Trends in guideline-adherent chemoradiation therapy for locally advanced cervical cancer before and after the affordable care act.

OBJECTIVE: To assess trends in guideline-adherent chemoradiation therapy (GA-CRT) for locally advanced cervical cancer relative to Patient Protection and Affordable Care Act (ACA) implementation. METHODS: National Cancer Database patients treated with chemoradiation for locally advanced cervical cancer (FIGO 2018 Stage IB3-IVA) from 2004 to 2016 were included. GA-CRT was defined according to NCCN guidelines and included: 1) delivery of external beam radiation, 2) brachytherapy, and 3) chemotherapy, 4) no radical hysterectomy. Logistic regression was used to determine trends in GA-CRT relative to the ACA. Survival was also estimated using Kaplan-Meier analysis. RESULTS: 37,772 patients met inclusion criteria (Pre-ACA:16,169; Post-ACA:21,673). A total of 33,116 patients had squamous cell carcinoma and 4626 patients had other histologies. Forty-five percent of patients had lymph node-positive disease. A total of 14.6% of patients had Stage I disease, 41.8% had Stage II disease, 36.4% had Stage III disease, and 7.9% had Stage IVA disease. On multivariable analysis, medicare insurance (OR 0.91; 95%CI: 0.84-0.99 compared to commercial insurance), non-squamous histology (OR 0.83; 95%CI: 0.77-0.89 for adenocarcinoma) and increasing Charlson-Deyo score were associated with decreased odds of receiving GA care. Increasing T-stage was associated with greater receipt of GA-CRT. The percentage of the population that received guideline adherent care increased post-ACA (Pre-ACA 28%; Post-ACA 34%; p < 0.001). Adherence to treatment guidelines increased 2-year survival by 15% (GA 76%; Not GA 61%; p < 0.001). Increased 2-year survival was seen in the post-ACA cohort (Pre-ACA 62%; Post-ACA 69%; p < 0.001). CONCLUSIONS: Implementation of the ACA was associated with improved GA-CRT and survival in patients with locally advanced cervical cancer.

Trends in inpatient palliative care use for primary brain malignancies.

INTRODUCTION: Primary brain malignancies (PBMs) pose significant morbidity and poor prognosis. Despite NCCN recommendations that palliative care should be integrated into general oncologic care plans, it has been historically underused in patients with PBM. We sought to examine trends and factors associated with inpatient palliative care use in patients with PBM. METHODS: Data from the 2007-2016 National (Nationwide) Inpatient Sample was analyzed for descriptive statistics and trends. Multivariable logistic regression was used to identify factors associated with inpatient palliative care in patients with PBMs. RESULTS: Of the 510,238 observed hospitalizations of adults with PBM in a 10-year period, 37,365 (7.3%) had an associated inpatient palliative care consult. Rates of inpatient palliative care have increased significantly over the 10-year period, from 2.3 in 2007 to 11.9% in 2011. Patients receiving inpatient palliative care were less likely to receive inpatient oncologic treatment such as brain surgery, chemotherapy, or radiation compared to those without palliative care (14.6% with palliative care vs. 42.4% without, p < 0.001). They were more likely to receive life-sustaining treatments such as intubation, mechanical ventilation, tracheostomy, nutritional support, hemodialysis, or CPR (21.0% with palliative care vs. 10.4% without, p < 0.001). Palliative care was associated with decreased cost of admission ($18,602 with palliative care vs. $20,077 without). In a multiple variable logistic regression, age, non-elective admission, comorbidities, history of chemotherapy and radiation, and mechanical ventilation were associated with significantly increased odds of receiving palliative care. CONCLUSIONS: Inpatient palliative care utilization for patients hospitalized with PBM significantly increased between 2007 and 2016, though the service is still underutilized in the context of the severe symptoms and poor prognosis associated with PBM.

Trends in guideline-adherent fertility-sparing surgery for early-stage cervical cancer before and after the Affordable Care Act.

