Publications by authors named "Pin-Chieh Wang"

68 Publications

Retrospective Detection of SARS-CoV-2 in Symptomatic Patients prior to Widespread Diagnostic Testing in Southern California.

Clin Infect Dis 2021 May 3. Epub 2021 May 3.

Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles (UCLA), California, USA.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused one of the worst pandemics in recent history. Few reports have revealed that SARS-CoV-2 was spreading in the United States as early as the end of January. In this study, we aimed to determine if SARS-CoV-2 had been circulating in the Los Angeles (LA) area at a time when access to diagnostic testing for coronavirus disease 2019 (COVID-19) was severely limited.

Methods: We used a pooling strategy to look for SARS-CoV-2 in remnant respiratory samples submitted for regular respiratory pathogen testing from symptomatic patients from November 2019 to early March 2020. We then performed sequencing on the positive samples.

Results: We detected SARS-CoV-2 in 7 specimens from 6 patients, dating back to mid-January. The earliest positive patient, with a sample collected on January 13, 2020 had no relevant travel history but did have a sibling with similar symptoms. Sequencing of these SARS-CoV-2 genomes revealed that the virus was introduced into the LA area from both domestic and international sources as early as January.

Conclusions: We present strong evidence of community spread of SARS-CoV-2 in the LA area well before widespread diagnostic testing was being performed in early 2020. These genomic data demonstrate that SARS-CoV-2 was being introduced into Los Angeles County from both international and domestic sources in January 2020.
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http://dx.doi.org/10.1093/cid/ciab360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135745PMC
May 2021

Pathology Trainees' Experience and Attitudes on Use of Digital Whole Slide Images.

Acad Pathol 2020 Jan-Dec;7:2374289520951922. Epub 2020 Sep 30.

Department of Pathology and Laboratory Medicine, University of Vermont, Larner College of Medicine, Burlington, VT, USA.

Digital whole slide images are Food and Drug Administration approved for clinical diagnostic use in pathology; however, integration is nascent. Trainees from 9 pathology training programs completed an online survey to ascertain attitudes toward and experiences with whole slide images for pathological interpretations. Respondents (n = 76) reported attending 63 unique medical schools (45 United States, 18 international). While 63% reported medical school exposure to whole slide images, most reported ≤ 5 hours. Those who began training more recently were more likely to report at least some exposure to digital whole slide image training in medical school compared to those who began training earlier: 75% of respondents beginning training in 2017 or 2018 reported exposure to whole slide images compared to 54% for trainees beginning earlier. Trainees exposed to whole slide images in medical school were more likely to agree they were comfortable using whole slide images for interpretation compared to those not exposed (29% vs 12%; = .06). Most trainees agreed that accurate diagnoses can be made using whole slide images for primary diagnosis (92%; 95% CI: 86-98) and that whole slide images are useful for obtaining second opinions (93%; 95% CI: 88-99). Trainees reporting whole slide image experience during training, compared to those with no experience, were more likely to agree they would use whole slide images in 5 years for primary diagnosis (64% vs 50%; = .3) and second opinions (86% vs 76%; = .4). In conclusion, although exposure to whole slide images in medical school has increased, overall exposure is limited. Positive attitudes toward future whole slide image diagnostic use were associated with exposure to this technology during medical training. Curricular integration may promote adoption.
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http://dx.doi.org/10.1177/2374289520951922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545516PMC
September 2020

Excess Patient Visits for Cough and Pulmonary Disease at a Large US Health System in the Months Prior to the COVID-19 Pandemic: Time-Series Analysis.

J Med Internet Res 2020 09 10;22(9):e21562. Epub 2020 Sep 10.

Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States.

Background: Accurately assessing the regional activity of diseases such as COVID-19 is important in guiding public health interventions. Leveraging electronic health records (EHRs) to monitor outpatient clinical encounters may lead to the identification of emerging outbreaks.

Objective: The aim of this study is to investigate whether excess visits where the word "cough" was present in the EHR reason for visit, and hospitalizations with acute respiratory failure were more frequent from December 2019 to February 2020 compared with the preceding 5 years.

Methods: A retrospective observational cohort was identified from a large US health system with 3 hospitals, over 180 clinics, and 2.5 million patient encounters annually. Data from patient encounters from July 1, 2014, to February 29, 2020, were included. Seasonal autoregressive integrated moving average (SARIMA) time-series models were used to evaluate if the observed winter 2019/2020 rates were higher than the forecast 95% prediction intervals. The estimated excess number of visits and hospitalizations in winter 2019/2020 were calculated compared to previous seasons.

