Publications by authors named "Carla L Warneke"

59 Publications

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

Cancer 2022 Apr 5;128(7):1458-1466. Epub 2022 Jan 5.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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 DIGEST grading criteria (per DIGEST version 2 [DIGEST ]).

Methods: Refined safety criteria were developed and vetted with clinical and research users. DIGEST 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 DIGEST 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 DIGEST 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 DIGEST 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. DIGEST 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.
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http://dx.doi.org/10.1002/cncr.34079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917062PMC
April 2022

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

Invest New Drugs 2021 08 13;39(4):1113-1122. Epub 2021 Feb 13.

Department of Investigational Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.
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http://dx.doi.org/10.1007/s10637-021-01074-wDOI Listing
August 2021

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.

PLoS One 2020 10;15(7):e0235461. Epub 2020 Jul 10.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

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 (
Conclusions: Two of three analyses supported non-inferiority of INF versus IVH, while one analysis was inconclusive. Compared to IVH, INF had the advantage of shorter time to administration.

Trial Registration: ClinicalTrials.gov Identifier: NCT02459964.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235461PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351205PMC
September 2020

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

Support Care Cancer 2021 Jan 20;29(1):97-105. Epub 2020 Apr 20.

Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.
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http://dx.doi.org/10.1007/s00520-020-05456-3DOI Listing
January 2021

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

Clin Cancer Res 2020 07 8;26(13):3211-3219. Epub 2020 Apr 8.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: In oropharyngeal squamous cell carcinoma (OPC), high CD8 tumor-infiltrating lymphocyte (CD8TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8TIL 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 CD8TIL 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 CD8TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment ( = 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 CD8TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8TIL change in patients with a MPR was seen ( = 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 CD8TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362306PMC
July 2020

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

JAMA Otolaryngol Head Neck Surg 2019 Nov;145(11):1053-1063

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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.
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http://dx.doi.org/10.1001/jamaoto.2019.2725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763976PMC
November 2019

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

Lancet Haematol 2018 Oct;5(10):e474-e478

Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.
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http://dx.doi.org/10.1016/S2352-3026(18)30152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247917PMC
October 2018

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

Oncologist 2018 11 17;23(11):1282-1288. Epub 2018 Aug 17.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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 ( = 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.
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http://dx.doi.org/10.1634/theoncologist.2018-0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291319PMC
November 2018

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

NPJ Breast Cancer 2018 25;4. Epub 2018 Jan 25.

3Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.

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 ( < .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 ( < .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 ( < .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.
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http://dx.doi.org/10.1038/s41523-018-0054-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785511PMC
January 2018

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

Oncologist 2018 03 6;23(3):360-366. Epub 2017 Dec 6.

Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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).
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http://dx.doi.org/10.1634/theoncologist.2017-0408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905685PMC
March 2018

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

Laryngoscope 2018 07 8;128(7):1615-1621. Epub 2017 Nov 8.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, U.S.A.

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 H 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.
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http://dx.doi.org/10.1002/lary.26986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940582PMC
July 2018

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

Dysphagia 2018 04 23;33(2):185-191. Epub 2017 Aug 23.

Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1445, Houston, TX, 77030, USA.

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.
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http://dx.doi.org/10.1007/s00455-017-9843-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423507PMC
April 2018

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

Ann Surg Oncol 2017 Oct 1;24(10):2981-2988. Epub 2017 Aug 1.

Department of Breast Surgical Oncology, University of Texas, MD Anderson Cancer Center, 1400 Pressler Drive, Unit 1434, FCT 7.5046, Houston, TX, 77030, USA.

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.
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http://dx.doi.org/10.1245/s10434-017-5952-xDOI Listing
October 2017

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

Oncologist 2017 11 1;22(11):1368-1373. Epub 2017 Aug 1.

Department of Emergency Medicine, The University of Texas Health Science Center at Houston School of Nursing, Houston, Texas, USA.

