tbuckley/cabot-search huggingface dataset:
Association between markers of malnutrition (MN) and toxicity (T) during neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer (EC).
Authors: Rishi Jain, Talha Shaikh, Jia-Llon Yee, Cherry Au, Elizabeth Handorf, Efrat Dotan, Joshua E. Meyer
Journal: Journal of Clinical Oncology (2017)

191 Background: EC is associated with significant MN. Resultant weight loss (WL) can be further exacerbated by toxicity of nCRT. We evaluated the association of surrogates of MN and T during nCRT for EC. Methods: A retrospective analysis of EC patients (pts) treated with nCRT as part of tri-modality therapy between 2002-2014 was performed. The following pre and post-CRT factors were assessed: presence of jejunostomy tube (J-tube), weight change (gain, loss of &lt; 5%, 5-10%, ≥ 10%) and albumin change (decrease by &lt; 0.5 or ≥ 0.5). We recorded rates of chemotherapy (ctx) dose reduction/interruption (DRI), hospitalizations (H), grade 3/4 T (G3+T), any grade non-hematologic (NHT) or hematologic T (HT). Multivariate regression analyses (MVA) were used to determine associations between MN and T, adjusting for age, gender, smoking status, stage, CRT regimen, performance status, and co-morbidities. Results: 125 patients were identified. Median age was 63 (range 35-80). Pre-CRT body mass index ranged from 17-45 kg/m2, with 74% overweight or obese. Mean WL during nCRT was 10 lbs (5%). Increased WL was noted in pts who received cisplatin/5-FU as compared to other ctx (p &lt; 0.001) or ≥ 50 Gy (p = 0.025). In MVA, increased NHT was noted in pts with ≥ 5% WL (p &lt; 0.05) and more G3+T was noted in pts with ≥ 10% WL (p = 0.002). A decrease in albumin by ≥ 0.5 was associated with increased DRI (p = 0.043), NHT (p = 0.004), HT (p = 0.002), and G3+T (p = 0.004). Sixty-three pts (50%) had a J-tube prior to nCRT. Pts with a J-tube had reduced mean WL (8 lbs vs 13 lbs) during nCRT. No differences in T were noted based on J-tube status. No associations between MN and H rates were observed. Conclusions: Hypoalbuminemia and WL during nCRT were associated with multiple T endpoints. The presence of a prophylactic J-tube did not reduce T rates. Other methods to prevent MN and reduce T during nCRT should be studied.
Neurocognitive function of children treated for high-risk B-acute lymphoblastic leukemia (HR-ALL) randomized to Capizzi (CMTX) versus high-dose methotrexate (HDMTX): A report from the Children’s Oncology Group (COG).
Authors: Naomi J. Winick, Leanne M Embry, Kristina K. Hardy, John A Kairalla, Meenakshi Devidas, Daniel Armstrong, Stephen Hunger, William L. Carroll, Eric Larsen, Elizabeth A. Raetz, Mignon L. Loh, Robert Noll
Journal: Journal of Clinical Oncology (2015)

