelectric memory devices and the whole internet system.

Exradin W1 plastic scintillation detector for in vivo skin dosimetry in passive scattering proton therapy.

In vivo skin dosimetry is desirable in passive scattering proton therapy because of the possibility of high entrance dose with a small number of fields. However, suitable detectors are needed to determine skin dose in proton therapy. Plastic scintillation detectors (PSDs) are particularly well suited for applications in proton therapy because of their water equivalence, small size, and ease of use. We investigated the utility of the Exradin W1, a commercially available PSD, for in vivo skin dosimetry during passive scattering proton therapy. We evaluated the accuracy of the Exradin W1 in six patients undergoing proton therapy for prostate cancer, as part of an Institutional Review Board-approved protocol. Over 22 weeks, we compared in vivo PSD measurements with in-phantom ionization chamber measurements and doses from the treatment planning system, resulting in 96 in vivo measurements. Temperature and ionization quenching correction factors were applied on the basis of the dose response of the PSD in a phantom. The calibrated PSD exhibited an average 7.8% under-response (±1% standard deviation) owing to ionization quenching. We observed 4% under-response at 37 °C relative to the calibration-temperature response. After temperature and quenching corrections were applied, the overall PSD dose response was within ±1% of the expected dose for all patients. The dose differences between the PSD and ionization chamber measurements for all treatment fields were within ±2% (standard deviation 0.67%). The PSD was highly accurate for in vivo skin dosimetry in passively scattered proton beams and could be useful in verifying proton therapy delivery.

Patient-reported health-related quality of life for men treated with low-dose-rate prostate brachytherapy as monotherapy with 125-iodine, 103-palladium, or 131-cesium: Results of a prospective phase II study.

PURPOSE: To compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes. METHODS AND MATERIALS: Patients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs. RESULTS: From 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively. CONCLUSIONS: The three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance.

Patient-reported Urinary, Bowel, and Sexual Function After Hypofractionated Intensity-modulated Radiation Therapy for Prostate Cancer: Results From a Randomized Trial.

OBJECTIVES: Hypofractionated prostate radiotherapy may increase biologically effective dose delivered while shortening treatment duration, but information on patient-reported urinary, bowel, and sexual function after dose-escalated hypofractionated radiotherapy is limited. We report patient-reported outcomes (PROs) from a randomized trial comparing hypofractionated and conventional prostate radiotherapy. METHODS: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity-modulated radiation therapy (CIMRT, 75.6 Gy in 1.8 Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4 Gy fractions). Questionnaires assessing urinary, bowel, and sexual function were completed pretreatment and at 2, 3, 4, and 5 years after treatment. RESULTS: Of 203 eligible patients, 185 were evaluable for PROs. A total of 173 completed the pretreatment questionnaire (82 CIMRT, 91 HIMRT) and 102 completed the 2-year questionnaire (46 CIMRT, 56 HIMRT). Patients who completed PROs were similar to those who did not complete PROs (all P>0.05). Patient characteristics, clinical characteristics, and baseline symptoms were well balanced between the treatment arms (all P>0.05). There was no difference in patient-reported bowel (urgency, control, frequency, or blood per rectum), urinary (dysuria, hematuria, nocturia, leakage), or sexual symptoms (erections firm enough for intercourse) between treatment arms at 2, 3, 4, and 5 years after treatment (all P>0.01). Concordance between physician-assessed toxicity and PROs varied across urinary and bowel domains. DISCUSSION: We did not detect an increase in patient-reported urinary, bowel, and sexual symptom burden after dose-escalated intensity-modulated prostate radiation therapy using a moderate hypofractionation regimen (72 Gy in 2.4 Gy fractions) compared with conventionally fractionated radiation.

Prospective Phase 2 Trial of Permanent Seed Implantation Prostate Brachytherapy for Intermediate-Risk Localized Prostate Cancer: Efficacy, Toxicity, and Quality of Life Outcomes.

