tbuckley/cabot-search huggingface dataset:
Comparison of different treatment methods in craniospinal radiotherapy.
Authors: Elif eda Tiken, Yasin Coban, Mustafa Akin, Songul Karacam, Omer erol Uzel, Tahir sedat Turkan
Journal: Journal of Clinical Oncology (2014)

e13004 Background: Intensity modulated radiation therapy (IMRT) and volumetric arc treatment (IMAT) was planned in patients who have undergone craniospinal (CSRT) 3 dimensional conformal radiotherapy (3 D CRT) for curative and postoperative purposes. Target volume in dosimetric plans and doses received by organs at risk were compared Methods: Eleven patients treated with conventional 3DCRT method with the indication of craniospinal radiation therapy in our clinic between January 2010 and June 2012 were included in our study. Organs at risk and target volumes were defined. Planned target volume (PTV) was the brain CTV and the entire spine PTV. A total of 36 Gy at 1.8 Gy/fraction was given to all patients. IMAT and IMRT plans of the patients were carried out in the eclipse planning system. All plans were compared regarding target wraps, dose homogenity, doses of organs at risk and integral doses Results: At mean doses of the optic nerve, thyroid, esophagus, heart and oral cavity, IMAT was significantly superipor to IMRT. At mean doses of the lungs and kidneys, IMRT plans were found to be better. Dmax of IMAT plans were at low limits in all organs at risk. When IMRT and IMAT plans were compared regarding low doses received by the body, IMRT was better in V2 and V5 and IMAT was better in V15 and V 20. Integral doses were lower in IMRT plans. PTV was 102.7% in Dmean IMRT and 102.3% in IMAT. V95 was 99% in IMRT and 97% in IMAT. V110 was below 1% in both methods and V107 was 2.6% in IMRT and 4% in IMAT. Regarding monitor units (MU), IMAT was significantly less than IMRT therapy. Duration of treatment was significantly shorter with IMRT than with IMAT Conclusions: IMRT and IMAT are suitable treatment choices for CSRT. These methods can be used to decrease late adverse effects and increase disease free survival in patients receiving craniospinal radiotherapy. Nevertheless, risk of developing secondary cancer should be kept in mind.
Factors associated with nonadherence to oral 6-mercaptopurine (6MP) in children with acute lymphoblastic leukemia (ALL): A report from Children’s Oncology Group (COG) study AALL03N1.
Authors: Wendy Landier, Yanjun Chen, Lindsey Hageman, Heeyoung Kim, Bruce C. Bostrom, Jacqueline N. Casillas, David S. Dickens, William E. Evans, Kelly W. Maloney, Leo Mascarenhas, Arthur Kim Ritchey, Amanda M. Termuhlen, William L. Carroll, Mary V. Relling, Florence Lennie Wong, Smita Bhatia
Journal: Journal of Clinical Oncology (2014)

10013 Background: We have previously shown that poor adherence (adherence rate <95%) to oral 6MP is prevalent in children with ALL, and increases relapse risk (JCO 30[17]:2094-101). However, behavioral predictors of non-adherence to oral 6MP have not been examined. Methods: We addressed this gap in 462 children (non-Hispanic Whites: 34%; Hispanics: 36%, Asians: 15%, African-Americans: 15%) with ALL diagnosed at age ≤21 years, and receiving maintenance therapy. 6MP adherence was measured over 6 months using Medication Event Management System (MEMS) that recorded dates/times of 6MP bottle opening (adherence rate=days bottle opened/days 6MP prescribed). A 37-item questionnaire assessed barriers/facilitators (addressing the Health Belief Model [HBM]) to adherence. Results: Median age at study was 6 years (2-20); 67% were males; 40% had high-risk disease. MEMS monitoring for 76,174 person-days yielded a non-adherence rate of 44.4%. Multivariable analysis identified the following predictors of non-adherence: i) age ≥12 years (Odds ratio [OR]=2.2, p=0.02); ii) Hispanic ethnicity (OR=2.1, p=0.005); iii) African-American race (OR=4.2, p<.001); iv) parental education ≤high school (OR=1.8, p=0.02); v) annual household income <$50,000 (OR=1.6, p=0.05); vi) involvement of ≥2 adults in 6MP supervision (OR=2.4; p=.004); vii) failure (on part of parents/patients) to understand the purpose of 6MP (OR=2.8; p<.001); viii) failure to take 6MP at the same time each day (OR=1.8; p<.01); and ix) taking 6MP with milk/dairy (OR=1.9; p=.03). Conclusions: In addition to sociodemographic predictors, we identified behavioral determinants of 6MP non-adherence that align with HBM. Lack of perceived benefits (not understanding the purpose of 6MP), absence of cues to action (not taking medication at same time each day), low self-efficacy (absence of a designated adult assuming primary responsibility for 6MP administration), and presence of barriers (dietary restrictions) contributed to non-adherence. These findings identify vulnerable populations that could benefit from targeted interventions to improve adherence in pediatric ALL. Clinical trial information: NCT00268528.
Smooth Muscle Cells: A Novel Site of P-Selectin Expression with Pathophysiological and Therapeutic Relevance in Pulmonary Hypertension
Authors: Prithu Sundd, Wolfgang M. Kuebler
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

