Publications by authors named "Jimin Wu"

126 Publications

Oncology patients' perception of physicians who use an integrated electronic health record (EHR) during clinic visits: PRIME-EHR double-blind, randomized controlled trial.

Cancer 2021 Jul 15. Epub 2021 Jul 15.

Department of Palliative Care, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Patients with cancer prefer and positively perceive physicians who communicate face-to-face without the use of a computer. However, the use of electronic health records (EHRs) in the examination room remains a practical necessity. On the basis of existing literature, the authors developed and tested an integration model, PRIME-EHR, that focuses on the best-practice guidelines. To their knowledge, no randomized controlled trials (RCTs) have been conducted to test the effectiveness of such models.

Methods: In this double-blind, crossover RCT, 120 eligible patients with cancer were enrolled between April 1, 2019 and February 15, 2020 at The University of Texas MD Anderson Cancer Center. The objectives were to compare patients' perceptions of physicians' skills and their overall preference after they watched 2 standardized, scripted video vignettes of physicians: 1 portraying the use of a standard EHR and the other portraying the use of a PRIME-EHR. Actors and patients were blinded to the purpose of the study. Investigators were blinded to the sequence of videos watched by the patients. Validated questionnaires to rate physicians' compassion (0 = best, 50 = worst), communication skills (14 = poor, 70 = excellent), and professionalism (4 = poor, 20 = very good) were used.

Results: PRIME-EHR, compared with the standard EHR, resulted in better scores for physician compassion (median score, 5 [interquartile range, 0-10] vs 12 [interquartile range, 4-25]; P = .0009), communication skills (median score, 69 [interquartile range, 63-70] vs 61 [interquartile range, 50-69]; P = .0026), and professionalism (median score, 20 [interquartile range, 18-20] vs 18 [interquartile range, 14-20]; P = .0058). The majority of patients preferred physicians who used PRIME-EHR (n = 70 [77%] vs n = 21 [23%]; P < .0001).

Conclusions: The PRIME-EHR approach significantly improved patients' perceptions of and preference for the physicians. This integrated model of health care delivery has the potential to improve communication and compassion in cancer care.
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http://dx.doi.org/10.1002/cncr.33778DOI Listing
July 2021

IDH mutation status and the development of venous thromboembolism in astrocytoma patients.

J Neurol Sci 2021 Jun 15;427:117538. Epub 2021 Jun 15.

The University of Texas MD Anderson Cancer Center, Department of Neuro-Oncology, Unit 431, 1515 Holcombe Blvd, Houston, TX 77030-4009, United States of America. Electronic address:

Background: Venous thromboembolism (VTE) is a very common adverse event for astrocytoma patients, but validation of proposed risk biomarkers has been elusive. We examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients.

Methods: We conducted a retrospective chart review of 282 astrocytoma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC) from 9/1/2000 until 12/31/2013.

Results: We identified 282 astrocytoma patients consisting of 49 IDH mutant astrocytomas and 233 IDH wildtype astrocytomas. Glioblastoma was the initial histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45(19.3%) of the IDH wild type astrocytoma s (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p = 0.8663).

Conclusions: IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.
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http://dx.doi.org/10.1016/j.jns.2021.117538DOI Listing
June 2021

Changes in Overall Survival over Time for Patients with de novo Metastatic Breast Cancer.

Cancers (Basel) 2021 May 28;13(11). Epub 2021 May 28.

Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. In addition, median OS was significantly longer in patients with non-inflammatory breast cancer ( = 0.02) and patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all < 0.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for the ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.
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http://dx.doi.org/10.3390/cancers13112650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198851PMC
May 2021

A retrospective review of the use of oxymorphone immediate release for long term pain control in cancer patients with gastrostomy tubes.

Ann Palliat Med 2021 Mar 27;10(3):2662-2667. Epub 2021 Jan 27.

Department of Palliative, Rehabilitation, and Integrative Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.

Background: Cancer patients often require feeding or venting gastrostomy-tubes (G-tubes) for enteral nutrition or symptom palliation. The administration of most extended-release (ER) opioids via the G-tube or orally followed by clamping of the venting G-tube is contraindicated. Oxymorphone immediate release (IR) may be useful because of its longer half-life compared to other IR opioids. We examined the use of oxymorphone IR administered every 8 hours in patients with G-tubes.

Methods: This was a retrospective chart review of 40 consecutive cancer patients with G-tubes who underwent opioid rotation (OR) to oxymorphone. Demographics, symptoms, morphine equivalent daily dose (MEDD), and oxymorphone dose were collected. Successful OR was defined as a 2-point or 30% reduction in pain score and continued use of oxymorphone at follow-up in outpatient setting, or discharge in inpatient setting. Opioid rotation ration (ORR) between MEDD and oxymorphone in patients with successful OR was calculated as MEDD before the OR divided by total oxymorphone dose/day at follow-up or discharge.

Results: The median age was 56 years, 57.5% were white, 68% male, 47.5% (n=19) had head and neck cancer, 90% had advanced disease, 67.5% (n=27) were inpatient, and 15% (n=6) had venting G-tubes. 25/40 (62.5%) patients had successful OR to oxymorphone. The median ORR from MEDD to oxymorphone was 3.5 (IQR, 3.1-4). There were no independent predictors for successful OR, and ORR did not significantly differ among various groups.

Conclusions: Oxymorphone IR can be used successfully in cancer patients with G-tubes using an ORR of 3.5 to calculate dose from MEDD.
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http://dx.doi.org/10.21037/apm-20-969DOI Listing
March 2021

Rapid Transition to Virtual Care during the COVID-19 Epidemic: Experience of a Supportive Care Clinic at a Tertiary Care Cancer Center.