PURPOSE: To report the efficacy, physician-reported toxicity, and patient-reported outcomes of men with intermediate-risk prostate cancer after brachytherapy in a prospective phase 2 trial. METHODS AND MATERIALS: This prospective phase 2 trial involved 300 patients with previously untreated prostate cancer treated from 2006 through 2013. Eligible patients had ≤cT2b (T3 excluded according to magnetic resonance imaging), Gleason score (GS) 6 with prostate-specific antigen (PSA) level 10-15 ng/mL, or GS 7 with PSA <10 ng/mL, and were treated with prostate brachytherapy (without hormonal therapy). RESULTS: Median patient age was 64.9 years; 3.7% had GS 6, 78.7% had GS 7 (3+4), and 17.7% had GS 7 (4+3). Median follow-up time was 5.1 years. Median PSA at 5 years was 0.01 ng/mL (range, 0-6.0 ng/mL). Ten biochemical failures occurred, for a 5-year freedom from biochemical failure rate of 97.3% (95% confidence interval [CI], 95.1-99.5), and 16 patients died, only 1 from prostate cancer, for 5-year rates of overall and biochemical progression-free survival of 94.9% (95% CI, 92.1-97.9) and 92.7% (95% CI, 89.3-96.2%). Four patients had late grade 3 genitourinary toxicity, and 2 patients had late grade 3 rectal toxicity; no grade 4 or 5 toxicity was observed. Rates of "moderate or big problems" at 4 years were 7.4% for urinary (vs 0.4% at baseline), 2.9% bowel (vs 0.4%), and 29.7% sexual function (vs 19.7%). Most men were "satisfied or extremely satisfied" (91% at 2 years after treatment and 93% at 4 years). CONCLUSIONS: Brachytherapy monotherapy is safe and effective and leads to good quality of life for some men with localized intermediate-risk prostate cancer.

Quality of life after brachytherapy or bilateral nerve-sparing robot-assisted radical prostatectomy for prostate cancer: a prospective cohort.

OBJECTIVE: To provide comparative data on quality of life (QoL) after prostate cancer treatment to help patients make an informed decision regarding their choice of treatment. METHODS: Patients with pathologically proven, non-metastatic, T1-T3bN0 prostate cancer were included in this prospective non-randomized study if they were to receive treatment with curative intent. Sample size was at least 181 patients per cohort/treatment type. QoL was recorded at baseline and at each follow-up using the Expanded Prostate Cancer Index Composite (EPIC) instrument. The minimal clinically important difference was defined as half of the standard deviation of the baseline score for each domain. A mixed effects model was used to compare the different treatments. Data are presented on the brachytherapy and the bilateral nerve-sparing robot-assisted radical prostatectomy (RARP) cohorts. Hormonotherapy was not allowed. RESULTS: Between November 2007 and January 2013, 181 patients who received brachytherapy and 210 patients who underwent RARP were included. Of the patients who underwent RARP, 178 had bilateral nerve-sparing and were included in the present analysis. Response rate to EPIC questionnaires were higher in the brachytherapy than in the RARP arm: 82% vs 57% at 2 years after treatment and 55% vs 45% at 4 years after treatment. In the mixed effects model, patients in the RARP arm had better QoL with regard to urinary irritation/obstruction or bother and bowel function, and lower QoL regarding sexual function and urinary incontinence. Results were confirmed in a propensity score-matched model. Patient satisfaction was significantly higher in the brachytherapy group at 1, 2 and 3 years after treatment. CONCLUSION: This prospective non-randomized study shows long-term differences in QoL domains after bilateral nerve-sparing RARP and brachytherapy. Differences in patient satisfaction should be further explored. These results could be used to counsel patients in the decision-making process.

Association between intensity modulated radiotherapy and survival in patients with stage III non-small cell lung cancer treated with chemoradiotherapy.

