Mixed methods evaluation of a specialty-specific system to promote physician engagement in safety and quality reporting in a large academic health system.

BACKGROUND: Incident reporting systems (IRS) can improve care quality and patient safety, yet their impact is limited by clinician engagement. Our objective was to assess barriers to reporting in a hospital-wide IRS and use data to inform ongoing improvement of a specialty-specific IRS embedded in the electronic health record targeting anaesthesiologists. METHODS: This quality improvement (QI) evaluation used mixed methods, including qualitative interviews, faculty surveys and user data from the specialty-specific IRS. We conducted 24 semi-structured interviews from January to May 2023 in a large academic health system in Northern California. Participants included adult and paediatric anaesthesiologists, operating room nurses, surgeons and QI operators, recruited through convenience and snowball sampling. We identified key themes and factors influencing engagement, which were classified using the Systems Engineering Initiative for Patient Safety framework. We surveyed hospital anaesthesiologists in January and May 2023, and characterised the quantity and type of reports submitted to the new system. RESULTS: Participants shared organisation and technology-related barriers to engagement in traditional system-wide IRSs, many of which the specialty-specific IRS addressed-specifically those related to technological access to the system. Barriers related to building psychological safety for those who report remain. Survey results showed that most barriers to reporting improved following the specialty-specific IRS launch, but limited time remained an ongoing barrier (25 respondents out of 44, 56.8%). A total of 964 reports with quality/safety concerns were submitted over the first 8 months of implementation; 47-76 unique anaesthesiologists engaged per month. The top safety quality categories of concern were equipment and technology (25.9%), clinical complications (25.3%) and communication and scheduling (19.9%). CONCLUSIONS: These findings suggest that a specialty-specific IRS can facilitate increased physician engagement in quality and safety reporting and complement existing system-wide IRSs.

An initiative to promote value-based stress test selection in primary care and cardiology clinics: A mixed methods evaluation.

OBJECTIVES: Exercise stress echocardiograms (stress echos) are overused, whereas exercise stress electrocardiograms (stress ECGs) can be an appropriate, lower-cost substitute. In this post hoc, mixed methods evaluation, we assessed an initiative promoting value-based, guideline-concordant ordering practices in primary care (PC) and cardiology clinics. METHODS: Change in percent of stress ECGs ordered of all exercise stress tests (stress ECGs and echos) was calculated between three periods: baseline (January 2019-February 2020); Period 1 with reduced stress ECG report turnaround time + PC-targeted education (began June 2020); and Period 2 with the addition of electronic health record-based alternative alert (AA) providing point-of-care clinical decision support. The AA was deployed in two of five PC clinics in July 2020, two additional PC clinics in January 2021, and one of four cardiology clinics in February 2021. Nineteen primary care providers (PCPs) and five cardiologists were interviewed in Period 2. RESULTS: Clinicians reported reducing ECG report turnaround time was crucial for adoption. PCPs specifically reported that value-based education helped change their practice. In PC, the percent of stress ECGs ordered increased by 38% ± 6% (SE) (p < 0.0001) from baseline to Period 1. Most PCPs identified the AA as the most impactful initiative, yet stress ECG ordering did not change (6% ± 6%; p = 0.34) between Periods 1 and 2. In contrast, cardiologists reportedly relied on their expertise rather than AAs, yet their stress ECGs orders increased from Period 1 to 2 to a larger degree in the cardiology clinic with the AA (12% ± 5%; p = 0.01) than clinics without the AA (6% ± 2%; p = 0.01). The percent of stress ECGs ordered was higher in Period 2 than baseline for both specialties (both p < 0.0001). CONCLUSIONS: This initiative influenced ordering behaviour in PC and cardiology clinics. However, clinicians' perceptions of the initiative varied between specialties and did not always align with the observed behaviour change.

Gearing Up for a Vaccine Requirement: A Mixed Methods Study of COVID-19 Vaccine Confidence Among Workers at an Academic Medical Center.