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 ( = 22); by the MDAS only, or group B ( = 22); and by neither CAM nor MDAS, or group C ( = 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 ( = .0013). Intensive care unit rates were 18%, 14%, and 2% for groups A, B, and C, respectively ( = .0004). Percentages with advance directives were 52%, 27%, and 43% for groups A, B, and C, respectively ( = .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 ( = .6392), but OS in group C exceeded those of the other groups ( < .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.
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http://dx.doi.org/10.1634/theoncologist.2017-0115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679826PMC
November 2017

Oncologic progress for the treatment of parathyroid carcinoma is needed.

J Surg Oncol 2016 Nov 18;114(6):708-713. Epub 2016 Oct 18.

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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.
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http://dx.doi.org/10.1002/jso.24407DOI Listing
November 2016

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

J Pediatr Surg 2016 Dec 17;51(12):2063-2067. Epub 2016 Sep 17.

Department of Pediatric Surgery, The McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Suite 5.258, Houston, TX 77030; Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, 1400 Pressler, Unit 1484, Houston, TX 77030. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.09.039DOI Listing
December 2016

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

Cancer 2016 09 25;122(18):2918-24. Epub 2016 Jul 25.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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.
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http://dx.doi.org/10.1002/cncr.30133DOI Listing
September 2016

Differentiating Atypical Parathyroid Neoplasm from Parathyroid Cancer.

Ann Surg Oncol 2016 09 9;23(9):2889-97. Epub 2016 May 9.

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Introduction: The differentiation of benign parathyroid gland atypia and true parathyroid carcinoma (PC) can be challenging. In some instances, patients are classified as having 'atypical parathyroid neoplasms' (APNs), explicitly acknowledging that the distinction between benign and malignant disease appears impossible to determine. This 'grey area' diagnosis makes rendering an accurate prognosis difficult, and clouds clinical management and treatment planning.

Methods: We performed a retrospective chart review of all patients undergoing operation for primary hyperparathyroidism in our institution (2000-2014). Patients with a histopathological diagnosis of PC or APN were included. Demographics, clinical characteristics, and survival rates were analyzed, and analysis was conducted using SAS 9.4 (SAS Institute, Inc., Cary, NC, USA).

Results: Fifty-four patients were included in the study-31 (57.41 %) with PC and 23 (42.59 %) with APN. PC versus APN was associated with higher parathyroid hormone (PTH) (p = 0.005) and with males (p = 0.002). Five-year overall survival (OS) from diagnosis was 82.64 % [95 % confidence interval (CI) 59.82-93.17] for the PC group and 93.33 % (95 % CI 61.26-99.03) for the APN group, while the 5-year recurrence-free survival rate was 59.63 % (95 % CI 36.32-76.81) in the PC group and 90.91 % (95 % CI 50.81-98.67) in the APN group.

Conclusion: PC and APN are distinct clinical entities with differences in tumor biology reflected in overall recurrence rates, disease-free survival, and OS. APNs present with a less accentuated biochemical profile and demonstrate an indolent clinical course compared with PCs. Efforts to improve categorization and staging of PC and APN are needed.
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http://dx.doi.org/10.1245/s10434-016-5248-6DOI Listing
September 2016

The impact of FGFR1 and FRS2α expression on sorafenib treatment in metastatic renal cell carcinoma.

BMC Cancer 2015 Apr 18;15:304. Epub 2015 Apr 18.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.

Background: Angiogenesis plays a role in tumor growth and is partly mediated by factors in both the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) pathways. Durable clinical responses with VEGF tyrosine kinase inhibitors (TKIs) may be limited by intrinsic tumor resistance. We hypothesized that FGF signaling may impact clinical responses to sorafenib.

Methods: Nephrectomy material was available from 40 patients with metastatic renal cell carcinoma (RCC) enrolled in a phase II clinical trial of sorafenib ± interferon (ClinicalTrials.gov Identifier NCT00126594). Fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor receptor substrate 2 alpha (FRS2α) expression was assessed by in situ hybridization and immunofluorescence, respectively. The relationship between fibroblast growth factor pathway marker levels and progression-free survival (PFS) was analyzed using Kaplan-Meier and Cox proportional hazards regression methods.

