Publications by authors named "John V Hegde"

30 Publications

  • Page 1 of 1

Automated Non-Coplanar VMAT for Dose Escalation in Recurrent Head and Neck Cancer Patients.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Department of Radiation Oncology, University of California, Los Angeles, CA 90095, USA.

This study evaluates the potential for tumor dose escalation in recurrent head and neck cancer (rHNC) patients with automated non-coplanar volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) planning (HyperArc). Twenty rHNC patients are planned with conventional VMAT SBRT to 40 Gy while minimizing organ-at-risk (OAR) doses. They are then re-planned with the HyperArc technique to match these minimal OAR doses while escalating the target dose as high as possible. Then, we compare the dosimetry, tumor control probability (TCP), and normal tissue complication probability (NTCP) for the two plan types. Our results show that the HyperArc technique significantly increases the mean planning target volume (PTV) and gross tumor volume (GTV) doses by 10.8 ± 4.4 Gy (25%) and 11.5 ± 5.1 Gy (26%) on average, respectively. There are no clinically significant differences in OAR doses, with maximum dose differences of <2 Gy on average. The average TCP is 23% (± 21%) higher for HyperArc than conventional plans, with no significant differences in NTCP for the brainstem, cord, mandible, or larynx. HyperArc can achieve significant tumor dose escalation while maintaining minimal OAR doses in the head and neck-potentially enabling improved local control for rHNC SBRT patients without increased risk of treatment-related toxicities.
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http://dx.doi.org/10.3390/cancers13081910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071369PMC
April 2021

A Practical Guide for Navigating the Design, Build, and Clinical Integration of Electronic Patient-Reported Outcomes in the Radiation Oncology Department.

Pract Radiat Oncol 2021 Jul-Aug;11(4):e376-e383. Epub 2021 Jan 15.

Department of Radiation Oncology, University of California, Los Angeles, California.

The development and integration of electronic patient-reported outcomes (ePROs) into the radiation oncology clinic workflow provide novel opportunities, accompanied by unique design considerations and implementation challenges. The processes required for implementation of ePROs are entirely distinct from standard paper-based surveys, with the majority of time devoted to conception and design before initiating questionnaire build, detailed workflow process mapping including development of new workflows, comprehensive communication of the vision between providers and the information technology team, and quality assurance. Based on our experience with implementation of ePROs in our radiation oncology department, we developed a stepwise framework for approaching ePRO conceptual design, build, workflow integration, and the electronic health record interface. Here, we provide a guide for the numerous considerations, decision points, and solutions associated with the implementation of ePROs in the radiation oncology department setting. Although various ePRO tools and electronic health record capabilities impose different requirements, opportunities, and limitations, the conceptual processes and many of the electronic build considerations are broadly applicable.
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http://dx.doi.org/10.1016/j.prro.2020.12.007DOI Listing
September 2021

Time-Driven Activity-Based Costing Comparison of Stereotactic Radiosurgery to Multiple Brain Lesions Using Single-Isocenter Versus Multiple-Isocenter Technique.

Int J Radiat Oncol Biol Phys 2020 11 27;108(4):999-1007. Epub 2020 Jun 27.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California. Electronic address:

Purpose: Stereotactic radiosurgery (SRS) historically has been used to treat multiple brain lesions using a multiple-isocenter technique-frequently associated with significant complexity in treatment planning and long treatment times. Recently, given innovations in planning algorithms, patients with multiple brain lesions may now be treated with a single-isocenter technique using fewer total arcs and less time spent during image guidance (though with stricter image guided radiation therapy tolerances). This study used time-driven activity-based costing to determine the difference in cost to a provider for delivering SRS to multiple brain lesions using single-isocenter versus multiple-isocenter techniques.

Methods And Materials: Process maps, consisting of discrete steps, were created for each phase of the SRS care cycle and were based on interviews with department personnel. Actual treatment times (including image guidance) were extracted from treatment record and verify software. Additional sources of data to determine costs included salary/benefit data of personnel and average list price/maintenance costs for equipment.

Results: Data were collected for 22 patients who underwent single-isocenter SRS (mean lesions treated, 5.2; mean treatment time, 30.2 minutes) and 51 patients who underwent multiple-isocenter SRS (mean lesions treated, 4.4; mean treatment time, 75.2 minutes). Treatment time for multiple-isocenter SRS varied substantially with increasing number of lesions (11.8 minutes/lesion; P < .001), but to a much lesser degree in single-isocenter SRS (1.8 minutes/lesion; P = .029). The resulting cost savings from single-isocenter SRS based on number of lesions treated ranged from $296 to $3878 for 2 to 10 lesions treated. The 2-mm planning treatment volume margin used with single-isocenter SRS resulted in a mean 43% increase of total volume treated compared with a 1-mm planning treatment volume expansion.

Conclusions: In a comparison of time-driven activity-based costing assessment of single-isocenter versus multiple-isocenter SRS for multiple brain lesions, single-isocenter SRS appears to save time and resources for as few as 2 lesions, with incremental benefits for additional lesions treated.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.035DOI Listing
November 2020

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

Eur Urol 2020 01 13;77(1):3-10. Epub 2019 Apr 13.

Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Background: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.

Objective: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).

Design, Setting, And Participants: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT).

Outcome Measurements And Statistical Analysis: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.

Results And Limitations: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS).

Conclusions: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.

Patient Summary: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
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http://dx.doi.org/10.1016/j.eururo.2019.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521828PMC
January 2020

Patient perspectives and treatment regret after de-escalated chemoradiation for human papillomavirus-positive oropharyngeal cancer: Findings from a phase II trial.

