Publications by authors named "Susan Wu"

80 Publications

Radiation and CAR T-cell Therapy in Lymphoma: Future Frontiers and Potential Opportunities for Synergy.

Front Oncol 2021 25;11:648655. Epub 2021 Mar 25.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

CAR T-cell therapy has revolutionized the treatment approach to patients with relapsed/refractory hematologic malignancies; however, there continues to be opportunity for improvement in treatment toxicity as well as response durability. Radiation therapy can play an important role in combined modality treatments for some patients undergoing CAR T-cell therapy in various clinical settings. In this review, we discuss the current evidence for RT in the setting of CAR T-cell therapy for patients with hematologic malignancies and propose potential opportunities for future investigation of RT and CAR T-cell treatment synergy. Future research frontiers include investigation of hypotheses including radiation priming of CAR T-cell mediated death, pre-CAR T-cell tumor debulking with radiation therapy, and selection of high risk patients for early radiation salvage after CAR T cell therapy.
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http://dx.doi.org/10.3389/fonc.2021.648655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027336PMC
March 2021

National Inpatient Immunization Patterns: Variation in Practice and Policy Between Vaccine Types.

Hosp Pediatr 2021 May 5;11(5):462-471. Epub 2021 Apr 5.

The Saban Research Institute and Southern California Clinical and Translational Science Institute Biostatistics Core, Children's Hospital Los Angeles, Los Angeles, California; and.

Background: Many hospitalized children are underimmunized, yet little is known about current systems supporting inpatient vaccination. We aim to describe national pediatric inpatient immunization practices and determine if variation exists among adolescent, childhood, and influenza vaccines.

Methods: An electronic survey regarding hospital vaccination practices was sent to physician, nurse, and pharmacy leaders via the Pediatric Research in Inpatient Settings Network in spring 2019. Hospitals reported the presence of various practices to support inpatient vaccination stratified by vaccine type: tetanus, diphtheria, and acellular pertussis, meningococcal, human papillomavirus, childhood series, and influenza. One-way analysis of variance testing compared differences in numbers of practices and χ tests compared proportions of sites reporting each practice between vaccine types. Qualitative responses were evaluated via content analysis.

Results: Fifty-one of 103 eligible hospitals completed the survey (50%). Standardized policies existed in 92% of hospitals for influenza, 41% for childhood, and 29% for adolescent vaccines. Hospitals identified an average of 5.1 practices to deliver influenza vaccines, compared with 1.5 for childhood; 0.9 for tetanus, diphtheria, and acellular pertussis; 0.7 for meningococcal; and 0.6 for human papillomavirus vaccines ( < .001). Standardized screening tools, visual prompts, standing orders, nurse- or pharmacy-driven screening or ordering, staff education, and quality improvement projects were reported more often for influenza vaccines than other vaccine types ( < .01 for all comparisons). Common barriers to delivery included communication difficulties, lack of systems optimization, and parent and provider discomfort with inpatient immunization.

Conclusions: Existing hospital infrastructure supports influenza vaccine delivery over other vaccine types, potentially creating missed inpatient vaccination opportunities.
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http://dx.doi.org/10.1542/hpeds.2020-002634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074110PMC
May 2021

Timing of Urgent Inpatient Palliative Radiation Therapy.

Adv Radiat Oncol 2021 May-Jun;6(3):100670. Epub 2021 Feb 11.

Department of Radiation Oncology, University of California, San Francisco, California.

Purpose: Urgent indications for palliative radiation therapy (RT) include malignant spinal cord compression, symptomatic brain metastases, pain, airway obstruction, and bleeding. Data on the timing of palliative RT in the inpatient setting are limited. We report our experience with inpatient palliative RT at a tertiary academic center and evaluate the effect of a dedicated inpatient palliative RT nurse practitioner (NP) on treatment timelines.

Methods And Materials: We performed a retrospective, single-institution review of 219 inpatients consulted for RT to sites of metastatic disease between May 2012 and May 2018. We compared time-to-treatment intervals before and after integrating an NP for palliative RT in August 2017.

Results: The median age of the 219 patients receiving RT was 61 years (interquartile range [IQR], 51-69 years). The most frequent indications were symptomatic brain metastases (73 patients [33%]), pain (61 patients [28%]), and cord/cauda compression (48 patients [22%]). The median time from consultation request to consult was 1 day (IQR, 0-2 days), and the median time from consultation request to first RT fraction was 3 days (IQR, 2-6 days). The median time from consultation request to RT was shorter for cord compression (2 [IQR, 1-4] days) than for pain (5 [IQR, 2-7] days) ( = .001) or symptomatic brain metastases (3 [IQR, 1-6] days; = .037). With an NP, patients were more likely to undergo same-day consultation and simulation (75% vs 60%; = .045), which was associated with shorter median duration from consultation to initiation of RT (1 [IQR, 0-3] days vs 4 [IQR, 2-7] days; <.001). After the integration of an NP for palliative RT, patients had a higher median Karnofsky Performance Score (70 [IQR, 60-80] vs 50 [IQR, 40-60]; < .001) and were more likely to complete their prescribed RT course (93% vs 82%; = .05).

Conclusions: Time from consultation request to RT is necessarily short for urgent inpatient palliative RT. Advanced practice providers may facilitate and potentially expedite treatment, with significantly shorter times to treatment among patients who undergo same-day consultation and simulation.
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http://dx.doi.org/10.1016/j.adro.2021.100670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005735PMC
February 2021

A mixed community of skin microbiome representatives influences cutaneous processes more than individual members.