PURPOSE: To determine the effect of radiotherapy (RT) technique on treatment compliance and overall survival (OS) in patients with stage III non-small lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT). METHODS AND MATERIALS: This study included patients with stage III NSCLC in the National Cancer Database treated between 2003 and 2011 with definitive CRT to 60-63 Gray (Gy). Radiation treatment interruption (RTI) was defined as a break of ≥4 days. Treatment technique was dichotomized as intensity modulated (IMRT) or non-IMRT techniques. RESULTS: Out of the cohort of 7492, 35% had a RTI and 10% received IMRT. With a median follow-up of surviving patients of 32 months, the median survival for those with non-IMRT vs. IMRT was 18.2 months vs. 20 months (p<0.0001). Median survival for those with and without an RTI≥4 days was 16.1 months vs. 19.8 months (p<0.0001). Use of IMRT predicted for a decreased likelihood of RTI (odds ratio, 0.84, p=0.04). On multivariable analysis for OS, IMRT had a HR of 0.89 (95% CI: 0.80-0.98, p=0.01) and RTI had a HR of 1.2 (95% confidence interval (CI): 1.14-1.27, p=0.001). CONCLUSIONS: IMRT was associated with small but significant survival advantage for patients with stage III NSCLC treated with CRT. A RTI led to inferior survival, and both IMRT and RTI were independently associated with OS. Additional research should investigate whether improved tolerability, reduced normal tissue exposure, or superior coverage drives the association between IMRT and improved survival.

The declining utilization of brachytherapy for the treatment of prostate cancer: Can magnetic resonance imaging reverse the trend?

The utilization of brachytherapy for the treatment of prostate cancer has fluctuated over the years. Whereas initial excitement led to rapid expansion of this modality, more recent data suggest that prostate brachytherapy is in decline. This article reviews previous and current trends in the utilization of prostate brachytherapy and postulates the potential impact of the integration of magnetic resonance imaging imaging on this modality.

Permanent prostate brachytherapy postimplant magnetic resonance imaging dosimetry using positive contrast magnetic resonance imaging markers.

PURPOSE: Permanent prostate brachytherapy dosimetry using computed tomography-magnetic resonance imaging (CT-MRI) fusion combines the anatomic detail of MRI with seed localization on CT but requires multimodality imaging acquisition and fusion. The purpose of this study was to compare the utility of MRI only postimplant dosimetry to standard CT-MRI fusion-based dosimetry. METHODS AND MATERIALS: Twenty-three patients undergoing permanent prostate brachytherapy with use of positive contrast MRI markers were included in this study. Dose calculation to the whole prostate, apex, mid-gland, and base was performed via standard CT-MRI fusion and MRI only dosimetry with prostate delineated on the same T2 MRI sequence. The 3-dimensional (3D) distances between seed positions of these two methods were also evaluated. Wilcoxon-matched-pair signed-rank test compared the D90 and V100 of the prostate and its sectors between methods. RESULTS: The day 0 D90 and V100 for the prostate were 98% versus 94% and 88% versus 86% for CT-MRI fusion and MRI only dosimetry. There were no differences in the D90 or V100 of the whole prostate, mid-gland, or base between dosimetric methods (p > 0.19), but prostate apex D90 was high by 13% with MRI dosimetry (p = 0.034). The average distance between seeds on CT-MRI fusion and MRI alone was 5.5 mm. After additional automated rigid registration of 3D seed positions, the average distance between seeds was 0.3 mm, and the previously observed differences in apex dose between methods was eliminated (p > 0.11). CONCLUSIONS: Permanent prostate brachytherapy dosimetry based only on MRI using positive contrast MRI markers is feasible, accurate, and reduces the uncertainties arising from CT-MRI fusion abating the need for postimplant multimodality imaging.

Prostate brachytherapy, either alone or in combination with external beam radiation, is associated with longer overall survival in men with favorable pathologic Group 4 (Gleason score 8) prostate cancer.