Head Neck 2019 08 8;41(8):2768-2776. Epub 2019 Apr 8.

Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California.

Background: We evaluated priorities, expectations, and regret among patients treated on a phase II trial of de-escalated chemoradiation for human papillomavirus (HPV)-positive oropharyngeal cancer.

Methods: Eligibility included stage III/IV squamous cell carcinoma of the oropharynx, p16-positivity, age ≥18 years, and Zubrod score 0-1. Participants were surveyed with validated measures evaluating their treatment experience.

Results: Twenty-four of 27 (89%) patients participated with a median follow-up of 24 months. Twenty-three subjects (96%) selected "being cured" or "living as long as possible" as top priority. No patient reported any regret about the decision to enroll on a de-escalation protocol. Sixteen participants (67%) found retrospectively reported long-term swallowing function to be either better than or as originally expected.

Conclusions: These data offer a baseline landscape of perspectives and priorities for patients treated with de-escalation for HPV-positive oropharyngeal carcinoma and provide support to the fundamental premise underlying ongoing efforts to establish a new standard of care.
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http://dx.doi.org/10.1002/hed.25760DOI Listing
August 2019

Clinical Outcomes for Patients With Gleason Score 10 Prostate Adenocarcinoma: Results From a Multi-institutional Consortium Study.

Int J Radiat Oncol Biol Phys 2018 07 5;101(4):883-888. Epub 2018 Apr 5.

Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California.

Purpose: Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity.

Methods And Materials: The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer-specific survival, and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding.

Results: The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P < .01 by χ test), though the durations were similar (median, 24 months vs 22.5 months). Of the RP patients, 34% received postoperative EBRT, and 35% received neoadjuvant systemic therapy. The propensity score-adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT group. The corresponding adjusted 5-year prostate cancer-specific survival rates were 87%, 75%, and 94%, respectively. The EBRT-BT group trended toward superior DMFS when compared with the RP group (hazard ratio, 0.3; 95% confidence interval 0.1-1.06; P = .06) and had superior DMFS when compared with the EBRT group (hazard ratio, 0.4; 95% confidence interval 0.1-0.99; P = .048).

Conclusions: To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.
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http://dx.doi.org/10.1016/j.ijrobp.2018.03.060DOI Listing
July 2018

Magnetic Resonance Imaging Guidance Mitigates the Effects of Intrafraction Prostate Motion During Stereotactic Body Radiotherapy for Prostate Cancer.

Cureus 2018 Apr 6;10(4):e2442. Epub 2018 Apr 6.

Department of Radiation Oncology, University of California, Los Angeles.

The accurate delivery of stereotactic body radiotherapy (SBRT) for definitive prostate cancer treatment is aided by intrafraction image guidance. The common methods for intrafraction imaging require the invasive placement of fiducial markers or electromagnetic transponders. Recently, a magnetic resonance imaging (MRI)-guided tri-cobalt-60 head radiotherapy system has become available for treatment, which can utilize real-time cine MRI to non-invasively track prostate motion. We report on a clinical vignette using this technique to deliver SBRT for the definitive treatment of intermediate-risk prostate cancer. The incorporation of an MRI-guided radiotherapy system and the implementation of real-time adaptive dose delivery accounting for intrafraction anatomic motion may improve outcomes using this technique.
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http://dx.doi.org/10.7759/cureus.2442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990029PMC
April 2018

Respiratory motion-resolved, self-gated 4D-MRI using Rotating Cartesian K-space (ROCK): Initial clinical experience on an MRI-guided radiotherapy system.

Radiother Oncol 2018 06 9;127(3):467-473. Epub 2018 May 9.

Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, USA. Electronic address:

Purpose: To optimize and evaluate the respiratory motion-resolved, self-gated 4D-MRI using Rotating Cartesian K-space (ROCK-4D-MRI) method in a 0.35 T MRI-guided radiotherapy (MRgRT) system.

Methods And Materials: The study included seven patients with abdominal tumors treated on the MRgRT system. ROCK-4D-MRI and 2D-CINE, was performed immediately after one of the treatment fractions. Motion quantification based on 4D-MRI was compared with those based on 2D-CINE. The image quality of 4D-MRI was evaluated against 4D-CT. The gross tumor volumes (GTV) were defined based on individual respiratory phases of both 4D-MRI and 4D-CT and compared for their variability over the respiratory cycle.

Result: The motion measurements based on 4D-MRI matched well with 2D-CINE, with differences of 1.04 ± 0.52 mm in the superior-inferior and 0.54 ± 0.21 mm in the anterior-posterior directions. The image quality scores of 4D-MRI were significantly higher than 4D-CT, with better tumor contrast (3.29 ± 0.76 vs. 1.86 ± 0.90) and less motion artifacts (3.57 ± 0.53 vs. 2.29 ± 0.95). The GTVs were more consistent in 4D-MRI than in 4D-CT, with significantly smaller GTV variability (9.31 ± 4.58% vs. 34.27 ± 23.33%).

Conclusion: Our study demonstrated the clinical feasibility of using the ROCK-4D-MRI to acquire high quality, respiratory motion-resolved 4D-MRI in a low-field MRgRT system. The 4D-MRI image could provide accurate dynamic information for radiotherapy treatment planning.
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http://dx.doi.org/10.1016/j.radonc.2018.04.029DOI Listing
June 2018

Accelerated 3D bSSFP imaging for treatment planning on an MRI-guided radiotherapy system.