Microbiome 2021 01 22;9(1):22. Epub 2021 Jan 22.

Research and Exploratory Development, Johns Hopkins University Applied Physics Laboratory, Laurel, MD, USA.

Background: Skin, the largest organ of the human body by weight, hosts a diversity of microorganisms that can influence health. The microbial residents of the skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various skin disorders. Still, much remains to be discovered in terms of the host pathways influenced by skin microorganisms, as well as the higher-level skin properties impacted through these microbe-host interactions. Towards this direction, recent efforts using mouse models point to pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community. However, there is a need to quantify the roles of microorganisms at both the individual and community-level in healthy human skin. In this study, we utilize human skin equivalents to study the effects of individual taxa and a microbial community in a precisely controlled context. Through transcriptomics analysis, we identify key genes and pathways influenced by skin microbes, and we also characterize higher-level impacts on skin processes and properties through histological analyses.

Results: The presence of a microbiome on a 3D skin tissue model led to significantly altered patterns of gene expression, influencing genes involved in the regulation of apoptosis, proliferation, and the extracellular matrix (among others). Moreover, microbiome treatment influenced the thickness of the epidermal layer, reduced the number of actively proliferating cells, and increased filaggrin expression. Many of these findings were evident upon treatment with the mixed community, but either not detected or less pronounced in treatments by single microorganisms, underscoring the impact that a diverse skin microbiome has on the host.

Conclusions: This work contributes to the understanding of how microbiome constituents individually and collectively influence human skin processes and properties. The results show that, while it is important to understand the effect of individual microbes on the host, a full community of microbes has unique and pronounced effects on the skin. Thus, in its impacts on the host, the skin microbiome is more than the sum of its parts. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00963-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825201PMC
January 2021

Acute respiratory infections in hospitalised infants with congenital heart disease.

Cardiol Young 2021 Apr 14;31(4):547-555. Epub 2020 Dec 14.

Division of Hospital Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.

Objectives: To assess the overall burden and outcomes of acute respiratory infections in paediatric inpatients with congenital heart disease (CHD).

Methods: This is a retrospective cross-sectional study of non-neonates <1 year with CHD in the Kid's Inpatient Database from 2012. We compared demographics, clinical characteristics, cost, length of stay, and mortality rate for those with and without respiratory infections. We also compared those with respiratory infections who had critical CHD versus non-critical CHD. Multi-variable regression analyses were done to look for associations between respiratory infections and mortality, length of stay, and cost.

Results: Of the 28,696 infants with CHD in our sample, 26% had respiratory infections. Respiratory infection-associated hospitalisations accounted for $440 million in costs (32%) for all CHD patients. After adjusting for confounders including severity, mortality was higher for those with respiratory infections (OR 1.5, p = 0.003), estimated mean length of stay was longer (14.7 versus 12.2 days, p < 0.001), and estimated mean costs were higher ($53,760 versus $46,526, p < 0.001). Compared to infants with respiratory infections and non-critical CHD, infants with respiratory infections and critical CHD had higher mortality (4.5 versus 2.3%, p < 0.001), longer mean length of stay (20.1 versus 15.5 days, p < 0.001), and higher mean costs ($94,284 versus $52,585, p < 0.001).

Conclusion: Acute respiratory infections are a significant burden on infant inpatients with CHD and are associated with higher mortality, costs, and longer length of stay; particularly in those with critical CHD. Future interventions should focus on reducing the burden of respiratory infections in this population.
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http://dx.doi.org/10.1017/S1047951120004333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058167PMC
April 2021

What Is the Predictive Value of a Single Nasopharyngeal SARS-CoV-2 PCR Swab Test in a Patient With COVID-Like Symptoms and/or Significant COVID-19 Exposure?

Open Forum Infect Dis 2020 Oct 1;7(10):ofaa399. Epub 2020 Sep 1.

Mount Sinai South Nassau, Oceanside, New York, USA.

Utilizing results of polymerase chain reaction (PCR) testing and subsequent antibody titers, we report on the test characteristics of a PCR screening test for severe acute respiratory syndrome coronavirus 2 among hospital workers. The PCR test was found to be 87% sensitive and 97% specific, with a positive predictive value of 0.98 and a negative predictive value of 0.80.
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http://dx.doi.org/10.1093/ofid/ofaa399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499796PMC
October 2020

Evaluation of a National Comprehensive Cancer Network Guidelines-Based Decision Support Tool in Patients With Non-Small Cell Lung Cancer: A Nonrandomized Clinical Trial.

JAMA Netw Open 2020 09 1;3(9):e209750. Epub 2020 Sep 1.

Department of Radiation Oncology, University of California, San Francisco.

Importance: The association of guideline-based decision support with the quality of care in patients with non-small cell lung cancer (NSCLC) is not known.

Objective: To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients' decisional conflict.

Design, Setting, And Participants: A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction.

Interventions: An online tool customizing the NCCN guidelines to patients' clinical and pathologic features was used during consultation, facilitated by a trained coordinator.

Main Outcomes And Measures: Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients' decisional conflict.

Results: Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P < .001) and less adjuvant chemotherapy (0 of 7 vs 7 of 11 [63.6%]; P = .012). There was no significant change in mutation testing of non-squamous cell stage IV disease (20 of 20 [100%] vs 48 of 57 [84.2%]; P = .10). There was no significant change in pathologic mediastinal staging or initial chemoradiotherapy for patients with stage III disease. After consultation with the tool, decisional conflict scores improved by a median of 20 points (IQR, 3-34; P < .001).