Results: The percentage of patients presenting with an EHR reason for visit containing the word "cough" to clinics exceeded the 95% prediction interval the week of December 22, 2019, and was consistently above the 95% prediction interval all 10 weeks through the end of February 2020. Similar trends were noted for emergency department visits and hospitalizations starting December 22, 2019, where observed data exceeded the 95% prediction interval in 6 and 7 of the 10 weeks, respectively. The estimated excess over the 3-month 2019/2020 winter season, obtained by either subtracting the maximum or subtracting the average of the five previous seasons from the current season, was 1.6 or 2.0 excess visits for cough per 1000 outpatient visits, 11.0 or 19.2 excess visits for cough per 1000 emergency department visits, and 21.4 or 39.1 excess visits per 1000 hospitalizations with acute respiratory failure, respectively. The total numbers of excess cases above the 95% predicted forecast interval were 168 cases in the outpatient clinics, 56 cases for the emergency department, and 18 hospitalized with acute respiratory failure.

Conclusions: A significantly higher number of patients with respiratory complaints and diseases starting in late December 2019 and continuing through February 2020 suggests community spread of SARS-CoV-2 prior to established clinical awareness and testing capabilities. This provides a case example of how health system analytics combined with EHR data can provide powerful and agile tools for identifying when future trends in patient populations are outside of the expected ranges.
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http://dx.doi.org/10.2196/21562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485935PMC
September 2020

Dermatopathologists' Experience With and Perceptions of Patient Online Access to Pathologic Test Result Reports.

JAMA Dermatol 2020 03;156(3):320-324

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

Importance: Many patients presently have access to their pathologic test result reports via online patient portals, yet little is known about pathologists' perspective on this topic.

Objective: To examine dermatopathologists' experience and perceptions of patient online access to pathology reports.

Design, Setting, And Participants: A survey of 160 dermatopathologists currently practicing in the United States who are board certified and/or fellowship trained in dermatopathology was conducted between July 15, 2018, and September 23, 2019. Those who reported interpreting skin biopsies of melanocytic lesions within the previous year and expected to continue interpreting them for the next 2 years were included.

Main Outcomes And Measures: Dermatopathologists' demographic and clinical characteristics, experiences with patient online access to pathologic test result reports, potential behaviors and reactions to patient online access to those reports, and effects on patients who read their pathologic test result reports online.

Results: Of the 160 participating dermatopathologists from the 226 eligible for participation (71% response rate), 107 were men (67%); mean (SD) age was 49 (9.7) years (range, 34-77 years). Ninety-one participants (57%) reported that patients have contacted them directly about pathologic test reports they had written. Some participants noted that they would decrease their use of abbreviations and/or specialized terminology (57 [36%]), change the way they describe lesions suspicious for cancer (29 [18%]), and need specialized training in communicating with patients (39 [24%]) if patients were reading their reports. Most respondents perceived that patient understanding would increase (97 [61%]) and the quality of patient-physician communication would increase (98 [61%]) owing to the availability of online reports. Slightly higher proportions perceived increased patient worry (114 [71%]) and confusion (116 [73%]). However, on balance, most participants (114 [71%]) agreed that making pathologic test result reports available to patients online is a good idea.

Conclusions And Relevance: Dermatopathologists in this survey study perceived both positive and negative consequences of patient online access to pathologic test result reports written by the respondents. Most participants believe that making pathologic test result reports available to patients online is a good idea; however, they also report concerns about patient worry and confusion increasing as a result. Further research regarding best practices and the effect on both patients and clinicians is warranted.
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http://dx.doi.org/10.1001/jamadermatol.2019.4194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990839PMC
March 2020

Immunologic mediators of outcome for irradiated oropharyngeal carcinoma based on human papillomavirus status.

Oral Oncol 2019 02 4;89:121-126. Epub 2019 Jan 4.

Department of Radiation Oncology, Los Angeles, CA 90095, USA; Department of Radiation Oncology, University of California, Irvine, School of Medicine, 101 The City Drive, Building 23, Orange, CA 92868, USA. Electronic address:

Purpose: To investigate the prognostic value of pre-treatment immune parameters including white blood cell count (WBC) and circulating lymphocyte count (CLC) among patients with oropharyngeal carcinoma treated by radiation therapy.

Methods And Materials: A total of 136 consecutive patients were treated by radiation therapy for locally advanced (stage III/IV) squamous cell carcinoma of the oropharynx with known human papillomavirus (HPV) status. Medical records were reviewed to identify patients with documented pre-treatment laboratory bloodwork. The Kaplan-Meier method and linear regression models were used to evaluate the association between pre-treatment CBC and CLC values with survival endpoints.

Results: One hundred and eleven patients satisfied inclusion criteria. Median age was 62 years (range, 22-91). Eighty-four patients were HPV-positive (76%) and 27 (24%) were HPV-negative. There was no difference in WBC and CLC mean values at baseline between HPV-positive and HV-negative (p > 0.05, for both). Trends were detected in the HPV-positive cohort favoring patients with higher CLC, with respect to 2-year local-regional control (93% vs. 82%, p = 0.06) and distant control (88% vs. 82%, p = 0.10) using the median CLC as cut-off. HPV-positive patients with CLC values in the lowest quartile had inferior local-regional control compared to those in the upper 3 quartiles (69% vs. 89%, p = 0.01).