Med Phys 2018 Jun 6;45(6):2595-2602. Epub 2018 May 6.

Department of Radiological Sciences, University of California, Los Angeles, CA, 90095, USA.

Purpose: The purpose of this study was to introduce a compressed sensing and parallel imaging-combined technique to reduce the acquisition time of planning MRI for MR-guided radiotherapy (MRgRT) systems.

Methods And Materials: A variable-density Poisson-Disk (VDPD) undersampling acquisition along with compressed sensing reconstruction technique was developed and compared with the current planning MR protocol, which uses an optimized balanced steady-state free precession sequence with 7.5-fold (7.5×) acceleration achieved by GRAPPA and partial Fourier. The image quality of GRAPPA and VDPD with 7.5× and 15× acceleration was compared with fully sampled images on a phantom. Two volunteers were recruited to compare the in vivo imaging performance. Ten patients with abdominal tumors were scanned using the conventional GRAPPA 7.5× (25 s) and the proposed VDPD 15× (12.5 s) sequences. Three readers scored the two approaches in terms of the quality for organ and tumor delineation. The gross tumor volume (GTV) and two kidneys were contoured. Differences in centroid location and contour volumes, Dice coefficients, and mean distance-to-agreement (MDA) between contours draw on the two techniques were calculated. All studies were performed on a 0.35 T MRgRT system.

Results: In the phantom study, VDPD with 15× acceleration rate had lower noise level than GRAPPA with 7.5× acceleration. In both the phantom and volunteer study, noise amplification was apparent when the acceleration rate was increased from 7.5× to 15× in the GRAPPA acquisition, whereas it was minimally increased using the VDPD approach. In the patient study, no significant difference was found for the scoring and contouring statistics between the two techniques, whereas VDPD only took half the scan time as GRAPPA. Volume difference for the GTV and two kidneys between GRAPPA 7.5× and VDPD 15× was around 7.6%, 1.3%, and 2.8%, respectively; while the Dice index was approximately 0.85, 0.92, and 0.90, respectively.

Conclusion: The proposed technique reduced the acquisition time by half and provided comparable or improved image quality than the standard planning MRI protocol.
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http://dx.doi.org/10.1002/mp.12924DOI Listing
June 2018

Potential Impact of Ga-PSMA-11 PET/CT on the Planning of Definitive Radiation Therapy for Prostate Cancer.

J Nucl Med 2018 11 13;59(11):1714-1721. Epub 2018 Apr 13.

Department of Radiation Oncology, UCLA, Los Angeles, California

Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate-specific membrane antigen (PSMA) PET/CT detects PCa metastasis with superior accuracy, having a potential impact on the planning of definitive radiation therapy (RT) for nonmetastatic PCa. Our objectives were to determine how often definitive RT planning based on standard target volumes covers Ga-PSMA-11 PET/CT-defined disease and to assess the potential impact of Ga-PSMA-11 PET/CT on definitive RT planning. This was a post hoc analysis of an intention-to-treat population of 73 patients with localized PCa without prior local therapy who underwent Ga-PSMA PET/CT for initial staging as part of an investigational new drug trial. Eleven of the 73 were intermediate-risk (15%), 33 were high-risk (45%), 22 were very-high-risk (30%), and 7 were N1 (9.5%). Clinical target volumes (CTVs), which included the prostate, seminal vesicles, and (in accord with the Radiation Therapy Oncology Group consensus guidelines) pelvic lymph nodes (LNs), were contoured on the CT portion of the PET/CT images by a radiation oncologist masked to the PET findings. Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. Ga-PSMA-11-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. All patients had one or more Ga-PSMA-11-positive primary prostate lesions. Twenty-five (34%) and 7 (9.5%) of the 73 patients had Ga-PSMA-11-positive pelvic LN and distant metastases, respectively. The sites of LN metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper diaphragm (4%), and presacral (1.5%). The median size of the LN lesions was 6 mm (range, 4-24 mm). RT planning based on the CTVs covered 69 (94.5%) of the 73 primary lesions and 20 (80%) of the 25 pelvic LN lesions, on a per-patient analysis. Ga-PSMA-11 PET/CT had a major impact on intended definitive RT planning for PCa in 12 (16.5%) of the 73 patients whose RT fields covered the prostate, seminal vesicles, and pelvic LNs and in 25 (37%) of the 66 patients whose RT fields covered the prostate and seminal vesicles but not the pelvic LNs.
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http://dx.doi.org/10.2967/jnumed.118.209387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225538PMC
November 2018

Head and neck cancer reirradiation with interstitial high-dose-rate brachytherapy.

Head Neck 2018 07 23;40(7):1524-1533. Epub 2018 Mar 23.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.

Background: As high-dose-rate (HDR) brachytherapy can preferentially spare normal anatomic structures surrounding the radiation target, we report on our experience using this technique in head and neck cancer reirradiation.

Methods: Twenty patients received HDR brachytherapy reirradiation with curative or palliative intent from 2010-2015. Clinical and toxicity outcomes were recorded. Actuarial outcomes were calculated using Kaplan-Meier analysis.

Results: For curative treatment, actuarial 2-year rates of local control and overall survival (OS) were 73% and 56%, respectively. Palliatively, a 6-month local control rate of 65% was seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage resection showed a trend toward improved local control and OS (P = .069 and P = .063, respectively). Thirty-three percent had grade 3 to 4 late toxicities.