normal PAP is considered to be 14.0 6 3.3 mm Hg, at the 6th World Symposium on Pulmonary Hypertension held in Nice in 2018, a change in the definition of PAH was proposed that would decrease the lower limit of mPAP to 20 mm Hg and a pulmonary vascular resistance .3 WU; however, no conclusion was made regarding whether patients with an mPAP between 20 and 25 mm Hg should be treated (11).The ability to obtain an early diagnosis in PAH remains an important goal to be pursued.Sawada and colleagues have contributed to this quest by evaluating the performance of a large ECG-based screening program in healthy schoolchildren.Unfortunately, the studied screening program did not resolve this problem, and thus early diagnosis remains an important goal to pursue in children with PAH.
Cost-effectiveness of pazopanib (PAZ) versus sunitinib (SUN) as first-line treatment of metastatic renal cell carcinoma (mRCC) patients in the United States.
Authors: Hamid Reza Nakhaipour, Tom Delea, Jordan Amdahl, Jose Diaz, Michelle Denise Hackshaw
Journal: Journal of Clinical Oncology (2014)

e17551 Background: COMPARZ and PISCES were randomized, phase 3 trials of PAZ vs SUN in patients with mRCC who had not received prior systemic therapy. COMPARZ demonstrated non-inferiority of PAZ vs SUN with respect to the protocol-defined non-inferiority margin for progression-free survival (PFS). PISCES demonstrated statistically significant patient preferences in favor of PAZ vs SUN. Methods: We assessed the cost-effectiveness of PAZ vs SUN from the perspective of a US healthcare system using a partitioned survival analysis model with states for PFS, post-progression survival (PPS), and death. The proportion of patients in each state over time was calculated based on survival distributions for PFS and overall survival (OS) from COMPARZ. Costs were based on medical resource utilization (MRU) data from COMPARZ, Medicare fees and published sources. Utility values were from PISCES. The base-case model time horizon was 163 weeks (38 months or 3.1 years) corresponding to the maximum duration of follow-up for PFS and OS in COMPARZ. Costs and quality-adjusted life years (QALYs) were discounted at 3% annually. Results: Life expectancy (not discounted) was estimated to be 0.054 higher with PAZ vs SUN (2.122 vs 2.068). QALYs (discounted) were 0.090 more with PAZ vs SUN (1.361 vs 1.270). Expected total costs (discounted) were estimated to be $6,828 lower with PAZ vs SUN ($154,559 vs $161,387), reflecting $6,264 savings in medication costs and $3,674 savings in monthly on-treatment costs based on MRU data from COMPARZ, offset in part by a $2,809 increase in post-progression costs (due to longer projected PPS) and a $301 increase in dispensing costs (due to 28 vs 42 day dispensing). Because PAZ provides more QALYs at lower cost vs SUN, it was dominant vs SUN in the base-case. At a cost-effectiveness threshold of $100,000/QALY, the net monetary benefit with PAZ vs SUN was estimated to be $15,857. In probabilistic sensitivity analyses, the probability that PAZ is cost effective was estimated to be ≥88% for cost-effectiveness thresholds ≤$200,000 per QALY gained. Conclusions: This analysis demonstrates that PAZ is cost-effective vs SUN as first-line treatment of mRCC patients in the US.
Place-Based Inequity in Smoking Prevalence in the Largest Cities in the United States
Authors: Eric C. Leas, Nina C. Schleicher, Judith J. Prochaska, Lisa Henriksen
Journal: JAMA Internal Medicine (2019)