J Palliat Med 2021 Feb 2. Epub 2021 Feb 2.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

COVID-19 pandemic necessitated rapid adoption of telemedicine at our supportive care center (SCC) to ensure continuity of care while maintaining social distancing. To document the process of transition from in-person to virtual care. The charts of 1744 consecutive patients in our SCC located in the United States were retrospectively reviewed during the four weeks before transition (February 14-March 12), four weeks after transition (March 20-April 16), and transition week (March 13-March 19). Patient demographics, vital aspects of a supportive care visit such as assessments (Edmonton Symptom Assessment Scale-Financial and Spiritual [ESAS-FS], Cut-down, Annoyed, Guilty, Eye-opener Screen-Adapted to Include Drugs [CAGE-AID], and Memorial Delirium Assessment Scale [MDAS]), interdisciplinary team involvement, and visit type were recorded. In total 763 patients were seen before transition, 168 during the transition week, and 813 after transitioning to virtual care. Patient characteristics, ESAS-FS, CAGE-AID, and nurse assessment did not significantly differ among the three groups. The after-transition group had a small reduction in counseling intervention compared with before (20.2% vs. 26.2%;  = 0.0068). MDAS completion was higher after transition (99.6% vs. 98%;  = 0.007). In-person visits decreased from 100% before to 12.7% after transition ( < 0.0001) and virtual visits increased to 49.3% (video) and 38% (telephone). In-person visits decreased to 49% in the week one, 3% in week two, and <2% in week four after transition ( < 0.0001). Our supportive care team transitioned from in-person care to virtual visits within weeks while maintaining a high patient volume, continuity of care, and adherence to social distancing. Our transition can serve as a model for other centers.
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http://dx.doi.org/10.1089/jpm.2020.0737DOI Listing
February 2021

Prevalence of potential interactions of medications, including herbs and supplements, before, during, and after chemotherapy in patients with breast and prostate cancer.

Cancer 2021 Jun 1;127(11):1827-1835. Epub 2021 Feb 1.

Section of Hematology/Oncology, Department of Medicine, Northwestern University, Chicago, Illinois.

Background: The use of herbs and supplements (HS) is common among patients with cancer, yet limited information exists about potential medication interactions (PMIs) with HS use around chemotherapy.

Methods: Patients with breast or prostate cancer who had recently finished chemotherapy at 2 academic medical centers were surveyed by telephone. Interviewers inquired about all medications, including HS, before, during, and after chemotherapy. Micromedex, Lexicomp, and Natural Medicines Comprehensive Database interaction software programs were used to determine PMIs.

Results: A total of 67 subjects (age range, 39-77 years) were evaluated in this study. Participants were primarily White patients (73%) with breast cancer (87%). The median number of medications was 11 (range, 2-28) during the entire study and was highest during chemotherapy (7; range, 2-22). Approximately four-fifths (84%) used HS. A total of 1747 PMIs were identified, and they represented 635 unique PMIs across all 3 timeframes, with most occurring during chemotherapy. Prescription-related PMIs (70%) were the most common type, and they were followed by HS-related (56%) and anticancer treatment-related PMIs (22%). Approximately half of the PMIs (54%) were categorized as moderate interactions, and more than one-third (38%) were categorized as major interactions. Patient use of HS increased from 51% during chemotherapy to 66% after chemotherapy, and this correlated with an increased prevalence of HS PMIs (46% to 60%). HS users were more likely to be at risk for a major PMI than non-HS users (92% vs 70%; P = .038).

Conclusions: The use of HS remains prevalent among patients with cancer and may place them at risk for PMIs both during chemotherapy and after the completion of treatment.

Lay Summary: This study evaluates the risk of potential medication interactions for patients with breast or prostate cancer undergoing chemotherapy. The results show that patients often use herbs and supplements during treatment. Prescription medications are most often associated with medication interactions, which are followed by herb and supplement-related interactions. More than one-third of potential medication interactions are considered major. Patients should be educated about the risk of herb and supplement-related medication interactions during treatment.
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http://dx.doi.org/10.1002/cncr.33324DOI Listing
June 2021

Frequency of and Factors Associated With Nonmedical Opioid Use Behavior Among Patients With Cancer Receiving Opioids for Cancer Pain.

JAMA Oncol 2021 Mar;7(3):404-411

Department of Palliative Care, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston.

Importance: One of the main aims of research on nonmedical opioid use (NMOU) is to reduce the frequency of NMOU behaviors through interventions such as universal screening, reduced opioid exposure, and more intense follow-up of patients with elevated risk. The absence of data on the frequency of NMOU behavior is the major barrier to conducting research on NMOU.

Objective: To determine the overall frequency of and the independent predictors for NMOU behavior.

Design, Setting, And Participants: In this prognostic study, 3615 patients with cancer were referred to the supportive care center at MD Anderson Cancer Center from March 18, 2016, to June 6, 2018. Patients were eligible for inclusion if they had cancer and were taking opioids for cancer pain for at least 1 week. Patients were excluded if they had no follow-up within 3 months of initial consultation, did not complete the appropriate questionnaire, or did not have scheduled opioid treatments. After exclusion, a total of 1554 consecutive patients were assessed for NMOU behavior using established diagnostic criteria. All patients were assessed using the Edmonton Symptom Assessment Scale, the Screener and Opioid Assessment for Patients with Pain (SOAPP), and the Cut Down, Annoyed, Guilty, Eye Opener-Adapted to Include Drugs (CAGE-AID) survey. Data were analyzed from January 6 to September 25, 2020.

Results: A total of 1554 patients (median [interquartile range (IQR)] age, 61 [IQR, 52-69] years; 816 women [52.5%]; 1124 White patients [72.3%]) were evaluable for the study, and 299 patients (19.2%) had 1 or more NMOU behaviors. The median (IQR) number of NMOU behaviors per patient was 1 (IQR, 1-3). A total of 576 of 745 NMOU behaviors (77%) occurred by the first 2 follow-up visits. The most frequent NMOU behavior was unscheduled clinic visits for inappropriate refills (218 of 745 [29%]). Eighty-eight of 299 patients (29.4%) scored 7 or higher on SOAPP, and 48 (16.6%) scored at least 2 out of 4 points on the CAGE-AID survey. Results from the multivariate model suggest that marital status (single, hazard ratio [HR], 1.58; 95% CI, 1.15-2.18; P = .005; divorced, HR, 1.43; 95% CI, 1.01-2.03; P = .04), SOAPP score (positive vs negative, HR, 1.35; 95% CI, 1.04-1.74; P = .02), morphine equivalent daily dose (MEDD) (HR, 1.003; 95% CI, 1.002-1.004; P < .001), and Edmonton Symptom Assessment Scale pain level (HR, 1.11; 95% CI, 1.06-1.16; P < .001) were independently associated with the presence of NMOU behavior. In recursive partition analysis, single marital status, MEDD greater than 50 mg, and SOAPP scores greater than 7 were associated with a higher risk (56%) for the presence of NMOU behavior.