Conclusion: Curative-intent HDR brachytherapy reirradiation can provide excellent local control and encouraging OS. Given the late toxicity rates, patient selection is essential, with particular utility for younger patients or those treated with salvage resection.
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http://dx.doi.org/10.1002/hed.25137DOI Listing
July 2018

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

JAMA 2018 03;319(9):896-905

Department of Urology, University of California, Los Angeles.

Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown.

Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment.

Design, Setting, And Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013.

Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy.

Main Outcomes And Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes.

Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]).

Conclusions And Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.
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http://dx.doi.org/10.1001/jama.2018.0587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885899PMC
March 2018

The patient's perspective on breast radiotherapy: Initial fears and expectations versus reality.

Cancer 2018 04 26;124(8):1673-1681. Epub 2018 Feb 26.

Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, California.

Background: Although the efficacy and toxicity of breast radiotherapy (RT) has been studied extensively, to the authors' knowledge little is known regarding the patient's perspective on the modern breast RT experience. To better inform future patients and providers, the authors explored patient perceptions of their RT experience.

Methods: Consecutive patients who were free of disease recurrence and who had been treated between 2012 and 2016 were surveyed regarding their original fears, how short-term and long-term toxicities compared with initial expectations, and how pretreatment beliefs concerning RT compared with the actual experience.

Results: A total of 502 patients were surveyed, with a response rate of 65% (327 patients). The median patient age and posttreatment follow-up was 59 years and 31 months, respectively. Approximately 83% of patients (269 patients) underwent breast conservation therapy. Although approximately 68% of patients (221 patients) endorsed that they initially had little to no knowledge regarding RT, approximately 47% (152 patients) reported that they had heard frightening stories. Approximately 2% of patients (6 patients) agreed that the negative stories they previously heard about RT were actually true. Approximately 92% of patients treated with breast conservation (247 patients) and 81% of patients who underwent mastectomy (47 patients) agreed with the statement "If future patients knew the real truth about RT, they would be less scared about treatment." Approximately 83% (272 patients) and 84% (274 patients), respectively, of all patients reported the overall severity of short-term and long-term side effects to be better than or as expected.

Conclusions: Breast RT is associated with misconceptions and fears. Patients' experiences with modern breast RT appear to be superior to expectations, and the majority of patients in the current study agreed that their initial negative impressions were unfounded. Cancer 2018;124:1673-81. © 2018 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31159DOI Listing
April 2018

Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial.

Int J Radiat Oncol Biol Phys 2018 03 6;100(3):647-651. Epub 2017 Nov 6.

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address:

Purpose: To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus-positive oropharyngeal cancer.

Methods And Materials: Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175 mg/m, and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m, every 7 days with dose-reduced radiation therapy of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy-Head and Neck Scale.

Results: Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m vs 22.3 kg/m; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6 months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up.

Conclusions: De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels.
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http://dx.doi.org/10.1016/j.ijrobp.2017.10.045DOI Listing
March 2018

Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning.

J Nucl Med 2018 02 9;59(2):230-237. Epub 2017 Nov 9.

Department of Radiation Oncology, UCLA, Los Angeles, California.

Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of Ga-PSMA-11 PET/CT on SRT. This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. The median PSA level at the time of Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Post hoc analysis of Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome.
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http://dx.doi.org/10.2967/jnumed.117.201749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807533PMC
February 2018

Assessing the Effect of Lifetime Contralateral Breast Cancer Risk on the Selection of Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer.

Clin Breast Cancer 2018 04 27;18(2):e205-e218. Epub 2017 Sep 27.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA.

Introduction: Contralateral prophylactic mastectomy (CPM) rates are rising, with fear implicated as a contributing factor. This study used a contralateral breast cancer (CBC) risk stratification tool to assess whether the selection of CPM is reflective of future CBC risk.

Patients And Methods: This retrospective study evaluated 404 women with unilateral breast cancer treated with breast conservation, unilateral mastectomy, or bilateral mastectomy within a single multidisciplinary clinic. Women were evaluated by the Manchester risk tool to calculate lifetime CBC risk. Logistic regression analysis was used to evaluate whether CBC risk was associated with CPM, and the clinical rationale for prophylactic mastectomy justification was recorded.

Results: Sixty-two percent underwent breast conservation, 18% unilateral mastectomy, and 20% bilateral mastectomy. In the CPM cohort, 36% had > 20% calculated lifetime CBC risk. In the invasive cohort, younger age (odds ratio 2.65, P < .0001) and genetic mutation positivity (odds ratio 35.39, P = .019) independently predicted CPM. Other contributing factors included benign contralateral breast findings (29%) and recommendations against breast conservation due to disease burden (28%). Six percent selected CPM as a result of an unsubstantiated fear regarding breast cancer.

Conclusion: The majority of women (63%) who selected CPM had < 20% CBC risk. In these lower-risk women selecting CPM, factors increasing reasonable fear dominated surgical choice (81% of this subset).
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http://dx.doi.org/10.1016/j.clbc.2017.09.010DOI Listing
April 2018

Patient-reported quality-of-life outcomes after de-escalated chemoradiation for human papillomavirus-positive oropharyngeal carcinoma: Findings from a phase 2 trial.

Cancer 2018 02 17;124(3):521-529. Epub 2017 Oct 17.

Department of Radiation Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.

Background: The current study represents a subset analysis of quality-of-life (QOL) outcomes among patients treated on a phase 2 trial of de-escalated chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer.

Methods: Eligibility included newly diagnosed, (American Joint Committee on Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16 positivity, age ≥ 18 years, and a Zubrod performance status of 0 to 1. Treatment was induction paclitaxel at a dose of 175 mg/m and carboplatin at an area under the curve of 6 for 2 cycles followed by response-adapted, dose-reduced radiation of 54 Gy or 60 Gy with weekly concurrent paclitaxel at a dose of 30 mg/m . The University of Washington Quality of Life (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck questionnaires were used to assess patient-reported QOL as a secondary endpoint.