Conclusions And Relevance: The findings of this study suggest that exposure to the NCCN guidelines is associated with increased guideline-concordant care for 2 of 6 preselected recommendations and improvement in decisional conflict.

Trial Registration: ClinicalTrials.gov Identifier: NCT03982459.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.9750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527870PMC
September 2020

In Reply to Leung.

Int J Radiat Oncol Biol Phys 2020 07;107(3):604-605

Department of Radiation Oncology, University of California, San Francisco, San Francisco, California.

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http://dx.doi.org/10.1016/j.ijrobp.2020.03.031DOI Listing
July 2020

Consolidative Whole Brain Radiation for Those with Residual Disease, Reserving Focal Radiation for Salvage.

Authors:
Susan Y Wu

Int J Radiat Oncol Biol Phys 2020 07;107(3):401-402

Department of Radiation Oncology, University of California, San Francisco, San Francisco, California.

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http://dx.doi.org/10.1016/j.ijrobp.2020.03.045DOI Listing
July 2020

The Challenges of Applying Radiation in Primary Central Nervous System Lymphoma.

Int J Radiat Oncol Biol Phys 2020 07;107(3):398-400

Department of Radiation Oncology, University of Toronto, Princess Margaret Hospital, Toronto, Canada.

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http://dx.doi.org/10.1016/j.ijrobp.2020.02.466DOI Listing
July 2020

Characterizing Avoidable Transfer Admissions in Infants Hospitalized for Bronchiolitis.

Hosp Pediatr 2020 05 8;10(5):415-423. Epub 2020 Apr 8.

Massachusetts General Hospital, Boston, Massachusetts.

Objectives: The appropriateness of interfacility transfer admissions for bronchiolitis to pediatric centers is uncertain. We characterized avoidable transfer admissions for bronchiolitis. We hypothesized that a higher proportion of hospitalized infants transferred from a community emergency department (ED) or hospital (transfer admission) would be discharged within 48 hours with little or no intervention, compared with direct admissions from an enrolling ED (nontransfer admission).

Methods: We analyzed a 17-center, prospective infant cohort (age <1 year) hospitalized for bronchiolitis (2011-2014). An avoidable transfer admission (primary outcome) was hospitalization for <48 hours without an intervention for severe illness in which a pediatric specialist could be beneficial (oxygen, advanced airway management, life support). Parenteral fluids and routine medications were excluded. We compared admissions by patient, ED, inpatient, and transferring hospital characteristics to identify factors associated with avoidable transfer admissions. Multivariable logistic regression was used to identify predictors of avoidable transfer admission.

Results: Among 1007 infants, 558 (55%) were nontransfer admissions, 164 (16%) were transfer admissions, and 204 (20%) were referrals from clinics; 81 (8%) were missing referral type. Significantly fewer transferred infants were hospitalized for <48 hours with little or no intervention (40 of 164; 24% [95% confidence interval 18%-32%]) than nontransferred infants (199 of 558; 36% [95% confidence interval 32%-40%]; = .007). Avoidable transfer admissions were more likely to be children of color, have nonprivate insurance, receive fewer ED interventions, and originate from small EDs. A multivariable model revealed that minority race and/or ethnicity, normal oxygenation, and small ED transfers increased odds of avoidable transfer admission.

Conclusions: Although most transferred infants hospitalized for bronchiolitis required interventions for severe illness, 1 in 4 admissions were potentially avoidable.
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http://dx.doi.org/10.1542/hpeds.2019-0226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187394PMC
May 2020

Pediatric Resident Attitudes Toward Inpatient Immunization of Children and Adolescents: Highlighting Differences in Human Papillomavirus Vaccination.

Glob Pediatr Health 2019 7;6:2333794X19894123. Epub 2019 Dec 7.

Children's Hospital Los Angeles, Los Angeles, CA, USA.

Over a decade after its debut, human papillomavirus (HPV) vaccine coverage remains suboptimal. The inpatient setting presents a largely unexplored opportunity to increase vaccination rates. This study aims to describe pediatric resident attitudes toward inpatient immunization and compare differences by vaccine, in particular HPV. An anonymous survey of beliefs and practices regarding inpatient vaccines was distributed to pediatric resident physicians at a single freestanding urban children's hospital in September 2017. A total of 58 surveys were collected (64% response rate). We found that pediatric residents were more likely to report that they never or rarely discuss the HPV vaccine during hospitalization compared with the primary childhood series ( = .001), Tdap ( = .02), and the influenza vaccine ( < .001), and rarely offer the HPV vaccine during hospitalization compared with childhood vaccines ( = .003) and influenza ( = .001). This suggests that provider hesitancy still exists for the HPV vaccine, presenting opportunities for further education and inpatient interventions.
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http://dx.doi.org/10.1177/2333794X19894123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900615PMC
December 2019

Current Standards for Organ Preservation in Locoregionally Advanced Non-nasopharyngeal Head and Neck Cancer and Evolving Strategies for Favorable-Risk and Platinum-Ineligible Populations.

Curr Treat Options Oncol 2019 12 4;20(12):89. Epub 2019 Dec 4.

Department of Radiation Oncology, University of California San Francisco, 1600 Divisadero St, H1031, San Francisco, CA, 94115, USA.