Conclusions And Relevance: This prognostic study of patients with cancer taking opioids for cancer pain found that 19% of patients developed NMOU behavior within a median duration of 8 weeks after initial supportive care clinic consultation. Marital status (single or divorced), SOAPP score greater than 7, higher levels of pain severity, and MEDD level were independently associated with NMOU behavior. This information will assist clinicians and investigators designing clinical and research programs in this important field.
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http://dx.doi.org/10.1001/jamaoncol.2020.6789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791402PMC
March 2021

High Flow Nasal Cannula Therapy for Exertional Dyspnea in Cancer Patients: A Pilot Randomized Clinical Trial.

Oncologist 2020 Dec 2. Epub 2020 Dec 2.

Department of Palliative Care, Rehabilitation and Integrative Medicine, MD Anderson Cancer Center, Houston, TX, USA.

Background: Exertional dyspnea is common in cancer patients and limits their function. The impact of high-flow nasal cannula (HFNC) on exertional dyspnea in non-hypoxemic patients is unclear. In this double-blind, parallel-group, randomized trial, we assessed the effect of flow rate (high vs. low) and gas (oxygen vs. air) on exertional dyspnea in non-hypoxemic cancer patients.

Patients And Methods: Cancer patients with oxygen saturation >90% at rest and exertion completed incremental and constant work (80% maximal) cycle ergometry while breathing low-flow air at 2 L/min. They were then randomized to receive high-flow oxygen, high-flow air, low-flow oxygen or low-flow air while performing symptom-limited endurance cycle ergometry at 80% maximal. The primary outcome was modified 0-10 Borg scale dyspnea intensity at isotime. Secondary outcomes included dyspnea unpleasantness, exercise time and adverse events.

Results: 74 patients were enrolled and 44 completed the study (mean age 63; 41% female). Compared to low-flow air at baseline, dyspnea intensity was significantly lower at isotime with high-flow oxygen (mean change [95% CI]: -1.1 [-2.1, -0.12]) and low-flow oxygen (-1.83 [-2.7, -0.9]), but not high-flow air (-0.2 [-0.97, 0.6]) nor low-flow air (-0.5 [-1.3, 0.4]). Compared to low-flow air, high-flow oxygen also resulted in significantly longer exercise time (difference +2.5 min, P=0.009), but not low-flow oxygen (+0.39 min, P=0.65) nor high-flow air (+0.63 min, P=0.48). The interventions were well tolerated without significant adverse effects.

Conclusions: Our preliminary findings support that high-flow oxygen improved both exertional dyspnea and exercise duration in non-hypoxemic cancer patients (Clinicaltrials.gov NCT02357134).

Implications For Practice: In this 4-arm, double-blind randomized clinical trial examining the role of high-flow nasal cannula on exertional dyspnea in cancer patients without hypoxemia, high-flow oxygen, but not high flow air, resulted in significantly lower dyspnea scores and longer exercise time. High-flow oxygen delivered by high-flow nasal cannula devices may improve clinically relevant outcomes even in patients without hypoxemia.
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http://dx.doi.org/10.1002/onco.13624DOI Listing
December 2020

An Exploratory Study on Physical Function in Stem Cell Transplant Patients Undergoing Corticosteroid Treatment for Acute Graft-Versus-Host-Disease.

Am J Phys Med Rehabil 2021 04;100(4):402-406

From the Departments of Palliative, Rehabilitation, and Integrative Medicine (AN-H, RY, SB, J. Williams, JBF, EB), Biostatistics (J. Wu), and Stem Cell Transplantation and Cellular Therapy (AMA), University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract: Acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation is treated with corticosteroids, placing patients at risk for steroid myopathy. In this single-arm cohort study, 23 patients who were started on high-dose corticosteroids for acute graft-versus-host disease underwent a series of functional tests (baseline and days 14, 28, and 56): 6-min walk test, hip flexor and knee extensor strength via dynamometry, five times sit-to-stand, Brooke scale for myopathy, modified Adult Myopathy Assessment Tool, and manual muscle testing. Participants were prescribed home exercises including walking and resistance exercises, with low adherence. Fifteen (63%) participants were male and median (range) age was 60 (36-70) yrs. Median (range) corticosteroid duration and cumulative equivalent methylprednisolone dose were 66 (22-165) days and 3625 (1020-11720) mg, respectively. At day 14, there was a significant decline in five times sit-to-stand (P = 0.0132), knee extensor (P = 0.0182), and manual muscle testing (P = 0.0466). Functional tests negatively associated with cumulative corticosteroid dose included 6-min walk test distance (P = 0.0103), hip flexor strength (P = 0.0262), knee extensor strength (P = 0.0369), and manual muscle testing strength (P = 0.0319). Five times sit-to-stand was positively associated with corticosteroid dose (P = 0.0003). In conclusion, stem cell transplant patients receiving high-dose corticosteroids for acute graft-versus-host disease are at risk for weakness detected as early as day 14. Increasing adherence to exercise may mitigate these changes.
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http://dx.doi.org/10.1097/PHM.0000000000001660DOI Listing
April 2021

Rate of reclassification of HER2-equivocal breast cancer cases to HER2-negative per the 2018 ASCO/CAP guidelines and response of HER2-equivocal cases to anti-HER2 therapy.

PLoS One 2020 12;15(11):e0241775. Epub 2020 Nov 12.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Purpose: The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline on HER2 testing in breast cancer permits reclassification of cases with HER2-equivocal results by FISH. The impact of such reclassification is unclear. We sought to determine the proportion of HER2-equivocal cases that are reclassified as HER2-negative and the impact of anti-HER2 therapy on survival in HER2-equivocal cases.