OBJECTIVE: To assess trends in guideline-adherent fertility-sparing surgery (GA-FSS) for early-stage cervical cancer relative to Patient Protection and Affordable Care Act (ACA) implementation. METHODS: National Cancer Database patients treated for Stage IA1-IB1 cervical cancer from 2004 to 2016 were included. Multivariable logistic regression was used to determined trends in GA-FSS relative to the ACA and identify patient factors independently associated with GA-FSS. RESULTS: Odds of GA-FSS increased in the post- compared to pre-ACA cohort (aOR = 1.65; 95%CI: 1.34-2.03). Decreasing age, Asian/Pacific Islander race, higher education and income levels, more recent treatment year, and lower clinical stage were independently associated with increased odds of receiving GA-FSS. In the pre- and post-ACA samples, decreasing age (per 1 year age increase; pre-ACA aOR = 0.87, 95%CI:0.85-0.90; post-ACA aOR = 0.85, 95%CI:0.83-0.87), higher education level (top vs. lowest education quartile; pre-ACA aOR = 2.08, 95%CI:1.19-3.65; post-ACA aOR = 2.00, 95%CI:1.43-2.80), and lower clinical stage (stages IA2 [pre-ACA aOR = 0.19, 95%CI:0.09-0.41; post-ACA aOR = 0.29, 95%CI:0.19-0.45] and IB1 [pre-ACA aOR = 0.06, 95%CI:0.06-0.16; post-ACA aOR = 0.16, 95%CI: 0.12-0.20] relative to stage IA1) were independently associated with increased odds of GA-FSS receipt. After the ACA, Asian/Pacific Islander race (aOR = 2.81, 95%CI: 1.81-4.36) and more recent treatment year (Spearman's ρ = 0.0348, p-value = 0.008) were also independently associated with increased odds of GA-FSS receipt. When adjusted for the pre- vs. post-ACA treatment periods, Medicaid patients were less likely to undergo GA-FSS than privately-insured patients (aOR = 1.65; 95%CI:1.34-2.03). CONCLUSIONS: Patients were more likely to receive GA-FSS post-ACA. Though the proportion of publicly-insured women increased after ACA implementation, women on Medicaid remained less likely to receive GA-FSS than women with private insurance.

Treatment Patterns and Overall Survival Outcomes of Octogenarians with Muscle Invasive Cancer of the Bladder: An Analysis of the National Cancer Database.

PURPOSE: Elderly patients with muscle invasive bladder cancer can pose a therapeutic dilemma, given multiple comorbidities which may preclude surgery. In this registry based analysis we investigated treatment patterns and survival outcomes in this group of patients. MATERIALS AND METHODS: We queried the National Cancer Database for muscle invasive (cT2-T4aN0M0) bladder cancer in patients 80 years old or older who were diagnosed from 2004 to 2013. Patients included in study underwent transurethral resection of bladder tumor followed by radical cystectomy, radical cystectomy plus chemotherapy, radiation therapy alone, chemotherapy alone, chemoradiation or no treatment. We performed Kaplan-Meier, log rank and multivariate Cox proportional hazards regression and propensity score matching. RESULTS: A total of 9,270 patients were identified with a median followup of 12.8 months. Median overall survival in patients treated with radical cystectomy alone was 23.2 months (95% CI 19.8-26.6), which was superior to that of chemotherapy alone or radiation therapy alone (p <0.0001). Those treated with chemoradiation had a median overall survival of 27.3 months (95% CI 25.0-29.7), which did not statistically differ from that of radical cystectomy alone (p = 0.39). Surgery plus chemotherapy showed the longest median overall survival of 34.5 months (95% CI 22.2-46.7, vs chemoradiation and radical cystectomy alone p <0.0001). On multivariate analysis and propensity score matching the best overall survival was seen in patients treated with surgery plus chemotherapy and there was no difference in overall survival between chemoradiation and radical cystectomy alone. CONCLUSIONS: In elderly patients with muscle invasive bladder cancer chemoradiation is an alternative definitive treatment strategy with survival equal to that of surgery alone and superior to that of chemotherapy alone or radiation therapy alone. If a patient was able to receive neoadjuvant or adjuvant chemotherapy with surgery, additional survival was observed in this nonrandomized study.