Conclusion: Low pre-treatment CLC was correlated with local-regional recurrence and distant failure among HPV-positive patients. These associations were not observed in the HPV-negative cohort.
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http://dx.doi.org/10.1016/j.oraloncology.2018.11.030DOI Listing
February 2019

Hazards of sparing the ipsilateral parotid gland in the node-positive neck with intensity modulated radiation therapy: Spatial analysis of regional recurrence risk.

Adv Radiat Oncol 2018 Apr-Jun;3(2):111-120. Epub 2017 Dec 14.

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

Purpose: The practice of deliberately sparing the ipsilateral parotid gland with intensity modulated radiation therapy (IMRT) in patients with node-positive head and neck cancer is controversial. We sought to compare the clinical outcomes among consecutive cohorts of patients with head and neck cancer who were treated with differing strategies to spare the parotid gland that is ipsilateral to the involved neck using IMRT.

Methods And Materials: A total of 305 patients were treated with IMRT for node-positive squamous cell carcinoma of the head and neck. The first 139 patients were treated with IMRT whereby the ipsilateral parotid gland was delineated and intentionally designated as an avoidance structure during planning. The subsequent 166 patients were treated by IMRT without the deliberate sparing of the ipsilateral parotid gland.

Results: The 2-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 84%, 73%, and 87%, respectively. The 2-year estimates of overall survival were 77% and 86% among patients who were treated by IMRT with and without the sparing of the ipsilateral parotid gland, respectively ( = .01). The respective rates of 2-year regional control were 76% and 90% ( < .001). A trend was observed between increased nodal burden in the ipsilateral cervical neck and the likelihood of regional failure for both groups. A spatial evaluation revealed a significantly higher incidence of marginal failures and true misses in the cohort of patients who underwent IMRT with the sparing of the ipsilateral parotid gland.

Conclusion: Caution is urged when using IMRT to spare patients' parotid gland on the involved side of neck disease. Our study showed a significantly higher preponderance of regional failure, which highlights the need for careful patient selection and consideration of clinical and pathological factors that influence the likelihood of disease recurrence in the ipsilateral neck.
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http://dx.doi.org/10.1016/j.adro.2017.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999932PMC
December 2017

Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas.

Am J Clin Oncol 2018 12;41(12):1154-1161

Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA.

Objectives: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery.

Materials And Methods: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/β 10] 36.4 Gy [α/β 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P<0.05.

Results: Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS.

Conclusions: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.
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http://dx.doi.org/10.1097/COC.0000000000000443DOI Listing
December 2018

FDG-PET metabolic tumor parameters for the reirradiation of recurrent head and neck cancer.

Laryngoscope 2018 10 24;128(10):2345-2350. Epub 2018 Mar 24.

Department of Radiation Oncology, Los Angeles, California.

Objective: The utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to predict outcome has been well-established for patients undergoing definitive radiation in the initial management of head and neck cancer. However, the usefulness of this modality in the recurrent setting remains uncertain. We sought to evaluate the prognostic value of metabolic tumor parameters measured on FDG-PET in patients treated by reirradiation for recurrent head and neck cancer.

Methods: Thirty-four tumors occurring in 29 patients were reirradiated and were evaluable. The most common disease sites were the oropharynx (n = 9), oral cavity (N = 8), and nasopharynx (n = 6). Potential correlations of FDG-PET maximum standardized uptake value (SUV) and metabolic tumor volume (MTV) with survival endpoints were explored. Multivariate analysis was performed using Cox proportional hazard.

Results: The median MTV, SUV, and gross tumor volume, as delineated using the 50% SUVmax threshold, were 366 cc (range, 0-3,567 cc), 8.1 (range, 0-25), and 48.5 cc (range, 1-190 cc), respectively. On univariate analysis, both MTVs (as measured as a continuous variable and using the median value of 266 cc as cutoff) were predictive of decreased overall survival (P < 0.05 for both). A strong trend toward decreased progression-free survival (P = 0.05), in-field control (P = 0.06), and locoregional control (P = 0.07) was also observed with increasing MTV when analyzed as a continuous variable. Multi-variate analysis confirmed MTV as an independent predictor of mortality.

Conclusion: The PET-derived parameter MTV may serve as a potentially valuable factor for risk stratification and for guiding treatment in future reirradiation trials.

Level Of Evidence: 4. Laryngoscope, 128:2345-2350, 2018.
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http://dx.doi.org/10.1002/lary.27173DOI Listing
October 2018

Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck.

Am J Otolaryngol 2018 May - Jun;39(3):257-260. Epub 2018 Feb 7.

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

Purpose: To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field.

Methods And Materials: The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test.

Results: HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40).

Conclusions: The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.
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http://dx.doi.org/10.1016/j.amjoto.2018.01.011DOI Listing
October 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

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

Predictors of Local Recurrence in Patients With Myxofibrosarcoma.