Opinion Statement: Standard-of-care treatment for the majority of patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is either upfront surgery followed by adjuvant treatment as indicated by intraoperative or pathologic findings or concurrent chemoradiation reserving surgical salvage for non-responsive disease. An attempt at upfront complete resection should be pursued if feasible in patients with oral cavity or paranasal sinus primary tumors. Given multimodality treatment paradigms, patients with locoregionally advanced SCCHN should be managed in a multidisciplinary setting. Modern radiation therapy, whether postoperative or definitive in intent, is based on target delineation guided by high-quality imaging, using an intensity-modulated radiation technique to spare organs at risk. In select groups of low-risk patients, most notably those with HPV-associated oropharyngeal SCC (OPSCC), several treatment deintensification approaches are currently under investigation. Major experimental strategies within this non-surgical organ preservation domain include reductions in the intensity of the chemotherapy or radiation therapy components of the chemoradiation program, use of induction chemotherapy, or imaging-based selection of patients eligible for deintensified radiation-based treatment. Of note, recent efforts to substitute cetuximab for cisplatin in low-risk HPV-associated OPSCC have demonstrated the inferiority of cetuximab to cisplatin in cisplatin-eligible patients, re-confirming cisplatin as the standard systemic therapy of choice in HNSCC. In patients who are not candidates for any type of cisplatin administration, carboplatin-based therapy or cetuximab remain options, and other non-cisplatin therapies are under investigation. Altered fractionation may be considered in patients who are not candidates for any type of systemic therapy. The role of immunotherapy in the management of locoregional SCCHN remains investigational.
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http://dx.doi.org/10.1007/s11864-019-0688-4DOI Listing
December 2019

Targeted Needs Assessment of Treatment Planning Education for United States Radiation Oncology Residents.

Int J Radiat Oncol Biol Phys 2020 03 28;106(4):677-682. Epub 2019 Nov 28.

Department of Radiation Oncology, University of California, San Francisco, California. Electronic address:

Purpose: Prior surveys suggest almost one-third of chief residents report insufficient exposure to treatment planning. We evaluated the state of treatment planning education among United States residents.

Methods And Materials: A web-based survey was sent to current residents identified using the Association of Residents in Radiation Oncology directory.

Results: The response rate was 33%. Twenty-six percent of residents reported a mandatory treatment planning rotation. Seventy-one percent of residents reported reviewing ≤50% of plans with an attending. Twenty-three percent of respondents were not at all or only slightly comfortable (1 or 2 on a 1-5 scale) evaluating treatment plans. Residents with mandatory treatment planning rotations were more comfortable evaluating plans compared with those without mandatory rotations (P = .045). Overall, 60% reported insufficient exposure to treatment planning. Among postgraduate year 5 residents, this rate was 52%. Ninety-two percent of residents expressed interest in free supplemental treatment planning resources.

Conclusions: A significant proportion of residents surveyed report insufficient exposure to treatment planning. Development of a practical treatment planning curriculum would offer the opportunity to improve resident education, and ultimately quality of care, at the national level.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.023DOI Listing
March 2020

Diagnosis, Staging, Radiation Treatment Response Assessment, and Outcome Prognostication of Head and Neck Cancers Using PET Imaging: A Systematic Review.

PET Clin 2020 Jan;15(1):65-75

Department of Radiation Oncology, Helen Diller Comprehensive Cancer Care Center, University of California San Francisco, 1600 Divisadero Street, Suite H-1031, San Francisco, CA 94143-1708, USA. Electronic address:

This systematic review summarizes the current applications of F-FDG PET imaging in the diagnosis, staging, radiation treatment response assessment, and outcome prognostication of head and neck cancers. For head and neck cancers of unknown primary origin, F-FDG PET/CT increases the likelihood of identifying the primary tumor and establishing the diagnosis. F-FDG PET/CT is important in the accurate staging of locoregionally advanced cases of HNSCC, which can greatly affect recommendations for treatment. Following definitive chemoradiation, F-FDG PET/CT is validated as a means of treatment response assessment. Emerging PET tracers of hypoxia and their potential applications are reviewed.
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http://dx.doi.org/10.1016/j.cpet.2019.08.010DOI Listing
January 2020

Genomic Risk Predicts Molecular Imaging-detected Metastatic Nodal Disease in Prostate Cancer.

Eur Urol Oncol 2019 11 15;2(6):685-690. Epub 2019 Jan 15.

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA; Department of Urology, University of California San Francisco, San Francisco, CA, USA. Electronic address:

Background: The Decipher genomic classifier (GC) is increasingly being used to determine metastasis risk in men with localized prostate cancer (PCa). Whether GCs predict for the presence of occult metastatic disease at presentation or subsequent metastatic progression is unknown.

Objective: To determine if GC scores predict extraprostatic Ga prostate-specific membrane antigen (Ga-PSMA-11) positron emission tomography (PET) positivity at presentation.

Design, Setting, And Participants: Between December 2015 and September 2018, 91 PCa patients with both GC scores and pretreatment Ga-PSMA-11 PET scans were identified. Risk stratification was performed using the National Comprehensive Cancer Network (NCCN), Cancer of the Prostate Risk Assessment (CAPRA), and GC scores.

Outcome Measurements And Statistical Analysis: Logistic regression was used to identify factors correlated with PSMA-positive disease.

Results And Limitations: The NCCN criteria identified 23 (25.3%) and 68 patients (74.7%) as intermediate and high risk, while CAPRA scores revealed 28 (30.8%) and 63 (69.2%) as low/intermediate and high risk, respectively. By contrast, only 45 patients (49.4%) had high-risk GC scores. PSMA-avid pelvic nodal involvement was identified in 27 patients (29.7%). Higher GC score was significantly associated with pelvic nodal involvement (odds ratio [OR] 1.38 per 0.1 units; p=0.009) and any PSMA-avid nodal involvement (pelvic or distant; OR 1.40 per 0.1 units; p=0.007). However, higher GC score was not significantly associated with PSMA-avid osseous metastases (OR 1.11 per 0.1 units; p=0.50). Limitations include selection bias for patients able to receive both tests and the sample size.

