Publications by authors named "Muhammad S Beg"

54 Publications

Clinical Efficiency and Safety Outcomes of Virtual Care for Oncology Patients During the COVID-19 Pandemic.

JCO Oncol Pract 2021 Jun 21:OP2100092. Epub 2021 Jun 21.

Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.

Purpose: Telehealth has been an integral response to the COVID-19 pandemic. However, no studies to date have examined the utility and safety of telehealth for oncology patients undergoing systemic treatments. Concerns of the adequacy of virtual patient assessments for oncology patients include the risk and high acuity of illness and complications while on treatment.

Methods: We assessed metrics related to clinical efficiency and treatment safety after propensity matching of newly referred patients starting systemic therapy where care was in large part replaced by telehealth between March and May 2020, and 206 newly referred patients from a similar time period in 2019 where all encounters were in-person visits.

Results: Patient-initiated telephone encounters that capture care or effort outside of visits, time to staging imaging, and time to therapy initiation were not significantly different between cohorts. Similarly, 3 month all-cause or cancer-specific emergency department presentations and hospitalizations, and treatment delays were not significantly different between cohorts. There were substantial savings in travel time with virtual care, with an average of 211.4 minutes saved per patient over a 3-month interval.

Conclusion: Our results indicate that replacement of in-person care with virtual care in oncology does not lead to worse efficiency or outcomes. Given the increased barriers to patients seeking oncology care during the pandemic, our study indicates that telehealth efforts may be safely intensified. These findings also have implications for the continual use of virtual care in oncology beyond the pandemic.
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http://dx.doi.org/10.1200/OP.21.00092DOI Listing
June 2021

Projected 30- day out-of-pocket costs and total spending on pancreatic enzyme replacement therapy under Medicare Part D.

Pancreatology 2021 May 11. Epub 2021 May 11.

Department of Health Policy, Vanderbilt University School of Medicine, Nashville, TN, USA; Vanderbilt Ingram Cancer Center, Nashville, TN, USA.

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http://dx.doi.org/10.1016/j.pan.2021.05.002DOI Listing
May 2021

AXL Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer.

Mol Cancer Res 2021 Apr 2. Epub 2021 Apr 2.

Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.

Pancreatic ductal adenocarcinoma (PDA), a leading cause of cancer-related death in the United States, has a high metastatic rate, and is associated with persistent immune suppression. AXL, a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family, is a driver of metastasis and immune suppression in multiple cancer types. Here we use single-cell RNA-sequencing to reveal that AXL is expressed highly in tumor cells that have a mesenchymal-like phenotype and that AXL expression correlates with classic markers of epithelial-to-mesenchymal transition. We demonstrate that AXL deficiency extends survival, reduces primary and metastatic burden, and enhances sensitivity to gemcitabine in an autochthonous model of PDA. PDA in AXL-deficient mice displayed a more differentiated histology, higher nucleoside transporter expression, and a more active immune microenvironment compared with PDA in wild-type mice. Finally, we demonstrate that AXL-positive poorly differentiated tumor cells are critical for PDA progression and metastasis, emphasizing the potential of AXL as a therapeutic target in PDA. IMPLICATIONS: These studies implicate AXL as a marker of undifferentiated PDA cells and a target for therapy.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0860DOI Listing
April 2021

Early Palliative Care Is Associated With Reduced Emergency Department Utilization in Pancreatic Cancer.

Am J Clin Oncol 2021 05;44(5):181-186

Departments of Internal Medicine.

Objectives: Most patients with pancreatic cancer have high symptom burden and poor outcomes. Palliative care (PC) can improve the quality of care through expert symptom management, although the optimal timing of PC referral is still poorly understood. We aimed to assess the association of early PC on health care utilization and charges of care for pancreatic cancer patients.

Materials And Methods: We selected patients with pancreatic cancer diagnosed between 2000 and 2009 who received at least 1 PC encounter using the Surveillance, Epidemiology, and End Results (SEER)-Medicare. Patients who had unknown follow-up were excluded. We defined "early PC" if the patients received PC within 30 days of diagnosis.

Results: A total of 3166 patients had a PC encounter; 28% had an early PC. Patients receiving early PC were more likely to be female and have older age compared with patients receiving late PC (P<0.001). Patients receiving early PC had fewer emergency department (ED) visits (2.6 vs. 3.0 visits, P=0.004) and lower total charges of ED care ($3158 vs. $3981, P<0.001) compared with patients receiving late PC. Patients receiving early PC also had lower intensive care unit admissions (0.82 vs. 0.98 visits, P=0.006) and total charges of intensive care unit care ($14,466 vs. $18,687, P=0.01). On multivariable analysis, patients receiving early PC were significantly associated with fewer ED visits (P=0.007) and lower charges of ED care (P=0.018) for all patients.

Conclusions: Early PC referrals were associated with lower ED visits and ED-related charges. Our findings support oncology society guideline recommendations for early PC in patients with advanced malignancies such as pancreatic cancer.
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http://dx.doi.org/10.1097/COC.0000000000000802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062302PMC
May 2021

Disparities in Characteristics, Access to Care, and Oncologic Outcomes in Young-Onset Colorectal Cancer at a Safety-Net Hospital.

JCO Oncol Pract 2021 05 11;17(5):e614-e622. Epub 2021 Jan 11.

Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX.

Purpose: Young-onset colorectal cancer is an emerging cause of significant morbidity and mortality globally. Despite this, limited data exist regarding clinical characteristics and outcomes, particularly in safety-net populations where access to care is limited. We aimed to study disparities in clinical characteristics and outcomes in patients with young-onset colorectal cancer in the safety-net setting.

Methods: We performed a retrospective review of patients < 50 years old diagnosed and/or treated for colorectal cancer between 2001 and 2017 at a safety-net hospital. Kaplan-Meier and Cox regression models were constructed to compare overall survival (OS), progression-free survival (PFS), and relapse-free survival (RFS) by race and ethnicity, stratifying for relevant clinical and pathologic factors.