Am J Clin Oncol 2018 09;41(9):827-831

Departments of Radiation Oncology.

Objectives: Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR.

Materials And Methods: We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as ≤5 cm (35%), >5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR.

Results: Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049).

Conclusions: In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR.
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http://dx.doi.org/10.1097/COC.0000000000000382DOI Listing
September 2018

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

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study.

Lancet Oncol 2017 06 20;18(6):803-811. Epub 2017 Apr 20.

Department of Radiation Oncology, University of California, Davis, School of Medicine, Sacramento, CA, USA.

Background: Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma.

Methods: We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195.

Findings: Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment.

Interpretation: Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients.

Funding: University of California.
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http://dx.doi.org/10.1016/S1470-2045(17)30246-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488353PMC
June 2017

Re-irradiation for recurrent and second primary cancers of the head and neck.

Oral Oncol 2017 04 7;67:46-51. Epub 2017 Feb 7.

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

Purpose: To evaluate a single-institutional experience with the use of re-irradiation for recurrent and new primary cancers of the head and neck.

Methods: The medical charts of 80 consecutive patients who underwent re-irradiation for local-regionally recurrent or second primary head and neck cancer between November 1998 and December 2015 were analyzed. Multivariate analysis was performed using Cox proportional hazard and logistic regression to determine predictors of clinical outcomes.

Results: Seventy-six of the 80 patients were evaluable. The median age was 57.5 (range 26.6-84.9); Intensity-modulated radiotherapy (IMRT) was used in 71 (93.4%) patients with a median dose of 60Gy. Thirty-one patients (40.8%) underwent salvage surgery before re-irradiation and 47 (61.8%) received concurrent systemic therapy. The median time interval between radiation courses was 25.3months (range 2-322months). The 2-year estimates of overall survival, progression free survival, locoregional control, and distant control were 51.0%, 31.3%, 36.8% and 68.3%, respectively. Patients who underwent salvage surgery prior to re-irradiation had significantly improved locoregional control, progression free survival, and overall survival (p<0.05, for all). On multivariate analysis, gross tumor volume (GTV) at re-irradiation and interval between radiation courses were associated with improved overall survival. Severe (grade⩾3) late complications were observed in 25 patients (32.8%).

Conclusions: Re-irradiation for recurrent or second primary head and neck cancer is feasible and effective in select patients with head and neck cancer. The high observed rate of treatment-related morbidity highlights the continue challenges that accompany this approach.
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http://dx.doi.org/10.1016/j.oraloncology.2017.01.007DOI Listing
April 2017

Discord Among Radiation Oncologists and Urologists in the Postoperative Management of High-Risk Prostate Cancer.

Am J Clin Oncol 2018 08;41(8):739-746

Departments of Radiation Oncology.

Objective: To query specialty-specific differences regarding postoperative radiotherapy (RT) for high-risk prostate cancer.

Materials And Methods: Electronic mail survey of radiation oncologists (ROs) and urologists. We sought to maximize absolute response number to capture contemporary practice ethos. The outcome of interest was association between response and specialty. Training level/expertise, practice setting, percentage of consultation caseload consisting of high-risk prostate cancer, and nationality were set as effect modifiers for multivariate logistic regression.

Results: In total, 846 ROs and 407 urologists responded. ROs were more likely to prefer adjuvant radiotherapy (ART). ART or early salvage radiotherapy (SRT, with early SRT defined as that delivered at prostate-specific antigen<0.2), whereas urologists were more likely to prefer early or delayed SRT (P<0.0001). ROs were more likely to prefer lower PSA thresholds for initiating SRT (P<0.0001), and more likely to recommend ART in the setting of adverse pathologic features or node-positive disease (P<0.0001). Significantly more ROs would recommend concurrent androgen deprivation therapy or pelvic nodal RT in the setting of node-positive or Gleason score 8 to 10 disease (P<0.0001).

Conclusions: Specialty-specific differences were readily elucidated with respect to timing and indications for ART and SRT, as well as for indications for androgen deprivation therapy and nodal RT. These differences are likely to create a sense of dissonance for patients, which may in turn explain the underutilization of postoperative RT in general practice.
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http://dx.doi.org/10.1097/COC.0000000000000381DOI Listing
August 2018

Exploring Value From the Patient's Perspective Between Modern Radiation Therapy Modalities for Localized Prostate Cancer.

Int J Radiat Oncol Biol Phys 2017 03 24;97(3):516-525. Epub 2016 Nov 24.

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

Purpose: Patients' perspectives on their treatment experiences have not been compared between modern radiation modalities for localized prostate cancer. We evaluated treatment regret and patients' perceptions of their treatment experiences to better inform our understanding of a treatment's value.