Results: Univariate analysis indicated that more intense FGFR1 staining was associated with shorter PFS (log-rank P = 0.0452), but FRS2α staining was not significantly associated with PFS (log-rank P = 0.2610). Multivariate Cox proportional hazards regression models were constructed for FGFR1 and FRS2α individually, adjusting for baseline Eastern Cooperative Oncology Group performance status, treatment arm and anemia status. When adjusted for each of these variables, the highest intensity level of FGFR1 (level 3 or 4) had increased progression risk relative to the lowest intensity level of FGFR1 (level 1) (P = 0.0115). The highest intensity level of FRS2α (level 3 or 4) had increased progression risk relative to the lowest intensity level of FRS2α (level 1) (P = 0.0126).

Conclusions: Increased expression of FGFR1 and FRS2α was associated with decreased PFS among patients with metastatic RCC treated with sorafenib. The results suggest that FGF pathway activation may impact intrinsic resistance to VEGF receptor inhibition.
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http://dx.doi.org/10.1186/s12885-015-1302-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406182PMC
April 2015

Effect of concurrent metastatic disease on survival in children and adolescents undergoing lung resection for metastatic osteosarcoma.

J Pediatr Surg 2015 Jan 28;50(1):157-60; discussion 160. Epub 2014 Oct 28.

Department of Pediatric Surgery, The University of Texas Medical School at Houston, Houston, Texas; Department of Pediatrics, Children's Cancer Hospital at the University of Texas M.D. Anderson Cancer Center, Houston, Texas; Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: To evaluate the impact of treated extra-pulmonary metastatic disease on overall (OS) and event-free survival (EFS) for pediatric osteosarcoma patients undergoing pulmonary metastatectomy.

Methods: We retrospectively reviewed pediatric patients who were treated for osteosarcoma at our institution from 2001 to 2011 and received pulmonary metastatectomy (n=76). We compared OS and EFS between patients with metastases limited to the lungs (Group A, n=58) to those with treated extra-pulmonary metastases (Group B, n=18) at the time of first pulmonary metastatectomy.

Results: The estimated median OS and EFS from first pulmonary metastatectomy were 2.0years (95% CI 1.5-2.8years) and 5.5months (95% CI 3.0-8.1months), respectively. Median OS was significantly greater for Group A (2.6years, 95% CI 1.9-3.8) compared to Group B (0.9years, 95% CI 0.6-1.5) (log rank p=0.0001). Median EFS was significantly greater for Group A (7.9months, 95% CI 5.0-10.7) compared to Group B (1.6months, 95% CI 0.8-2.7) (log rank p<0.0001). Independent predictors of OS included extra-pulmonary metastatic disease at the time of first thoracotomy, bilateral pulmonary metastases, and >4 nodules resected at first thoracotomy (all p<0.001).

Conclusions: Osteosarcoma patients with treated extra-pulmonary metastatic disease at the time of pulmonary metastatectomy have significantly worse survival compared to those with disease limited to the lungs.
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http://dx.doi.org/10.1016/j.jpedsurg.2014.10.038DOI Listing
January 2015

Fewer adverse events after reoperative parathyroidectomy associated with initial minimally invasive parathyroidectomy.

Am J Surg 2014 Nov 11;208(5):850-855. Epub 2014 Jul 11.

Section of Surgical Endocrinology, Department of Surgical Oncology, Houston, TX, USA. Electronic address:

Background: This study compared reoperative complication rates after initial minimally invasive parathyroidectomy and standard cervical exploration.

Methods: Records from patients who underwent 1 reoperative parathyroidectomy at a single institution (1998 to 2012) were retrospectively reviewed.

Results: Seventy-seven patients were included; 74% underwent initial standard cervical exploration. Preoperative and operative characteristics were similar between groups; 74% underwent focused, unilateral reoperation. A significantly higher rate of postoperative complications occurred in the initial standard cervical exploration group (42% vs 15%, P = .03) that could not be explained by differences in the rates of symptomatic hypocalcemia (P = .5). The type of prior parathyroidectomy was significantly associated with postoperative complications (odds ratio 4.1, 95% confidence interval 1.1 to 15.7, P = .04). In a multivariable logistic regression model that included body mass index, type of operation (for initial and reoperation), and initial operation performed prereferral as covariates, type of prior parathyroidectomy remained a significant predictor of postoperative complications.