Results: A total of 395 young-onset patients diagnosed at a safety-net hospital were identified and 270 were included in the analysis (49.6% Hispanic, 25.9% non-Hispanic Black, 20.0% non-Hispanic White, and 4.4% other). Non-Hispanic White race was independently associated with worse OS (hazzard ratio [HR], 0.53; 95% CI, 0.29 to 0.97), as were lack of insurance, higher clinical stage, and mismatch repair proficiency. There was no significant difference seen in PFS or RFS between racial and ethnic groups.

Conclusion: Non-Hispanic White race or ethnicity was found to be independently associated with worse OS in a safety-net population of patients with young-onset colorectal cancer. Other independent predictors of worse OS include higher stage, lack of insurance, and mismatch repair proficiency.
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http://dx.doi.org/10.1200/OP.20.00777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120665PMC
May 2021

Racial/Ethnic Disparities and Survival Characteristics in Non-Pancreatic Gastrointestinal Tract Neuroendocrine Tumors.

Cancers (Basel) 2020 Oct 15;12(10). Epub 2020 Oct 15.

Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.

: We studied the effect of race and ethnicity on disease characteristics and survival in gastrointestinal neuroendocrine tumors. : The Surveillance, Epidemiology, and End Results database was used to select patients with non-pancreatic gastrointestinal neuroendocrine tumors diagnosed between 2004 and 2015. Trends in survival were evaluated among three groups: Hispanic, non-Hispanic White, and non-Hispanic Black. Kaplan-Meier and Cox regression methods were performed to calculate overall survival and cause-specific survival after adjusting for patient and tumor characteristics. A total of 26,399 patients were included in the study: 65.1% were non-Hispanic White, 19.9% were non-Hispanic Black, and 15% were Hispanic. Non-Hispanic White patients were more likely to be male (50.0%, < 0.001), older than 60 years (48.0%, < 0.001), and present with metastatic disease (17.7%, < 0.001). Non-Hispanic White patients had small intestine neuroendocrine tumors, while Hispanic and non-Hispanic Black patients had rectum neuroendocrine tumors as the most common primary site. Hispanic patients had better overall survival, while non-Hispanic Black patients had better cause-specific survival versus non-Hispanic White patients. This finding was confirmed on multivariable analysis where Hispanic patients had improved overall survival compared to non-Hispanic White patients (Hazard ratio (HR): 0.89 (0.81-0.97)), whereas non-Hispanic Black patients had better cause-specific survival compared to non-Hispanic White patients (HR: 0.89 (0.80-0.98)). : Race/ethnicity is an independent prognostic factor in patients with gastrointestinal neuroendocrine tumors.
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http://dx.doi.org/10.3390/cancers12102990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602558PMC
October 2020

Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016.

Am J Clin Oncol 2020 12;43(12):850-856

Surgery, University of Texas Southwestern, Dallas, TX.

Background: When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC.

Methods: Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression.

Results: Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P<0.0001; absolute percentage: 62.3% to 43.8%). Similar trends by year for PTR were observed among each of the subgroups, although patients with colon primary, young adults (age younger than 50 y), and patients also undergoing metastasectomy were more likely to undergo PTR (P<0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with a later year of diagnosis (adjusted odds ratio=2.21, 95% confidence interval: 2.04-2.40, P<0.0001).

Conclusions: From 2000 to 2016, there was a sharp decline in the rate of PTR for patients with metastatic CRC, while the use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC.
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http://dx.doi.org/10.1097/COC.0000000000000764DOI Listing
December 2020

Racial Disparities in Time to Treatment Initiation and Outcomes for Early Stage Anal Squamous Cell Carcinoma.

Am J Clin Oncol 2020 11;43(11):762-769

Department of Radiation Oncology.

Objectives: Although cure rates for early stage anal squamous cell cancer (ASCC) are overall high, there may be racial disparities in receipt of treatment and outcome precluding favorable outcomes across all patient demographics. Therefore, the authors aimed to assess the time to treatment initiation and overall survival (OS) in Black and White patients receiving definitive chemoradiation for early stage ASCC.

Materials And Methods: The authors identified patients diagnosed with early stage (stage I-II) ASCC and treated with chemoradiation diagnosed between 2004 and 2016 in the National Cancer Database. Clinical and treatment variables were compared by race using the χ test, and OS assessed through Cox regression with 1:1 nearest neighbor propensity score matching.

Results: Among 9331 patients, 90.6% were White. Black patients had longer median time to treatment initiation as compared with White patients (47 vs. 36 d, P<0.001), and on multivariable analysis, the Black race was associated with higher odds of >6 weeks of time to treatment initiation (hazard ratio, 1.78; 95% confidence interval, 1.53-2.08; P<0.001). Furthermore, Black patients had worse OS (5-year survival 71% vs. 77%; P<0.001), which persisted after propensity score matching (P=0.007).

Conclusions: Black patients had a longer time to treatment initiation and worse OS as compared with White patients with early stage ASCC treated with chemoradiation. Further research is needed to better elucidate the etiologies of these disparities.
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http://dx.doi.org/10.1097/COC.0000000000000744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584763PMC
November 2020

Feasibility and Outcome of Routine Use of Concurrent Chemoradiation in HIV-positive Patients With Squamous Cell Anal Cancer.

Am J Clin Oncol 2020 10;43(10):701-708

Departments of Radiation Oncology.

Objectives: Clinical concerns about hematologic toxicities in human immunodeficiency virus (HIV)+ patients with squamous cell anal cancer (SCAC) may lead to de-escalation of treatment intensity. The objective of this study is to evaluate clinical outcomes including toxicity following standard concurrent curative-intent chemoradiation for HIV+ and HIV- patients with SCAC.