Conclusions: Each 0.1-unit increase in GC score was associated with an approximate 40% increase in the odds of PSMA-avid lymph node involvement. These data suggest that patients with GC high risk might benefit from more nodal imaging and treatment intensification, potentially via pelvic nodal dissection, pelvic nodal irradiation, and/or the addition of chemohormonal agents.

Patient Summary: Patients with higher genomic classifier scores were found to have more metastatic lymph node involvement on prostate-specific membrane antigen imaging.
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http://dx.doi.org/10.1016/j.euo.2018.11.002DOI Listing
November 2019

Radiotherapy for recurrent intracranial epidermoid cysts without malignant transformation: a single-institution case series.

J Neurooncol 2019 Aug 5;144(1):89-96. Epub 2019 Jun 5.

Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, Rm. M-779, San Francisco, CA, 94143-0112, USA.

Introduction: Recurrent intracranial epidermoid cysts may be difficult to address surgically given their proximity to critical neurovascular structures of the skull base. There are emerging reports of using radiotherapy (RT) for the treatment of recurrent epidermoid cysts. Here, we report a case series of adjuvant fractionated external beam RT for recurrent intracranial epidermoid cysts.

Methods: A single-institution review of all recurrent epidermoid cysts treated with adjuvant therapy between 2000 and 2017 was performed.

Results: Eight patients with recurrent epidermoid cysts who underwent adjuvant external beam RT were identified. Average age at initial diagnosis was 42.2 years, and median clinical follow-up after initial diagnosis and RT was 16.4 and 2.9 years, respectively. The median number of surgical resections prior to RT was 3 (range 2-5). Rationale for RT included multiple recurrent disease, rapid recurrence following prior resection, increased risk of further surgical morbidity, and patient preference. Median dose was 50.4 delivered in 1.8 Gy fractions (median 28 fractions). By the date of last follow-up, no patient has demonstrated progression, and there have been no cases of malignant degeneration.

Conclusion: Adjuvant RT should be considered in the context of recurrent epidermoid cysts to decrease the likelihood of further recurrences.
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http://dx.doi.org/10.1007/s11060-019-03202-2DOI Listing
August 2019

Association of Rhinovirus C Bronchiolitis and Immunoglobulin E Sensitization During Infancy With Development of Recurrent Wheeze.

JAMA Pediatr 2019 06;173(6):544-552

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Rhinovirus infection in early life, particularly with allergic sensitization, is associated with higher risks of developing recurrent wheeze and asthma. While emerging evidence links different rhinovirus species (eg, rhinovirus C) to a higher severity of infection and asthma exacerbation, to our knowledge, little is known about longitudinal associations of rhinovirus C infection during infancy with subsequent morbidities.

Objective: To examine the association of different viruses (respiratory syncytial virus [RSV], rhinovirus species) in bronchiolitis with risks of developing recurrent wheeze.

Design, Setting, And Participants: This multicenter prospective cohort study of infants younger than 1 year who were hospitalized for bronchiolitis was conducted at 17 hospitals across 14 US states during 3 consecutive fall to winter seasons (2011-2014).

Exposures: Major causative viruses of bronchiolitis, including RSV (reference group) and 3 rhinovirus species (rhinovirus A, B, and C).

Main Outcomes And Measures: Development of recurrent wheeze (as defined in national asthma guidelines) by age 3 years.

Results: This analytic cohort comprised 716 infants who were hospitalized for RSV-only or rhinovirus bronchiolitis. The median age was 2.9 months (interquartile range, 1.6-3.8 months), 541 (76%) had bronchiolitis with RSV only, 85 (12%) had rhinovirus A, 12 (2%) had rhinovirus B, and 78 (11%) had rhinovirus C infection. Overall, 231 (32%) developed recurrent wheeze by age 3 years. In the multivariable Cox model, compared with infants with RSV-only infection, the risk of recurrent wheeze was not significantly different in those with rhinovirus A or B (rhinovirus A: hazard ratio [HR], 1.27; 95% CI, 0.86-1.88; rhinovirus B: HR, 1.39; 95% CI, 0.51-3.77; both P > .10). By contrast, infants with rhinovirus C had a significantly higher risk (HR, 1.58; 95% CI, 1.08-2.32). There was a significant interaction between virus groups and IgE sensitization on the risk of recurrent wheeze (P for interaction < .01). Only infants with both rhinovirus C infection and IgE sensitization (to food or aeroallergens) during infancy had significantly higher risks of recurrent wheeze (HR, 3.03; 95% CI, 1.20-7.61). Furthermore, compared with RSV-only, rhinovirus C infection with IgE sensitization was associated with significantly higher risks of recurrent wheeze with subsequent development of asthma at age 4 years (HR, 4.06; 95% CI, 1.17-14.1).

Conclusions And Relevance: This multicenter cohort study of infants hospitalized for bronchiolitis demonstrated between-virus differences in the risk of developing recurrent wheeze. Infants with rhinovirus C infection, along with IgE sensitization, had the highest risk. This finding was driven by the association with a subtype of recurrent wheeze: children with subsequent development of asthma.
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http://dx.doi.org/10.1001/jamapediatrics.2019.0384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547078PMC
June 2019

Location of Recurrence by Gallium-68 PSMA-11 PET Scan in Prostate Cancer Patients Eligible for Salvage Radiotherapy.