Methods And Materials: Patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT), intensity modulated radiation therapy (IMRT), or high-dose-rate (HDR) brachytherapy between 2008 and 2014 with at least 1 year of follow-up were surveyed. The questionnaire explored the decision-making experience, expectations of toxicities versus the reality, and treatment regret by means of a validated tool.

Results: Three hundred twenty-nine consecutive patients were surveyed, with an 86% response rate (IMRT, n=74; SBRT, n=108; HDR, n=94). The median patient age and posttreatment follow-up time were 68 years and 47 months, respectively. Eighty-two percent of patients had T1c disease with either Gleason 6 (42%) or Gleason 7 (58%) pathologic features and a median initial prostate-specific antigen of 5.8 ng/mL. Thirteen percent expressed regret with their treatment. Among patients with regret, 71% now wish they had elected for active surveillance. The incidence of regret was significantly different between treatment modalities: 5% of patients treated with SBRT expressed regret versus 18% with HDR and 19% with IMRT (P<.01). On multivariable logistic regression, patients treated with HDR versus SBRT were 7.42 times more likely to have regret, and patients treated with IMRT versus SBRT were 11.11 times more likely to have regret (P<.01 and P<.01, respectively). Significantly more patients treated with SBRT selected that their actual long-term toxicities were significantly less than originally expected, compared with IMRT and HDR patients (SBRT 43% vs IMRT 20% vs HDR 10%, P<.01).

Conclusions: We found significant differences in patients' experiences between SBRT, IMRT, and HDR, with significantly less treatment regret and less toxicity than expected among SBRT patients. The majority of patients with regret would now opt for active surveillance; therefore, pretreatment counseling is essential.
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http://dx.doi.org/10.1016/j.ijrobp.2016.11.007DOI Listing
March 2017

Long term results from a prospective database on high dose rate (HDR) interstitial brachytherapy for primary cervical carcinoma.

Gynecol Oncol 2016 Oct 29. Epub 2016 Oct 29.

California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United States. Electronic address:

Objective: Present long-term outcomes in primary cervical cancer treated with external beam and high dose rate interstitial brachytherapy.

Methods: High dose rate (HDR) interstitial (IS) brachytherapy (BT) and external beam (EBRT) were administered from 1992 to 2009 to 315 patients who were unsuitable for intracavitary (IC) BT alone. Histology was 89% squamous cell, 8% adenocarcinoma, and 3% adenosquamous. FIGO stage was I-14%, II-47%, III-34%, and IVA-5%. Median tumor size was 6cm. Lymph node metastases were 26% pelvic and 9.5% para-aortic. Treatment planning was 49% 2D and 51% 3D-CT. The mean doses were central EBRT EQD2 37.3±4.3Gy (sidewall 49.2±3.6Gy) and HDR EQD2 42.3±5.3Gy (nominal 5.4Gy×6 fractions using a mean of 24 catheters and 1 tandem). Total EQD2 mean target dose was 79.5±5.4Gy. Standardized planned dose constraints were ICRU points or D bladder 80%, rectum 75% and urethra 90% of the HDR dose per fraction. Morbidity assessment was CTCAEv3. Median and mean follow-up were 50 and 61months (3-234).

Results: The 10-year actuarial local control was 87%, regional control 84%, and loco-regional control 77%. Distant metastasis free survival was 66%, cause specific survival 56%, disease free survival 54%, and overall survival 40%. The rates of late grade GU and GI toxicities were 4.8% G3 and 5.4% G4.

Conclusions: Template-guided interstitial can be safely performed to successfully deliver high radiation dose to locally advanced cervix cancer and avoid excessive dose and injury to adjacent vital pelvic organs. We achieved high tumor control with low morbidity in patients who were poor candidates for intracavitary brachytherapy.
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http://dx.doi.org/10.1016/j.ygyno.2016.10.020DOI Listing
October 2016

Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx.

Am J Otolaryngol 2017 Jan - Feb;38(1):31-37. Epub 2016 Sep 28.

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

Purpose: To evaluate the prognostic significance of p16 expression among patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HSCC).

Methods: The medical records of all patients with locally advanced, non-metastatic LSCC/HSCC were reviewed. p16 (p16) protein expression was evaluated on pathological specimens by immunohistochemistry (IHC), and the Kaplan-Meier method was used to estimate overall survival (OS) and locoregional control (LRC). In select cases, p16 expression was correlated to high-risk and low-risk HPV genotypes using in situ hybridization (ISH).

Results: Thirty-one patients (23 LSCC; 8 HSCC) were identified. Seventeen (54.8%) patients were p16 negative; 14 (45.2%) were p16-positive. The primary treatment modality was radiation therapy for 22 (71.0%) patients and surgery for 9 (29.0%). Nineteen (61.3%) patients were evaluated for high-risk HPV and low-risk HPV genotypes by IHC, of whom 2 (10.5%) patients were positive for high-risk HPV and 1 (5.3%) was positive for low-risk HPV. For high-risk HPV, the positive predictive value (PPV), sensitivity, and specificity of p16 was 20.0%, 100%, and 52.9%. There was no significant difference in the 2-year actuarial rates of OS (91% vs. 64%, p=0.34) or LRC (51% vs. 46%, p=0.69) between the p16-positive and p-16 negative patients.