GOAL: Assessing barriers to vaccination among healthcare workers may be particularly important given their roles in their respective communities. We conducted a mixed methods study to explore healthcare worker perspectives on receiving COVID-19 vaccines at a large multisite academic medical center. METHODS: A total of 5,917 employees completed the COVID-19 vaccine confidence survey (20% response rate). Most participants were vaccinated (93%). Compared to vaccinated participants, unvaccinated participants were younger (60% < 44 years), more likely to be from a non-Asian minority group (48%), and more likely to be nonclinical employees (57% vs. 46%). Among the unvaccinated respondents, 53% indicated they would be influenced by their healthcare provider, while 19% reported that nothing would influence them to get vaccinated. Key perceived barriers to vaccination from the qualitative analysis included the need for more long-term safety and efficacy data, a belief in the right to make an individual choice, mistrust, a desire for greater public health information, personal health concerns, circumstances such as prior COVID-19 infection, and access issues. PRINCIPAL FINDINGS: Strategies endorsed by some participants to address their concerns about safety and access included a communication campaign, personalized medicine approaches (e.g., individual appointments to discuss how the vaccine might interact with personal health conditions), and days off to recover. Mistrust and a belief in the right to make an individual choice may be harder barriers to overcome; further dialogue is needed. APPLICATIONS TO PRACTICE: These findings reflect potential strategies for vaccine requirements that healthcare organizations can implement to enhance vaccine confidence. In addition, organizations can ask respected health professionals to serve as spokespeople, which may help shift the perspectives of unvaccinated healthcare workers.

Financial Incentives for Medical Assistants: A Mixed-Methods Exploration of Bonus Structures, Motivation, and Population Health Quality Measures.

PURPOSE: Medical assistants (MAs) have seen their roles expand as a result of team-based primary care models. Unlike their physician counterparts, MAs rarely receive financial incentives as a part of their compensation. This exploratory study aims to understand MA acceptability of financial incentives and perceived MA control over common population health measures. METHODS: We conducted semistructured focus groups between August and December of 2019 across 10 clinics affiliated with 3 institutions in California and Utah. MAs' perceptions of experienced and hypothetical financial incentives, their potential influence on workflow processes, and perceived levels of control over population health measures were discussed, recorded, and qualitatively analyzed for emerging themes. Perceived levels of control were further quantified using a Likert survey; measures were grouped into factors representing vaccinations, and workflow completed in the same day or multiple days (multiday). Mean scores for each factor were compared using repeated 1-way ANOVA with Tukey-Kramer adjustment. RESULTS: MAs reported little direct experience with financial incentives. They indicated that a hypothetical bonus representing 2% to 3% of their average annual base pay would be acceptable and influential in improving consistent performance during patient rooming workflow. MAs reported having greater perceived control over vaccinations (P <.001) and same-day measures (P <.001) as compared with multiday measures. CONCLUSIONS: MAs perceived that relatively small financial incentives would increase their motivation and quality of care. Our findings suggests target measures should focus on MA work processes that are completed in the same day as the patient encounter, particularly vaccinations. Future investigation is needed to understand the effectiveness of MA financial incentives in practice.

Relationship of socio-demographics, comorbidities, symptoms and healthcare access with early COVID-19 presentation and disease severity.

