Self-administered Meditation Application Intervention for Cancer Patients With Psychosocial Distress: A Pilot Study.

BACKGROUND: We explored the use of a novel smart phone-based application (APP) for delivery and monitoring of meditation to treat mood symptoms experienced by cancer patients. METHODS: We assessed the feasibility of using a meditation delivery and tracking APP over 2-weeks and its impact on cancer patients' self-reported anxiety and depression. Outpatients reporting depression and/or anxiety were recruited and randomized to the APP or waitlist control group. Assessments included an expectancy scale, exit survey, mood rating before and after each meditation, and the Edmonton Symptom Assessment Scale (ESAS-FS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) at baseline and after 2-weeks. The primary aim was to assess feasibility; secondary aims included satisfaction with the APP, association between meditation frequency and length with self-reported symptoms, and change in symptom measures (symptoms, anxiety, depression, and sleep). RESULTS: Our study included 35 participants (17 meditation group; 18 controls) who were primarily female (94%) with breast cancer (60%). The 61% enrollment rate and 71% adherence rate met pre-specified feasibility criteria. Most meditation group participants described the APP as "Useful" to "Very Useful" and would "Probably" or "Definitely" recommend its use. Mixed model analysis revealed a statistically significant association between meditation length (5, 10, or 15 minutes) and change in anxiety, with 15-minute sessions associated with greater reductions in anxiety. In the exit survey, more meditation group vs. control group participants reported improved focus, mood, and sleep. Study groups differed significantly by ESAS fatigue score change; the meditation group decreased a median of 1.5 pts (IQR 2.5) and the control group increased a median of 0.5 points (IQR 2). The meditation group, but not the control group, experienced statistically significant improvement in ESAS fatigue, depression, anxiety, appetite, and physical, psychological, and global distress. Change in PSQI and HADS anxiety and depression scores did not reveal any statistically significant between-group differences. CONCLUSIONS: This pilot study demonstrated the feasibility and acceptability of a meditation APP for cancer patients. Meditation APP users reported improvement in several measures of symptom distress. Future studies should explore ways to enhance the APP's usability and clinical benefit.

"Triple Threat" Conditions Predict Mortality Among Patients With Advanced Cancer Who Present to the Emergency Department.

BACKGROUND: Delirium, poor performance status, and dyspnea predict short survival in the palliative care setting. OBJECTIVE: Our goal was to determine whether these three conditions, which we refer to as a "triple threat," also predict mortality among patients with advanced cancers in the emergency department (ED). METHODS: The study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis. RESULTS: Twenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25-0.53), 0.28 (95% CI 0.18-0.40), and 0.15 (95% CI 0.07-0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34-0.66) vs. 0.05 (95% CI 0.02-0.09) for patients with none or one of the conditions. CONCLUSIONS: Patients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days.

Refining measurement of swallowing safety in the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) criteria: Validation of DIGEST version 2.

BACKGROUND: Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) is a validated method to grade the severity of pharyngeal swallowing impairment as a toxicity of cancer based on the degree and patterns of penetration/aspiration and pharyngeal residue over a standardly acquired radiographic modified barium swallow (MBS) study. Since its implementation in 2016, areas for the refinement of grading mild safety impairments have been identified by clinical and research users. The objective of this study was to assess the performance and validity of refined DIGESTsafety grading criteria (per DIGEST version 2 [DIGESTv2 ]). METHODS: Refined safety criteria were developed and vetted with clinical and research users. DIGESTv2 included 2 changes to the safety criteria. All MBSs with blinded DIGEST version 1 grading were sampled from a registry database (1331 patients underwent MBS over the period of December 2005 to July 2019). New criteria were applied to derive DIGESTsafety grading version 2. Measures of criterion validity, including the MD Anderson Dysphagia Inventory [MDADI] composite score, the Modified Barium Swallow Impairment Profile (MBSImP) pharyngeal total, the MBSImP hyolaryngeal components (items 8-11), and the Performance Status Scale for Head and Neck Cancer Patients [PSS-HN] diet, were correlated with DIGESTsafety and overall DIGEST grades from versions 1 and 2 and were compared pairwise between reassigned grades. RESULTS: With the application of version 2 safety criteria, 112 of 1331 examinations (8.4%) and 79 of 1331 examinations (5.9%) changed in their DIGESTsafety and overall grades, respectively. The safety and overall DIGEST grades (versions 1 and 2) significantly correlated with criterion measures, including the MBSImP pharyngeal total, laryngeal MBSImP parameters of interest, MDADI, and PSS-HN (P < .0001); correlations maintained a similar magnitude between versions 1 and 2. Forty-six upgraded examinations (reassigned from safety grade 1 per version 1 to grade 2 per version 2) performed similarly to other safety grade 2 examinations (version 1), and this was likewise true for 66 downgraded examinations (reassigned from safety grade 1 per version 1 to grade 0 per version 2). CONCLUSIONS: Refined criteria defining mild safety impairments with the DIGEST methodology changed grades in small numbers of examinations. DIGESTv2 criteria maintained criterion validity, demonstrated ordinality, and improved the performance of the method in these rare scenarios. LAY SUMMARY: Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) is a method developed and validated by the investigators in 2016 to grade the severity of pharyngeal swallowing dysfunction (dysphagia) with a decision tree or flowsheet to guide the clinician's review of a standard radiographic modified barium swallow study. This work reports on the validity of updated DIGEST criteria (version 2) that incorporate 2 modifications to the decision tree.