This study uses data from the 500 Cities Project to characterize inequities in cigarette smoking both between and within cities and their association with sociodemographic factors and chronic diseases.
Etirinotecan pegol (EP, NKTR-102) in the treatment of high-grade glioma (HGG): A phase 2 trial.
Authors: Seema Nagpal, Cathy Kahn Recht, Urooj Imtiaz, Sophie Bertrand, Reena Parada Thomas, Abdulrazag Ajlan, Justine Pena, Megan Gershon, Pamela L. Kunz, Gordon Li, Lawrence David Recht
Journal: Journal of Clinical Oncology (2014)

2096 Background: Patients with recurrence of HGG after bevacizumab (BEV) have an extremely poor prognosis and generally do not respond to further treatment. EP is the first long-acting topoisomerase-I inhibitor designed to concentrate in and provide continuous tumor exposure throughout the entire chemotherapy cycle. Becasue irinotecan has demonstrated activity against HGG, we conducted a Phase 2, single arm, open label trial to evaluate EP in HGG patients who progressed after BEV. Methods: Patients age >18 with histologically proven anaplastic astrocytoma (AA) or glioblastoma (GB) who previously received standard chemo-radiation and recurred after BEV were eligible. A predicted life expectancy > 6 weeks, KPS ≥ 50 and adequate organ and bone marrow functions were required for entry. Primary endpoint was PFS at 6-week, secondary endpoints were survival from first EP infusion, overall survival from date of pathologic diagnosis of HGG, and safety profile of EP. Response was assessed by RANO criteria. EP as a single agent is administered IV every 3 weeks at 145mg/m2. Patients did not receive BEV while on EP. Results: Between August 2012-May 2013, 20 patients were enrolled. Median age was 50 years, median KPS was 70%. 90% of patients had GB with a median time of 1 year from a diagnosis of HGG to study entry with a median of 3 prior lines of therapy. Patients received a median of 3 cycles (1-19) of EP. All patients were evaluable for PFS and toxicity. 2 patients (both with GB) had partial MRI responses. 10 patients had stable disease. 2 patients are still on treatment after receiving 19 and 9 treatment cycles. 6-week PFS was 55%. Median and 6-month PFS were 1.9 mos and 10%, respectively. Median overall survival from first EP infusion was 4.1 months. Only one patient (5%) had a Grade 3 toxicity (diarrhea with dehydration) attributable to EP. Hematologic toxicity was mild. Conclusions: Despite discontinuing BEV prior to starting EP, 2 patients had confirmed partial responses (10%) according to RANO criteria and an additional six patients had stable disease at their 1st and 2nd imaging assessment. These encouraging clinical data combined with a favorable safety profile warrant further clinical investigation of this agent in GB. Clinical trial information: NCT01663012.
Incidence and localization of tumor-infiltrating CD163<sup>+</sup> macrophages and T-cells in early breast cancer patients.
Authors: Anna Koumarianou, Maria Ioanna Christodoulou, Michael Vaslamatzis, Nikolaos Xiros, Varvara Panteleon, Ioanna Themeli, Christina Magkou, Dimitra Rontogianni
Journal: Journal of Clinical Oncology (2014)

11084 Background: CD163+ macrophages (MΦ) infiltrate malignant tissue of breast cancer patients (BrCa) and suppress immunity, through a Th2 microenvironment characterized by high numbers of CD4+ and low numbers of CD8+ T-cells. We examined the associations between immune cell counts and clinicopathological characteristics. Methods: Serial sections of 59 paraffin-embedded BrCa tissues were immunohistochemically analyzed for the presence of total MΦ, their CD163+ subpopulation, helper and cytototoxic T-cells by antibodies to CD68, CD163, CD4, and CD8 markers, respectively. Cells were counted in the intratumoral and peritumoral compartments by two independent observers, and expressed as number of cells for high power field. The medical records of the patients were retrospectively evaluated for various clinicopathologic parameters. Statistical analyses were performed by Tukey’s multiple comparison tests and/or t-tests, or Spearman's correlation test. Results: Highly significant associations were found between the occurrence of CD163+ MΦ cells and CD4+ (p<0.0001) or CD8+ (p=0.0005) T-cells as well as between total CD68+ MΦ and CD4+ T-cells (p=0.01), detected intratumorally. Importantly, intratumoral CD68+ MΦ were positively correlated to relapse (p=0.003), and negatively correlated to survival (p=0.01) in patients treated only with chemotherapy (n=19). Among patients treated with both chemotherapy and hormonal therapy (n=18), relapse was positively associated with peritumoral CD163+ MΦ (p=0.04) and negatively with intratumoral CD163+ MΦ (p=0.03). The grade of the disease was correlated with the number of total CD4+ T-cells peri- and intratumorally (p<0.05), while the CD4+ peritumoral population was also associated with nodal disease (p=0.03). Moreover, a positive correlation was revealed between CD8+peritumoral T-cells and p53 intense staining (p=0.01). Conclusions: Our study provides evidence that tumor associated macrophages, and specifically their CD163+ subpopulation may serve as significant prognostic factors in BrCa, and supports the need for analysis also in terms of localization rather than solely incidence of infiltrating cells in the tumor tissue.
Why Pregnant Women May Justifiably Choose to Use Cannabis—Reply
Authors: Kelly C. Young-Wolff, Amy Conway, Nancy Goler
Journal: JAMA Internal Medicine (2019)