Conclusion: In this small cohort of 31 LSCC and HSCC patients, p16 was not a significant predictive of either LRC or OS. Furthermore, p16 was poorly correlated with HPV genotyping as identified by ISH.
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http://dx.doi.org/10.1016/j.amjoto.2016.09.007DOI Listing
October 2017

Locoregional recurrence by molecular subtype after multicatheter interstitial accelerated partial breast irradiation: Results from the Pooled Registry Of Multicatheter Interstitial Sites research group.

Brachytherapy 2016 Nov - Dec;15(6):788-795. Epub 2016 Oct 12.

Arizona Breast Cancer Specialists, Scottsdale, AZ.

Purpose: To determine in breast tumor recurrence (IBTR) and regional nodal recurrence (RNR) rates for women treated with multicatheter interstitial accelerated partial breast irradiation.

Methods And Materials: Data from five institutions were collected for patients treated from 1992 to 2013. We report outcomes of 582 breast cancers with ≥1 year of followup. Molecular subtype approximation was performed using estrogen receptor, progesterone receptor, Her2, and grade. The Kaplan-Meier method was used to calculate overall survival, IBTR, RNR, and distant recurrence rates. Univariate and multivariate Cox proportional hazard models were performed to estimate risks of IBTR and RNR.

Results: With a median followup time of 5.4 years, the 5-year IBTR rate was 4.7% overall, 3.5% for Luminal A, 4.1% for Luminal B, 5.2% for Luminal Her2, 13.3% for Her2, and 11.3% for triple-negative breast cancer. Positive surgical margins and high grade were associated with increased risk for IBTR, as was Her2 subtype in comparison with Luminal A subtype. Other individual subtypes comparisons did not show a significant difference. Analysis of Luminal A vs. all other subtypes demonstrated lower IBTR risk for Luminal A (5-year IBTR 3.5% vs. 7.3%, p = 0.02). The 5-year RNR rate was 2.1% overall, 0.3% for Luminal A, 4.6% for Luminal B, 2.6% for Luminal Her2, 34.5% for Her2, and 2.3% for triple-negative breast cancer. RNR risk was higher for women with Her2 compared to the other four subtypes and for Luminal B compared to Luminal A subtype.

Conclusions: Molecular subtype influences IBTR and RNR rates in women treated with multicatheter interstitial accelerated partial breast irradiation.
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http://dx.doi.org/10.1016/j.brachy.2016.08.012DOI Listing
July 2017

Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

Am J Clin Oncol 2018 06;41(6):538-543

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

Objectives: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients.

Materials And Methods: From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy.

Results: The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence.

Conclusions: Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients.
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http://dx.doi.org/10.1097/COC.0000000000000334DOI Listing
June 2018

Does Specialty Bias Trump Evidence in the Management of High-risk Prostate Cancer?

Am J Clin Oncol 2018 06;41(6):549-557

Departments of Radiation Oncology.

Objective: The objective was to query how specialty influences treatment recommendations for high-risk prostate cancer in 3 clinical settings: upfront management, postoperative management, and management of biochemical recurrences (BCRs) after radiotherapy (RT). We hypothesized that specialty bias would manifest in all settings, trumping available evidence.

Methods: A survey of practicing urologists and radiation oncologists was distributed through electronic mail. Questions pertained to upfront management, postoperative treatment, and local salvage for postradiation BCRs. The associations between 26 selected categorical responses and specialty were assessed using multivariate logistic regression. Training level/expertise, practice setting, percentage of consultation caseload consisting of prostate cancer, and nationality were set as effect modifiers.

Results: One thousand two hundred fifty-three physicians (846 radiation oncologists and 407 urologists) completed the survey. Radiation oncologists were more likely to recommend adjuvant RT and consider it to be underutilized, and more likely to recommend salvage RT at lower prostate-specific antigen thresholds (P<0.0001). Urologists were more likely to recommend salvage radical prostatectomy or cryoablation for local salvage after RT, whereas radiation oncologists were more likely to recommend RT-based modalities and more likely to report that local salvage was underutilized after RT (P<0.0001). Urologists were more likely to report that upfront radical prostatectomy was a better definitive treatment (P<0.0001), whereas radiation oncologists were more likely to report the opposite (P=0.005).

Conclusions: Specialty biases permeate recommendations for upfront management and management in the postoperative and post-RT BCR setting, irrespective of available evidence. These data reveal the critical need for multidisciplinary clinics and cross-specialty training as potential solutions for overcoming specialty bias.
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http://dx.doi.org/10.1097/COC.0000000000000323DOI Listing
June 2018

Clinical Outcomes for Patients with Gleason Score 9-10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis.