Manual Therapy for Fibrosis-Related Late Effect Dysphagia in head and neck cancer survivors: the pilot MANTLE trial.

INTRODUCTION: Late dysphagia that develops or persists years after head and neck cancer (HNC) is a disabling survivorship issue. Fibrosis is thought to stiffen connective tissues and compress peripheral nerve tracts, thereby contributing to diminished strength, flexibility, and in some cases denervation of swallowing muscles. Manual therapy (MT) is used in cancer survivors for pain and other indications, but it is unknown if increasing blood flow, flexibility and cervical range of motion (CROM) in the head and neck may improve late dysphagia. METHODS AND ANALYSIS: Manual Therapy for Fibrosis-Related Late Effect Dysphagia (MANTLE) is a National Cancer Institute-funded prospective single-arm pilot trial evaluating the feasibility, safety and therapeutic potential of MT in patients with late dysphagia after radiotherapy (RT) for HNC. Disease-free survivors ≥2 years after curative-intent RT for HNC with at least moderate dysphagia and grade ≥2 Common Terminology Criteria for Adverse Events version 4.0 fibrosis are eligible. The target sample size is 24 participants who begin the MANTLE programme. MANTLE is delivered in 10 MT sessions over 6 weeks with an accompanying home exercise programme (HEP). Patients then transition to a 6-week post-washout period during which they complete the HEP and then return for a final post-washout evaluation. Feasibility (primary endpoint) and safety will be examined. Serial assessments include CROM, modified barium swallow studies, quantitative MRI, electromyography (optional) and patient-reported outcomes as secondary, tertiary and exploratory endpoints. ETHICS AND DISSEMINATION: The research protocol and informed consent document was approved by the Institutional Review Board at the University of Texas MD Anderson Cancer Center. Findings will be disseminated through peer-reviewed publication that will be made publicly available on PubMed Central on acceptance for publication, in compliance with NIH public access policy. TRIAL REGISTRATION NUMBER: NCT03612531.

Effects of glutamine for prevention of radiation-induced esophagitis: a double-blind placebo-controlled trial.

Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%-30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p < .03) but not in head and neck specific symptom severity (1.2 vs 1.1, p < .60) nor in symptom interference (2.1 vs 1.7, p < .22). There was no grade 3 or higher adverse event at least possibly related to glutamine. The study was terminated for futility following interim analysis. Conclusion Oral glutamine was not associated with significant improvement in severity of ARIE, weight loss, head and neck specific symptoms or symptom interference compared with placebo in patients with advanced thoracic malignancies receiving radiotherapy to the esophagus.Clinical trial information. NCT01952847, and date of registration is September 30, 2013.

Strategies to identify hepatitis C virus infection in patients receiving anticancer therapy: a cross-sectional study.