Methods: We reviewed medical records of breast cancer patients who had HER2 testing by fluorescence in stitu hybridization (FISH) and immunohistochemistry (IHC) performed or verified at The University of Texas MD Anderson Cancer Center during April 2014 through March 2018 and had equivocal results according to the 2013 ASCO/CAP guideline. The population was divided into 2 cohorts according to whether the biopsy specimen analyzed came from primary or from recurrent or metastatic disease. HER2 status was reclassified according to the 2018 ASCO/CAP guideline. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method, and the relationship between anti-HER2 therapy and clinical outcomes was assessed.

Results: We identified 139 cases with HER2-equivocal results according to the 2013 ASCO/CAP guideline: 90 cases of primary disease and 49 cases of recurrent/metastatic disease. Per the 2018 ASCO/CAP guideline, these cases were classified as follows: overall, HER2-negative 112 cases (80%), HER2-positive 1 (1%), and unknown 26 (19%); primary cohort, HER2-negative 85 (94%), HER2-positive 1 (1%), unknown 4 (4%); and recurrent/metastatic, HER2-negative 27 (55%) and unknown 22 (45%). Five patients in the primary-disease cohort and 1 patient in the recurrent/metastatic-disease cohort received anti-HER2 therapy. There was no significant association between anti-HER2 therapy and OS or EFS in either cohort (primary disease: OS, p = 0.67; EFS, p = 0.49; recurrent/metastatic-disease, OS, p = 0.61; EFS, p = 0.78.

Conclusions: The majority of HER2-equivocal breast cancer cases were reclassified as HER2-negative per the 2018 ASCO/CAP guideline. No association between anti-HER2 therapy and OS or EFS was observed. HER2-equivocal cases seem to have clinical behavior similar to that of HER2-negative breast cancers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241775PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660495PMC
January 2021

A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma.

Neuro Oncol 2021 03;23(3):468-477

Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Background: No standard medical treatment exists for adult patients with recurrent ependymoma, and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network conducted a prospective phase II clinical trial of dose-dense temozolomide (TMZ) and lapatinib, targeting the unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status and increased expression of ErbB2 (human epidermal growth factor receptor 2) and ErbB1 (epidermal growth factor receptor) in ependymomas.

Methods: Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense TMZ and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)/MDASI-Spine Tumor modules were collected.

Results: The 50 patients enrolled had a median age of 43.5 years, median Karnofsky performance status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI: 5.5,12.2); the 6- and 12-month PFS rates were 55% and 38%, with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients.

Conclusions: This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements, is an option as a salvage regimen for adult patients with recurrent ependymoma.
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http://dx.doi.org/10.1093/neuonc/noaa240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992893PMC
March 2021

Terminal agitation and delirium in patients with cancer - Authors' reply.

Lancet Oncol 2020 09;21(9):e411

Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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http://dx.doi.org/10.1016/S1470-2045(20)30471-XDOI Listing
September 2020

Rapidly progressive cognitive impairment: an unusual presentation of cerebral venous thrombosis caused by JAK2 V617F-positive primary myelofibrosis: A case report.

Medicine (Baltimore) 2020 Aug;99(34):e21757

Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou.

Rationale: Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition, which mainly manifests as headaches, seizures, and focal neurological deficits. JAK2 mutation in myeloproliferative diseases increases the risk of CVT.

Patient Concerns: This 40-year-old woman suffered from rapidly progressive cognitive impairment and limb weakness. Her symptoms worsened while being treated with mannitol with the diagnose of cerebral hemorrhage.

Diagnosis: The patient was diagnosed with CVT and multiple intracranial hemorrhage caused by JAK2 V617F mutation-positive primary myelofibrosis by neuroimage and whole-exome sequencing.

Intervention: She received low-molecular-weight heparin sodium 3800 IU twice a day followed by oral anticoagulant therapy.

Outcomes: The patient showed full recovery from limb weakness and in the follow-up period she noticed no change in her memory.

Lessons: Clinicians should be aware of the possibility of the JAK2 V617F mutation in CVT patients without known causes or risk factors.
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http://dx.doi.org/10.1097/MD.0000000000021757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447497PMC
August 2020

The development of a nomogram to determine the frequency of elevated risk for non-medical opioid use in cancer patients.

Palliat Support Care 2021 02;19(1):3-10

Department of Palliative Care, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Objective: Non-medical opioid use (NMOU) is a growing crisis. Cancer patients at elevated risk of NMOU (+risk) are frequently underdiagnosed. The aim of this paper was to develop a nomogram to predict the probability of +risk among cancer patients receiving outpatient supportive care consultation at a comprehensive cancer center.

Method: 3,588 consecutive patients referred to a supportive care clinic were reviewed. All patients had a diagnosis of cancer and were on opioids for pain. All patients were assessed using the Edmonton Symptom Assessment Scale (ESAS), Screener and Opioid Assessment for Patients with Pain (SOAPP-14), and CAGE-AID (Cut Down-Annoyed-Guilty-Eye Opener) questionnaires. "+risk" was defined as an SOAPP-14 score of ≥7. A nomogram was devised based on the risk factors determined by the multivariate logistic regression model to estimate the probability of +risk.

Results: 731/3,588 consults were +risk. +risk was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD (morphine equivalent daily dose), and CAGE-AID score. The C-index was 0.8. A nomogram was developed and can be accessed at https://is.gd/soappnomogram. For example, for a male Hispanic patient, married, never smoked, with ESAS scores for depression = 3, anxiety = 3, financial distress = 7, a CAGE score of 0, and an MEDD score of 20, the total score is 9 + 9+0 + 0+6 + 10 + 23 + 0+1 = 58. A nomogram score of 58 indicates the probability of +risk of 0.1.