Eur Urol 2017 05 21;71(5):766-773. Epub 2016 Jul 21.

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

Background: The long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons.

Objective: To compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP.

Design, Setting, Participants: Retrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy.

Outcome Measurements And Statistical Analysis: Kaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS).

Results And Limitations: The median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p<0.0001). Five-yr and 10-yr distant metastasis-free survival rates were significantly higher with EBRT+BT (94.6% and 89.8%) than with EBRT (78.7% and 66.7%, p=0.0005) or RP (79.1% and 61.5%, p<0.0001). The 5-yr and 10-yr CSS and OS rates were similar across all three cohorts.

Conclusions: Radiotherapy and RP provide equivalent CSS and OS. Extremely dose-escalated radiotherapy with ADT in particular offers improved systemic control when compared with either EBRT or RP. These data suggest that extremely dose-escalated radiotherapy with ADT might be the optimal upfront treatment for patients with biopsy GS 9-10 CaP.

Patient Summary: While some prostate cancers are slow-growing requiring many years, sometimes decades, of follow-up in order to compare between radiation and surgery, high-risk and very aggressive cancers follow a much shorter time course allowing such comparisons to be made and updated as treatments, especially radiation, rapidly evolve. We showed that radiation-based treatments and surgery, with contemporary standards, offer equivalent survival for patients with very aggressive cancers (defined as Gleason score 9-10). Extremely-dose escalated radiotherapy with short-course androgen deprivation therapy offered the least risk of developing metastases, and equivalent long term survival.
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http://dx.doi.org/10.1016/j.eururo.2016.06.046DOI Listing
May 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

Clinical Indicators of Psychosocial Distress Predict for Acute Radiation-Induced Fatigue in Patients Receiving Adjuvant Radiation Therapy for Breast Cancer: An Analysis of Patient-Reported Outcomes.

Int J Radiat Oncol Biol Phys 2016 07 11;95(3):946-955. Epub 2016 Feb 11.

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

Purpose: To assess the magnitude and predictors of patient-reported fatigue among breast cancer patients receiving radiation therapy (RT).

Methods And Materials: Patients receiving breast RT completed a survey querying fatigue at each weekly on-treatment visit. Patient-reported fatigue severity and interference was assessed on an ordinal scale of 0 to 4, using a validated scoring system. Baseline anxiety and depression scores were also obtained. The kinetics of mean fatigue scores per week and the maximum fatigue scores over the course of the entire treatment were assessed, and clinical predictors were identified by univariate and multivariate regression.

Results: The average fatigue severity and interference scores were 0.6 and 0.46. The average fatigue scores increased to an equivalent extent from week to week, with expected increases of 0.99 in fatigue severity and 0.85 in interference over 7 weeks. Patients treated with hypofractionated RT (HF-RT) versus conventionally fractionated RT (CF-RT) had significantly fewer maximum fatigue severity or interference scores that were >2 (ie, severe or very severe; 29% vs 10% for severity, and 26% vs 8% for interference, P<.01). Age ≤45 years, presence of psychiatric/pain-related comorbidities, and baseline sadness and anxiety severity were predictive of average and maximum fatigue scores (P<.05), but variables related to treatment intensity (eg, mastectomy vs lumpectomy, chemotherapy use, radiation target volumes) and other host factors (working, children, marital status, proximity to RT facility) were not.

Conclusion: Patient-reported fatigue modestly increases over RT courses, with less maximum fatigue reported with HF-RT. Younger age and baseline sadness, anxiety, and psychiatric/pain-related comorbidities are powerful predictors of fatigue, whereas other factors, such as treatment intensity, are not. Future studies will investigate interventions for patients at high risk for fatigue.
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http://dx.doi.org/10.1016/j.ijrobp.2016.01.062DOI Listing
July 2016

SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer.

Pract Radiat Oncol 2016 Jul-Aug;6(4):268-275. Epub 2015 Nov 10.

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

Purpose: To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP).

Methods And Materials: Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables.

Results: Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them.

Conclusions: Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT.
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http://dx.doi.org/10.1016/j.prro.2015.11.002DOI Listing
March 2017

A treatment planning comparison between modulated tri-cobalt-60 teletherapy and linear accelerator-based stereotactic body radiotherapy for central early-stage non-small cell lung cancer.