Materials And Methods: Among 97 evaluable patients treated between 2009 and 2016 (median age 52.2 y), 43 (44.3%) were HIV+ and 54 (55.7%) HIV-. The majority of the radiation was delivered using intensity-modulated radiation therapy and chemotherapy consisting primarily (93%) of 5-fluorouracil and mitomycin C. Clinical outcomes assessed included toxicity, locoregional control (LRC), distant metastasis (DM), progression-free survival (PFS), colostomy-free survival (CFS), overall survival (OS), and cause-specific survival (CSS).

Results: With a median follow-up of 45 months, HIV+ patients exhibited a trend toward reduced OS compared with HIV- patients (4 y OS 61.2% vs. 78.3%; HR 2.09; 95% CI, 0.97-4.52; P=0.055) on univariable analysis, but HIV status was not significant after adjusting for additional parameters on multivariable analysis. Toxicity rates, LRC, CFS, PFS, freedom from DM, and CSS were similar between the 2 cohorts. On multivariable analysis, tumor size >5 cm impacted all clinical outcomes (trend for LRC) except CFS. Radiation treatment extension beyond 7 days was found to negatively impact LRC and CSS. Male sex was associated with worse CFS.

Conclusions: Radiation therapy with concurrent 5-fluorouracil and mitomycin C chemotherapy is reasonably well-tolerated as curative treatment for HIV+ patients with SCAC, and no significant difference in outcomes was noted relative to HIV- patients.
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http://dx.doi.org/10.1097/COC.0000000000000736DOI Listing
October 2020

DNA Repair Gene Mutations as Predictors of Immune Checkpoint Inhibitor Response beyond Tumor Mutation Burden.

Cell Rep Med 2020 Jun;1(3)

Children's Research Institute, Department of Pediatrics, and Department of Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but prediction of their benefit is challenging. Neoantigens generated through impaired non-mismatch DNA repair may result in greater ICI activity. By analyzing 1,661 ICI-treated patients, we show that deletions and mutations in nucleotide excision repair (NER) and homologous repair (HR) pathways are predictors of ICI benefit independent of tumor mutation burden and tumor type. NER and HR mutations are also associated with objective response rates to ICIs in esophagogastric and non-small-cell lung cancers. In a cohort of 40,181 unique patients, NER and HR mutations are present in 3.4% and 13.9% of cancers, respectively. These results indicate that NER and HR gene mutations occur in a subpopulation of cancer patients and may aid patient selection for ICI therapy. Assessing NER and HR mutations in the context of other biomarkers may yield powerful predictors of ICI activity across different cancer types.
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http://dx.doi.org/10.1016/j.xcrm.2020.100034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365618PMC
June 2020

Recent Trends and Overall Survival of Young Versus Older Adults With Stage II to III Rectal Cancer Treated With and Without Surgery in the United States, 2010-2015.

Am J Clin Oncol 2020 10;43(10):694-700

Departments of Radiation Oncology.

Background: The omission of surgery via nonoperative management (NOM) for rectal cancer may be increasing, and this strategy could be particularly attractive for younger patients, whose incidence of rectal cancer has been rising. We sought to assess trends in NOM in young (younger than 55 y) versus older adult (55 y and older) rectal cancer cohorts.

Methods: The National Cancer Database was used to identify patients diagnosed with stage II to III rectal cancer between 2010 and 2015. Multivariable logistic regression defined the association between sociodemographic variables and odds of NOM, including an age (18 to 54 vs. 55+ y)×surgery (surgery vs. NOM) interaction term. Adjusted Cox regression models compared overall survival between NOM versus surgery.

Results: Among 22,561 patients with a median follow-up of 37.5 months, the utilization rate of NOM increased from 10.7% (2010) to 15.2% (2015). Older patients were more likely to receive NOM, although rates also increased among young (7.1% to 10.6%). Black patients were also more likely to receive NOM (P<0.001). Among the entire cohort, NOM was associated with worse overall survival (adjusted hazard ratio [AHR]=2.90, 95% confidence interval [CI]: 2.67-3.15) and there was a statistically significant age×NOM interaction (P=0.01) such that the effect of NOM on survival was worse for younger (AHR=3.37, 95% CI: 2.82-4.02) as compared with older patients (AHR=2.49, 95% CI: 2.27-2.74).

Conclusions: The increasing trend for NOM in stage II to III rectal cancer may be driven by disparities in treatment. Management with NOM appears to be associated with poorer survival, particularly in younger patients and could worsen outcomes for groups already at risk for suboptimal cancer care.
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http://dx.doi.org/10.1097/COC.0000000000000733DOI Listing
October 2020

Stage-specific Conditional Survival Among Young (Age Below 50 y) Versus Older (Age 50 y and Above) Adults With Colorectal Cancer in the United States.

Am J Clin Oncol 2020 07;43(7):526-530

Departments of Radiation Oncology.

Background: Conditional survival (CS) is a relevant prognostic measure and may be particularly important for young adult patients with colorectal cancer (CRC), whose incidence is rising. We sought to compare CS among young versus older adults with CRC.

Methods: Patients diagnosed with CRC between 2004 and 2010 were identified from the Surveillance, Epidemiology, and End Results registry. Smoothed yearly hazards of death due to CRC, other causes and any cause were estimated, stratified by age at diagnosis (below 50 vs. 50 y and above) and stage (I-III vs. IV). Stage-specific conditional 5-year overall survival and cancer-specific survival given that patients had already survived 1 to 5 years after diagnosis was calculated.

Results: Among 161,859 patients with median follow-up of 54 months, 35,411 (21.9%) were aged below 50 years. For older adults with nonmetastatic CRC, hazards of death due to noncancer causes exceeded that of rectal and colon cancer ∼6.1 and 3.8 years after diagnosis, respectively. Patients experienced improved CS over time with greater improvement seen for more advanced stages. However, young adults had less CS improvement over time than older adults. For example, the 5-year cancer-specific survival for stage IV colon cancer improved from 15.6% to 77.2% (change=61.6%) 0 to 5 years after diagnosis for older adults but only 20.3% to 67.7% (change=47.4%) for young adults.