Significance Of Results: We established a practical nomogram to assess the +risk. The application of a nomogram based on routinely collected clinical data can help clinicians establish patients with +risk and positively impact care planning.
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http://dx.doi.org/10.1017/S1478951520000322DOI Listing
February 2021

Effects of Center-Based Delivery of Tai Chi and Qi Gong Group Classes on Self-Reported Symptoms in Cancer Patients and Caregivers.

Integr Cancer Ther 2020 Jan-Dec;19:1534735420941605

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

There is increasing interest in complementary approaches such as Tai Chi (TC) and Qi Gong (QG) in oncology settings. We explored the effects of TC/QG delivered in group classes at a comprehensive cancer center. Patients and caregivers who participated in TC or QG completed assessments before and after an in-person group class. Assessments included questions about expectancy/satisfaction and common cancer symptoms (Edmonton Symptom Assessment Scale [ESAS]). ESAS distress subscales analyzed included global (GDS), physical (PHS), and psychosocial (PSS). Three hundred four participants (184 patients, 120 caregivers) were included in the analysis. At baseline, caregivers had a greater expectancy for change in energy level as a result of class participation compared with patients (22.9% vs 9.9%). No significant difference was observed between baseline patient and caregiver PSS. Clinically significant improvement in well-being was observed among patients in TC classes (1.0) and caregivers in QG classes (1.2). For fatigue, patients (1.4) and caregivers (1.0) participating in QG experienced clinically significant improvement. Both TC and QG classes were associated with clinically significant improvements (ESAS GDS decrease ≥3) in global distress for patients (TC = 4.52, SD= 7.6; QG = 6.05, SD = 7.9) and caregivers (TC = 3.73, SD = 6.3; QG = 4.02, SD = 7.8). Eighty-nine percent of participants responded that their expectations were met. Patients and caregivers participating in TC or QG group classes were satisfied overall and experienced significant improvement in global distress. Additional research is warranted to explore the integration of TC and QG in the delivery of supportive cancer care.
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http://dx.doi.org/10.1177/1534735420941605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374530PMC
July 2020

Pathological matrix stiffness promotes cardiac fibroblast differentiation through the POU2F1 signaling pathway.

Sci China Life Sci 2021 Feb 29;64(2):242-254. Epub 2020 Jun 29.

Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China.

Cardiac fibroblast (CF) differentiation into myofibroblasts is a crucial cause of cardiac fibrosis, which increases in the extracellular matrix (ECM) stiffness. The increased stiffness further promotes CF differentiation and fibrosis. However, the molecular mechanism is still unclear. We used bioinformatics analysis to find new candidates that regulate the genes involved in stiffness-induced CF differentiation, and found that there were binding sites for the POU-domain transcription factor, POU2F1 (also known as Oct-1), in the promoters of 50 differentially expressed genes (DEGs) in CFs on the stiffer substrate. Immunofluorescent staining and Western blotting revealed that pathological stiffness upregulated POU2F1 expression and increased CF differentiation on polyacrylamide hydrogel substrates and in mouse myocardial infarction tissue. A chromatin immunoprecipitation assay showed that POU2F1 bound to the promoters of fibrosis repressors IL1R2, CD69, and TGIF2. The expression of these fibrosis repressors was inhibited on pathological substrate stiffness. Knockdown of POU2F1 upregulated these repressors and attenuated CF differentiation on pathological substrate stiffness (35 kPa). Whereas, overexpression of POU2F1 downregulated these repressors and enhanced CF differentiation. In conclusion, pathological stiffness upregulates the transcription factor POU2F1 to promote CF differentiation by inhibiting fibrosis repressors. Our work elucidated the crosstalk between CF differentiation and the ECM and provided a potential target for cardiac fibrosis treatment.
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http://dx.doi.org/10.1007/s11427-019-1747-yDOI Listing
February 2021

Biomarker Modulation Study of Celecoxib for Chemoprevention in Women at Increased Risk for Breast Cancer: A Phase II Pilot Study.

Cancer Prev Res (Phila) 2020 09 8;13(9):795-802. Epub 2020 Jun 8.

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

In preclinical studies, celecoxib has been associated with reduced risk of breast cancer. In this study, the aim was to assess the biomodulatory effect of celecoxib on blood and benign breast tissue biomarkers in women at increased risk for breast cancer. Women at increased risk for breast cancer [5-year Gail risk score of >1.67%, history of atypical hyperplasia, lobular carcinoma , or previous estrogen receptor (ER)-negative breast cancer] were treated with celecoxib at 400 mg orally twice daily for 6 months. Participants underwent random periareolar fine needle aspiration and blood draw at baseline and at 6 months for analysis of biomarkers: serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1 (IGFBP-1), and IGFBP-3; tissue expression of Ki-67 and ER; as well as cytology. Forty-nine patients were eligible for analysis. Median IGFBP-1 levels increased significantly from 6.05 ng/mL at baseline to 6.93 ng/mL at 6 months ( = 0.04), and median IGFBP-3 levels decreased significantly from 3,593 ng/mL to 3,420 ng/mL ( = 0.01). We also detected favorable changes in cytology of 52% of tested sites after 6 months of celecoxib therapy. No changes in tissue Ki-67 and ER expression levels were observed. No grade 3 or 4 toxicity was recorded. Celecoxib was well tolerated and induced favorable changes in serum biomarkers as well as cytology in this pilot phase II trial. A phase IIb placebo-controlled study with celecoxib could be considered for women at increased risk for breast cancer.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0095DOI Listing
September 2020

Cardia Laxity under Retroflexed Endoscopy Is a Reflection of Esophageal Hiatus Enlargement.

Gastroenterol Res Pract 2020 16;2020:9180167. Epub 2020 May 16.

Department of Gastroesophageal Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, China.

Methods: Information from patients who underwent endoscopy and CT scan in our department was collected and analyzed retrospectively. Three-dimensional reconstruction of hiatus from CT images was performed using 3DSlicer software, and the degree of esophageal hiatus enlargement was compared with the degree of gastroesophageal laxity under retroflexed endoscopy.