Urology 2019 07 27;129:165-171. Epub 2019 Mar 27.

Department of Radiation Oncology, University of California, San Francisco, CA; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. Electronic address:

Objective: To identify locations of recurrence after radical prostatectomy (RP) with prostate-specific antigen (PSA) <2 by Gallium-68 prostate-specific membrane antigen (PSMA)-11 Positron Emission Tomography (PET) imaging, and to determine whether standard nodal radiation fields would cover the location of prostate cancer recurrence.

Materials And Methods: We performed a retrospective review of patients with PSMA-PET imaging for biochemical recurrence following RP with PSA ≤2.0 ng/mL and assessed if the recurrent disease was within standard radiation target volumes. We compared patient and clinical variables between men with recurrences covered by standard salvage radiation fields and those with recurrences outside of standard fields.

Results: We identified 125 patients for study inclusion. The median PSA at imaging was 0.40 ng/mL (interquartile range 0.28-0.63). PSMA-avid disease was found in 66 patients (53%). Of these, 25 patients (38%) had PSMA-avid lesions found outside of the pelvis, 33 (50%) had lesions confined to the pelvic lymph nodes and prostate bed, and 8 (12%) men had PSMA-avid recurrence only in the prostate bed. Salvage radiation including standard Intensity Modulated Radiation Therapy (IMRT) pelvic nodal volumes would not cover PSMA-avid nodal disease in 38 men (30%). PSA at the time of imaging was statistically associated with having PSMA-avid disease outside of standard nodal fields (P <.01).

Conclusion: The 68Ga-PSMA-11 PET detects disease in a majority of patients with PSA ≤2.0 following RP. Nearly one-third of men had PSMA-avid disease that would be missed by standard radiation fields. This imaging modality may dramatically impact the design and use of post-RP salvage radiotherapy.
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http://dx.doi.org/10.1016/j.urology.2018.12.055DOI Listing
July 2019

Palliative radiotherapy near the end of life.

BMC Palliat Care 2019 Mar 23;18(1):29. Epub 2019 Mar 23.

Department of Radiation Oncology, University of California, San Francisco, 505 Parnassus Ave, L-75, 1600 Divisadero St., H1031, San Francisco, CA, 94143, USA.

Background: A significant proportion of patients with advanced cancer undergo palliative radiotherapy (RT) within their last 30 days of life. This study characterizes palliative RT at our institution and aims to identify patients who may experience limited benefit from RT due to imminent mortality.

Methods: Five hundred and-eighteen patients treated with external beam RT to a site of metastatic disease between 2012 and 2016 were included. Mann-Whitney U and chi-squared tests were used to identify factors associated with RT within 30 days of death (DRT).

Results: Median age at RT was 63 years (IQR 54-71). Median time from RT to death was 74 days (IQR 33-174). One hundred and twenty-five patients (24%) died within 30 days of RT. DRT was associated with older age at RT (64 vs. 62 years, p = 0.04), shorter interval since diagnosis (14 vs. 31 months, p <  0.001), liver metastasis (p = 0.02), lower KPS (50 vs. 70, p <  0.001), lower BMI (22 vs. 24, p = 0.001), and inpatient status at consult (56% vs. 26%, p < 0.001). Patients who died within 30 days of RT were less likely to have hospice involved in their care (44% vs. 71%, p = 0.001). DRT was associated with higher Chow and TEACHH scores at consult (p < 0.001 for both).

Conclusions: Twenty-four percent of patients received palliative RT within 30 days of death. Additional tools are necessary to help physicians identify patients who would benefit from short treatment courses or alternative interventions to maximize quality at the end of life.
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http://dx.doi.org/10.1186/s12904-019-0415-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431041PMC
March 2019

A convolutional neural network algorithm for automatic segmentation of head and neck organs at risk using deep lifelong learning.

Med Phys 2019 May 4;46(5):2204-2213. Epub 2019 Apr 4.

Department of Radiation Oncology, University of California, San Francisco, CA, 94115, USA.

Purpose: This study suggests a lifelong learning-based convolutional neural network (LL-CNN) algorithm as a superior alternative to single-task learning approaches for automatic segmentation of head and neck (OARs) organs at risk.

Methods And Materials: Lifelong learning-based convolutional neural network was trained on twelve head and neck OARs simultaneously using a multitask learning framework. Once the weights of the shared network were established, the final multitask convolutional layer was replaced by a single-task convolutional layer. The single-task transfer learning network was trained on each OAR separately with early stoppage. The accuracy of LL-CNN was assessed based on Dice score and root-mean-square error (RMSE) compared to manually delineated contours set as the gold standard. LL-CNN was compared with 2D-UNet, 3D-UNet, a single-task CNN (ST-CNN), and a pure multitask CNN (MT-CNN). Training, validation, and testing followed Kaggle competition rules, where 160 patients were used for training, 20 were used for internal validation, and 20 in a separate test set were used to report final prediction accuracies.

Results: On average contours generated with LL-CNN had higher Dice coefficients and lower RMSE than 2D-UNet, 3D-Unet, ST- CNN, and MT-CNN. LL-CNN required ~72 hrs to train using a distributed learning framework on 2 Nvidia 1080Ti graphics processing units. LL-CNN required 20 s to predict all 12 OARs, which was approximately as fast as the fastest alternative methods with the exception of MT-CNN.

Conclusions: This study demonstrated that for head and neck organs at risk, LL-CNN achieves a prediction accuracy superior to all alternative algorithms.
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http://dx.doi.org/10.1002/mp.13495DOI Listing
May 2019

AUTHOR REPLY.