Assessment of the treatment approach and survival outcomes in a modern cohort of patients with atypical teratoid rhabdoid tumors using the National Cancer Database.

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRTs) are rare brain tumors that occur primarily in children under the age of 3 years. This report evaluates the treatment approach and survival outcomes in a large cohort of patients treated in the United States. METHODS: Using the National Cancer Database, the analysis included all ATRT patients aged 0 to 18 years who were diagnosed between 2004 and 2012 and had complete treatment data. RESULTS: Three hundred sixty-one ATRT patients were evaluated. The 5-year overall survival (OS) rate was 29.9%, and it was significantly lower for children who were less than 3 years old (5-year OS, 27.7%) versus those who were 3 years old or older (5-year OS, 37.5%; P < .001). The best outcome was seen for patients with localized disease who received trimodality therapy (surgery, chemotherapy, and radiation therapy [RT]) with a 5-year OS rate of 46.8%. The utilization of trimodality therapy significantly increased during the study period (27.7% in 2004-2008 vs 45.1% in 2009-2012; P < .01), largely because of the increased use of RT. In a multivariate analysis, treatment that did not utilize trimodality therapy was associated with significantly worse OS (hazard ratio, 2.52; 95% confidence interval (1.82-3.51). Children aged 0 to 2 years were significantly less likely to receive trimodality therapy because of decreased utilization of RT in this age group. CONCLUSIONS: The use of trimodality therapy significantly increased during the study period and was associated with improved outcomes. For patients with localized disease who received trimodality therapy, the OS rate at 5 years approached 50%. However, further research into the optimal management of children less than 3 years old is needed because of their significantly worse OS in comparison with older children. Cancer 2017;123:682-687. © 2016 American Cancer Society.

Comparison of unilateral versus bilateral intensity-modulated radiotherapy for surgically treated squamous cell carcinoma of the palatine tonsil.

BACKGROUND: The authors hypothesized that unilateral intensity-modulated radiotherapy (IMRT) would decrease toxicity compared with bilateral IMRT for patients with lateralized palatine tonsillar cancer and a neck classification of N0 to N2b, with similar oncological outcomes. METHODS: A total of 154 patients were treated with postoperative IMRT from 1997 through 2013. Data were collected prospectively from 2005 to 2013 and retrospectively collected before 2005. Of those patients with lateralized primary and N0 to N2b disease, 48 received unilateral IMRT (group 1) and 59 received bilateral IMRT (group 2); a total of 47 patients had nonlateralized primary or N2c to N3 disease and received bilateral IMRT (group 3). RESULTS: The median follow-up was 5.5 years. The 5-year locoregional control rates were similar in group 1, group 2, and group 3 (100%, 96%, and 94%, respectively; pooled comparison: P = .39 and group 1 vs group 2 comparison: P = .19). The 5-year overall survival rates were similar in group 1, group 2, and group 3 (85%, 79%, and 76%, respectively; pooled comparison: P = .60 and group 1 vs group 2 comparison: P = .25). There were no contralateral neck recurrences noted among unilaterally treated patients. Unilateral IMRT reduced acute toxicity and improved patient-reported quality of life compared with bilateral IMRT. CONCLUSIONS: Unilateral IMRT appears to reduce acute toxicity and achieves oncological outcomes similar to those of bilateral IMRT in selected patients with lateralized palatine tonsillar cancer with a neck classification of N0 to N2b. Cancer 2017;123:4594-4607. © 2017 American Cancer Society.

Improved survival with definitive chemoradiation compared to definitive radiation alone in squamous cell carcinoma of the vulva: A review of the National Cancer Database.