Results: Information from 104 patients was included for analysis. The Spearman correlation coefficient was 0.617 ( ≤ 0.001). When subgroup correlation analysis was performed according to the presence of hiatal hernia on CT, the Spearman correlation coefficient was 0.816 ( ≤ 0.001) in the hernia group and 0.351 ( = 0.002) in the nonhernia group. The proportion of hiatal hernia and severe esophagitis was increasing gradually with the degree of gastroesophageal laxity.

Conclusion: The degree of gastroesophageal laxity (cardia or hiatus) under retroflexed endoscopy reflects the degree of esophageal hiatus enlargement; with the degree of gastroesophageal laxity increasing, the proportion of HH and severe esophagitis increases gradually. This may be useful for physicians in China to guide themselves in the selection of patients for endoscopic antireflux treatment.
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http://dx.doi.org/10.1155/2020/9180167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246414PMC
May 2020

Frequency of Concomitant Use of Gabapentinoids and Opioids among Patients with Cancer-Related Pain at an Outpatient Palliative Care Clinic.

J Palliat Med 2021 01 2;24(1):91-96. Epub 2020 Jun 2.

M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA.

Patients with cancer-related pain use opioids for nociceptive pain, while gabapentinoids are common to treat neuropathic pain. The simultaneous use of opioids with gabapentinoids has been associated with an increased risk of opioid-related death. Determine the frequency of combined use of gabapentinoids among patients receiving opioids for cancer-related pain. We also examined if concomitant use of opioids and gabapentinoids together was associated with increased scores of fatigue and drowsiness on the Edmonton Symptom Assessment Scale (ESAS) compared to patients on opioids. Retrospective study of patients on opioids and opioids plus gabapentinoids at their third visit to the outpatient Supportive Care Center. We found that 48% (508/1059) of patients were on opioids. Of these patients, 51% (257/508) were on opioids only, and 49% (251/508) were on opioids plus gabapentinoids. The median (interquartile range [IQR]) morphine equivalent daily dose for patients on opioids was 75 (45, 138) mg, and opioids plus gabapentinoids was 68 (38, 150) mg ( = 0.94). The median (IQR) gabapentinoid equivalent daily dose was 900 (300, 1200) mg. The median (IQR) for ESAS-fatigue in patients on opioids was 5 (3, 7), and opioids plus gabapentinoids was 5 (3, 7) ( = 0.27). The median (IQR) for ESAS-drowsiness in patients on opioids was 3 (0, 5), and opioids plus gabapentinoids was 3 (0, 6) ( = 0.11). Almost 50% of advanced cancer patients receiving opioids for pain were exposed to gabapentinoids. Maximal efforts should be made to minimize potential complications from the concomitant use of opioids with gabapentinoids.
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http://dx.doi.org/10.1089/jpm.2019.0614DOI Listing
January 2021

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

Lancet Oncol 2020 07 29;21(7):989-998. Epub 2020 May 29.

Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium.

Methods: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486.

Findings: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths.

Interpretation: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group.

Funding: National Institute of Nursing Research.
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http://dx.doi.org/10.1016/S1470-2045(20)30307-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433183PMC
July 2020

High Rates of Obesity at Presentation Persist into Survivorship across Childhood Cancer Types.

Child Obes 2020 06 13;16(4):250-257. Epub 2020 Mar 13.

Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Subtypes of pediatric oncology patients and childhood cancer survivors who are overweight or obese have worse prognosis than their healthy-weighted peers. Several studies have examined weight status in either pediatric patients or survivors with acute leukemia, but few have compared these data across various diagnoses. We examined BMI from oncology diagnosis or presentation, through treatment, and into survivorship across the most common cancer types seen in pediatric oncology. Patients were categorized into three oncologic diagnoses: leukemia and lymphoma ( = 69), neural tumors ( = 80), and non-neural solid tumors ( = 80) at yearly intervals over the course of 11 years. To allow for comparisons across age groups, BMI percentiles were calculated with <5th percentile classified as underweight ( = 11), the 5th-84th percentile classified as a healthy weight ( = 129), and above the 85th percentile classified as overweight and obese ( = 87). At presentation, 45.6% of leukemia and lymphoma patients were overweight or obese, and 44.3% of neural tumor patients were overweight or obese. These high obesity rates persisted into survivorship. Compared to the non-neural tumor group, the leukemia and lymphoma group had a significant increase in BMI percentile over time, while the neural tumor group did not. Pediatric patients with leukemia, lymphoma, and neural tumors and who are overweight or obese at presentation continue this trend into survivorship, indicating a need for management of overweight and obesity through lifestyle interventions concurrent with therapy.
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http://dx.doi.org/10.1089/chi.2019.0180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262646PMC
June 2020

A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with recurrent glioblastoma.

Neuro Oncol 2020 10;22(10):1505-1515

Neuro-Oncology Branch, National Institute of Health, Bethesda, Maryland.

Background: Bevacizumab has promising activity against recurrent glioblastoma (GBM). However, acquired resistance to this agent results in tumor recurrence. We hypothesized that vorinostat, a histone deacetylase (HDAC) inhibitor with anti-angiogenic effects, would prevent acquired resistance to bevacizumab.

Methods: This multicenter phase II trial used a Bayesian adaptive design to randomize patients with recurrent GBM to bevacizumab alone or bevacizumab plus vorinostat with the primary endpoint of progression-free survival (PFS) and secondary endpoints of overall survival (OS) and clinical outcomes assessment (MD Anderson Symptom Inventory Brain Tumor module [MDASI-BT]). Eligible patients were adults (≥18 y) with histologically confirmed GBM recurrent after prior radiation therapy, with adequate organ function, KPS ≥60, and no prior bevacizumab or HDAC inhibitors.

Results: Ninety patients (bevacizumab + vorinostat: 49, bevacizumab: 41) were enrolled, of whom 74 were evaluable for PFS (bevacizumab + vorinostat: 44, bevacizumab: 30). Median PFS (3.7 vs 3.9 mo, P = 0.94, hazard ratio [HR] 0.63 [95% CI: 0.38, 1.06, P = 0.08]), median OS (7.8 vs 9.3 mo, P = 0.64, HR 0.93 [95% CI: 0.5, 1.6, P = 0.79]) and clinical benefit were similar between the 2 arms. Toxicity (grade ≥3) in 85 evaluable patients included hypertension (n = 37), neurological changes (n = 2), anorexia (n = 2), infections (n = 9), wound dehiscence (n = 2), deep vein thrombosis/pulmonary embolism (n = 2), and colonic perforation (n = 1).