PURPOSE: Conventional prostate cancer risk stratification results in considerable heterogeneity within each prognostic group. Men with pathologic grade Group 4 (Gleason score 8) but otherwise low-risk features have been identified as a favorable subset of high-risk prostate cancer. Given recent randomized data supporting improved cancer outcome with brachytherapy in intermediate- and high-risk prostate cancer, we sought to evaluate brachytherapy utilization and overall survival (OS) for these patients. METHODS AND MATERIALS: We queried the National Cancer Database for clinical T1c-T2a N0 M0 prostate cancer with prostate-specific antigen <10 ng/mL and Gleason score 8 adenocarcinoma on biopsy. All patients received androgen deprivation therapy and either external beam radiation therapy (EBRT) alone, brachytherapy alone, or a combination of EBRT with brachytherapy boost (brachytherapy + EBRT). Kaplan-Meier OS estimates as well as univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score-matched analyses were performed to further control for baseline confounders. RESULTS: Four thousand four hundred ninety-six patients were identified with a median followup of 62.5 months (range, 2.3-119.8). Median age was 72 years (range, 41-90+). Utilization of brachytherapy decreased from 2004 to 2009. The odds ratio for brachytherapy by year (continuous variable) was 0.86 (p < 0.001). Five-year OS was 84%, 88%, and 89% for the EBRT alone, brachytherapy alone, and brachytherapy + EBRT groups, respectively. On multivariate analysis, higher median income, low comorbidity score, and treatment with brachytherapy alone (hazard ratio, 0.66; p = 0.005) or brachytherapy + EBRT (hazard ratio, 0.70; p = 0.001) remained associated with longer OS. Propensity score matching confirmed longer OS associated with either brachytherapy regimen. CONCLUSIONS: Of those men with World Health Organization pathologic grade Group 4 (Gleason score 8) prostate cancer and otherwise favorable prognostic features treated with androgen deprivation therapy and radiation therapy, longer OS was achieved when prostate brachytherapy was included, whether used alone or in combination with supplemental EBRT. In spite of these excellent outcomes, prostate brachytherapy utilization is declining in the United States.

Permanent prostate brachytherapy pubic arch evaluation with diagnostic magnetic resonance imaging.

PURPOSE: Pubic arch interference (PAI), when it occurs, is often a limiting factor for patients pursuing brachytherapy treatment of prostate cancer. Pre-brachytherapy pubic arch evaluation is often performed by CT or transrectal ultrasound (TRUS), but MRI has increasingly replaced these modalities for prostate cancer evaluation. The purpose of this study was to determine if staging MRI could be used to evaluate PAI and compare it with these other imaging methods. METHODS AND MATERIALS: Forty-one consecutive patients undergoing brachytherapy evaluation had pelvic MRI-, CT-, and TRUS-based brachytherapy simulation. Pubic arch overlap on T2-weighted MRI and CT was determined by contouring the prostate gland on its largest axial slice and superimposing this contour onto the pubic arch bones. The largest degree of overlap of the prostate gland on MRI and CT was used to predict the existence of PAI as determined by TRUS-based simulation. The correlation between prostate contour overlap was also compared between MRI and CT. RESULTS: Nineteen patients (48%) exhibited PAI on TRUS brachytherapy simulation evaluation. The average (±standard error) amount of prostate contour overlap on the pubic arch on CT was 2.9 ± 0.6 mm and on MRI was 2.0 ± 0.6 mm (linear correlation, R, of 0.783, p < 0.001). CT and MRI were equally predictive of PAI on TRUS evaluation (area under the curve = 0.75). CONCLUSION: Pre-brachytherapy pubic arch assessment with diagnostic MRI provides similar predictability of PAI compared with CT, potentially obviating the need for additional pre-brachytherapy CT in the setting of staging MRI.

Insurance Status and Racial Disparities in Cancer-Specific Mortality in the United States: A Population-Based Analysis.