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Aging of Bone Marrow Microenvironment Promotes Myeloid Bias of Hematopoietic Progenitors and Is a Target in Age-Related Myeloproliferative Neoplasms
Authors: Ya-Hsuan Ho, Raquel del Toro, José Rivera-Torres, Justyna Rak, Claudia Korn, Andrés García-García, Lucia Kubovcakova, David Macías, Lorena Arranz, Cristina González-Gómez, Monika Wittner, Ronny Nienhold, Amie K Waller, Holly R Foster, Carlos Lopez-Otin, Randall S Johnson, Claus Nerlov, William Vainchenker, Cedric Ghevaert, Fawzia Louache, Radek C. Skoda, Vicente Andrés, Simon Mendez-Ferrer
Journal: Blood (2018)
Comparison of Salvage Chemotherapy Regimens in Relapsed/Refractory Acute Myeloid Leukemia
Authors: Muhammad Umair Mushtaq, Sibgha Gull Chaudhary, Laura C. Michaelis, Karen-Sue B. Carlson, Sameem Abedin, Lyndsey Runass, Michael J. Fallon, Alexandra M. Harrington, Mark Juckett, Aric C. Hall, Ryan J. Mattison, Ehab L. Atallah, Guru Subramanian Guru Murthy
Journal: Blood (2018)
A prospective biomarker trial of microbiome, immune, and genomic markers as predictors of radiation response in anal squamous cell carcinoma.
Authors: Lauren Elizabeth Colbert, Daniel Lin, Bruce D. Minsky, Emma Brey Holliday, Ann Klopp, Prajnan Das, Cathy Eng, Van Karlyle Morris, Cullen M. Taniguchi
Journal: Journal of Clinical Oncology (2018)

TPS869 Background: Preclinical evidence suggests that the microbiome plays a significant role in carcinogenesis and in response to immunotherapy and chemotherapy, but little is known about the role of the microbiome in response to radiation. Our group previously demonstrated that in patients with cervical squamous cell carcinoma (SCC), radiation response and immune response to radiation are improved with increased rectal microbial diversity. Methods: We are currently enrolling patients with local anal SCC undergoing definitive chemoradiation on a prospective biomarker trial evaluating changes in the gastrointestinal microbiome, immune microenvironment, and whole genome sequencing using a novel, non-invasive swab biopsy technique in addition to serial blood collections. This biopsy technique allows novel evaluation of dynamic changes throughout the course of chemoradiation. Microbiome sequencing is performed using 16s rRNA sequencing. Immune profiling is done using multiparametric flow cytometry for T-cell activation and exhaustion phenotypes and T-cell receptor sequencing. Inclusion criteria are biopsy proven HPV-related SCC of the anus, with no evidence of metastatic disease, and undergoing definitive chemoradiation. Our population is uniquely treated with cisplatin/5-FU based chemotherapy, rather than lymphotoxic mitomycin-C, allowing unique evaluation of immune populations. The primary endpoint of this study is complete tumor response based on pelvic MRI and digital rectal exam at three weeks. Secondary endpoints include FDG-avid diseases at 3 months and disease recurrence. To date we have accrued 10 patients out a planned 30 patient pilot cohort. We expect the remainder of these patients to be accrued by December 2017.
Intensive care unit admissions and in-hospital mortality in patients admitted through the emergency department of a comprehensive cancer center.
Authors: Ahmed F. Elsayem, Kelly W. Merriman, Carmen E. Gonzalez, Sai-ching J. Yeung, Patrick S. Chaftari, Jerry D. Henderson, Knox H. Todd
Journal: Journal of Clinical Oncology (2014)