Results: A total of 45 patients were registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores were reached at 4 weeks after treatment but returned to baseline at 3 months. Nearly all functional indices returned to baseline levels by 6 to 9 months. The mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3, and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy. The percentage of patients rating their overall QOL as "very good" or "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and 84%, respectively.

Conclusions: This de-escalation regimen achieved QOL outcomes that were favorable compared with historical controls. These results serve as powerful evidence that ongoing de-escalation efforts lead to tangible gains in function and QOL. Cancer 2018;124:521-9. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916816PMC
February 2018

Pretreatment 3T multiparametric MRI staging predicts for biochemical failure in high-risk prostate cancer treated with combination high-dose-rate brachytherapy and external beam radiotherapy.

Brachytherapy 2017 Nov - Dec;16(6):1106-1112. Epub 2017 Aug 12.

Department of Radiation Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Purpose: To determine whether pretreatment 3T multiparametric MRI (mpMRI) staging impacts biochemical recurrence-free survival (BRFS) or distant metastasis-free survival (DMFS) for men with high-risk prostate cancer treated with combination high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT).

Materials And Methods: This institutional review board-approved retrospective study included a cohort of 37 men with high-risk prostate cancer treated with HDR brachytherapy and EBRT after 3T mpMRI. Kaplan-Meier analysis was used to evaluate whether mpMRI evidence of extracapsular extension or seminal vesicle invasion (SVI) resulted in differences in BRFS or DMFS. Pretreatment and treatment-related variables were evaluated for association with biochemical failure (Phoenix definition) and distant metastatic failure using univariate Cox regression analysis.

Results: The median prostate-specific antigen at diagnosis was 9 ng/mL (range 2-100). Biopsy Gleason score (bGS) was ≤8 in 38% and nine in 62%. Clinical T-category was T1-T2 in 89%, T3a in 8%, and T3b in 3%. With a median followup of 30.6 months, actuarial 3-year BRFS and DMFS were 76% and 86%, respectively. Kaplan-Meier analysis revealed that mpMRI evidence of extracapsular extension or SVI resulted in significantly higher rates of both biochemical recurrence and distant failure. Using Cox regression analysis, only mpMRI evidence of SVI vs. no SVI predicted for biochemical failure (hazard ratio 13.98, p = 0.0055).

Conclusions: For high-risk prostate cancer treated with combination HDR brachytherapy and EBRT, mpMRI evidence of SVI predicted for biochemical failure, whereas traditional pretreatment variables did not. Therefore, pretreatment 3T mpMRI appears useful for identifying men who may benefit from treatment intensification.
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http://dx.doi.org/10.1016/j.brachy.2017.07.008DOI Listing
June 2018

Predictors associated with MRI surveillance screening in women with a personal history of unilateral breast cancer but without a genetic predisposition for future contralateral breast cancer.

Breast Cancer Res Treat 2017 Nov 12;166(1):145-156. Epub 2017 Jul 12.

Department of Radiation Oncology, University of California, Los Angeles, 1223 16th Street, Suite 1100, Santa Monica, CA, 90404, USA.

Purpose: For women with a personal history of breast cancer (PHBC), no validated mechanisms exist to calculate future contralateral breast cancer (CBC) risk. The Manchester risk stratification guidelines were developed to evaluate CBC risk in women with a PHBC, primarily for surgical decision making. This tool may be informative for the use of MRI screening, as CBC risk is an assumed consideration for high-risk surveillance.

Methods: Three hundred twenty-two women with a PHBC were treated with unilateral surgery within our multidisciplinary breast clinic. We calculated lifetime CBC risk using the Manchester tool, which incorporates age at diagnosis, family history, genetic mutation status, estrogen receptor positivity, and endocrine therapy use. Univariate and multivariate logistic regression analyses (UVA/MVA) were performed, evaluating whether CBC risk predicted MRI surveillance.

Results: For women with invasive disease undergoing MRI surveillance, 66% had low, 23% above-average, and 11% moderate/high risk for CBC. On MVA, previous mammography-occult breast cancer [odds ratio (OR) 18.95, p < 0.0001], endocrine therapy use (OR 3.89, p = 0.009), dense breast tissue (OR 3.69, p = 0.0007), mastectomy versus lumpectomy (OR 3.12, p = 0.0041), and CBC risk (OR 3.17 for every 10% increase, p = 0.0002) were associated with MRI surveillance. No pathologic factors increasing ipsilateral breast cancer recurrence were significant on MVA.

Conclusions: Although CBC risk predicted MRI surveillance, 89% with invasive disease undergoing MRI had <20% calculated CBC risk. Concerns related to future breast cancer detectability (dense breasts and/or previous mammography-occult disease) predominate decision making. Pathologic factors important for determining ipsilateral recurrence risk, aside from age, were not associated with MRI surveillance.
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http://dx.doi.org/10.1007/s10549-017-4392-4DOI Listing
November 2017

Juxtapapillary and circumpapillary choroidal melanoma: globe-sparing treatment outcomes with iodine-125 notched plaque brachytherapy.

Graefes Arch Clin Exp Ophthalmol 2017 Sep 9;255(9):1843-1850. Epub 2017 Jun 9.