Background: Cancer-specific mortality (CSM) is known to be higher among blacks and lower among Hispanics compared with whites. Private insurance confers CSM benefit, but few studies have examined the relationship between insurance status and racial disparities. We sought to determine differences in CSM between races within insurance subgroups.Methods: A population-based cohort of 577,716 patients age 18 to 64 years diagnosed with one of the 10 solid malignancies causing the greatest mortality over 2007 to 2012 were obtained from Surveillance, Epidemiology, and End Results. A Cox proportional hazards model for CSM was constructed to adjust for known prognostic factors, and interaction analysis between race and insurance was performed to generate stratum-specific HRs.Results: Blacks had similar CSM to whites among the uninsured [HR = 1.01; 95% confidence interval (CI), 0.96-1.05], but higher CSM among the Medicaid (HR = 1.04; 95% CI, 0.01-1.07) and non-Medicaid (HR = 1.14; 95% CI, 1.12-1.16) strata. Hispanics had lower CSM compared with whites among uninsured (HR = 0.80; 95% CI, 0.76-0.85) and Medicaid (HR = 0.88; 95% CI, 0.85-0.91) patients, but there was no difference among non-Medicaid patients (HR = 0.99; 95% CI, 0.97-1.01). Asians had lower CSM compared with whites among all insurance types: uninsured (HR = 0.80; 95% CI, 0.76-0.85), Medicaid (HR = 0.81; 95% CI, 0.77-0.85), and non-Medicaid (HR = 0.85; 95% CI, 0.83-0.87).Conclusions: The disparity between blacks and whites was largest, and the advantage of Hispanic race was absent within the non-Medicaid subgroup.Impact: These findings suggest that whites derive greater benefit from private insurance than blacks and Hispanics. Further research is necessary to determine why this differential exists and how disparities can be improved. Cancer Epidemiol Biomarkers Prev; 26(6); 869-75. ©2017 AACR.

Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

PURPOSE: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. RESULTS: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. CONCLUSION: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.

Development of a magnetic resonance imaging protocol to visualize encapsulated contrast agent markers in prostate brachytherapy recipients: initial patient experience.

PURPOSE: Computed tomography (CT)-based prostate post-implant dosimetry allows for definitive seed localization but is associated with high interobserver variation in prostate contouring. Currently, magnetic resonance imaging (MRI)-based post-implant dosimetry allows for accurate anatomical delineation but is limited due to inconsistent seed localization. Encapsulated contrast agent markers were previously proposed to overcome the seed localization limitation on MRI images by placing hyperintense markers adjacent to hypointense seeds. The aim of this study was to assess the appearance of these markers in prostatic tissue, and develop an MRI protocol to enable marker visualization. MATERIAL AND METHODS: We acquired MRI scans in prostate implant patients (n = 10) on day 0 (day of implant) and day 30 (month after implant). Before implantation of the markers, the routine post-implant MRI protocol included a 3D T2-weighted fast-spin-echo (FSE) sequence with which markers and seeds could not be clearly visualized. To visualize the MRI markers, a 3D fast radiofrequency-spoiled gradient-recalled echo (FSPGR) sequence was evaluated for marker and seed visibility, as well as prostate boundary definitions. RESULTS: The 3D FSPGR sequence allowed for the visualization of markers in the prostate, enabling the distinction of signal voids as seeds versus needle tracks. The updated post-implant MRI protocol consists of this 3D FSPGR scan and an optional 3D T2-weighted FSE scan. The optional 3D T2-weighted FSE sequence may be employed to better visualize intraprostatic detail. We also described the observed image artifacts, including seed susceptibility, marker chemical shift, partial volume averaging, motion, and wraparound artifacts. CONCLUSIONS: We have demonstrated an MRI protocol for use with hyperintense encapsulated contrast agent markers to assist in the identification of hypointense seeds.