Conclusions: Prognosis for CRC improves over time for all patients, although the increase in survival appears to be less for young than older adults. Up to 10 years after diagnosis, the primary cause of death in young adults with CRC remains their incident cancer.
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http://dx.doi.org/10.1097/COC.0000000000000698DOI Listing
July 2020

Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer.

Clin Cancer Res 2020 07 17;26(14):3557-3564. Epub 2020 Apr 17.

Department of Oncology, University of Texas Southwestern Medical Center of Dallas, Dallas, Texas.

Purpose: Patients with metastatic colorectal cancer refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric mAb targeting a variant of with specificity to colorectal cancer.

Patients And Methods: Single-arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required on the basis of the assumption that ensituximab would improve median overall survival (OS) by 7 months using a one-sided significance level of 10% and 80% power. Written informed consent was obtained from all patients.

Results: Sixty-three patients with advanced, refractory colorectal cancer were enrolled and 53 subjects were treated in phase II arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment-related adverse events (AE) at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%), and diarrhea (6%). Serious AEs at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin, and hypoxia. No patients discontinued treatment due to drug-related AEs.

Conclusions: Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0426DOI Listing
July 2020

Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours.

Br J Cancer 2020 05 2;122(11):1630-1637. Epub 2020 Apr 2.

The University of Texas Southwestern Medical Center, Dallas, TX, USA.

Background: In this first-in-human, Phase 1 study of a microRNA-based cancer therapy, the recommended Phase 2 dose (RP2D) of MRX34, a liposomal mimic of microRNA-34a (miR-34a), was determined and evaluated in patients with advanced solid tumours.

Methods: Adults with various solid tumours refractory to standard treatments were enrolled in 3 + 3 dose-escalation cohorts and, following RP2D determination, expansion cohorts. MRX34, with oral dexamethasone premedication, was given intravenously daily for 5 days in 3-week cycles.

Results: Common all-cause adverse events observed in 85 patients enrolled included fever (% all grade/G3: 72/4), chills (53/14), fatigue (51/9), back/neck pain (36/5), nausea (36/1) and dyspnoea (25/4). The RP2D was 70 mg/m for hepatocellular carcinoma (HCC) and 93 mg/m for non-HCC cancers. Pharmacodynamic results showed delivery of miR-34a to tumours, and dose-dependent modulation of target gene expression in white blood cells. Three patients had PRs and 16 had SD lasting ≥4 cycles (median, 19 weeks, range, 11-55).

Conclusion: MRX34 treatment with dexamethasone premedication demonstrated a manageable toxicity profile in most patients and some clinical activity. Although the trial was closed early due to serious immune-mediated AEs that resulted in four patient deaths, dose-dependent modulation of relevant target genes provides proof-of-concept for miRNA-based cancer therapy.

Clinical Trial Registration: NCT01829971.
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http://dx.doi.org/10.1038/s41416-020-0802-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251107PMC
May 2020

Patterns of Care for Stage II-III Rectosigmoid Cancers in the United States, 2004-2015.

Am J Clin Oncol 2020 05;43(5):311-318

Departments of Radiation Oncology.

Objectives: Although current guidelines continue to recommend trimodality therapy for stage II to III rectal cancers, a lower incidence of local recurrence has been observed in patients with upper rectal tumors, including those in the rectosigmoid. In practice, patients with upper rectal tumors may not be receiving all 3 modalities of therapy. Patterns of care for patients with rectosigmoid cancers have not previously been described.

Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with stage II to III rectosigmoid cancer who underwent definitive surgery between 2004 and 2015. Multivariable logistic regression defined adjusted odds ratio and associated 95% confidence intervals of receipt of any pelvic radiotherapy and preoperative and postoperative pelvic radiotherapy. Multivariable logistic regression also assessed odds of treatment with any chemotherapy and multiagent chemotherapy.

Results: Among 8410 patients, 3566 (42.4%) received any pelvic radiotherapy, of which 2516 (70.6%) were treated with preoperative radiotherapy. Factors associated with receipt of radiotherapy included male sex, white race, younger age, positive clinical nodes and positive margins (P<0.001). Among patients with clinically positive nodes, 1980 (48.6%) received any radiotherapy and among those with pathologically positive nodes, 1532 (37.9%) received radiotherapy. A total of 5708 patients (67.9%) received any chemotherapy including 3020 (52.9%) with multiagent chemotherapy. A total of 2579 (30.7%) of the cohort was treated with surgery alone and among patients who were T3N0, this proportion rose to 42.5%.

Conclusions: Less than half of patients with stage II to III rectosigmoid cancers are treated with radiation therapy and approximately one third do not receive chemotherapy. Ongoing and future studies may help to better tailor treatment for rectosigmoid tumors to optimize the therapeutic ratio. Our work may serve as a benchmark on which to compare future practice patterns.
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http://dx.doi.org/10.1097/COC.0000000000000674DOI Listing
May 2020

The association of lymphotoxin-beta receptor with the subsequent diagnosis of incident gastrointestinal cancer: results from the Dallas Heart Study.

J Gastrointest Oncol 2020 Feb;11(1):36-44

Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Background: Lymphotoxin-beta receptor (LTβR) is an immunological protein associated with inflammation, and from preclinical studies is implicated in tumorigenesis. The epidemiological relationships with cancer are unknown, hence this study investigated their associations.

Methods: From a multiethnic population-based cohort, 3,032 participants without a prevalent cancer (a diagnosis prior to or within one year of enrollment) at baseline underwent measurement of plasma LTβR. These participants were followed for incident cancer using the Texas Cancer Registry (TCR).