BACKGROUND: COVID-19 studies are primarily from the inpatient setting, skewing towards severe disease. Race and comorbidities predict hospitalization, however, ambulatory presentation of milder COVID-19 disease and characteristics associated with progression to severe disease is not well-understood. METHODS: We conducted a retrospective chart review including all COVID-19 positive cases from Stanford Health Care (SHC) in March 2020 to assess demographics, comorbidities and symptoms in relationship to: 1) their access point of testing (outpatient, inpatient, and emergency room (ER)) and 2) development of severe disease. RESULTS: Two hundred fifty-seven patients tested positive: 127 (49%), 96 (37%), and 34 (13%) at outpatient, ER and inpatient, respectively. Overall, 61% were age < 55; age > 75 was rarer in outpatient setting (11%) than ER (14%) or inpatient (24%). Most patients presented with cough (86%), fever/chills (76%), or fatigue (63%). 65% of inpatients reported shortness of breath compared to 30-32% of outpatients and ER patients. Ethnic/minority patients had a significantly higher risk of developing severe disease (Asian OR = 4.8 [1.6-14.2], Hispanic OR = 3.6 [1.1-11.9]). Medicare-insured patients were marginally more likely (OR = 4.0 [0.9-17.8]). Other factors associated with developing severe disease included kidney disease (OR = 6.1 [1.0-38.1]), cardiovascular disease (OR = 4.7 [1.0-22.1], shortness of breath (OR = 5.4 [2.3-12.6]) and GI symptoms (OR = 3.3 [1.4-7.7]; hypertension without concomitant CVD or kidney disease was marginally significant (OR = 2.3 [0.8-6.5]). CONCLUSIONS: Early widespread symptomatic testing for COVID-19 in Silicon Valley included many less severely ill patients. Thorough manual review of symptomatology reconfirms the heterogeneity of COVID-19 symptoms, and challenges in using clinical characteristics to predict decline. We re-demonstrate that socio-demographics are consistently associated with severity.

Effectiveness of a Lay Navigation Program in an Academic Cancer Center.

PURPOSE: A navigation program with lay navigators that targets patients with cancer who are receiving multiple treatment modalities was launched with the goal of improving care coordination. PATIENTS AND METHODS: Pseudo-randomization and mixed methods were used to evaluate the program: patients with even-numbered medical records were assigned to navigation help, and patients with odd-numbered medical records made up the control group. Eligible patients were those scheduled to receive at least two treatment modalities. Intent-to-treat, as-treated, and high-user cohorts with propensity matched controls were used to assess the outcomes: patient experience, emergency room (ER) use, and unplanned hospitalizations. In-depth patient interviews explored how and why patients interacted with the navigator program and overall patient experience. RESULTS: Marginally lower incidence rate ratios (IRRs) for both ER visits (IRR, 1.17; 95% CI, 1.00 to 1.36) and unplanned hospitalizations (IRR, 1.18; 95% CI, 0.97 to 1.43) occurred in as-treated patients who used navigation help and who lived within 50 miles of Stanford Hospital compared with their matched controls; other cohort analyses had similar results. Survey scores for patients who received help with navigation did not differ significantly from those for corresponding controls in any of the analytic cohorts. Patient interviews suggested that the navigation program had low visibility among patients and that lay navigators drove use of the program. Patient-reported positive experiences included getting help with complex scheduling, alleviating anxiousness through access to information and educational resources, and getting help with activities outside traditional health care; negative experiences stemmed from having expectations that were not met. CONCLUSION: Marginally lower rates of ER visits and unplanned hospitalizations for a small subset of patients, low penetration of the navigation program, and mixed comments from patient interviews suggest that a navigation program with a broad scope that targets a large population is not effective. Modifying the program to have a narrower scope of practice may help better target anxious or high-risk patients.

Negotiating Lay and Clinical Issues: Implementing a Lay Navigation Program in Cancer Care.

PURPOSE: Patients with cancer face daunting coordination problems at a vulnerable time. Lay navigation programs offer 1 approach to address these problems, but how to best implement these programs presents challenges. We sought to describe those implementation challenges at 1 academic cancer center to inform future efforts. METHODS: We performed a mixed methods study using standard implementation outcomes 1 year after program initiation. Quantitative data from the electronic medical record and qualitative data from in-depth interviews, focus groups, and ethnographic observations were included in analyses. The study took place at a National Cancer Institute-designated comprehensive cancer center across 12 tumor-specific clinics. RESULTS: Supportive care concerns, scheduling, and clinical-related issues were the most frequent issues navigators encountered. Effective navigation required continuous, time-consuming, invisible work, including building and maintaining a broad knowledge base of resources and health system processes, as well as cultivating relationships with diverse and changing clinical teams. The acceptability and appropriateness of lay navigator activities were mixed among clinic and social work staff, related to negotiating lines between clinical and nonclinical care. CONCLUSION: After 1 year of implementation, lay navigators still found it difficult to interpret and prioritize complex patient needs in a way that all clinical staff found appropriate. Negotiating these issues has made it difficult to develop the strong relationships with clinical teams that are needed for an integrated approach to patient care. To successfully coordinate patient care, it seems that lay navigation programs should be integrated with clinical teams to provide more seamless patient care.