Conclusions: Bevacizumab combined with vorinostat did not yield improvement in PFS or OS or clinical benefit compared with bevacizumab alone or a clinical benefit in adults with recurrent GBM. This trial is the first to test a Bayesian adaptive design with adaptive randomization and Bayesian continuous monitoring in patients with primary brain tumor and demonstrates the feasibility of using complex Bayesian adaptive design in a multicenter setting.
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http://dx.doi.org/10.1093/neuonc/noaa062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686463PMC
October 2020

Randomized Feasibility Study of Meditative Practices in Hospitalized Cancer Patients.

Integr Cancer Ther 2020 Jan-Dec;19:1534735420909903

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

There is limited research regarding the benefits of mind-body practices such as meditation in hospitalized patients with an active diagnosis of any cancer type. We conducted a prospective, randomized, clinical trial (NCT03445572) comparing 2 meditative practices-Isha Kriya (IK) and meditative slow breathing (MSB)-versus wait-list controls in hospitalized cancer patients. Our aim was to determine the feasibility of meditation practice in cancer inpatients. Feasibility was defined as recruitment of more than 50% of the eligible patients approached and at least 60% of the patients having meditated at least 4 days by day 7. Acceptability was assessed on day 7 as a positive response on at least 2 questions on the modified Global Symptom Evaluation (GSE) scale. Forty patients (39% of the eligible patients approached) consented to participate in the study and were randomly assigned to the MSB (n = 13), IK (n = 14), or wait-list (n = 13) groups. Of the 27 patients assigned to receive MSB and IK meditations, day 7 data were available for 18 patients. Fifteen of the 18 patients meditated at least once in the first 7 days, and most (12/15) responded positively on the GSE. Both IK and MSB meditations were acceptable among the hospitalized cancer patients. Feasibility for enrollment and practice was likely not achieved due to limited uninterrupted time for daily meditation, high levels of morbidity in some participants, and limited research staff support. Shorter term outcomes should be explored in future meditation studies involving hospitalized cancer patients.
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http://dx.doi.org/10.1177/1534735420909903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065431PMC
March 2021

Prognostic Value of HER2 to CEP17 Ratio on Fluorescence In Situ Hybridization Ratio in Patients with Nonmetastatic HER2-Positive Inflammatory and Noninflammatory Breast Cancer Treated with Neoadjuvant Chemotherapy with or without Trastuzumab.

Oncologist 2020 06 31;25(6):e909-e919. Epub 2020 Jan 31.

Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: We previously reported that in patients with HER2-positive (HER2+) locally advanced breast cancer treated with neoadjuvant trastuzumab-containing regimens, high HER2 to centromere enumerator probe 17 ratio on fluorescence in situ hybridization (HER2 FISH ratio) was an independent predictor of high pathologic complete response (pCR) rate, which translated into improved recurrence-free survival (RFS). We sought to determine whether high HER2 FISH ratio is a predictor of pCR and prognosis in patients with HER2+ nonmetastatic inflammatory breast cancer (IBC) and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab.

Materials And Methods: This study included all patients with histologically proven stage III, HER2+ primary IBC, and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab and definitive surgery during 1999-2012. Univariate and multivariate logistic regression models were applied to assess the effect of covariates on pCR. Kaplan-Meier estimates with log-rank test were employed for survival analysis. Univariate and multivariate Cox proportional hazards models were used to assess the effect of covariates on RFS and overall survival (OS).

Results: The study included 555 patients with stage III, HER+ breast cancer, 181 patients with IBC, and 374 with non-IBC. In the IBC cohort, HER2 FISH ratio was not significantly associated with pCR, RFS, or OS. In the non-IBC cohort, higher HER2 FISH ratio was significantly associated with higher pCR rate and longer OS.

Conclusion: HER2 FISH ratio showed prognostic value among patients with HER2+ non-IBC but not HER2+ IBC treated with neoadjuvant chemotherapy. This disparity may be due to the underlying aggressive nature of IBC.

Implications For Practice: The findings of this study indicate that the HER2 to fluorescence in situ hybridization ratio as a continuous variable has promise as a predictor of pathologic complete response to neoadjuvant chemotherapy in patients with HER2-positive (HER2+) noninflammatory breast cancer (non-IBC) regardless of the results on HER2 immunohistochemical testing. In the future, some patients with HER2+ non-IBC and a high HER2 FISH ratio might even be offered personalized treatment options, such as nonsurgical treatment.
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http://dx.doi.org/10.1634/theoncologist.2018-0611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288623PMC
June 2020

Cellular Oxidative Stress in Pediatric Leukemia and Lymphoma Patients Undergoing Treatment Is Associated with Protein Consumption.

Nutrients 2019 Dec 27;12(1). Epub 2019 Dec 27.

Department of Pediatric Research, University of Texas MD Anderson, Houston, TX 77030, USA.

Over and under nutrition are associated with worse outcomes for children with leukemia and lymphoma; however, the molecular basis for this clinical observation is not well understood. Many chemotherapeutics used for leukemia treatment are known to generate oxidative stress in vitro; therefore, we evaluated redox status and diet in pediatric leukemia patients during therapy in order to ascertain relationships between nutrition and oxidative stress. Dietary intake and redox measures in peripheral blood mononuclear cells from 32 pediatric leukemia and lymphoma patients were collected over six months during treatment. Baseline measures when patients were off chemotherapy and subsequent assessments were collected after one, two and six months. Oxidative stress increased over time in all patients, consistent with chemotherapy-induced redox effects. Older and younger children showed significantly different baseline levels of reactive oxygen species, which increased over time in all age ranges. Diet was assessed at points proximal to oxidative stress measurements and revealed a novel association with consumption of animal protein, vegetable protein, and total protein intake. Our findings demonstrate that chemotherapy increases oxidative stress in pediatric leukemia patients, and raises the possibility that dietary protein or altered protein metabolism could contribute to clinical outcomes.
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http://dx.doi.org/10.3390/nu12010075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019785PMC
December 2019

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages.