Results: Over a median follow-up of 12.1 years, 178 participants developed incident cancer, of which 30 participants developed incident gastrointestinal (GI) cancer. Median plasma LTβR (1.10 1.00 ng/mL, P<0.02) levels were higher in individuals with overall incident cancer compared to those without cancer. After adjustments for age, sex, and race/ethnicity, these relationships were no longer significant. When analyses were stratified by cancer type, LTβR was positively associated with GI cancer after adjustments: HR, 95% CI per 1-standard deviation increase in concentration 2.64 (1.23-5.68), P=0.013. LTβR stratified by quartiles was significantly associated temporally with the risk of incident GI cancer, log-rank: P=0.011. The median interval to incident GI cancer diagnosis was 5.9 years.

Conclusions: Increased plasma levels of LTβR are associated with the development of GI cancer. The antecedent findings years prior to a subsequent diagnosis of incident GI cancer suggest a role for LTβR in the pathogenesis of GI cancer. Further studies are needed to determine if LTβR can serve as an immune biomarker for GI cancer, in particular hepatocellular and colorectal cancers.
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http://dx.doi.org/10.21037/jgo.2020.01.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052776PMC
February 2020

Phase II Multicenter, Open-Label Study of Oral ENMD-2076 for the Treatment of Patients with Advanced Fibrolamellar Carcinoma.

Oncologist 2020 12 10;25(12):e1837-e1845. Epub 2020 Mar 10.

University of California San Francisco, San Francisco, California, USA.

Lessons Learned: The fibrolamellar carcinoma-associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and, thus, overexpression of Aurora kinase A. ENMD-2076 showed a favorable toxicity profile. The limited results, one patient (3%) with a partial response and 57% of patients with stable disease, do not support further evaluation of ENMD-2076 as single agent. Future studies will depend on the simultaneous targeting approach of DNAJB1-PRKACA and the critical downstream components.

Background: Fibrolamellar carcinoma (FLC) represents approximately 0.85% of liver cancers. The associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and overexpression of Aurora kinase A (AURKA). ENMD-2076 is a selective anti-AURKA inhibitor.

Methods: Patients aged >12 years with pathologically confirmed incurable FLC, with measurable disease, Eastern Cooperative Oncology Group performance status 0-2 or Lansky 70-100, and adequate organ function were eligible. Patients were prescribed ENMD-2076 based on body surface area. The primary endpoint was overall objective response rate by RECIST v1.1, with a null hypothesis of true response rate of 2% versus one-sided alternative of 15%. Secondary endpoints included 6-month progression-free survival (PFS) rate (Fig. 1), median PFS, time to progression (TTP), and overall survival (OS). Safety was evaluated throughout the study.

Results: Of 35 patients who enrolled and received treatment, 1 (3%) had a partial response (PR) and 20 (57%) had stable disease (SD). Median TTP, PFS, and OS were 5, 3.9, and 19 months, respectively. The most frequently reported drug-related serious adverse event was hypertension in three patients. Three deaths were reported on-study-two due to disease progression and one due to pulmonary embolism not related to ENMD-2076.

Conclusion: The study provided no rationale for further studying ENMD-2076 as a single agent in FLC.
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http://dx.doi.org/10.1634/theoncologist.2020-0093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186410PMC
December 2020

Improving the Time to Activation of New Clinical Trials at a National Cancer Institute-Designated Comprehensive Cancer Center.

JCO Oncol Pract 2020 04 16;16(4):e324-e332. Epub 2020 Jan 16.

Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX.

Purpose: The time it takes a performing site to activate a clinical trial can directly affect the ability to provide innovative and state-of-the-art care to patients. We sought to understand the process of activating an oncology clinical trial at a matrix National Cancer Institute-designated comprehensive cancer center.

Methods: A multidisciplinary team of stakeholders within the cancer center, university, and affiliate hospitals held a retreat to map out the process of activating a clinical trial. We applied classical quality improvement and Six Sigma methodology to determine bottlenecks and non-value-added time in activating a clinical trial. During this process, attention was paid to time to pass through each step, and perceived barriers and bottlenecks were identified through group discussions.

Results: The process map identified 66 steps with 12 decision points to activate a new clinical trial. The following two steps were instituted first: allow parallel scientific committee and institutional review board (IRB) review and allow the clinical research coordination committee, a group that determines university interest and feasibility, to review protocols independent of the IRB and scientific committee approval. The clinical research coordination committee continues to track the activation time, and this framework is used to identify additional improvement steps.

Conclusion: By applying quality improvement methodologies and Six Sigma principles, we were able to identify redundancies in the process to activate a clinical trial. This allowed us to redesign the process of activating a clinical trial at a matrix comprehensive cancer center. More importantly, the process map provides a framework to maintain these gains and implement additional changes and serves as an example to deploy across the campus and at other similar institutions.
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http://dx.doi.org/10.1200/OP.19.00325DOI Listing
April 2020

Head and neck neuroendocrine tumors at a single institution over 15 years.

Clin Case Rep 2019 Dec 17;7(12):2508-2512. Epub 2019 Nov 17.

Division of Hematology and Oncology/Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical Center Dallas Texas.

Head and neck cancer is a diverse group of rare diseases such as neuroendocrine tumors which can be thought of as extrapulmonary small-cell cancer. Surgery, chemotherapy, and radiation can frequently cure this disease, possibly due to early detection.
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http://dx.doi.org/10.1002/ccr3.2545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935626PMC
December 2019

Ascites, or Fluid in the Belly, in Patients With Cancer.

JAMA Oncol 2020 02;6(2):308

The University of Texas Southwestern Medical Center, Dallas.

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http://dx.doi.org/10.1001/jamaoncol.2019.5409DOI Listing
February 2020

Unique Patterns of Distant Metastases in HPV-Positive Head and Neck Cancer.

Oncology 2020 17;98(3):179-185. Epub 2019 Dec 17.

Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas and Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas, USA,

Background: HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC) demonstrates favorable outcomes compared to HPV-negative SCC, but distant metastases (DM) still occur. The pattern of DM in HPV+ HNSCC is unclear.

Methods: 1,494 HNSCC patients were treated from 2006 to 2012. Recurrence time and metastatic sites in HPV+ HNSCC (Group 1) were compared to patients with HPV-negative/unknown cancers arising in the hypopharynx, larynx, or glottis (Group 2) as well as to patients with HPV-negative/unknown cancers in theoral cavity, oropharynx, hard palate, or tonsil (Group 3).

Results: 7/109 (6.4%) patients with HPV+ HNSCC developed DM. The median time to metastases was 11 months. At a median follow-up of 18-25 months, there was no difference in the overall rate of DM for the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.21) and Group 3 (HPV-/unknown) (p = 0.13). There was a significant difference in the rate of DM to the lung in the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.012) and Group 3 (HPV-/unknown) (p = 0.002).

Conclusions: There was no observed difference in the time to development of DM between the HPV-/unknown and HPV+ HNSCC groups. However, the HPV+ HNSCC group showed a higher rate of DM to the lung compared to the HPV-/unknown -HNSCC group (p = 0.002).
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http://dx.doi.org/10.1159/000504651DOI Listing
March 2020

Liquid Biopsy for Cancer: Review and Implications for the Radiologist.

Radiology 2020 01 19;294(1):5-17. Epub 2019 Nov 19.

From the Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Tex (J.J.U.); Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (R.S.Q., H.S., P.D.S.); Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital, 55 Fruit St, GRB-290, Boston, Mass 02114 (S.P.K., P.D.S.); Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Tex (A.R.S., M.S.B.).

Imaging and image-guided procedures play an imperative role in the screening, diagnosis, and surveillance of cancer. Although emerging imaging techniques now enable more precise molecular characterization of tumors, multigenetic tumor profiling for targeted therapeutic selection remains limited to direct tissue acquisition. Even in the context of targeted therapy, tumors adapt to acquire resistance. This necessitates serial monitoring, traditionally through tissue acquisition, to identify the molecular mechanism of resistance and to guide second-line therapy. An alternative to tissue acquisition is the collection of circulating tumor markers such as cell-free nucleic acids and circulating tumor cells in the peripheral blood. This noninvasive diagnostic approach is referred to as the liquid biopsy. The liquid biopsy is currently used clinically for therapeutic guidance when tissue acquisition is impossible or when the specimen is inadequate. It is also being studied in the context of screening, diagnosis, and surveillance. As cancer treatment continues to move toward a focus on precision medicine, this developing technology may alter and/or augment the role of imaging in the management of cancer. This review aims to outline the use of liquid biopsy in cancer and its potential impact on diagnostic imaging and image-guided procedures.
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http://dx.doi.org/10.1148/radiol.2019182584DOI Listing
January 2020

Sociodemographic Disparities in the Receipt of Adjuvant Chemotherapy Among Patients With Resected Stage I-III Pancreatic Adenocarcinoma.

J Natl Compr Canc Netw 2019 11;17(11):1292-1300

Department of Radiation Oncology, and.

Background: Adjuvant therapy for resected pancreatic adenocarcinoma was given a category 1 NCCN recommendation in 2000, yet many patients do not receive chemotherapy after definitive surgery. Whether sociodemographic disparities exist for receipt of adjuvant chemotherapy is poorly understood.

Methods: The National Cancer Database was used to identify patients diagnosed with nonmetastatic pancreatic adenocarcinoma who underwent definitive surgery from 2004 through 2015. Multivariable logistic regression defined the adjusted odds ratio (aOR) and associated 95% CI of receipt of adjuvant chemotherapy. Among patients receiving chemotherapy, multivariable logistic regression assessed the odds of treatment with multiagent chemotherapy.

Results: Among 18,463 patients, 11,288 (61.1%) received any adjuvant chemotherapy. Sociodemographic factors inversely associated with receipt of any adjuvant chemotherapy included uninsured status (aOR, 0.61; 95% CI, 0.50-0.74), Medicaid insurance (aOR, 0.66; 95% CI, 0.57-0.77), and lower income (P<.001 for all income levels compared with ≥$46,000). Black race (aOR, 0.72; 95% CI, 0.57-0.90) and female sex (aOR, 0.75; 95% CI, 0.65-0.86) were associated with lower odds of receiving multiagent chemotherapy. There was a statistically significant interaction term between black race and age/comorbidity status (P=.03), such that 26.4% of black versus 35.8% of nonblack young (aged ≤65 years) and healthy (Charlson-Deyo comorbidity score 0) patients received multiagent adjuvant chemotherapy (P=.006), whereas multiagent adjuvant chemotherapy rates were similar among patients who were not young and healthy (P=.15).

Conclusions: In this nationally representative study, receipt of adjuvant chemotherapy appeared to be associated with sociodemographic characteristics, independent of clinical factors. Sociodemographic differences in receipt of adjuvant chemotherapy may represent a missed opportunity for improving outcomes and a driver of oncologic disparities.
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http://dx.doi.org/10.6004/jnccn.2019.7322DOI Listing
November 2019

Efficacy and Safety of Bavituximab in Combination with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial.

Target Oncol 2019 10;14(5):541-550

Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.

Background: Bavituximab, an immunomodulator, targets phosphatidylserine (PS), a membrane lipid externalized on tumor and endothelial cells in response to sorafenib.

Objective: The objective of this phase II study was to assess the efficacy of combination bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC).

Methods: In this single-arm phase II study, patients with HCC determined to be unresectable with Eastern Cooperative Oncology Group (ECOG) score ≤ 2, Child-Pugh score A/B7 received intravenous bavituximab 3 mg/kg weekly and oral sorafenib 400 mg twice daily until disease progression or intolerable toxicity. We investigated time to progression (TTP) for patients receiving combination bavituximab and sorafenib compared with that for sorafenib-only historical controls.