BACKGROUND: Optimal hepatitis C virus (HCV) screening strategies for cancer patients have not been established. We compared the performance of selective HCV screening strategies. METHODS: We surveyed patients presenting for first systemic anticancer therapy during 2013-2014 for HCV risk factors. We estimated the prevalence of positivity for HCV antibody (anti-HCV) and examined factors associated with anti-HCV status using Fisher's exact test or Student's t test. Sensitivity was calculated for screening patients born during 1945-1965, patients with ≥ 1 other risk factor, or both cohorts ("combined screening"). RESULTS: We enrolled 2122 participants. Median age was 59 years (range, 18-91); 1138 participants were women. Race/ethnicity distribution was white non-Hispanic, 76% (n = 1616); Hispanic, 11% (n = 233); black non-Hispanic, 8% (n = 160); Asian, 4% (n = 78); and other, 2% (n = 35). Primary cancer distribution was non-liver solid tumor, 78% (n = 1664); hematologic cancer, 20% (n = 422); and liver cancer, 1% (n = 28). Prevalence of anti-HCV was 1.93% (95% CI, 1.39%-2.61%). Over 28% of patients with detectable HCV RNA were unaware of infection. Factors significantly associated with anti-HCV positivity included less than a bachelor's degree, birth in 1945-1965, chronic liver disease, injection drug use, and blood transfusion or organ transplant before 1992. A total of 1315 participants (62%), including 39 of 41 with anti-HCV, reported ≥ 1 risk factor. Sensitivity was 80% (95% CI, 65-91%) for birth-cohort-based, 68% (95% CI, 52-82%) for other-risk-factor-based, and 95% (95% 83-99%) for combined screening. CONCLUSION: Combined screening still missed 5% of patients with anti-HCV. These findings favor universal HCV screening to identify all HCV-infected cancer patients.

Intranasal fentanyl spray versus intravenous opioids for the treatment of severe pain in patients with cancer in the emergency department setting: A randomized controlled trial.

OBJECTIVE: Intranasal fentanyl (INF) quickly and noninvasively relieves severe pain, whereas intravenous hydromorphone (IVH) reliably treats severe cancer pain but requires vascular access. The trial evaluated the efficacy of INF relative to IVH for treating cancer patients with severe pain in an emergency department (ED) setting. METHODS: We randomized 82 patients from a comprehensive cancer center ED to receive INF (n = 42) or IVH (n = 40). Eligible patients reported severe pain at randomization (≥7, scale: 0 "none" to 10 "worst pain"). We conducted non-inferiority comparisons (non-inferiority margin = 0.9) of pain change from treatment initiation (T0) to one hour later (T60). T0 pain ratings were unavailable; therefore, we estimated T0 pain by comparing 1) T60 ratings, assuming similar group T0 ratings; 2) pain change, estimating T0 pain = randomization ratings, and 3) pain change, with T0 pain = 10 (IVH group) or T0 pain = randomization rating (INF group). RESULTS: At T60, the upper 90% confidence limit (CL) of the mean log-transformed pain ratings for the INF group exceeded the mean IVH group rating by 0.16 points (>pain). Substituting randomization ratings for T0 pain, the lower 90% CL of mean pain change in the INF group extended 0.32 points below (

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

PURPOSE: In oropharyngeal squamous cell carcinoma (OPC), high CD8+ tumor-infiltrating lymphocyte (CD8+TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8+TIL density, safety, and efficacy in patients with OPC. PATIENTS AND METHODS: Patients with newly diagnosed stage II-IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8+TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes. RESULTS: Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8+TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 0.97; 95% CI: -1.07-2.28). In each group, 6 patients (43%, 95% CI: 17.66-71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8+TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8+TIL change in patients with a MPR was seen (P = 0.059; 95% CI: -0.33-3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence. CONCLUSIONS: Durvalumab + tremelimumab did not increase CD8+TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.

Dysphagia After Primary Transoral Robotic Surgery With Neck Dissection vs Nonsurgical Therapy in Patients With Low- to Intermediate-Risk Oropharyngeal Cancer.