Department of Radiation Oncology, 200 UCLA Medical Plaza, Suite B265, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Purpose: Managing juxtapapillary and circumpapillary choroidal melanoma with brachytherapy is challenging because of technical complications with accurate plaque placement and high radiation toxicity given tumor proximity to the optic nerve. We evaluated our center's experience using ultrasound-guided, Iodine (I)-125 notched plaque brachytherapy for treating choroidal melanoma contiguous with (juxtapapillary) and at least partially surrounding the optic disc (circumpapillary).

Methods: All cases of choroidal melanoma treated with I-125 notched plaque brachytherapy at our center from September 2003-December 2013 were retrospectively reviewed. Only patients with ≥18 months of follow-up who had lesions contiguous with the optic disc (0 mm of separation) were included. The tumor apex prescription dose was 85 Gy. Outcomes evaluated included local control, distant metastasis-free survival (DMFS), cancer-specific survival (CSS), overall survival (OS), visual acuity, and radiation toxicity.

Results: Thirty-four patients were included with a median follow-up of 44.1 months (range 18.2-129.0). AJCC T-category was T1 in 58.8%, T2 in 26.5%, and T3 in 14.7%. Median circumferential optic disc involvement was 50% (range 10%-100%). Eye retention was achieved in 94.1%. Actuarial 2- and 4-year rates of local recurrence were 3.1% and 7.6%, DMFS were 97.0% and 88.5%, CSS were 97.0% and 92.8%, and OS were 97.0% and 88.9%, respectively. In addition, 23.5% had visual acuity ≥20/200 at last follow-up.

Conclusions: I-125 notched plaque brachytherapy provides high eye preservation rates with acceptable longer-term post-treatment visual outcomes. Based on our experience, choroidal melanoma directly contiguous with and partially encasing the optic disc may be effectively treated with this technique.
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http://dx.doi.org/10.1007/s00417-017-3703-0DOI Listing
September 2017

Prostate Cancer Antigen 3 Score Does Not Predict for Adverse Pathologic Features at Radical Prostatectomy or for Progression-free Survival in Clinically Localized, Intermediate- and High-risk Prostate Cancer.

Urology 2017 Sep 25;107:171-177. Epub 2017 May 25.

Department of Radiation Oncology, UCLA Medical Center, University of California, Los Angeles, CA. Electronic address:

Objective: To evaluate whether preoperative urinary prostate cancer antigen 3 (PCA3) scores predict for adverse pathologic features (APFs) or progression-free survival (PFS) in men with intermediate- or high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP).

Materials And Methods: One hundred nine men with intermediate- (n = 52) or high-risk (n = 57) PCa who underwent RP were retrospectively identified. Logistic regression analysis was performed to evaluate the association of PCA3 score with various APFs (eg, extracapsular extension, seminal vesicle invasion, etc.). Among 78 men with ≥1 year of follow-up, the association between PCA3 score and PFS was assessed using Cox regression analysis.

Results: At RP, 52% of patients had at least 1 APF, and with median follow-up of 2.3 years, overall 3-year PFS was 70%. PCA3 was not a significant predictor of any APF on multivariate analysis (MVA), whereas canonical predictors (eg, biopsy Gleason score and initial prostate-specific antigen) remained predictive of various APFs. No significant predictors for PFS were found on MVA, although certain canonical predictors (eg, National Comprehensive Cancer Network risk group) were significant predictors of PFS on univariate analysis (UVA). PCA3 score was not a significant predictor of PFS on either UVA or MVA.

Conclusion: Unlike in lower risk cohorts, increasing PCA3 score was not associated with any APF in this higher risk cohort, despite enrichment for APFs, nor was it associated with PFS. Notably, multiple known preoperative predictors for APFs were significant on MVA, and multiple predictors were associated with PFS on UVA. Therefore, PCA3 may not be a useful adjunct predictive marker in men with intermediate- or high-risk PCa.
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http://dx.doi.org/10.1016/j.urology.2017.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986738PMC
September 2017

Advances in Radiation Oncology: What to Consider.

Otolaryngol Clin North Am 2017 Aug 17;50(4):755-764. Epub 2017 May 17.

Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, 200 UCLA Medical Plaza, Suite B265, Los Angeles, CA 90095, USA. Electronic address:

Treatment of squamous cell carcinoma of the head and neck is rapidly evolving due to changing patient populations, an emphasis on quality of life-related outcomes, and advances in radiotherapy concepts and techniques to meet these new demands. This review includes recent and ongoing studies that are potentially practice changing, including improvements in intensity-modulated radiotherapy planning, the use of deintensified regimens in the human papilloma virus-related setting, and adjuvant therapy after transoral robotic surgery. Additionally, recent studies of modern proton therapy are reviewed.
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http://dx.doi.org/10.1016/j.otc.2017.03.011DOI Listing
August 2017

Imaging and Pathology Correlations for Different Risk Stratification Models for Intermediate-risk Prostate Cancer.

Anticancer Res 2017 03;37(3):1237-1242

Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA, U.S.A.

Background/aim: We evaluated whether sub-stratifying intermediate-risk (IR) prostate cancer using the Memorial Sloan Kettering Cancer (MSKCC) or Prostate Cancer Risk Stratification (ProCaRS) model predicts for adverse imaging or pathologic features.

Patients And Methods: 56 consecutive IR patients who underwent multi-parametric MRI (mpMRI) and radical prostatectomy (RP) were studied. The different groups were tested for correlation with adverse findings. 2-sample T-tests assuming unequal variance were used.