Results: In total, 38 patients were accrued. The median follow-up was 6.1 months. Patient characteristics were as follows: median age 61 years; male 82%; hepatitis C virus 79%; Black 39%, Hispanic 26%, White 29%; previous treatment 39%; macrovascular invasion 84%; and extrahepatic metastases 24%. The median TTP was 6.7 months (95% confidence interval [CI] 4-17). The median overall survival was 6.1 months (95% CI 5-8), and the median disease-specific survival was 8.6 months (95% CI 6-14). Two patients experienced partial responses; none had a complete response. The disease control rate was 58%. Treatment-related adverse events were observed in 63% of patients, with the most commonly reported therapy-related symptoms being diarrhea (32%), fatigue (26%), and anorexia (24%).

Conclusions: The efficacy of adding bavituximab to sorafenib for the treatment of advanced HCC was inconclusive; however, the combination regimen did not exacerbate toxicities associated with single-agent sorafenib. CLINICALTRIALS.

Gov Identifier: NCT01264705.
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http://dx.doi.org/10.1007/s11523-019-00663-3DOI Listing
October 2019

Self-reported Reasons and Patterns of Noninsurance Among Cancer Survivors Before and After Implementation of the Affordable Care Act, 2000-2017.

JAMA Oncol 2019 Oct 10;5(10):e191973. Epub 2019 Oct 10.

Dana-Farber Cancer Institute McGraw/Patterson Center for Population Sciences, Boston, Massachusetts.

Importance: Cancer survivors experience difficulties in maintaining health care coverage, but the reasons and risk factors for lack of insurance are poorly defined.

Objective: To assess self-reported reasons for not having insurance and demographic and socioeconomic factors associated with uninsured status among cancer survivors, before and after implementation of the Affordable Care Act (ACA) in 2014.

Design, Setting, And Participants: This survey study analyzes National Health Interview Survey (NHIS) data from January 1, 2000, through December 31, 2017. Included were adult participants (age, 18-64 years) reporting a cancer diagnosis; however, those with a diagnosis of nonmelanoma skin cancer were excluded.

Exposures: Insurance status.

Main Outcomes And Measures: Multivariable logistic regression was used to define the association between demographic and socioeconomic variables and odds of being uninsured. The prevalence of the most common self-reported reasons for not having insurance (cost, unemployment, employment-related reason, family-related reason) were estimated, with adjusted odds ratios (aORs) for each of the reasons defined by multivariable logistic regression.

Results: Among 17 806 survey participants, the mean (SD) age was 50.9 (10.8) years, and 6121 (34.4%) were men. A total of 1842 participants (10.3%) reported not having health insurance. Individuals surveyed in 2000 to 2013 had higher odds of not having insurance than those surveyed in 2014 to 2017 (10.6% vs 6.2%; aOR 1.75; 95% CI 1.49-2.08). Variables associated with higher odds of uninsured status included younger age (14.2% for age younger than mean vs 6.5% for age older than mean; aOR, 1.84; 95%, CI, 1.62-2.10), annual family income below the poverty threshold (21.4% vs 8.0%; aOR, 1.97; 95%, CI, 1.69-2.30), Hispanic ethnicity (18.8% vs 9.0%; aOR, 1.87; 95% CI, 1.51-2.33), noncitizen status (24.3% vs 9.2%; aOR, 2.38; 95% CI, 1.69-3.34), and current smoking (18.6% vs. 6.7%; aOR, 2.65; 95% CI, 2.32-3.02). Before the ACA, increasing interval from cancer diagnosis was associated with not having insurance (12.3% for ≥6 years vs 8.9% for 0-5 years; aOR, 1.47; 95% CI 1.26-1.70) as was black race (13.9% for black patients vs 10.4% for nonblack patients; AOR, 1.29; 95% CI, 1.04-1.61), but after the ACA, they no longer were (6.8% for ≥6 years vs 5.6% for 0-5 years; aOR, 1.12; 95% CI, 0.82-1.54; and 6.9% for black patients vs 6.2% for nonblack patients; aOR, 0.81; 95% CI, 0.46-1.43). The most commonly cited reason for not having insurance was cost, followed by unemployment, both of which decreased after ACA implementation (cost, 49.6% vs 37.6%, aOR [pre-ACA vs post-ACA], 0.62; 95% CI, 0.46-0.85; unemployment, 37.1% vs 28.5%; aOR 0.62; 95% CI, 0.45-0.87).

Conclusions And Relevance: The proportion of uninsured cancer survivors decreased after implementation of the ACA, but certain subgroups remained at greater risk of being uninsured. Cost was identified as the primary barrier to obtaining insurance, although more than half of cancer survivors reported other barriers to coverage.
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http://dx.doi.org/10.1001/jamaoncol.2019.1973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537771PMC
October 2019

Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling.

Head Neck 2019 06 13;41(6):1928-1934. Epub 2019 Feb 13.

Foundation Medicine, Inc., Cambridge, Massachusetts.

Introduction: Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Those ATC with genomic alterations (GAs) in TSC2, ALK, and BRAF may respond to targeted therapies.

Methods: Comprehensive genomic profiling on 90 ATC specimens identified base substitutions, short insertions and deletions, amplifications, copy number alterations, and genomic rearrangements in up to 315 cancer-related genes and 28 genes commonly rearranged in cancer.

Results: Median patient age was 65 (range, 33-86) years, 50 patients were male. There was a mean of 4.2 GA per case, range 1-11. The most common GA were TP53 (66%), BRAF (34%), TERT (32%), CDKN2A (32%), and NRAS (26%). BRAF V600E and NRAS/HRAS/KRAS alteration were mutually exclusive. BRAF, CDKN2A, PIK3CA, and JAK2 were more frequent in patients >70 years of age; while myc, PTEN, and NRAS were more common in those ≤50 years.