Conclusion: Higher rates of postoperative sequelae after initial standard cervical exploration should be considered before performing routine 4-gland exploration.
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http://dx.doi.org/10.1016/j.amjsurg.2014.05.006DOI Listing
November 2014

Number of excisions required to obtain clear surgical margins and prognostic value of AJCC T category for patients with eyelid melanoma.

Br J Ophthalmol 2014 Dec 22;98(12):1681-5. Epub 2014 Jul 22.

Orbital Oncology & Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Aims: To determine the number of excisions needed to achieve clear margins and the prognostic value of the 7th edition of American Joint Committee on Cancer (AJCC) classification for eyelid melanoma.

Methods: Retrospective chart review of consecutive patients treated for eyelid melanoma from January 2006 through May 2013 by the senior author at a tertiary care cancer centre.

Results: Of the 64 patients (25 men and 39 women), clear surgical margins were achieved with a single excision in 38 patients (62%), 2 excisions in 21 patients (34%), and 3 excisions in 2 patients (3%). Need for repeat excision was not correlated with the size of the surgical margin (p=0.14) or AJCC TNM classification (p=0.15). Nodal disease at presentation was significantly associated with T category greater than T2b (p=0.0026) and shorter time to disease progression (p=0.007). Patients followed for a minimum of 1 year with T category greater than T2b had a significantly higher risk of nodal or distant metastasis (p=0.0061).

Conclusions: More than a third of patients with eyelid melanoma required more than 1 excision to achieve clear margins, supporting delayed reconstruction for eyelid melanoma. Nodal metastasis at presentation was significantly correlated with AJCC T category and time to progression.
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http://dx.doi.org/10.1136/bjophthalmol-2014-305140DOI Listing
December 2014

Correlation of American Joint Committee on Cancer T category for eyelid carcinoma with outcomes in patients with periocular Merkel cell carcinoma.

Ophthalmic Plast Reconstr Surg 2014 Nov-Dec;30(6):480-5

*Orbital Oncology/Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, †Department of Biostatistics, and ‡Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Purpose: Merkel cell carcinoma is a rare but potentially deadly cancer of the eyelid. To date, no studies have reported on clinical parameters at initial presentation of the eyelid tumor that may correlate with disease-free survival (DFS). The purpose of this study was to determine whether the American Joint Committee on Cancer (AJCC) T category for eyelid carcinoma correlates with metastasis and DFS in patients with Merkel cell carcinoma of the periocular region.

Methods: This is a retrospective cohort study from a tertiary referral cancer center. All consecutive patients treated for eyelid or periocular Merkel cell carcinoma between November 1, 1998, and November 1, 2012, were reviewed. The main outcome measures included AJCC T category for eyelid carcinoma and Merkel cell carcinoma at presentation, nodal metastasis at presentation, metastasis during follow up, and DFS.

Results: The study included 18 patients, 7 men and 11 women, with median age of 68.5 years. The AJCC T categories for both eyelid carcinoma and Merkel cell carcinoma were significantly correlated with DFS. Using the T categories for eyelid carcinoma, when TX and T2a were grouped into a single category and T2b and T3a into another category, the estimated DFS rate at 3 years was 100% for patients with TX or T2a lesions and 57% for patients with T2b or T3a lesions (p=0.0298). Four patients (22%) had lymph node metastasis at presentation. Presence of lymph node metastasis at presentation was the strongest single predictor of shorter DFS and an increased risk of metastasis during follow up (p=0.0222).

Conclusions: The AJCC eyelid carcinoma T at presentation correlates with DFS in patients with Merkel cell carcinoma of the periocular region. The DFS rate at 3 years was significantly worse for patients with T2b or more extensive tumors by eyelid carcinoma T category. Presence of lymph node metastasis at presentation was predictive of shorter DFS and an increased risk of metastasis during follow up.
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http://dx.doi.org/10.1097/IOP.0000000000000153DOI Listing
May 2015

Impact of AJCC 'T' designation on risk of regional lymph node metastasis in patients with squamous carcinoma of the eyelid.