Results: On mpMRI the MSKCC unfavorable group had higher index lesion suspicion scores (p=0.044), while the ProCaRS model showed a higher maximum tumor diameter (MTD) in the high-risk group (p=0.047). At RP, a higher pathologic MTD (23.3 vs. 17.6 mm, p=0.005) was present in the MSKCC unfavorable group as well as the ProCaRS high vs. low group (26.6 vs. 19.3 mm, p=0.022).

Conclusion: Both models demonstrated a correlation with higher MTD for unfavorable IR patients. This is likely a driver of worse clinical outcomes.
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http://dx.doi.org/10.21873/anticanres.11439DOI Listing
March 2017

A Pooled Analysis of Biochemical Failure in Intermediate-risk Prostate Cancer Following Definitive Stereotactic Body Radiotherapy (SBRT) or High-Dose-Rate Brachytherapy (HDR-B) Monotherapy.

Am J Clin Oncol 2018 05;41(5):502-507

Department of Radiation Oncology, UCLA Medical Center, Los Angeles.

Objectives: To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy.

Materials And Methods: A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel χ metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure.

Results: The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ≤3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS.

Conclusions: With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.
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http://dx.doi.org/10.1097/COC.0000000000000311DOI Listing
May 2018

Does the addition of targeted prostate biopsies to standard systemic biopsies influence treatment management for radiation oncologists?

BJU Int 2016 Apr 4;117(4):584-91. Epub 2015 May 4.

Department of Urology, University of California Los Angeles, Los Angeles, CA, USA.

Objectives: To study the management impact that magnetic resonance imaging (MRI)-guided targeted prostate biopsies could provide relative to using only non-targeted systematic biopsies in men with clinically localized prostate cancer (PCa).

Patients And Methods: A consecutive series of untreated men undergoing Artemis (MRI-ultrasonography fusion) biopsies between March 2010 and June 2013 was evaluated in this retrospective, institutional review board-approved study. Fusion biopsy included MRI-targeted and systematic sampling at the same session. 3-Tesla multiparametric MRI was performed at a median of 2 weeks before biopsy. Patients were included if ≥1 systematic core was found to harbour PCa. The impact of the information obtained from targeted vs systematic biopsies was studied with regard to the following: Gleason score (GS), National Comprehensive Cancer Network (NCCN) risk reclassification, cancer core length, percentage of core positive for tumour involvement, and percentage of positive biopsy cores.

Results: The study sample included 215 men (mean ± sd age 66 ± 8 years). The median (range) prostate-specific antigen (PSA) was 6.0 (0.7-181) ng/mL. The mean number of total biopsy samples was 18 (12 systematic and six targeted samples). Of 215 men, 34 (16%) had a higher GS on targeted vs systematic biopsy. A total of 21/183 men (12%) were stratified into a higher NCCN risk group when incorporating targeted biopsy GS results and 18/101 men (18%) were upgraded to intermediate- or high-risk from the low-risk group. Among the 34 men whose cancer severity was upgraded, increases in cancer core length, percentage of tumour involvement and percentage of cores involved were all statistically significant (P < 0.01).

Conclusion: Targeted prostate biopsy provided information about GS, NCCN risk and tumour volume beyond that obtained in systematic biopsies, specifically increasing the proportions of men in the intermediate- and high-risk groups. Such men may be recommended for additional treatments (pelvic nodal irradiation or hormonal therapy). The appropriateness of changing treatment because of targeted biopsy results is still unclear.
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http://dx.doi.org/10.1111/bju.13082DOI Listing
April 2016

How we used a patient visit tracker tool to advance experiential learning in systems-based practice and quality improvement in a medical student clinic.

Med Teach 2016 17;38(1):36-40. Epub 2014 Nov 17.

a Harvard Medical School , USA .

Poorly designed healthcare systems increase costs and preventable medical errors. To address these issues, systems-based practice (SBP) education provides future physicians with the tools to identify systemic errors and implement quality improvement (QI) initiatives to enhance the delivery of cost-effective, safe and multi-disciplinary care. Although SBP education is being implemented in residency programs and is mandated by the Accreditation Council for Graduate Medical Education (ACGME) as one of its core competencies, it has largely not been integrated into undergraduate medical education. We propose that Medical Student-Faculty Collaborative Clinics (MSFCCs) may be the ideal environment in which to train medical students in SBPs and QI initiatives, as they allow students to play pivotal roles in project development, administration, and management. Here we describe a process of experiential learning that was developed within a newly established MSFCC, which challenged students to identify inefficiencies, implement interventions, and track the results. After identifying bottlenecks in clinic operations, our students designed a patient visit tracker tool to monitor clinic flow and implemented solutions to decrease patient visit times. Our model allowed students to drive their own active learning in a practical clinical setting, providing early and unique training in crucial QI skills.
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http://dx.doi.org/10.3109/0142159X.2014.975193DOI Listing
October 2016

Maximum tumor diameter and the risk of prostate-specific antigen recurrence after radical prostatectomy.

Clin Genitourin Cancer 2014 Oct 28;12(5):e173-9. Epub 2014 Mar 28.

Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA.

Introduction/background: The aim of this study was to investigate whether the MTD could identify men at low risk of PSA recurrence after RP who might not benefit from ART despite other adverse features.

Patients And Methods: The study cohort consisted of 354 men with T1c to T2 prostate cancer diagnosed between September 2001 and December 2008 who underwent RP without adjuvant therapy. Multivariable Cox regression was used to assess the effect of MTD on the risk of PSA recurrence (> 0.1 ng/mL and verified), adjusting for known predictors.