IMPORTANCE: A major goal of primary transoral robotic surgery (TORS) for oropharyngeal cancer is to optimize swallowing outcomes by personalized treatment based on pathologic staging. However, swallowing outcomes after TORS are uncertain, as are the outcomes compared with nonsurgical options. OBJECTIVES: To estimate rates of acute dysphagia and recovery after TORS and to compare swallowing outcomes by primary treatment modality (TORS or radiotherapy). DESIGN, SETTING, AND PARTICIPANTS: This case series study was a secondary analysis of prospective registry data from 257 patients enrolled from March 1, 2015, to February 28, 2018, at a single academic institution who, according to the AJCC Staging Manual, 7th edition TNM classification, had low- to intermediate-risk human papillomavirus-related oropharyngeal squamous cell carcinoma possibly resectable by TORS. EXPOSURE: Patients were stratified by primary treatment (75 underwent TORS and 182 received radiotherapy). MAIN OUTCOMES AND MEASURES: Modified barium swallow (MBS) studies graded per Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) and the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) questionnaires were administered at standard intervals. Prevalence and severity of dysphagia were estimated per DIGEST before and after TORS and 3 to 6 months after treatment. Moderate-severe dysphagia (DIGEST grade ≥2) was assessed using logistic regression and compared by primary treatment group. The MDASI swallowing symptom severity item scores during and after radiotherapy were compared using generalized estimating equations by treatment status at the start of radiotherapy, after induction, and after TORS. RESULTS: A total of 257 patients (mean [SD] age, 59.54 [9.07] years; 222 [86.4%] male) were included in the study. Dysphagia severity (per DIGEST) was significantly worse after TORS (r = -0.63; 95% CI, -0.78 to -0.44): 17 patients (22.7%; 95% CI, 13.8%-33.8%) had moderate-severe (DIGEST grade ≥2) acute post-TORS dysphagia significantly associated with primary tumor volume (odds ratio, 1.43; 95% CI, 1.11-1.84). DIGEST improved by 3 to 6 months but remained worse than that at baseline; at 3 to 6 months, the number of patients with DIGEST grade 2 or higher dysphagia was 5 (6.7%; 95% CI, 2.2%-14.9%) after primary TORS and 29 (15.9%; 95% CI, 10.9%-22.1%) after radiotherapy. At the start of radiotherapy, MDASI swallowing symptom severity item scores were significantly worse in the post-TORS group compared with postinduction (mean [SD] change, 2.6 [1.1]) and treatment-naive (mean [SD] change, 1.7 [0.3]) patients. This result inverted at radiotherapy end, and all groups converged at 3 to 6 months. CONCLUSIONS AND RELEVANCE: Subacute swallowing outcomes were similar regardless of primary treatment modality among patients with low- to intermediate-risk oropharyngeal squamous cell carcinoma.

Passive transfer of anti-HBc after intravenous immunoglobulin administration in patients with cancer: a retrospective chart review.

BACKGROUND: Patients previously infected with hepatitis B virus (HBV; indicated by positivity for anti-HBc) can experience HBV reactivation during cancer chemotherapy. Intravenous immunoglobulin infusion, which is frequently used in supportive care, might facilitate passive transfer of anti-HBc. We aimed to estimate the probability of passive transfer of anti-HBc after intravenous immunoglobulin infusion in patients with cancer. METHODS: We reviewed institutional databases to identify adult patients who received outpatient chemotherapy between Jan 1, 2004, and Dec 31, 2011, at the University of Texas MD Anderson Cancer Center, Houston, TX, USA. Eligible patients had received intravenous immunoglobulin therapy, had tested negative for both anti-HBc and HBsAg before infusion, and had been tested for anti-HBc after infusion. The primary endpoint was the proportion of patients who became positive for anti-HBc after intravenous immunoglobulin infusion. FINDINGS: 950 of 18 874 patients who underwent chemotherapy within the study time frame received intravenous immunoglobulin, of whom 870 had been tested for anti-HBc before infusion. 199 patients who were negative for anti-HBc before receiving intravenous immunoglobulin were retested after infusion, of whom 29 (15% [95% CI 10-20]) became positive for anti-HBc. The probability of anti-HBc conversion at 1 week after intravenous immunoglobulin infusion was 34% (95% CI 22-48) and at 12 weeks was 4% (2-7). INTERPRETATION: Conversion of patients from anti-HBc negativity to anti-HBc positivity was common after intravenous immunoglobulin administration. However, the probability of a positive test decreased with time since infusion. Positive anti-HBc tests done shortly after intravenous immunoglobulin infusion should be interpreted with caution because they might indicate passive transfer instead of true infection. FUNDING: None.

Prognostic Factors in Patients with Metastatic Breast Cancer with Bone-Only Metastases.