Br J Ophthalmol 2014 Apr 15;98(4):498-501. Epub 2014 Jan 15.

Orbital Oncology & Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, , Houston, Texas, USA.

Background/aims: Squamous cell carcinoma (SCC) of eyelid is the second most common cancer of the eyelid with the potential for nodal metastasis. The purpose of this report is to determine whether primary tumour size and 'T' designation in the American Joint Committee on Cancer (AJCC) staging system, 7th edition, correlate with the risk of regional nodal metastasis in patients with eyelid SCC.

Methods: Sixty-five consecutive patients with eyelid SCC treated by one ophthalmologist from March 1999 through July 2011 were included in this retrospective cohort study. Disease was staged using the AJCC 7th edition criteria based on clinical, pathological and radiographical data. Main outcome measures included regional lymph node metastasis at presentation, local recurrence, distant metastasis and survival at last follow-up.

Results: 40 men and 25 women had a median age of 67.0 years (range 41-89). TNM designations at presentation per the AJCC 7th edition were as follows: T1N0M0, 6 patients; T2aN0M0, 11 patients; T2bN0M0, 17 patients; T2bN1M0, 2 patients; T3aN0M0, 22 patients; T3bN0M0, 2 patients; T3bN1M0, 1 patient; T4N0M0, 3 patients; and T4N1M0, 1 patient. Median follow-up was 27 months (range 1-150). Four patients had nodal metastasis at presentation. Two of these four patients had T2bN1M0 disease, one had T3bN1M0 disease and one had T4N1M0 disease. Two patients, with T3aN0M0 and T4N0M0 tumours, respectively, at presentation, developed lymph node metastasis at 2 weeks and 8.4 months, respectively, after tumour excision. The four patients who had lymph node metastases at presentation and the two who developed lymph node metastases during follow-up had tumours ≥18 mm in greatest dimension or T2b or higher at presentation. Seven local recurrences were observed during follow-up. Two-year and 3-year recurrence-free survival rates were 93% (95% CI 80% to 98%) and 82% (95% CI 63% to 92%), respectively. No distant metastasis or tumour-related death was observed during follow-up. The 2-year and 3-year disease-free survival rates were 90% (95% CI 77% to 96%) and 79% (95% CI 61% to 89%), respectively.

Conclusions: Regional nodal metastases were observed among patients who presented with tumours >T2b. Tumour size and the AJCC TNM designations correlate with metastasis and should be reported more often for eyelid SCCs to allow comparisons across centres.
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http://dx.doi.org/10.1136/bjophthalmol-2013-304434DOI Listing
April 2014

Pre-operative ultrasound identification of thyroiditis helps predict the need for thyroid hormone replacement after thyroid lobectomy.

Endocr Pract 2013 Nov-Dec;19(6):1015-20

Section of Surgical Endocrinology, Department of Surgical Oncology, University of Texas MD Anderson Cancer Center.

Objective: To evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy.

Methods: Data from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had ≥1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR.

Results: During follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 μ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 μIU/mL and US-identified thyroiditis had a 5.8-fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001).

Conclusion: A pre-operative TSH level >2.5 μIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months).
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http://dx.doi.org/10.4158/EP12334.ORDOI Listing
July 2014

Complications in the surgical treatment of pediatric melanoma.

J Pediatr Surg 2013 Jun;48(6):1249-53

Department of Pediatric Surgery, The University of Texas Medical School at Houston, Houston, TX 77030-1439, USA.

Purpose: The purpose of this study was to characterize the complications associated with surgical treatment of pediatric melanoma.

Methods: We retrospectively reviewed all pediatric patients who received surgical treatment for melanoma at our institution between 1992 and 2010. We compared complications between three groups: wide local excision only (WLE), WLE and sentinel lymph node biopsy (SLNB), and WLE and completion lymph node dissection (CLND).