BACKGROUND: It is unclear whether definitive chemoradiation (CRT) results in improved overall survival compared to radiation therapy (RT) alone in patients with vulvar cancer who are not candidates for surgery. We compared these treatment strategies in the National Cancer Database (NCDB). METHODS: We identified 1352 patients with pathologically-confirmed squamous cell carcinoma of the vulva treated with definitive RT (n=353) or definitive CRT (n=999) between 2003 and 2014 in the NCDB. Exclusion criteria were metastatic disease at diagnosis, RT dose <4000cGy, follow-up <6months, and surgical treatment. Overall survival was compared using Kaplan-Meier method with log-rank test. Cox proportional hazard modeling, propensity score matching, and subgroup analyses were performed. RESULTS: The median age overall was 66 (23-90) years. The CRT group was younger (p<0.001) and had more advanced FIGO staging (p<0.001) compared to the RT group. Median radiation dose was 5940 (4000-7920) cGy. The median follow-up for living patients was longer in the CRT group (45.2months [6.0-131.6]) than RT (34.4months [6.1-127.6]) (p=0.004). The 5-year overall survival was higher in the CRT group compared to RT (49.9% vs. 27.4%, p<0.001). On multivariate analysis, CRT was associated with a reduced hazard of death compared to RT (HR: 0.76 [0.63-0.91], p=0.003). The effect remained significant after propensity score matching (HR: 0.78 [0.63-0.97], p=0.023). On subgroup analysis, patients with FIGO stage I only had a trend towards improved survival with CRT (p=0.058). CONCLUSIONS: In the NCDB, definitive chemoradiation was associated with higher overall survival compared to radiation alone in patients with squamous cell carcinoma of the vulva who did not receive surgery. These findings suggest that concurrent chemoradiation may be beneficial for select patients in the definitive setting.

Multi-institutional external validation of a novel glioblastoma prognostic nomogram incorporating MGMT methylation.

A recent nomogram for glioblastoma (GBM) was designed to incorporate methylguanine-DNA methyltransferase (MGMT) methylation status in trial patients receiving temozolomide. Since clinical trial patients are strictly selected, compared to the general population, we performed a multi-institutional, external, independent assessment of the nomogram. Consecutive adult patients with supratentorial GBM diagnosed between June 2007 and December 2014 who initiated TMZ-based concurrent chemoradiotherapy (CRT) and were not enrolled on RTOG 0525 or 0825 were eligible. We collected age, gender, MGMT status, performance status, resection extent, race, and tumor site and Cox regression analysis of overall survival (OS) was conducted with the 1-year nomogram-predicted survival (NPS). The predictive accuracy was quantified by the concordance index (c-index) as well as by separating patients into quintile-groups of the population distribution of NPS and comparing mean NPS and observed OS. Of 514 patients with GBM, 309 had all nomogram factors. Median OS was 18.7 months. NPS and observed OS demonstrated a c-index of 0.695. On univariate analysis, the NPS and all included factors except gender were significant. On multivariable analysis (MVA) the only significant factor for worse survival was lower NPS. When separated into quintile-groups of NPS, the observed survival was slightly better than the predicted survival for all but the worst prognostic group. Our multi-institutional cohort provides independent external validation of a novel GBM nomogram incorporating MGMT methylation status. No individual factor included in the nomogram retained significance on MVA after adjusting for NPS.

Integrating Immunotherapy into Multimodal Treatment of Head and Neck Cancer.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, with a significant risk of progression or death despite multimodal treatment with surgery, chemotherapy, and radiotherapy. Immune checkpoint inhibitors targeting the programmed death receptor-1 (PD1) have dramatically changed the treatment landscape for recurrent/metastatic disease, improving overall survival in both the first- and second-line palliative settings. This success has driven the investigation of treatment strategies incorporating immunotherapy earlier into the multimodal curative-intent or salvage treatment of both locally advanced and recurrent/metastatic HNSCC. This review encompassed the following three subjects, with a focus on recently reported and ongoing clinical trials: (1) the use of neoadjuvant immunotherapy prior to surgery for locally advanced HNSCC, (2) the use of immunochemoradiotherapy for locally advanced head and neck cancers, and (3) novel uses of immunotherapy in the salvage of recurrent/metastatic HNSCC via a combined modality, including reirradiation paradigms. The results of these studies are eagerly awaited to improve patient outcomes in this challenging disease.

Intensified Adjuvant Treatment for High-Risk Resected Cutaneous Angiosarcoma of the Head and Neck.