BACKGROUND: Patients with metastatic breast cancer with bone-only metastases (BOM) are a unique patient population without consensus regarding high-risk characteristics, which we sought to establish. METHODS: We identified 1,445 patients with BOM followed for at least 6 months at MD Anderson Cancer Center from January 1, 1997, to December 31, 2015. RESULTS: Seventy-one percent (n = 936) of the 1,325 patients with BOM with available pain characterization were symptomatic at time of BOM diagnosis. Pain was more common in patients with lytic compared with blastic or sclerotic metastases (odds ratio [OR], 1.79; 95% confidence interval [CI,] 1.26-2.53) and multiple versus single bone metastases (OR, 1.37; 95% CI, 1.03-1.83). Poorer overall survival (OS) was also noted in patients with multiple bone metastases (median OS, 4.80 years; 95% CI, 4.49-5.07) compared with single bone metastasis (median OS, 7.54 years; 95% CI, 6.28-10.10) and in patients with metastases in both the axial and appendicular skeleton (median OS, 4.58 years; 95% CI, 4.23-4.96) compared with appendicular-only (median OS, 6.78 years; 95% CI, 5.26-7.96) or axial-only metastases (median OS, 5.62 years; 95% CI, 4.81-6.69). Black/non-Hispanic patients had poorer outcomes, and patients aged 40-49 years at time of breast cancer diagnosis had significantly better OS compared with both younger and older patient groups. CONCLUSION: Overall, several risk features for decreased OS were identified, including multiple bone metastases and both axial and appendicular skeleton involvement. Multiple bone metastases and lytic bone metastases were associated with increased pain. IMPLICATIONS FOR PRACTICE: Patients with metastatic breast cancer and bone-only metastases (BOM) represent a poorly characterized patient subset. The ability to identify unique patient characteristics at time of BOM diagnosis associated with increased morbidity or mortality would allow for recognition of patients who would benefit from more aggressive therapy. In this study, the largest sample of patients with BOM thus far reported is characterized, highlighting several higher-risk BOM groups, including those with multiple bone metastases and bone metastases in both the axial and appendicular skeleton at time of BOM diagnosis. In addition to tailoring current practices for these high-risk patients, ongoing studies of these patients are indicated.

Characterization of bone only metastasis patients with respect to tumor subtypes.

Metastatic breast cancer (MBC) patients with bone only metastasis (BOM) are a unique population with limited characterization. We identified patients followed at MD Anderson Cancer Center from 01/01/1997 to 12/31/2015 for at least 6 months with a BOM diagnosis as first site of metastasis. Tumor subtype (TS) was assessed by initial breast biopsy immunohistochemistry using hormonal receptor (HR) and HER2 status, with four subtypes identified: HR+/HER2-, HR+/HER2+, HR-/HER2-, HR-/HER2+. HR+ was defined as estrogen receptor or progesterone receptor ≥1%. We identified 1445 patients with BOM, 1048 with TS data available. Among these patients, the majority were HR+/HER2- (78%). Median time from breast cancer diagnosis to first bone metastasis was 2.3 years (95% CI 2.1, 2.5) and varied significantly by TS, with longer time to distant disease in HR+/HER2- patients relative to all other TS (p < .0001). Median overall survival (OS) from breast cancer diagnosis was 8.7 years (95% CI 8.0, 9.7) and varied significantly by TS with poorer OS for HR-/HER2- and HR-/HER2+ patients relative to HR+/HER2- TS (p < .0001). The 442 patients with de novo BOM disease, defined as bone metastasis diagnosis within 4 months of breast cancer diagnosis, had significantly shorter OS (p < .0001). Overall, several higher risk BOM subsets were identified in this analysis, most notably HR-/HER2+ and HR-/HER2- TS and de novo BOM patients.

Grading Dysphagia as a Toxicity of Head and Neck Cancer: Differences in Severity Classification Based on MBS DIGEST and Clinical CTCAE Grades.

Clinician-reported toxicity grading through common terminology criteria for adverse events (CTCAE) stages dysphagia based on symptoms, diet, and tube dependence. The new dynamic imaging grade of swallowing toxicity (DIGEST) tool offers a similarly scaled five-point ordinal summary grade of pharyngeal swallowing as determined through results of a modified barium swallow (MBS) study. This study aims to inform clinicians on the similarities and differences between dysphagia severity according to clinical CTCAE and MBS-derived DIGEST grading. A cross-sectional sample of 95 MBS studies was randomly selected from a prospectively-acquired MBS database among patients treated with organ preservation strategies for head and neck cancer. MBS DIGEST and clinical CTCAE dysphagia grades were compared. DIGEST and CTCAE dysphagia grades had "fair" agreement per weighted κ of 0.358 (95% CI .231-.485). Using a threshold of DIGEST ≥ 3 as reference, CTCAE had an overall sensitivity of 0.50, specificity of 0.84, and area under the curve (AUC) of 0.67 to identify severe MBS-detected dysphagia. At less than 6 months, sensitivity was 0.72, specificity was 0.76, and AUC was 0.75 while at greater than 6 months, sensitivity was 0.22, specificity was 0.90, and AUC was 0.56 for CTCAE to detect dysphagia as determined by DIGEST. Classification of pharyngeal dysphagia on MBS using DIGEST augments our understanding of dysphagia severity according to the clinically-derived CTCAE while maintaining the simplicity of an ordinal scale. DIGEST likely complements CTCAE toxicity grading through improved specificity for physiologic dysphagia in the acute phase and improved sensitivity for dysphagia in the late-phase.