Conclusion: ATC shows many GA with potential therapeutic significance and suggesting different molecular pathways can lead to ATC.
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http://dx.doi.org/10.1002/hed.25634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542589PMC
June 2019

Feasibility of Wearable Physical Activity Monitors in Patients With Cancer.

JCO Clin Cancer Inform 2018 12;2:1-10

Arjun Gupta, Nizar Bhulani, Ying Dong, Zain Rahimi, Kimberli Crane, Chad Rethorst, and Muhammad S. Beg, University of Texas Southwestern Medical Center, Dallas, TX; and Tyler Stewart, Yale University, New Haven, CT.

Purpose: The feasibility of using physical activity monitors (PAMs) to measure functional status in patients with cancer is unclear. We aimed to determine the feasibility of using PAMs to longitudinally assess physical activity and performance status (PS) in patients with cancer.

Methods: Patients with cancer who had Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2 and were receiving systemic therapy were enrolled in a prospective pilot trial of PAM use. Feasibility was defined as patients using the PAM for > 50% of the observation period. We correlated PAM-reported measures with scores from ECOG PS and quality-of-life tools (Functional Assessment of Cancer Therapy-General [FACT-G], Quick Inventory of Depressive Symptoms-Self-Rated 16 [QIDS-SR16], and Brief Fatigue Inventory [BFI]) using Pearson's correlation test. Patients were surveyed regarding their experience with PAMs at study completion.

Results: In all, 24 patients were enrolled; mean age was 54 years, 16 (67%) were women, and 19 (79%) were white. Twenty-three patients (96%) met the primary end point of feasibility. The median duration of follow-up was 69 days. Mean PAM-measured steps for ECOG PS of 0, 1, and 2 were 5,911, 1,890, and 845 steps per day, respectively ( P = .002). Minimum steps per day correlated with BFI ( r = -0.53; P < .01), FACT-G ( r = 0.45; P = .02), and QIDS-SR16 ( r = -0.57; P < .01). Eighteen patients (75%) reported a positive experience with the PAM.

Conclusion: PAMs are a feasible tool for measuring long-term physical activity in patients with cancer who are receiving systemic therapy. PAM-derived measures correlated with clinician-assessed PS.
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http://dx.doi.org/10.1200/CCI.17.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873942PMC
December 2018

NQO1-dependent, Tumor-selective Radiosensitization of Non-small Cell Lung Cancers.

Clin Cancer Res 2019 04 7;25(8):2601-2609. Epub 2019 Jan 7.

Department of Biochemistry and Molecular Biology, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.

Purpose: Development of tumor-specific therapies for the treatment of recalcitrant non-small cell lung cancers (NSCLC) is urgently needed. Here, we investigated the ability of β-lapachone (β-lap, ARQ761 in clinical form) to selectively potentiate the effects of ionizing radiation (IR, 1-3 Gy) in NSCLCs that overexpress NAD(P)H:Quinone Oxidoreductase 1 (NQO1).

Experimental Design: The mechanism of lethality of low-dose IR in combination with sublethal doses of β-lap was evaluated in NSCLC lines and validated in subcutaneous and orthotopic xenograft models . Pharmacokinetics and pharmacodynamics (PK/PD) studies comparing single versus cotreatments were performed to validate therapeutic efficacy and mechanism of action.

Results: β-Lap administration after IR treatment hyperactivated PARP, greatly lowered NAD/ATP levels, and increased double-strand break (DSB) lesions over time . Radiosensitization of orthotopic, as well as subcutaneous, NSCLCs occurred with high apparent cures (>70%), even though 1/8 β-lap doses reach subcutaneous versus orthotopic tumors. No methemoglobinemia or long-term toxicities were noted in any normal tissues, including mouse liver that expresses the highest level of NQO1 (∼12 units) of any normal tissue. PK/PD responses confirm that IR + β-lap treatments hyperactivate PARP activity, greatly lower NAD/ATP levels, and dramatically inhibit DSB repair in exposed NQO1 cancer tissue, whereas low NQO1 levels and high levels of catalase in associated normal tissue were protective.

Conclusions: Our data suggest that combination of sublethal doses of β-lap and IR is a viable approach to selectively treat NQO1-overexpressing NSCLC and warrant a clinical trial using low-dose IR + β-lap against patients with NQO1 NSCLCs.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-2560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788754PMC
April 2019

Staging systems of hepatocellular carcinoma: A review.

Indian J Gastroenterol 2018 Nov 29;37(6):481-491. Epub 2018 Dec 29.

Division of Vascular and Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Staging of hepatocellular carcinoma (HCC) is necessary for guiding prognostication, management, and research purposes that further aid in the improvement of existing clinical and epidemiological health services. Though there are some new staging systems for HCC developed in different parts of the world, there is no globally accepted staging system that allows for comparison of current management protocols among heterogeneous populations. In this review, we discuss the evolution and applicability in clinical practice of different clinical staging systems of HCC-Okuda, CLIP (Cancer of the Liver Italian Program) score, MESIAH (Model to Estimate Survival In Ambulatory HCC patients) score, ITA.LI.CA (Italian Liver Cancer) score, BCLC (Barcelona Clinic Liver Cancer) staging, HKLC (Hong Kong Liver Cancer) staging, and the Alberta algorithm. This review aims to highlight the main criteria for assessing the prognosis of HCC that these different staging systems take into account, their strengths and limitations for use in modern clinical practice. Despite the limitations of the BCLC staging system, it remains the most validated and reliable system for prognostication. However, there is a need to update the BCLC staging system to include recent data on locoregional and systemic therapies for HCC, expanded criteria for transplantation, and systemic therapy for hepatitis C infection.
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http://dx.doi.org/10.1007/s12664-018-0915-0DOI Listing
November 2018
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