OBJECTIVE: Previous studies have highlighted the poor survival of patients with cutaneous angiosarcoma of the head and neck. Therapeutic options are limited, and effective treatment strategies are yet to be discovered. The objective of this study is to evaluate overall survival following intensified adjuvant treatment for high-risk resected angiosarcoma of the head and neck. STUDY DESIGN: Retrospective observational. SETTING: National Cancer Database (NCDB). METHODS: Patients diagnosed with nonmetastatic cutaneous angiosarcoma of the head and neck from 2004 to 2016 were identified by NCDB. We retrospectively compared demographics and overall survival between patients who received surgery and radiation therapy (SR) and patients who received surgery and chemoradiation (SRC). The χ2 test, Kaplan-Meier method, and Cox regression models were used to analyze data. RESULTS: A total of 249 patients were identified, of which 79.5% were treated with surgery and radiation alone and 20.5% were treated with surgery and chemoradiation. The addition of chemotherapy, regardless of the sequence of administration, was not associated with significantly higher overall survival. Factors associated with worse survival in both groups included positive nodal status and positive margins. Patients with positive nodes had higher overall survival with radiation doses >50.4 Gy compared to ≤50.4 Gy (hazard ratio: 2.93, confidence interval: 1.60-5.36, p < 0.001). CONCLUSION: Adjuvant chemotherapy was not significantly associated with higher overall survival for resected nonmetastatic angiosarcoma of the head and neck. Higher radiation doses appear to be prognostic for high-risk diseases.

Unmasking a Privacy Concern: Potential Identification of Patients in an Immobilization Mask from 3-Dimensional Reconstructions of Simulation Computed Tomography.

Previous studies have demonstrated that patients can be identified from 3-dimensional (3D) reconstructions of computed tomography (CT) or magnetic resonance imaging data of the brain or head and neck. This presents a privacy and security concern for scan data released to public data sets. It is unknown whether thermoplastic immobilization masks used for treatment planning in radiation therapy are sufficient to prevent facial recognition. Our study sought to evaluate whether patients with an immobilization mask could be identified on 3D reconstructions of scan data. Our study reconstructed 3D images from simulation CT (SIM-CT) scans of 35 patients and compared these to original patient photographs to test if the thermoplastic mask obfuscated facial features. Blind review from 4 facial recognition algorithms and a human (radiation oncologist) was evaluated for the ability to match 3D reconstructions of patients scans to patient images. The matching procedure was repeated against an expanded testing data set of the 35 patient photographs plus 13,233 facial photographs from the "Labeled Faces in the Wild" data set (13,268 photographs in total). Facial recognition algorithms were able to match a maximum of 83% (range, 60%-83%) of patients to the corresponding images. Radiation Oncologist blinded review correctly matched 80% of patients to the corresponding images. Ethnicity and facial hair were the most common reasons for patient mismatch. In the expanded testing data set, algorithms were also able to match a maximum of 83% (range, 57%-83%) of patients. The majority of patients were able to be identified through computer algorithm or human review even under a SIM-CT mask. These results suggest there is a potential privacy and security concern when SIM-CT data are released to publicly available data sets.

Incidence and Prognosis of Brain Metastases in Head and Neck Cancer Patients at Diagnosis.

OBJECTIVES: Limited data is available on head and neck cancer (HNC) patients presenting with brain metastases (BM) at initial diagnosis. We sought to evaluate the incidence, management, and treatment outcomes of these patients using the National Cancer Database (NCDB). METHODS: We identified 465,925 patients diagnosed with HNC between 2010 and 2015 in the NCDB. 14,583 of these patients presented with metastatic disease to any site. 440 of these patients had BM at the time of initial diagnosis. Overall survival was compared using the Kaplan-Meier method. Cox proportional hazard modeling, propensity score matching, and subgroup analyses were performed. RESULTS: The median age overall was 62.0 years. Nasopharynx NOS (13.2%) and Parotid Gland (10.9%) were the most common anatomical sites with the highest frequency of BM. The overall median survival time was 7.1 months. Predictors for the presence of BM included distant metastasis to the bone, liver, or lung on univariate analysis, and bone or lung on multivariate analysis. High-risk Human Papilloma Virus status was associated with a lower chance of BM. No pattern was determined when comparing lymph node level involvement and BM. The median survival for patients receiving radiation therapy and multi-agent chemotherapy was 8.4 and 11.7 months, respectively. Immunotherapy administered as first course therapy did not influence median survival. Most patients received radiation (62.7%) therapy and chemotherapy (50.2%). CONCLUSIONS: The data extracted and analyzed from the NCDB should work to aid in the surveillance and management of BM in patients with HNC. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2543-E2552, 2021.