Results: One hundred twenty-five patients were identified: 37 patients received WLE only, 47 received WLE and SLNB, and 41 patients had WLE and CLND. Complication rates differed between the three groups: 19% in WLE, 11% in WLE+SLNB, and 39% in WLE+CLND (P=.006). The risk of complications was significantly lower among patients having WLE+SLNB versus WLE+CLND (OR 0.19, 95% CI 0.06-0.57, P=.0032). Lymphedema was a common complication with a higher incidence in the CLND group compared to the SLNB group (19.5% vs. 2.1%, P=.01). Complications were more frequent in inguinal compared to axillary dissections (52.0% vs. 17.1%, P=.006).

Conclusions: In the surgical treatment of pediatric melanoma, the addition of a completion lymph node dissection significantly increases complication risk. Thus, it is critical to determine which patients truly benefit from this procedure.
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http://dx.doi.org/10.1016/j.jpedsurg.2013.03.018DOI Listing
June 2013

P53 mutations in advanced cancers: clinical characteristics, outcomes, and correlation between progression-free survival and bevacizumab-containing therapy.

Oncotarget 2013 May;4(5):705-14

Phase I Clinical Trials Program, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Mutations in the p53 gene are amongst the most frequent aberrations seen in human cancer. Our objective was to characterize the clinical characteristics associated with p53 mutation in patients with advanced cancer.

Methods: We retrospectively reviewed and analyzed the clinical features and response to standard systemic therapy of 145 patients with documented tumor p53 mutational status (mutant-type [mtp53] vs. wild-type [wtp53]) referred to the Clinical Center for Targeted Therapy.

Results: Sixty-six (45.5%) patients had mtp53. Mutations in p53 occurred more frequently in older patients (p= 0.015) and in Caucasians (p=0.024). The incidence of liver metastases was 69.2% vs. 43%, p=0.002 in mtp53 and wtp53, respectively. PTEN loss by immunohistochemistry was found more frequently in mtp53-bearing tumors compared to wtp53 (33.3% vs. 10%, p=0.007). The best progression-free survival (PFS) on standard systemic therapy was significantly longer with bevacizumab-containing regimens as compared to non-bevacizumab containing regimen in patients with mtp53 (median 11.0 [95% CI 5.9-16.0], n=22 vs. 4.0 months [95% CI 3.6-5.7], n=35, p<0.0001) but not those with wtp53 (median 5.0 [95% CI 2.0-7.6] vs. 6.0 [95% CI 4.0-7.5] months, p=0.318. The median overall survival from diagnosis in patients with mtp53 and wtp53 was 7.4 [95% CI 6.3-9.8] vs. 11.8 [95% CI 2.9-21.5] years, respectively (p=0.365).

Conclusion: Patients with mtp53 tumors were older at diagnosis, had more incidence of liver metastasis, and more frequent PTEN loss. The best PFS on standard systemic therapy was significantly longer with bevacizumab-containing regimens in patients with mutant p53 tumors but not in those with wtp53.
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http://dx.doi.org/10.18632/oncotarget.974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742831PMC
May 2013

Case control study of women treated with chemotherapy for breast cancer during pregnancy as compared with nonpregnant patients with breast cancer.

Oncologist 2013 10;18(4):369-76. Epub 2013 Apr 10.

Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Unit 1354, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.

Background: The purpose of this analysis was to compare disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) between pregnant and nonpregnant patients with breast cancer.

Methods: From 1989 to 2009, 75 women were treated with chemotherapy during pregnancy. Each pregnant case was matched on age and cancer stage to two nonpregnant patients with breast cancer (controls). Fisher's exact test, the Kaplan-Meier method, and Cox proportional hazards regression models were used.

Results: Median follow-up time for patients who were alive at the end of follow-up (n = 159) was 4.20 years (range: 0.28-19.94 years). DFS at 5 years was 72% (95% confidence interval [CI]: 58.3%-82.1%) for pregnant patients and 57% (95% CI: 46.7%-65.8%) for controls (p = .0115). Five-year PFS was 70% (95% CI: 56.8%-80.3%) for pregnant patients and 59% (95% CI: 49.1%-67.5%) for controls (p = .0252). Five-year OS was 77% (95% CI: 63.9%-86.4%) for pregnant patients and 71% (95% CI: 61.1%-78.3%) for controls (p = .0461). Hazard ratio estimates favored improved survival for pregnant patients in univariate analyses and multivariate analyses, controlling for age, year of diagnosis, stage, and tumor grade.