Clinical Activity of Pazopanib in Patients with Advanced Desmoplastic Small Round Cell Tumor.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is an aggressive, often fatal soft tissue sarcoma that lacks an optimal salvage regimen. We retrospectively reviewed data from 29 pretreated DSRCT patients who received pazopanib at MD Anderson Cancer Center after failure of standard chemotherapies. SUBJECTS, MATERIALS, AND METHODS: Medical records of patients treated from January 2012 to December 2016 were reviewed and regression analyses were performed. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and differences in survival were assessed by a log-rank test. A landmark statistical analysis was used to assess OS at a predefined 12-week time point following pazopanib initiation. RESULTS: The mean age at pazopanib treatment was 27.5 years (range, 6.3-50.1 years). According to RECIST 1.1 criteria, 16 patients (55%) had stable disease, 1 patient (3%) had partial response, 1 patient (3%) had complete response, and 11 patients (38%) had progressive disease. Estimated median PFS was 5.63 months (95% confidence interval [CI]: 3.23-7.47). Median OS was 15.7 months (95% CI: 10.3-32.4). As of December 2016, 11 patients (38%) were still alive, with a median follow-up time of 16.8 (range 3.8-30.1) months. Doses between 400 and 800 mg were included. Pazopanib was well tolerated and 23 (79%) of the patients continued it until progression or death, 4 discontinued because of side effects, and 2 were still on pazopanib at the time of data analysis. CONCLUSION: In the largest study conducted to date in DSRCT, pazopanib was well tolerated and clinically active in heavily pretreated patients who otherwise lack good treatment options. IMPLICATIONS FOR PRACTICE: Desmoplastic small round cell tumor (DSRCT) is a rare, extremely aggressive soft tissue sarcoma subtype that most commonly occurs in adolescent and young adult males. No DSRCT-specific therapies exist, and for lack of a better treatment approach, current therapies have relied upon U.S. Food and Drug Administration-approved drugs like pazopanib that exhibit clinical activity in other sarcoma subtypes. This article describes the largest experience to date using pazopanib as salvage treatment in heavily pretreated DSRCT patients. Pazopanib was well tolerated and clinically active, surpassing predefined metrics proposed by the European Organization for Research and Treatment of Cancer indicative of "active" sarcoma drugs (5.63 months progression-free survival [PSF], with 62% of the study population achieving progression-free survival at 12 weeks).

Cough strength and expiratory force in aspirating and nonaspirating postradiation head and neck cancer survivors.

OBJECTIVE: Expiratory functions that clear aspiration from the airway are compromised in patients with neurogenic dysphagia for whom cough and expiratory force may be impaired by the primary disease process. The relationship between expiratory function, cough, and aspiration is less clear in head and neck cancer (HNC) survivors for whom the disease process does not directly impact the lower respiratory system. Our objective was to compare mechanisms of airway clearance (expiratory force and cough) with aspiration status in postradiated HNC survivors. STUDY DESIGN: Cross-sectional study. METHODS: One hundred and three disease-free HNC survivors ≥ 3-months postradiotherapy referred for modified barium swallow studies were prospectively enrolled regardless of dysphagia status. Maximum expiratory pressures (MEPs) and peak cough flow (PCF) measures were taken at enrollment and examined as a function of aspiration status using generalized linear regression methods. RESULTS: Thirty-four (33%) patients aspirated. Maximum expiratory pressure and PCF demonstrated a moderate positive correlation (Pearson's r = 0.35). Adjusting for sex and age, MEPs were on average 19.2% lower (21.1 cm H2 O, 95% confidence interval [CI] 5.3, 36.8) among aspirators. Peak cough flow was also 14.9% lower (59.6 L/minute, 95% CI 15.8, 103.3) among aspirators after adjusting for age and sex. CONCLUSION: Expiratory functions were depressed in postradiated HNC aspirators relative to nonaspirators, suggesting that airway protection impairments may extend beyond disrupted laryngopharyngeal mechanisms in the local treatment field. Exercises to strengthen subglottic expiratory force-generating capacity may offer an adjunctive therapeutic target to improve airway protection in chronic aspirators after head and neck radiotherapy. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1615-1621, 2018.