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

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 (P = .01). The respective rates of 2-year regional control were 76% and 90% (P < .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.

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

BACKGROUND: As high-dose-rate (HDR) brachytherapy can preferentially spare normal anatomic structures surrounding the radiation target, we report on our experience using this technique in head and neck cancer reirradiation. METHODS: Twenty patients received HDR brachytherapy reirradiation with curative or palliative intent from 2010-2015. Clinical and toxicity outcomes were recorded. Actuarial outcomes were calculated using Kaplan-Meier analysis. RESULTS: For curative treatment, actuarial 2-year rates of local control and overall survival (OS) were 73% and 56%, respectively. Palliatively, a 6-month local control rate of 65% was seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage resection showed a trend toward improved local control and OS (P = .069 and P = .063, respectively). Thirty-three percent had grade 3 to 4 late toxicities. CONCLUSION: Curative-intent HDR brachytherapy reirradiation can provide excellent local control and encouraging OS. Given the late toxicity rates, patient selection is essential, with particular utility for younger patients or those treated with salvage resection.

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

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.

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.

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.

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

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/m2, and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m2, 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/m2) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m2 vs 22.3 kg/m2; 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.

Impact of the Primary Information Source Used for Decision Making on Treatment Perceptions and Regret in Prostate Cancer.

OBJECTIVE: To assess the impact of the primary source of information used by prostate cancer patients to select a radiation treatment on their overall treatment experience and on treatment regret. METHODS: Patients with low to favorable intermediate-risk prostate cancer treated with stereotactic body radiation therapy, intensity-modulated radiation therapy, or high-dose rate brachytherapy were surveyed. The questionnaire explored the decision-making experience, treatment experience, and treatment regret. RESULTS: In total, 322 consecutive patients were surveyed with an 86% (n=276) response rate. In total, 48% (n=132) selected their radiation oncologist as the primary information source, 23% (n=62) selected their urologist, 16% (n=44) selected the Internet, 6% (n=17) selected other patients, and 8% (n=21) selected other. In total, 39% of patients who selected the Internet as their primary information source reported their actual treatment experience to be worse than expected versus 13% of respondents who selected their urologist, 12% who selected other patients, and 2% who selected their radiation oncologist (P<0.01). Similarly, 43% who selected the Internet as their primary information source endorsed treatment regret versus 10% who selected their urologist, and 7% who selected their radiation oncologist (P<0.01). On multivariate regression, only patients who selected the Internet as their primary information source were more likely to endorse treatment regret (odds ratio, 46.47; P<0.001) and a worse treatment perception (odds ratio, 83.33; P<0.001). CONCLUSIONS: Patients who used the Internet as their primary information source were significantly more likely to endorse treatment regret and a worse than expected overall treatment experience. These data highlight the potential dangers of Internet-based resources and the importance for physicians to proactively counsel patients.

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

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/m2 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/m2 . 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.