Urology 2019 03;125:161-162

University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA; Department of Radiology, San Francisco VA Medical Center, San Francisco, CA.

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http://dx.doi.org/10.1016/j.urology.2018.09.040DOI Listing
March 2019

WITHDRAWN: PSMA-PET: a maturing tool.

Urology 2018 Dec 20. Epub 2018 Dec 20.

University of California San Francisco Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging, University of California, San Francisco; Department of Radiology, San Francisco VA Medical Center. Electronic address:

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http://dx.doi.org/10.1016/j.urology.2018.12.012DOI Listing
December 2018

Impact of Staging Ga-PSMA-11 PET Scans on Radiation Treatment Plansin Patients With Prostate Cancer.

Urology 2019 03 21;125:154-162. Epub 2018 Dec 21.

University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA; Department of Radiology, San Francisco VA Medical Center, San Francisco, CA. Electronic address:

Objective: To evaluate the impact of staging Ga-PSMA-11 PET imaging on radiotherapy (RT) dose and volumes in patients with prostate cancer.

Methods: Forty-five patients (89% high or very high risk by NCCN criteria) who underwent Ga-PSMA-11 PET imaging prior to definitive treatment for prostate cancer between December 2015 and December 2016 were included. Locations of Ga-PSMA-11-avid lesions were compared to Radiation Therapy Oncology Group consensus pelvic nodal volumes (clinical target volume [CTV]); coverage of lesions outside the consensus CTV was considered a major change, while dose-escalation to lesions within the consensus CTV was considered a minor change.

Results: All patients had Ga-PSMA-11 PET uptake in the prostate. Twenty-five patients (56%) had N1/M1a disease on Ga-PSMA-11 PET scan, of whom 21 (47%) were previously N0. Six patients (13%) had bone metastases on Ga-PSMA-11 PET scan, of whom 4 had prior negative bone scans. Eight patients (18%) had lymph node metastases outside the consensus CTV. Twelve patients (27%) received a RT boost to nodes within the consensus CTV. Six patients (13%) had limited bone metastases treated with focal RT. Overall PSMA PET imaging resulted in major and/or minor changes to RT plans in 24 patients (53%).

Conclusion: Ga-PSMA-11 PET imaging resulted in RT changes in 53% of patients. Prospective investigation is needed to evaluate the clinical benefit of RT changes based on staging Ga-PSMA-11 PET imaging.
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http://dx.doi.org/10.1016/j.urology.2018.09.038DOI Listing
March 2019

Metabolic syndrome is a sequela of radiation exposure in hypothalamic obesity among survivors of childhood brain tumors.

J Investig Med 2019 02 9;67(2):295-302. Epub 2018 Dec 9.

University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Survivors of childhood brain tumors may be at risk for early onset of metabolic syndrome, possibly secondary to surgery and/or radiation exposure. This study examines effects of radiation exposure to hypothalamus-pituitary-adrenal axis (HPA) on metabolic risk among survivors of childhood brain tumors. One hundred forty-two met inclusion criteria; 60 had tumor surgery plus radiation exposure (1 Gray (Gy)) to HPA. The second subgroup of 82 subjects had surgery only and were not exposed to radiation. Both subgroups had survived for approximately 5 years at the time of study. All had clinical evaluation, vital signs, anthropometry, measurement of body composition by dual X-ray absorptiometry and fasting laboratory assays (metabolic panel, insulin, C-peptide, insulin-like growth factor-1, leptin and adiponectin). Body composition data for both subgroups was compared with the National Health and Nutrition Survey (NHANES) subgroup of similar age, gender and body mass index. Cranial surgery was associated with obesity of similar severity in both subgroups. However, survivors exposed to radiation to the HPA also had increased visceral fat mass and high prevalence of growth hormone deficiency and metabolic syndrome. Fat mass alone did not explain the prevalence of the metabolic syndrome in radiation exposure subgroup. Other factors such as growth hormone deficiency may have contributed to metabolic risk. We conclude that prevalence of metabolic syndrome among subjects exposed to hypothalamic radiation was higher than expected from hypothalamic obesity alone. Radiation exposure may exert untoward endocrinopathies due to HPA exposure that worsens metabolic risk. Early screening for metabolic syndrome in this population is indicated.
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http://dx.doi.org/10.1136/jim-2018-000911DOI Listing
February 2019

Hepatocellular carcinoma presenting as spinal cord compression in Native Americans with controlled hepatitis C: two case reports.

J Med Case Rep 2018 Sep 30;12(1):282. Epub 2018 Sep 30.

Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, 11212, USA.

Background: Hepatocellular carcinoma is a common malignancy in Asia. It is associated with chronic hepatitis B virus or hepatitis C virus infection and alcoholic hepatitis. Commonly, the tumor metastasizes to the lungs, regional lymph nodes, and bone. Recently, the incidence of metastatic spinal cord compression caused by primary hepatocellular carcinoma has been reported more frequently due to improved diagnosis and therapeutic modalities. The presentation of primary hepatocellular carcinoma with spinal cord compression is very rare. To the best of our knowledge, there are only 33 such cases published to date. The majority of cases involve patients of Asian origin and are associated with hepatitis B infection.

Case Presentation: We report consecutive cases of two Native American (American Indian) patients (a 64-year-old man and a 70-year-old man) who presented with symptoms of spinal cord compression due to metastatic spread of hepatocellular carcinoma and were associated with hepatitis C infection. In one of these cases, the hepatitis C infection had been successfully controlled (hepatitis C titers were undetectable for 1 year before he presented with spinal cord compression). This occurrence in a Native American with a controlled hepatitis C infection has not been reported previously.