Improved Locoregional Control in a Contemporary Cohort of Nonmetastatic Inflammatory Breast Cancer Patients Undergoing Surgery.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer characterized by rapid progression and early metastatic dissemination. The purpose of this study was to assess contemporary rates of local regional recurrence (LRR) in the era of trimodality therapy for nonmetastatic IBC and identify risk factors leading to local failure. METHODS: A total of 114 patients with nonmetastatic IBC receiving trimodality therapy (neoadjuvant chemotherapy, surgery, and radiation therapy) were identified from a prospectively collected database from 2007 to 2015 and outcomes analyzed. RESULTS: Median age at diagnosis was 52 years, and the median follow-up was 3.6 years. Sixty-three (55%) patients presented with N2 IBC, and 52 patients (45%) presented with N3 IBC. Local regional recurrence was observed during follow-up for four patients; 25 died, and 85 were censored at last follow-up. Surgical margins were negative in 99% of patients (n = 113). The 2-year probability of LRR was 3.19% (95% confidence interval 1.03-9.90%). Five-year overall survival for this cohort was 69.14%. Improvement in disease-free survival was seen among patients with HER2+ subtype, clinical stage IIIB, complete or partial radiologic response to neoadjuvant therapy, pathologic complete response, and lower nodal burden on presentation. CONCLUSIONS: Locoregional recurrences were rare at a median of 3.6 years follow-up in a contemporary cohort of IBC patients treated with trimodality therapy. Although longer follow-up is needed, aggressive surgical resection to negative margins in the frame of trimodality therapy with curative intent can lead to LRR rates that mirror non-IBC rates.

Advance Directives, Hospitalization, and Survival Among Advanced Cancer Patients with Delirium Presenting to the Emergency Department: A Prospective Study.

BACKGROUND: To improve the management of advanced cancer patients with delirium in an emergency department (ED) setting, we compared outcomes between patients with delirium positively diagnosed by both the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS), or group A (n = 22); by the MDAS only, or group B (n = 22); and by neither CAM nor MDAS, or group C (n = 199). MATERIALS AND METHODS: In an oncologic ED, we assessed 243 randomly selected advanced cancer patients for delirium using the CAM and the MDAS and for presence of advance directives. Outcomes extracted from patients' medical records included hospital and intensive care unit admission rate and overall survival (OS). RESULTS: Hospitalization rates were 82%, 77%, and 49% for groups A, B, and C, respectively (p = .0013). Intensive care unit rates were 18%, 14%, and 2% for groups A, B, and C, respectively (p = .0004). Percentages with advance directives were 52%, 27%, and 43% for groups A, B, and C, respectively (p = .2247). Median OS was 1.23 months (95% confidence interval [CI] 0.46-3.55) for group A, 4.70 months (95% CI 0.89-7.85) for group B, and 10.45 months (95% CI 7.46-14.82) for group C. Overall survival did not differ significantly between groups A and B (p = .6392), but OS in group C exceeded those of the other groups (p < .0001 each). CONCLUSION: Delirium assessed by either CAM or MDAS was associated with worse survival and more hospitalization in patients with advanced cancer in an oncologic ED. Many advanced cancer patients with delirium in ED lack advance directives. Delirium should be assessed regularly and should trigger discussion of goals of care and advance directives. IMPLICATIONS FOR PRACTICE: Delirium is a devastating condition among advanced cancer patients. Early diagnosis in the emergency department (ED) should improve management of this life-threatening condition. However, delirium is frequently missed by ED clinicians, and the outcome of patients with delirium is unknown. This study finds that delirium assessed by the Confusion Assessment Method or the Memorial Delirium Assessment Scale is associated with poor survival and more hospitalization among advanced cancer patients visiting the ED of a major cancer center, many of whom lack advance directives. Therefore, delirium in ED patients with cancer should trigger discussion about advance directives.

Oncologic progress for the treatment of parathyroid carcinoma is needed.