Adverse events of after-loading high dose rate brachytherapy reported to the United States Food and Drug Administration (FDA).

PURPOSE: To provide an assessment of safety regarding high-dose-rate after-loading brachytherapy (HDR-BT) based on adverse events reported to the OpenFDA, an open access database maintained by the United States Food and Drug Administration (FDA). METHODS: OpenFDA was queried for HDR-BT events between 1993 and 2019. A brachytherapist categorized adverse events (AEs) based on disease site, applicator, manufacturer, event type, dosimetry impact, and outcomes. Important findings are summarized. RESULTS: 372 AEs were reported between 1993 and 2019, with a downwards trend after 2014. Nearly half of AEs (48.9%) were caused by a device malfunction, and 27.4% resulted in patient injury. Breast (49.2%) and Gyn (23.7%) were the most common disease sites of AEs. Applicator breaks cause the majority of AEs (64.2%) and breast balloon implants were the most common applicator to malfunction (38.7%). User error contributed to only 16.7% of events. 11.0% of events required repair of the afterloader. There were no reported staff injuries or patient deaths from an AE, however 24.7% of patients received resultant incorrect radiation dose, 16.4% required additional procedures to rectify the AE, and 3.0% resulted in unintended radiation to staff. CONCLUSION: The OpenFDA database has shown a decreasing trend in AEs since 2014 for HDR-BT. Most AEs are not caused by user error and do not cause patient injury or incorrect radiation dose. Investigation into methods to prevent failures and improve applicators such as the breast balloon could improve safety. These results support the continued use of HDR-BT as a safe treatment modality for cancer.

Management of Muscle-Invasive Bladder Cancer During a Pandemic: Impact of Treatment Delay on Survival Outcomes for Patients Treated With Definitive Concurrent Chemoradiotherapy.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making to ensure that the benefit of early intervention for muscle-invasive bladder cancer exceeds the risk of contracting COVID-19 in the clinical setting. It is unknown whether treatment delays for patients eligible for curative chemoradiation (CRT) compromise long-term outcomes. PATIENTS AND METHODS: We used the National Cancer Data Base to investigate whether there is an association between a ≥ 90-day delay from transurethral resection of bladder tumor (TURBT) in initiating CRT and overall survival. We included patients with cT2-4N0M0 muscle-invasive bladder cancer from 2004 to 2015 who underwent TURBT and curative-intent concurrent CRT. Patients were grouped on the basis of timing of CRT: ≤ 89 days after TURBT (earlier) vs. ≥ 90 and < 180 days after TURBT (delayed). RESULTS: A total of 1387 (87.5%) received earlier CRT (median, 45 days after TURBT; interquartile range, 34-59 days), and 197 (12.5%) received delayed CRT (median, 111 days after TURBT; interquartile range, 98-130 days). Median overall survival was 29.0 months (95% CI, 26.0-32.0) versus 27.0 months (95% CI, 19.75-34.24) for earlier and delayed CRT (P = .94). On multivariable analysis, delayed CRT was not associated with an overall survival difference (hazard ratio, 1.05; 95% CI, 0.87-1.27; P = .60). CONCLUSION: Although these results are limited and require validation, short, strategic treatment delays during a pandemic can be considered on the basis of clinician judgment.

The role of brachytherapy in the management of brain metastases: a systematic review.