9562 Background: The National Cancer Policy Forum advocated for improving quality of end life care, and reducing cost for cancer patients. Identifying those at high risk for Intensive Care Unit (ICU) admission, and hospital death may allow earlier palliative care and avoid futile interventions. The purpose of this study is to examine risk factors for ICU admission, and hospital death among cancer patients admitted through the Emergency Department (ED). Methods: We queried MD Anderson Cancer Center databases for all patients who visited our ED in 2010. ICU admission and hospital deaths of these patients were reviewed, and individual patients’ data were analyzed. Results: In 2010, 16,038 ED visits were made by 9,246 unique cancer patients. Of these patients, 5,362 (58%) were admitted to the hospital at least once (range 1-13 admits). Of all patients admitted through the ED, 697 (13%) were admitted at least once to ICU. Of all patients admitted, 11% died during hospitalization; of those, 29% died in ICU. Among patients who died in ICU, 73/233 (31.3%) had hematologic malignancies and 96/354(27.1%) had solid tumors (P<.001). Patients admitted to ICU had median lengths of hospital stay (MLOS) of 13 days for hematologic and 8 days for solid tumors (P<.001; using means); patients without ICU admission had MLOS of 6 and 5 days, respectively (P<.001). In a multivariate logistic regression model for predicting in-hospital mortality, we found that ED presenting symptoms of respiratory distress or altered mental status (fever and pain non-significant); primary tumor of lung cancer, leukemia, unknown primary, or lymphoma; and non-white race were independent predictors of death, while controlling for age, gender and residence. Conclusions: Cancer patients admitted through the ED experience high ICU admission rates, and hospital mortality. Lung and certain other cancers; race; and symptoms of respiratory distress and altered mental status were associated with increased risk of in-hospital death. Patients with these risk factors may benefit from efforts to improve palliative care and prevent unnecessary interventions.
Does high normocalcemia predict ovarian cancer in patients with a pelvic mass?
Authors: Stuart S. Winkler, Michael Greg Kelly, Samuel S. Lentz, Steve H. Berliner, Melissa F. Swain, Halcyon G. Skinner, Gary Schwartz
Journal: Journal of Clinical Oncology (2014)

e16533 Background: Survival from ovarian cancer is improved when surgery is performed by a gynecologic oncologist. Accurately predicting malignant ovarian masses prior to surgery could improve the triage of women to appropriate care. We have previously demonstrated that women with high serum calcium levels were more likely to die from ovarian cancer. The purpose of this study is to determine if serum calcium levels predict a malignant ovarian neoplasm in women with a pelvic mass. Methods: 515 consecutive women with a pelvic mass who underwent surgical resection at our institution from July 2009 - June 2013 were included. Demographic data, albumin, creatinine, calcium, CA-125, tumor grade and stage were recorded. High normocalcemia was defined as an albumin-corrected serum calcium ≥ 10.0 mg/dl (cutpoint for hypercalcemia=10.4 mg/dl). Low malignant potential (LMP) tumors were classified as benign for this study. We used generalized additive models and receiver operator curves to evaluate the ability of high normocalcemia to distinguish women with malignant ovarian masses. Results: 181 women had malignant tumors, 305 had benign neoplasms and 29 had LMP tumors. The mean albumins of patients with benign versus malignant tumors were 3.8 g/dL and 3.2 g/dL, respectively (p<0.01). Patients with a malignant tumor had a significantly higher albumin-adjusted calcium level (9.94 mg/dL) than patients with a benign tumor (9.52 mg/dL, p < 0.0001). Ninety-four of 181 (52%) women with malignant tumors had high normocalcemia, versus 28 of 334 (8.4%) women with benign tumors. Women with high normocalcemia were > 10 times more likely to have a tumor that was malignant (OR = 10.57, 95% C.I. 6.41 - 17.42, p < 0.0001). This association persisted after adjusting for age, parity, menopausal status, body mass index and CA-125. A model including age, parity, body mass index, CA-125, albumin and albumin-adjusted calcium was highly predictive of a malignant tumor in women with a pelvic mass (AUC 0.90, p < 0.0001). Conclusions: In women with pelvic masses scheduled for resection, high normocalcemia is a powerful predictor of malignancy. High normocalcemia may be a simple and inexpensive guide for triaging women with a suspected malignancy to resection by a gynecologic oncologist.