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

PURPOSE: To determine whether pretreatment 3T multiparametric MRI (mpMRI) staging impacts biochemical recurrence-free survival (BRFS) or distant metastasis-free survival (DMFS) for men with high-risk prostate cancer treated with combination high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT). MATERIALS AND METHODS: This institutional review board-approved retrospective study included a cohort of 37 men with high-risk prostate cancer treated with HDR brachytherapy and EBRT after 3T mpMRI. Kaplan-Meier analysis was used to evaluate whether mpMRI evidence of extracapsular extension or seminal vesicle invasion (SVI) resulted in differences in BRFS or DMFS. Pretreatment and treatment-related variables were evaluated for association with biochemical failure (Phoenix definition) and distant metastatic failure using univariate Cox regression analysis. RESULTS: The median prostate-specific antigen at diagnosis was 9 ng/mL (range 2-100). Biopsy Gleason score (bGS) was ≤8 in 38% and nine in 62%. Clinical T-category was T1-T2 in 89%, T3a in 8%, and T3b in 3%. With a median followup of 30.6 months, actuarial 3-year BRFS and DMFS were 76% and 86%, respectively. Kaplan-Meier analysis revealed that mpMRI evidence of extracapsular extension or SVI resulted in significantly higher rates of both biochemical recurrence and distant failure. Using Cox regression analysis, only mpMRI evidence of SVI vs. no SVI predicted for biochemical failure (hazard ratio 13.98, p = 0.0055). CONCLUSIONS: For high-risk prostate cancer treated with combination HDR brachytherapy and EBRT, mpMRI evidence of SVI predicted for biochemical failure, whereas traditional pretreatment variables did not. Therefore, pretreatment 3T mpMRI appears useful for identifying men who may benefit from treatment intensification.

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

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.

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

OBJECTIVE: To evaluate whether preoperative urinary prostate cancer antigen 3 (PCA3) scores predict for adverse pathologic features (APFs) or progression-free survival (PFS) in men with intermediate- or high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP). MATERIALS AND METHODS: One hundred nine men with intermediate- (n = 52) or high-risk (n = 57) PCa who underwent RP were retrospectively identified. Logistic regression analysis was performed to evaluate the association of PCA3 score with various APFs (eg, extracapsular extension, seminal vesicle invasion, etc.). Among 78 men with ≥1 year of follow-up, the association between PCA3 score and PFS was assessed using Cox regression analysis. RESULTS: At RP, 52% of patients had at least 1 APF, and with median follow-up of 2.3 years, overall 3-year PFS was 70%. PCA3 was not a significant predictor of any APF on multivariate analysis (MVA), whereas canonical predictors (eg, biopsy Gleason score and initial prostate-specific antigen) remained predictive of various APFs. No significant predictors for PFS were found on MVA, although certain canonical predictors (eg, National Comprehensive Cancer Network risk group) were significant predictors of PFS on univariate analysis (UVA). PCA3 score was not a significant predictor of PFS on either UVA or MVA. CONCLUSION: Unlike in lower risk cohorts, increasing PCA3 score was not associated with any APF in this higher risk cohort, despite enrichment for APFs, nor was it associated with PFS. Notably, multiple known preoperative predictors for APFs were significant on MVA, and multiple predictors were associated with PFS on UVA. Therefore, PCA3 may not be a useful adjunct predictive marker in men with intermediate- or high-risk PCa.

Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.