Conclusions: Primary care physicians, oncologists, and gastroenterologists should be cognizant of this unusual presentation of hepatocellular carcinoma in a Native American. Such knowledge may help improve early diagnosis and survival.
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http://dx.doi.org/10.1186/s13256-018-1807-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164177PMC
September 2018

Evolution on the Biophysical Fitness Landscape of an RNA Virus.

Mol Biol Evol 2018 10;35(10):2390-2400

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA.

Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics that propagates millions of independent small viral subpopulations. We demonstrate that along the axis of binding affinity, selection for escape variants and drift due to random mutations have the same direction, an atypical case in evolution. However, along folding stability, selection and drift are opposing forces whose balance is tuned by viral population size. Our results demonstrate that predictable epistatic tradeoffs between molecular traits of viral proteins shape viral evolution.
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http://dx.doi.org/10.1093/molbev/msy131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188569PMC
October 2018

In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.

J Immunother Cancer 2018 05 30;6(1):43. Epub 2018 May 30.

Department of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero Street, Suite H-1031, San Francisco, CA, 94115, USA.

Background: Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT.

Case Presentation: Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease.

Conclusions: Short-course RT is a compelling strategy that could be a means to augment response in patients with mMCC who show progression on immune checkpoint blockade. Ongoing clinical trials are investigating the relationship between RT and immunotherapy in mMCC.
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http://dx.doi.org/10.1186/s40425-018-0352-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977737PMC
May 2018

Length of Stay and Hospital Revisit After Bacterial Tracheostomy-Associated Respiratory Tract Infection Hospitalizations.

Hosp Pediatr 2018 Jan 16. Epub 2018 Jan 16.

Divisions of Hospital Medicine and.

Objectives: To identify factors associated with longer length of stay (LOS) and higher 30-day hospital revisit rates for children hospitalized with bacterial tracheostomy-associated respiratory tract infections (bTARTIs).

Methods: This was a multicenter, retrospective cohort study using administrative data from the Pediatric Health Information System database between 2007 and 2014 of patients 30 days to 17 years old with a principal discharge diagnosis of bTARTI or a principal discharge diagnosis of bTARTI symptoms with a secondary diagnosis of bTARTI. Primary outcomes of LOS (in days) and 30-day all-cause revisit rates (inpatient, observation, or emergency department visit) were analyzed by using a 3-level hierarchical regression model (discharges within patients within hospital).

Results: We included 3715 unique patients and 7355 discharges. The median LOS was 4 days (interquartile range: 3-8 days), and the 30-day revisit rate was 30.5%. Compared with children 1 to 4 years old, children aged 30 days to 12 months had both longer LOS (adjusted length of stay [aLOS] = +0.9 days; 95% confidence interval [CI]: 0.6 to 1.3) and increased hospital revisit risk (adjusted odds ratio [aOR] = 1.5; 95% CI: 1.3 to 1.7). Other factors associated with longer LOS included public insurance (aLOS = +0.5 days; 95% CI: 0.2 to 0.8), 3 or more complex chronic conditions (CCCs), mechanical ventilation (acute or chronic), and empirical anti- antibiotics (aLOS = +0.6 days; 95% CI: 0.3 to 0.9). Other factors associated with 30-day revisit included 4 or more CCCs (aOR = 1.3; 95% CI: 1.1 to 1.6) and chronic ventilator dependency (aOR = 1.1; 95% CI: 1.0 to 1.3).

Conclusions: Ventilator-dependent patients <12 months old with at least 4 CCCs are at highest risk for both longer LOS and 30-day revisit after discharge for bTARTIs. They may benefit from bTARTI prevention strategies and intensive care coordination while hospitalized.
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http://dx.doi.org/10.1542/hpeds.2017-0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790296PMC
January 2018

Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate brachytherapy.

Brachytherapy 2018 Mar - Apr;17(2):259-264. Epub 2017 Dec 2.

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

Purpose: Hydrogel spacers have been suggested to limit rectal radiation dose with improvements in clinical outcomes in patients undergoing external beam radiation treatment for prostate cancer. No studies to date have assessed the utility and dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and Drug Administration-approved hydrogel rectal spacer, for high-dose-rate (HDR) brachytherapy.

Methods: Eighteen consecutive patients scheduled for HDR brachytherapy in the treatment of prostate cancer underwent transperineal ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter implantation. Treatment plans were generated using an inverse planning simulated annealing algorithm. Rectal dosimetry for these 18 patients was compared with the 36 preceding patients treated with HDR brachytherapy without SpaceOAR.

Results: Fifty-four plans were analyzed. There was no difference in age, pretreatment prostate-specific antigen, Gleason score, clinical stage, prostate volume, or contoured rectal volume between those who received SpaceOAR and those who did not. Patients who received SpaceOAR hydrogel had significantly lower dose to the rectum as measured by percent of contoured organ at risk (median, V < 0.005% vs. 0.010%, p = 0.003; V < 0.005% vs. 0.14%, p < 0.0005; V 0.09% vs. 0.88%, p < 0.0005; V = 1.16% vs. 3.08%, p < 0.0005); similar results were seen for rectal volume in cubic centimeters. One patient who received SpaceOAR developed a perineal abscess 1 month after treatment.

Conclusions: Transperineal insertion of SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases rectal radiation dose. Further investigation is needed to assess the clinical impact of this dosimetric improvement and potential toxicity reduction.
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http://dx.doi.org/10.1016/j.brachy.2017.10.014DOI Listing
January 2019