Results: After a median follow-up of 4.0 years, 34 men (9.6%) experienced PSA failure. In multivariable analysis, increasing MTD was significantly associated with an increased PSA recurrence risk (hazard ratio, 2.74; 95% confidence interval, 1.23-6.10; P = .01) within the interaction model. Estimates of PSA recurrence-free survival stratified around the median MTD value (1.2 cm) were significantly different in men with a pre-RP PSA > 4 ng/mL (P < .001; 5-year estimate: 74.5% vs. 99.0%) but not in men with PSA ≤ 4 ng/mL (P = .59; 5-year estimate: 89.6% vs. 92.6%), consistent with the significant interaction (P = .004) between PSA and MTD. Moreover, in men with a pre-RP PSA > 4 ng/mL these estimates were significantly different if at least 1 adverse feature (pT3, R1, or Gleason score ≥ 8) was present at RP (P = .01; 5-year estimate: 46.6% vs. 100%) versus none (P = .09; 5-year estimate: 93.4% vs. 98.9%).

Conclusion: Men with a low MTD (≤ 1.2 cm) appear to be at low risk of PSA recurrence despite adverse features at RP and might not benefit from ART.
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http://dx.doi.org/10.1016/j.clgc.2014.03.008DOI Listing
October 2014

The effect of differing Gleason scores at biopsy on the odds of upgrading and the risk of death from prostate cancer.

Clin Genitourin Cancer 2014 Oct 3;12(5):e181-7. Epub 2014 Mar 3.

Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA.

Introduction/background: The GS is an established prostate cancer prognostic factor. Whether the presence of differing GSs at biopsy (eg, 4+3 and 3+3), which we term ComboGS, improves the prognosis that would be predicted based on the highest GS (eg, 4+3) because of decreased upgrading is unknown. Therefore, we evaluated the odds of upgrading at time of radical prostatectomy (RP) and the risk of PCSM when ComboGS was present versus absent.

Patients And Methods: Logistic and competing risks regression were performed to assess the effect that ComboGS had on the odds of upgrading at time of RP in the index (n = 134) and validation cohorts (n = 356) and the risk of PCSM after definitive therapy in a long-term cohort (n = 666), adjusting for known predictors of these end points. We calculated and compared the area under the curve using a receiver operating characteristic analysis when ComboGS was included versus excluded from the upgrading models.

Results: ComboGS was associated with decreased odds of upgrading (index: adjusted odds ratio [AOR], 0.14; 95% confidence interval [CI], 0.04-0.50; P = .003; validation: AOR, 0.24; 95% CI, 0.11-0.51; P < .001) and added significantly to the predictive value of upgrading for the in-sample index (P = .02), validation (P = .003), and out-of-sample prediction models (P = .002). ComboGS was also associated with a decreased risk of PCSM (adjusted hazard ratio, 0.40; 95% CI, 0.19-0.85; P = .02).

Conclusion: Differing biopsy GSs are associated with a lower odds of upgrading and risk of PCSM. If validated, future randomized noninferiority studies evaluating deescalated treatment approaches in men with ComboGS could be considered.
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http://dx.doi.org/10.1016/j.clgc.2014.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153802PMC
October 2014

Multiparametric MRI of prostate cancer: an update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer.

J Magn Reson Imaging 2013 May;37(5):1035-54

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. J. Magn. Reson. Imaging 2013;37:1035-1054. © 2013 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmri.23860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741996PMC
May 2013

Preoperative 3-Tesla multiparametric endorectal magnetic resonance imaging findings and the odds of upgrading and upstaging at radical prostatectomy in men with clinically localized prostate cancer.

Int J Radiat Oncol Biol Phys 2013 Feb 3;85(2):e101-7. Epub 2012 Oct 3.

Harvard Medical School, and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Purpose: To investigate whether 3-T esla (3T) multiparametric endorectal MRI (erMRI) can add information to established predictors regarding occult extraprostatic or high-grade prostate cancer (PC) in men with clinically localized PC.

Methods And Materials: At a single academic medical center, this retrospective study's cohort included 118 men with clinically localized PC who underwent 3T multiparametric erMRI followed by radical prostatectomy, from 2008 to 2011. Multivariable logistic regression analyses in all men and in 100 with favorable-risk PC addressed whether erMRI evidence of T3 disease was associated with prostatectomy T3 or Gleason score (GS) 8-10 (in patients with biopsy GS ≤7) PC, adjusting for age, prostate-specific antigen level, clinical T category, biopsy GS, and percent positive biopsies.

Results: The accuracy of erMRI prediction of extracapsular extension and seminal vesicle invasion was 75% and 95%, respectively. For all men, erMRI evidence of a T3 lesion versus T2 was associated with an increased odds of having pT3 disease (adjusted odds ratio [AOR] 4.81, 95% confidence interval [CI] 1.36-16.98, P=.015) and pGS 8-10 (AOR 5.56, 95% CI 1.10-28.18, P=.038). In the favorable-risk population, these results were AOR 4.14 (95% CI 1.03-16.56), P=.045 and AOR 7.71 (95% CI 1.36-43.62), P=.021, respectively.

Conclusions: Three-Tesla multiparametric erMRI in men with favorable-risk PC provides information beyond that contained in known preoperative predictors about the presence of occult extraprostatic and/or high-grade PC. If validated in additional studies, this information can be used to counsel men planning to undergo radical prostatectomy or radiation therapy about the possible need for adjuvant radiation therapy or the utility of adding hormone therapy, respectively.
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http://dx.doi.org/10.1016/j.ijrobp.2012.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545042PMC
February 2013
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