Neuro Oncol 2020 04;22(4):539-549

Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.

Methods: In an open-label, single-center, single-arm phase II "window-of-opportunity" trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor.

Results: No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients' recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages.

Conclusions: Immune analyses indicated that pembrolizumab anti-programmed cell death 1 (PD-1) monotherapy alone can't induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.
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http://dx.doi.org/10.1093/neuonc/noz185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158647PMC
April 2020

Enhancing palliative care patient access to psychological counseling through outreach telehealth services.

Psychooncology 2020 01 10;29(1):132-138. Epub 2019 Nov 10.

Department of Palliative Care, Rehabilitation and Integrative Medicine, Houston, Texas.

Context: Palliative care encompasses an interdisciplinary team, including mental health care professionals, to address psychological distress of cancer patients.

Objectives: To present the implementation of an outreach counseling program via videoconferencing or telephone to patients receiving care in an outpatient palliative care clinic and to compare patients using this service to those who only received psychological counseling in our outpatient clinic.

Methods: We conducted a retrospective chart review of cancer patients seen for psychology counseling services in an outpatient supportive care center between June 2015 and March 2017.

Results: We reviewed 2072 unique patients (52% of the total patients seen at the outpatient Supportive Care Center), who had 4567 total counseling encounters across outreach and outpatient settings. A total of 452 (22%) patients participated in a combination of outpatient and outreach counseling services. Patients who participated in outreach services had significantly more encounters (311 [69%] had two to five sessions) compared with those who had outpatient services only (1137 [70%] had one session only) (P < .001). Outreach patients also had shorter times between the initial and follow-up encounters (median 14 days) compared with those who had outpatient services only (median 30 days) (P < .0001).

Conclusions: Outreach telehealth counseling services was found to enhance palliative care patient access to psychological counseling. These services represent an additional modality for providing continuous psychological care.
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http://dx.doi.org/10.1002/pon.5270DOI Listing
January 2020

Factors Associated with Improvement in Uncontrolled Cancer Pain without Increasing the Opioid Daily Dose among Patients Seen by an Inpatient Palliative Care Team.

J Palliat Med 2020 04 5;23(4):483-488. Epub 2019 Nov 5.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Increasing the total opioid dose is the standard approach for managing uncontrolled cancer pain. Other than simply increasing the opioid dose, palliative care interventions are multidimensional and may improve pain control in the absence of opioid dose increase. The purpose of this study was to determine the proportion of patients referred to our inpatient palliative care (IPC) team who achieved clinically improved pain (CIP) without opioid dose increase. We reviewed consecutive patients referred to our IPC team. Eligibility criteria included (1) taking opioid medication; (2) having ≥2 consecutive visits with the IPC team; and (3) an Edmonton Symptom Assessment Scale (ESAS) pain score ≥4 at consultation. We assessed patient demographics and clinical variables, including cancer type, opioid prescription data (type, route, and oral morphine equivalent daily dose [MEDD]), presence of opioid rotation, psychological consultation, changes in adjuvant medications (e.g., corticosteroids; antiepileptics-gabapentin and pregabalin; benzodiazepines; and neuroleptics), and achievement of CIP. Of the 300 patients enrolled, CIP was achieved in 196 (65%) patients. Of CIP patients, 85 (43%) achieved CIP without an increase in MEDD. CIP without MEDD increase was associated with more adjuvant medication changes ( = 0.003), less opioid rotation ( = 0.005), and lower symptom distress scale of ESAS ( = 0.04). Nearly half of the patients achieved CIP without MEDD increase, suggesting that the multidimensional palliative care intervention is effective in improving pain control in many opioid-tolerant patients without the need to increase the opioid dose.
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http://dx.doi.org/10.1089/jpm.2019.0243DOI Listing
April 2020

Treatment strategies for glioblastoma in older patients: age is just a number.

J Neurooncol 2019 Nov 23;145(2):357-364. Epub 2019 Oct 23.

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Unit 431, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA.

Background/purpose: Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival.

Methods: A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017.

Results: A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63-0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11-0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67-4.12) were independently associated with improved OS.

Conclusions: Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.
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http://dx.doi.org/10.1007/s11060-019-03304-xDOI Listing
November 2019

Wild-type defined gamma-secretase inhibitor sensitivity and synergistic activity with doxorubicin in GSCs.

Am J Cancer Res 2019 1;9(8):1734-1745. Epub 2019 Aug 1.

Department of Neuro-Oncology, Brain Tumor Center, The University of Texas MD Anderson Cancer Center Houston, TX, USA.

Glioblastoma (GBM) is the most common and lethal primary intracranial tumor. Aggressive surgical resection plus radiotherapy and temozolomide have prolonged patients' median survival to only 14.6 months. Therefore, there is a critical need to develop novel therapeutic strategies for GBM. In this study, we evaluated the effect of NOTCH signaling intervention by gamma-secretase inhibitors (GSIs) on glioma sphere-forming cells (GSCs). GSI sensitivity exhibited remarkable selectivity among wild-type (wt-p53) GSCs. GSIs significantly impaired the sphere formation of GSCs harboring wt-p53. We also identified a concurrence between GSI sensitivity, NOTCH1 expression, and wt-p53 activity in GSCs. Through a series of gene editing and drug treatment experiments, we found that wt-p53 did not modulate NOTCH1 pathway, whereas NOTCH1 signaling positively regulated wt-p53 expression and activity in GSCs. Finally, GSIs (targeting NOTCH signaling) synergized with doxorubicin (activating wt-p53) to inhibit proliferation and induce apoptosis in wt-p53 GSCs. Taken together, we identified wt-p53 as a potential marker for GSI sensitivity in GSCs. Combining GSI with doxorubicin synergistically inhibited the proliferation and survival of GSCs harboring wt-p53.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726980PMC
August 2019
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