PURPOSE: Brain metastases have a highly variable prognosis depending on the primary tumor and associated prognostic factors. Standard of care for patients with these tumors includes craniotomy, stereotactic radiosurgery (SRS), or whole brain radiotherapy (WBRT) for patients with brain metastases. Brachytherapy shows great promise as a therapy for brain metastases, but its role has not been sufficiently explored in the current literature. MATERIAL AND METHODS: The PubMed, Cochrane, and Scopus databases were searched using a combination of search terms and synonyms for brachytherapy, brain neoplasms, and brain metastases, for articles published between January 1st, 1990 and January 1st, 2018. Of the 596 articles initially identified, 37 met the inclusion criteria, of which 14 were review articles, while the remaining 23 papers with detailing individual studies were fully analyzed. RESULTS: Most data focused on 125I and suggested that it offers rates of local control and overall survival comparable to standard of care modalities such as SRS. However, radiation necrosis and regional recurrence were often high with this isotope. Studies using photon radiosurgery modality of brachytherapy have also been completed, resulting superior regional control as compared to SRS, but worse local control and higher rates of radiation necrosis than 125I. More recently, studies using the 131Cs for brachytherapy offered similar local control and survival benefits to 125I, with low rates of radiation necrosis. CONCLUSIONS: For a variety of reasons including absence of physician expertise in brachytherapy, lack of published data on treatment outcomes, and rates of radiation necrosis, brachytherapy is not presently a part of standard paradigm for brain metastases. However, our review indicates brachytherapy as a modality that offers excellent local control and quality of life, and suggested that its use should be further studied.

Overall survival comparison between androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) vs ADT plus EBRT with brachytherapy boost in clinically node-positive prostate cancer.

PURPOSE: Optimal therapy for clinically node-positive, nonmetastatic (cN1) prostate cancer (PC) patients remains controversial, ranging from aggressive local therapy to palliative systematic therapy alone. Despite guideline support, it is unclear if a brachytherapy (BT) boost should be considered for cN1 patients as these patients were excluded from randomized trials establishing its benefit. Herein, we compare definitive radiation therapy (RT) with or without a BT boost in cN1 PC. METHODS AND MATERIALS: The National Cancer Database was used to identify men with cN1 PC treated with definitive RT and concomitant androgen deprivation therapy between 2004 and 2013. Overall survival (OS) was compared between those who received external beam RT (EBRT) or combination EBRT plus BT boost (EBRT + BT) using Kaplan-Meier with propensity score matching and Cox proportional hazards. RESULTS: With a median followup of 48.5 months, 1,650 patients were eligible for this analysis, 103 (6.2%) of whom received EBRT + BT. Younger age, no medical comorbidities, and Gleason score of six were associated with higher likelihood of receiving EBRT + BT over EBRT alone. The mean (median) OS for EBRT and EBRT + BT was 99.0 (110.6) months vs 109.2 (not reached) months, respectively (p = 0.048). However, no significance difference in OS was observed between the groups after propensity score matching. On multivariable analysis, EBRT + BT was not significantly associated with improved OS (adjusted HR 0.67, 95% CI, 0.41-1.07, p = 0.098). CONCLUSIONS: In this retrospective, observational study of patients with cN1 PC treated with definitive RT and concomitant androgen deprivation therapy, EBRT + BT had an unadjusted improvement in OS compared with EBRT alone that lost statistical significance after multivariable adjustment and propensity score matching.

Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts.

Phosphodiesterases (PDEs) are enzymes that degrade cellular cAMP and cGMP and are thus essential for regulating the cyclic nucleotides. At least 11 families of PDEs have been identified, each with a distinctive structure, activity, expression, and tissue distribution. The PDE type-3, -4, and -5 (PDE3, PDE4, PDE5) are localized to specific regions of the cardiomyocyte, such as the sarcoplasmic reticulum and Z-disc, where they are likely to influence cAMP/cGMP signaling to the end effectors of contractility. Several PDE inhibitors exhibit remarkable hemodynamic and inotropic properties that may be valuable to clinical practice. In particular, PDE3 inhibitors have potent cardiotonic effects that can be used for short-term inotropic support, especially in situations where adrenergic stimulation is insufficient. Most relevant to this review, PDE inhibitors have also been found to have cytoprotective effects in the heart. For example, PDE3 inhibitors have been shown to be cardioprotective when given before ischemic attack, whereas PDE5 inhibitors, which include three widely used erectile dysfunction drugs (sildenafil, vardenafil and tadalafil), can induce remarkable cardioprotection when administered either prior to ischemia or upon reperfusion. This article provides an overview of the current laboratory and clinical evidence, as well as the cellular mechanisms by which the inhibitors of PDE3, PDE4 and PDE5 exert their beneficial effects on normal and ischemic hearts. It seems that PDE inhibitors hold great promise as clinically applicable agents that can improve cardiac performance and cell survival under critical situations, such as ischemic heart attack, cardiopulmonary bypass surgery, and heart failure.