Med Dosim 2016 2;41(1):87-91. Epub 2016 Jan 2.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address:

We evaluated the feasibility of planning stereotactic body radiotherapy (SBRT) for large central early-stage non-small cell lung cancer with a tri-cobalt-60 (tri-(60)Co) system equipped with real-time magnetic resonance imaging (MRI) guidance, as compared to linear accelerator (LINAC)-based SBRT. In all, 20 patients with large central early-stage non-small cell lung cancer who were treated between 2010 and 2015 with LINAC-based SBRT were replanned using a tri-(60)Co system for a prescription dose of 50Gy in 4 fractions. Doses to organs at risk were evaluated based on established MD Anderson constraints for central lung SBRT. R100 values were calculated as the total tissue volume receiving 100% of the dose (V100) divided by the planning target volume and compared to assess dose conformity. Dosimetric comparisons between LINAC-based and tri-(60)Co SBRT plans were performed using Student׳s t-test and Wilcoxon Ranks test. Blinded reviews by radiation oncologists were performed to assess the suitability of both plans for clinical delivery. The mean planning target volume was 48.3cc (range: 12.1 to 139.4cc). Of the tri-(60)Co SBRT plans, a mean 97.4% of dosimetric parameters per patient met MD Anderson dose constraints, whereas a mean 98.8% of dosimetric parameters per patient were met with LINAC-based SBRT planning (p = 0.056). R100 values were similar between both plans (1.20 vs 1.21, p = 0.79). Upon blinded review by 4 radiation oncologists, an average of 90% of the tri-(60)Co SBRT plans were considered acceptable for clinical delivery compared with 100% of the corresponding LINAC-based SBRT plans (p = 0.17). SBRT planning using the tri-(60)Co system with built-in MRI is feasible and achieves clinically acceptable plans for most central lung patients, with similar target dose conformity and organ at risk dosimetry. The added benefit of real-time MRI-guided therapy may further optimize tumor targeting while improving normal tissue sparing, which warrants further investigation in a prospective feasibility clinical trial.
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http://dx.doi.org/10.1016/j.meddos.2015.09.002DOI Listing
December 2016

Image-guided high-dose-rate brachytherapy: preliminary outcomes and toxicity of a joint interventional radiology and radiation oncology technique for achieving local control in challenging cases.

J Contemp Brachytherapy 2015 Oct 13;7(5):327-35. Epub 2015 Oct 13.

Department of Radiation Oncology.

Purpose: To determine the ability of image-guided high-dose-rate brachytherapy (IG-HDR) to provide local control (LC) of lesions in non-traditional locations for patients with heavily pre-treated malignancies.

Material And Methods: This retrospective series included 18 patients treated between 2012 and 2014 with IG-HDR, either in combination with external beam radiotherapy (EBRT; n = 9) or as monotherapy (n = 9). Lesions were located in the pelvis (n = 5), extremity (n = 2), abdomen/retroperitoneum (n = 9), and head/neck (n = 2). All cases were performed in conjunction between interventional radiology and radiation oncology. Toxicity was graded based on CTCAE v4.0 and local failure was determined by RECIST criteria. Kaplan-Meier analysis was performed for LC and overall survival.

Results: The median follow-up was 11.9 months. Two patients had localized disease at presentation; the remainder had recurrent and/or metastatic disease. Seven patients had prior EBRT, with a median equivalent dose in 2 Gy fractions (EQD2) of 47.0 Gy. The median total EQD2s were 34 Gy and 60.9 Gy for patients treated with monotherapy or combination therapy, respectively. Image-guided high-dose rate brachytherapy was delivered in one to six fractions. Six patients had local failures at a median interval of 5.27 months with a one-year LC rate of 59.3% and a one-year overall survival of 40.7%. Six patients died from their disease at a median interval of 6.85 months from the end of treatment. There were no grade ≥ 3 acute toxicities but two patients had serious long term toxicities.

Conclusions: We demonstrate a good one year LC rate of nearly 60%, and a favorable toxicity profile when utilizing IG-HDR to deliver high doses of radiation with high precision into targets not readily accessible by other forms of local therapy. These preliminary results suggest that further studies utilizing this approach may be considered for patients with difficult to access lesions that require LC.
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http://dx.doi.org/10.5114/jcb.2015.54947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663208PMC
October 2015

The American Board of Radiology Focused Practice Recognition in Brachytherapy (FPRB) Program: Opportunities lost, lessons learned, and future implications.

Pract Radiat Oncol 2015 Nov-Dec;5(6):427-32. Epub 2015 Aug 28.

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

In 2011, the American Board of Medical Specialties approved a pilot project submitted by the American Board of Radiology for a Focused Practice Recognition in Brachytherapy initiative. Developers had anticipated significant interest within the profession and had hoped that the project would stimulate clinical interest, research, and education in the modality. A centerpiece of the project was a National Brachytherapy Registry, which was to serve as a dynamic longitudinal database for participants and the profession. Ultimately, the project did not achieve its anticipated goals and was terminated by the American Board of Radiology in 2015. Development, implementation, problems encountered, and potential implications and solutions are discussed.
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http://dx.doi.org/10.1016/j.prro.2015.08.006DOI Listing
September 2016

In Regard to Mariados et al.

Int J Radiat Oncol Biol Phys 2015 Nov 19;93(4):936-7. Epub 2015 Oct 19.

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

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http://dx.doi.org/10.1016/j.ijrobp.2015.07.2295DOI Listing
November 2015
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