BACKGROUND AND OBJECTIVES: Parathyroid carcinoma (PC) is rare but potentially lethal. No standardized staging system or treatment guidelines have been established. We aimed to determine whether management of PC and patient outcomes have changed at our institution over the past 35 years. METHODS: Retrospective review of patients with PC at our institution between 1980 and 2015. Patients were grouped by date of initial surgery: group 1, 1980-2001; group 2, 2002-2015. RESULTS: About 57 patients (26 in group 1; 31 in group 2) were included. Group 2 had more female patients (61%) than group 1 (31%; P = 0.033). Patients in group 2 were older at the time of initial operation (mean age 48 years in group 1 (SD:14.3) and 56 years (SD:14.6) in group 2; P = 0.034). The 5-year OS rates were 82% (95%CI 59.6%, 93%) for group 1 and 72% (95%CI 45.0%, 87.7%) for group 2. The 5-year DFS rates were 62% (95%CI 36.4%, 79.9%) for group 1 and 66% (95%CI 40.6%, 82.2%) for group 2. CONCLUSION: Management of PC and patient outcomes (OS and DFS) have not significantly changed over the past 35 years at our institution. This rare malignancy needs oncologic improvement. J. Surg. Oncol. 2016;114:708-713. © 2016 Wiley Periodicals, Inc.

Treatment outcomes in pediatric melanoma-Are there benefits to specialized care?

PURPOSE: The purpose of this study was to evaluate the impact of hospital specialization on survival in pediatric melanoma. METHODS: We reviewed all patients under 18years old with cutaneous melanoma evaluated at MD Anderson Cancer Center, a National Cancer Institute (NCI)-designated center, from 2000 to 2014. We compared overall survival (OS) and disease-free survival (DFS) between patients who underwent all treatments at MDACC (Group A, n=146) and those who underwent initial surgical treatment at a non-NCI center (Group B, n=58). Kaplan-Meier survival curves were compared using the log-rank test. RESULTS: Group A patients had significantly better OS and DFS (both p<0.001). Five-year OS was 97% (95% CI 92%-99%) in Group A versus 88% (95% CI 74%-94%) in Group B. Group survival differences were most notable in Stage 3 and 4 patients. Group A patients presenting with stage III or IV disease had a 5-year OS rate of 91.2% (95% CI 75.1%-97.1%) compared to 80.8% (95% CI 59.8%-91.5%) in Group B. The DFS rate was 94.4% (95% CI 88.5%-97.3%) in Group A versus 77.2% (95% CI 62.5%-86.7%) in Group B. CONCLUSION: Surgical treatment at a comprehensive cancer center may improve outcomes for pediatric melanoma especially for patients presenting with later stage disease. LEVEL OF EVIDENCE: Case-control study: Level III.

Delirium frequency among advanced cancer patients presenting to an emergency department: A prospective, randomized, observational study.

BACKGROUND: The frequency of delirium among patients with cancer presenting to the emergency department (ED) is unknown. The purpose of this study was to determine delirium frequency and recognition by ED physicians among patients with advanced cancer presenting to the ED of The University of Texas MD Anderson Cancer Center. METHODS: The study population was a random sample of English-speaking patients with advanced cancer who presented to the ED and met the study criteria. All patients were assessed with the Confusion Assessment Method (CAM) to screen for delirium and with the Memorial Delirium Assessment Scale (MDAS) to measure delirium severity (mild, ≤15; moderate, 16-22; and severe, ≥23). ED physicians were also asked whether their patients were delirious. RESULTS: Twenty-two of the 243 enrolled patients (9%) had CAM-positive delirium, and their median MDAS score was 14 (range, 9-21 [30-point scale]). The median age of the enrolled patients was 62 years (range, 19-89 years). Patients with delirium had a poorer performance status than patients without delirium (P < .001); however, the 2 groups did not differ in other characteristics. Ten of the 99 patients who were 65 years old or older (10%) had CAM-positive delirium, whereas 12 of the 144 patients younger than 65 years (8%) did (P = .6). According to the MDAS scores, delirium was mild in 18 patients (82%) and moderate in 4 patients (18%). Physicians correctly identified delirium in 13 of the CAM-positive delirious patients (59%). CONCLUSIONS: Delirium is relatively frequent and is underdiagnosed by physicians in patients with advanced cancer who are visiting the ED. Further research is needed to identify the optimal screening tool for delirium in ED. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2918-2924. © 2016 American Cancer Society.