BACKGROUND: Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab. METHODS: We assessed patients with advanced NSCLC treated on the phase 1 KEYNOTE-001 trial at a single institution (University of California, Los Angeles, CA, USA). Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 1 or less, had adequate organ function, and no history of pneumonitis. Patients received pembrolizumab at a dose of either 2 mg/kg of bodyweight or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks, until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. Disease response and pulmonary toxicity were prospectively assessed by Immune-related Response Criteria and Common Terminology Criteria for Adverse Events version 4.0. The primary objective of the KEYNOTE-001 trial was to assess the safety, side-effect profile, and antitumour activity of pembrolizumab. For our secondary analysis, patients were divided into subgroups to compare patients who previously received radiotherapy with patients who had not. Our primary objective was to determine whether previous radiotherapy affected progression-free survival, overall survival, and pulmonary toxicity in the intention-to-treat population. The KEYNOTE-001 trial was registered with ClinicalTrials.gov, number NCT01295827. FINDINGS: Between May 22, 2012, and July 11, 2014, 98 patients were enrolled and received their first cycle of pembrolizumab. One patient was lost to follow-up. 42 (43%) of 97 patients had previously received any radiotherapy for the treatment of NSCLC before the first cycle of pembrolizumab. 38 (39%) of 97 patients received extracranial radiotherapy and 24 (25%) of 97 patients received thoracic radiotherapy. Median follow-up for surviving patients was 32·5 months (IQR 29·8-34·1). Progression-free survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (hazard ratio [HR] 0·56 [95% CI 0·34-0·91], p=0·019; median progression-free survival 4·4 months [95% CI 2·1-8·6] vs 2·1 months [1·6-2·3]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (HR 0·50 [0·30-0·84], p=0·0084; median progression-free survival 6·3 months [95% CI 2·1-10·4] vs 2·0 months [1·8-2·1]). Overall survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (HR 0·58 [95% CI 0·36-0·94], p=0·026; median overall survival 10·7 months [95% CI 6·5-18·9] vs 5·3 months [2·7-7·7]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (0·59 [95% CI 0·36-0·96], p=0·034; median overall survival 11·6 months [95% CI 6·5-20·5] vs 5·3 months [3·0-8·5]). 15 (63%) of 24 patients who had previously received thoracic radiotherapy had any recorded pulmonary toxicity versus 29 (40%) of 73 patients with no previous thoracic radiotherapy. Three (13%) patients with previous thoracic radiotherapy had treatment-related pulmonary toxicity compared with one (1%) of those without; frequency of grade 3 or worse treatment-related pulmonary toxicities was similar (one patient in each group). INTERPRETATION: Our data suggest that previous treatment with radiotherapy in patients with advanced NSCLC results in longer progression-free survival and overall survival with pembrolizumab treatment than that seen in patients who did not have previous radiotherapy, with an acceptable safety profile. Further clinical trials investigating this combination are needed to determine the optimal treatment strategy for patients with advanced NSCLC. FUNDING: US National Institutes of Health.

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

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.

High-dose-rate brachytherapy monotherapy without androgen deprivation therapy for intermediate-risk prostate cancer.

PURPOSE: Outcomes using high-dose-rate (HDR) brachytherapy monotherapy (without androgen deprivation therapy or external beam radiation therapy) for National Comprehensive Cancer Network-defined intermediate-risk (IR) patients are limited. We report our long-term data using HDR monotherapy for this patient population. METHODS AND MATERIALS: One-hundred ninety IR prostate cancer patients were treated 1996-2013 with HDR monotherapy. Biochemical prostate-specific antigen (PSA) failure was per the Phoenix definition. Acute and late genitourinary and gastrointestinal toxicities were graded according to Common Toxicity Criteria of Adverse Events, version 4. Kaplan-Meier (KM) biochemical progression-free survival (BPFS), cause-specific survival, and overall survival rates were calculated. Univariate analyses were performed to determine relationships with BPFS. The median patient age was 66 years (43-90), and the median initial PSA was 7.4 ng/mL. The Gleason score was ≤6 in 26%, 3 + 4 in 62%, and 4 + 3 in 12%. The median treatment BED1.5 was 254 Gy; 83% of patients were treated with a dose of 7.25 Gy × six fractions delivered in two separate implants. RESULTS: With a median follow-up of 6.2 years, KM BPFS at 5/8 years was 97%/90%, cause-specific survival at 8 years was 100%, and overall survival at 5/8 years was 93%/88%. Late genitourinary toxicities were 36.3% Grade 1, 18.9% Grade 2, and 3.7% Grade 3. Late gastrointestinal toxicities were 6.3% Grade 1, 1.1% Grade 2, and no Grade ≥3. Of the patients with no sexual dysfunction before treatment, 68% maintained potency. Age, initial PSA, T stage, Gleason score, prostate volume, and percent positive cores did not correlate with BPFS. Stratifying by favorable vs. unfavorable IR groups did not affect BPFS. CONCLUSIONS: HDR brachytherapy monotherapy represents a safe and highly effective treatment for IR prostate cancer patients with long-term follow-up.