Improved Survival With Prostate Radiation in Addition to Androgen Deprivation Therapy for Men With Newly Diagnosed Metastatic Prostate Cancer.

PURPOSE: There is growing interest in the role of local therapies, including external beam radiotherapy (RT), for men with metastatic prostate cancer (mPCa). We used the National Cancer Database (NCDB) to evaluate the overall survival (OS) of men with mPCa treated with androgen deprivation (ADT) with and without prostate RT. METHODS: The NCDB was queried for men with newly diagnosed mPCa, all treated with ADT, with complete datasets for RT, surgery, prostate-specific antigen (PSA) level, Gleason score, and Charlson-Deyo comorbidity score. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. RESULTS: From 2004 to 2012, 6,382 men with mPCa were identified, including 538 (8.4%) receiving prostate RT. At a median follow-up of 5.1 years, the addition of prostate RT to ADT was associated with improved OS on univariate (P < .001) and multivariate analysis (hazard ratio, 0.624; 95% CI, 0.551 to 0.706; P < .001) adjusted for age, year, race, comorbidity score, PSA level, Gleason score, T stage, N stage, chemotherapy administration, treating facility, and insurance status. Propensity score analysis with matched baseline characteristics demonstrated superior median (55 v 37 months) and 5-year OS (49% v 33%) with prostate RT plus ADT compared with ADT alone (P < .001). Landmark analyses limited to long-term survivors of ≥1, ≥3, and ≥5 years demonstrated improved OS with prostate RT in all subsets (all P < .05). Secondary analyses comparing the survival outcomes for patients treated with therapeutic dose RT plus ADT versus prostatectomy plus ADT during the same time interval demonstrated no significant differences in OS, whereas both therapies were superior to ADT alone. CONCLUSION: In this large contemporary analysis, men with mPCa receiving prostate RT and ADT lived substantially longer than men treated with ADT alone. Prospective trials evaluating local therapies for mPCa are warranted.

Improved survival time trends in Hodgkin's lymphoma.

There have been dramatic changes in the staging and treatment of Hodgkin's lymphoma (HL) over the past 30 years. We undertook this study to determine if a stage migration had occurred and also examined if treatment associated with later years has improved survival. Patients with stage I-IV HL between 1983 and 2011 were selected from the Surveillance, Epidemiology, and End Results database. Multivariable analysis (MVA) was performed using Cox proportional hazards modeling. The study cohort included 35,680 patients. The stage breakdown in 1983 according to A and B symptoms was follows: 18%, 21%, 12%, and 5% for stage IA, IIA, IIIA, and IVA disease, respectively, and 6%, 11%, 12%, and 15% for stage IB, IIB, IIIB, and IVB disease. The stage breakdown in 2011 according to A and B symptoms was follows: 9%, 29%, 10%, and 6% for stage IA, IIA, IIIA, and IVA disease, respectively, and 4%, 16%, 12%, and 13% for stage IB, IIB, IIIB, and IVB disease. The median follow-up for the entire cohort is 6.1 years. On MVA, the HR for mortality of patients diagnosed in 2006 was 0.60 (95% Confidence Interval (CI): 0.52-0.70) compared to 1983. For stage I and II patients diagnosed in 2006 the HR was 0.62 (95% CI: 0.44-0.87) and 0.40 (95% CI: 0.30-0.55), respectively, compared to patients diagnosed in 1983. For stage III and IV patients diagnosed in 2006 the HR was 0.72 (95% CI: 0.53-0.98) and 0.74 (95% CI: 0.56-0.99), respectively, compared to patients diagnosed in 1983. This is the first study to demonstrate a significant stage migration in early stage Hodgkin's lymphoma. Furthermore, these results demonstrate an improvement in survival over time for patients with Hodgkin's lymphoma which was particularly notable for those with early stage disease.

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation.

PURPOSE: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. METHODS AND MATERIALS: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. RESULTS: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. CONCLUSION: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.