Conclusions: For patients who received chemotherapy during pregnancy, survival was comparable to-if not better than-that of nonpregnant women. Pregnant patients with breast cancer should receive appropriate local and systemic therapy for breast cancer.
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http://dx.doi.org/10.1634/theoncologist.2012-0340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639522PMC
December 2013

Primary malignant pancreatic neoplasms in children and adolescents: a 20 year experience.

J Pediatr Surg 2012 Dec;47(12):2199-204

Department of Pediatric Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.

Background: Malignant pancreatic neoplasms in children and adolescents are rare. The clinical presentation, pathologic characteristics, management, and outcomes at two institutions are discussed.

Methods: We retrospectively reviewed all pediatric patients (age <= 18 years) treated for malignant pancreatic neoplasms at two institutions between 1991 and 2011.

Results: Thirty-one patients were identified with median age of 14.7 years (4-18 years). The most common histology was solid pseudopapillary tumor (SPT) (n=22, 71%) followed by neuroendocrine tumors (n=4, 13%), pancreatoblastoma (n=4, 13%), and one unclassified spindle cell neoplasm (3%). Most patients presented with abdominal pain (n=22, 71%). Complications included pancreatic leak, pseudocyst formation, pancreatitis, pancreatic insufficiency, and small bowel obstruction. The overall 1- and 5-year survival was 96% (95% CI 74%-99%) and 78% (95% CI 43%-93%). Median follow-up among patients alive at the end of follow-up was 20 months (<1 month-16.2 years). Patients with SPT had better overall survival compared to patients with neuroendocrine tumors or pancreatoblastomas (Log-rank; p=0.0143).

Conclusion: The majority of pediatric and adolescent patients present with SPTs which are usually resectable and associated with an excellent prognosis. Other histologic subtypes more often present with distant metastases and portend a worse prognosis.
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http://dx.doi.org/10.1016/j.jpedsurg.2012.09.005DOI Listing
December 2012

Long-term follow-up data may help manage patient and parent expectations for pediatric patients undergoing thyroidectomy.

Surgery 2012 Dec;152(6):1165-71

Section of Surgical Endocrinology, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA.

Background: We investigated the incidence and impact of postoperative complications in children who underwent total thyroidectomy (TTx).

Methods: The records of all pediatric patients undergoing TTx (2001-2011) at our institution were retrospectively reviewed for the occurrence of biochemical hypothyroidism (thyroid-stimulating hormone >10 mIU/mL), laboratory assessments, and medication nonadherence.

Results: The 74 patients (median age, 12.5 years) had thyroid cancer (differentiated, n = 39; medullary, n = 16) or benign pathology (n = 19; 16 with multiple endocrine neoplasia type 2A). The median postoperative follow-up was 3.2 years; 46 patients (62%) had ≥ 1 year follow-up. Forty-one percent had ≥ 1 period of medication nonadherence; this was not associated with age at TTx (P = .30). Non-treatment-related hypothyroidism occurred in 33% of patients during postoperative year (POY) 1. The number of POY1 laboratory assessments among the 30% of patients with parathyroid dysfunction was more than twice that among patients with normal parathyroid function (median assessments per year 8 vs 3; P < .0001). Forty-four percent of patients/families reported behavioral or physiologic changes; 40% were concomitant with abnormal thyroid function.

Conclusion: More than 40% of pediatric patients were unable to fully adhere to postoperative medication regimens, and non-treatment-related hypothyroidism was common. Postoperative hypoparathyroidism doubled the number of laboratory assessments obtained. These data may help families better prepare for TTx sequelae.
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http://dx.doi.org/10.1016/j.surg.2012.08.056DOI Listing
December 2012
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