Association of Posttreatment Lymphopenia and Elevated Neutrophil-to-Lymphocyte Ratio With Poor Clinical Outcomes in Patients With Human Papillomavirus-Negative Oropharyngeal Cancers.

IMPORTANCE: Better biomarkers are needed for human papillomavirus (HPV)-negative oropharyngeal cancer (OPC) to identify patients at risk of recurrence. Lymphopenia and an elevated ratio of neutrophils to lymphocytes (NLR) have been associated with poor disease outcomes in a number of solid tumors. OBJECTIVE: To test the hypothesis that postradiotherapy lymphopenia and elevated NLR are associated with poor clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: This single-institution retrospective analysis included patients with HPV-negative OPC treated from January 1, 1997, through January 4, 2017. Median follow-up was 37 months (range, 2-197 months). A total of 108 patients with HPV-negative OPC and at least 1 complete blood cell count 2 to 12 months after the start of radiotherapy were included. Data were analyzed from August 26 to September 7, 2017. INTERVENTIONS: Surgery followed by radiotherapy vs definitive radiotherapy, with or without chemotherapy. MAIN OUTCOMES AND MEASURES: Absolute lymphocyte (ALC) and absolute neutrophil (ANC) counts were tested as variables affecting locoregional control, recurrence-free survival, and overall survival. RESULTS: Of a total of 108 patients included in the analysis (87.0% male; mean age, 56 years [range, 35-84 years]), 57 received surgery followed by postoperative radiotherapy and 51 received definitive radiotherapy. During treatment, 67 of 79 patients (84.8%) had grades 3 to 4 lymphopenia and 17 of 79 (21.5%) had grade 4 lymphopenia. The ANC recovered by 6 months after radiotherapy, but ALC remained depressed to 1 year after radiotherapy. Posttreatment lymphopenia and elevated NLR were associated with worse recurrence-free and overall survival. The estimated 3-year LRC in patients with and without grades 3 to 4 lymphopenia at 3 months after radiotherapy start was 73% vs 82% (hazard ratio [HR], 0.58; 95% CI, 0.19-1.8); estimated 3-year recurrence-free survival, 36% vs 63% (HR, 0.45; 95% CI, 0.23-0.87); and estimated 3-year overall survival, 34% vs 64% (HR, 0.45; 95% CI, 0.23-0.88). In multivariable analysis, an association with worse overall survival was found for definitive radiotherapy (HR, 3.3; 95% CI, 1.6-7.1) and grades 3 to 4 lymphopenia (HR, 2.6; 95% CI, 1.3-5.5) at 3 months after radiotherapy. CONCLUSIONS AND RELEVANCE: Lymphopenia and NLR as early as 3 months after treatment start may serve as biomarkers of clinical outcomes in patients with HPV-negative OPC. These patients may benefit from adjuvant treatment intensification or closer surveillance.

The Role of PET Imaging in Gynecologic Radiation Oncology.

The goal of this review is to discuss the current utility of fluorine-18-fluorodeoxyglucose (FDG)-PET for radiation oncologists who treat gynecologic malignancies. FDG-PET/computed tomography (CT) is recommended for baseline assessment in cervical cancer and for staging in vulvar and vaginal cancer. The authors use FDG-PET/CT in definitive radiation treatment planning for cervical, vulvar, and vaginal cancer. PET may be helpful for salvage radiation treatment planning for any recurrent gynecologic malignancy. There are published data to support the use of PET in posttreatment evaluation of cervical and vulvar cancer.