10002 Background: Survivors of childhood HR-ALL are at risk for neurocognitive deficits. The causes are multifactorial including treatment, host and environmental factors. This study evaluated the relative impact of two different approaches to methotrexate delivery while simultaneously examining associations with demographic and treatment factors, in the absence of cranial radiation, on neurocognitive functioning after completion of therapy. Methods: Patients with HR-ALL, treated on COG AALL0232, were randomized to receive HD-MTX with leucovorin rescue versus lower dose, escalating CMTX with asparaginase. Intellectual functioning (IQ), working memory, and processing speed (PS) of participants was evaluated 8 - 24 months following completion of therapy. Results: Two-hundred thirty-seven participants were eligible and enrolled on study, with 195 (54% female) submitting valid data. Mean age at diagnosis was 8.9 years (SD = 5), with 46% (n = 90) under age 10 at diagnosis. Method of methotrexate delivery was unrelated to differences in neuropsychological outcomes. Survivors younger than 10 at diagnosis, however, had an 11.8 point decrement (SE = 2.1) in estimated IQ (p < .01), and a 5.3 (SE = 2.2) point estimated decrease in PS scores (p < .05), compared to older participants, after controlling for ethnicity, race, gender, insurance status and time off treatment [(raw IQ: 94.9 + 15 vs. 107.2 + 15), (PS: 94.9 + 15 vs. 98.7 + 16)]. Additionally, participants covered by US public insurers had adjusted IQs that were 12.0 points lower (SE = 2.8, p < .01), than participants with private insurance (raw IQ: 93.1 + 15 vs. 106.1 + 15). Conclusions: Even in the absence of cranial radiation, young survivors of HR-ALL are at risk for deficits in global intellectual functioning and processing speed. Critically, insurance status was also strongly associated with neurocognitive outcomes. These data may serve as a basis for developing screening protocols and potential interventions to both identify children with deficits and to ameliorate the impact of therapy on their neurocognitive outcomes. Clinical trial information: NCT00437060.
Effect of Home Monitoring via Mobile App on the Number of In-Person Visits Following Ambulatory Surgery
Authors: Kathleen A. Armstrong, Peter C. Coyte, Mitchell Brown, Brett Beber, John L. Semple
Journal: JAMA Surgery (2017)

<h3>Importance</h3> In the age of information and patient-centered care, new methods of delivering postoperative care must be developed and evaluated. <h3>Objective</h3> To determine whether follow-up care delivered via a mobile app can be used to avert in-person follow-up care visits compared with conventional, in-person follow-up care in the first 30 days following ambulatory surgery. <h3>Design, Setting, and Participants</h3> A randomized clinical trial was conducted from February 1 to August 31, 2015, among ambulatory patients undergoing breast reconstruction at an academic ambulatory care hospital. Patients were randomly assigned to receive follow-up care via a mobile app or at an in-person visit during the first 30 days after the operation. Analysis was intention-to-treat. <h3>Main Outcomes and Measures</h3> The primary end point was the number of in-person follow-up visits during the first 30 days after the operation. Secondary end points were the number of telephone calls and emails to health care professionals, patient-reported convenience and satisfaction scores, and rates of complications. <h3>Results</h3> Of the 65 women in the study (mean [SD] age, 47.7 [13.4] years), 32 (49%) were in the mobile app group, and 33 (51%) were in the in-person follow-up care group. Those in the mobile app group attended a mean of 0.66 in-person visits, vs 1.64 in-person visits in the in-person follow-up care group, for a difference of 0.40 times fewer in-person visits (95% CI, 0.24-0.66;<i>P</i> &lt; .001) and sent more emails to their health care professionals during the first 30 days after the operation (mean, 0.65 vs 0.15; incidence rate ratio, 4.13; 95% CI, 1.55-10.99;<i>P</i> = .005) than did patients in the in-person follow-up care group. This statistically significant difference was maintained at 3 months postoperatively. The mobile app group reported higher convenience scores than the in-person follow-up care group (incidence rate ratio, 1.39; 95% CI, 1.09-1.77;<i>P</i> = .008). There was no difference between groups in the number of telephone communications, satisfaction scores, or complication rates. <h3>Conclusions and Relevance</h3> Patients undergoing ambulatory breast reconstruction can use follow-up care via a mobile app to avert in-person follow-up visits during the first 30 days after the operation. Mobile app follow-up care affects neither complication rates nor patient-reported satisfaction scores, but it improves patient-reported convenience scores. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02318953
A randomized, open label, prospective study comparing the association between sorafenib (So) and interleukin-2 (IL-2) versus So alone in advanced untreated renal cell cancer (RCC): Rosorc Trial
Authors: G. Procopio, E. Verzoni, S. Bracarda, S. Ricci, C. Sacco, L. Ridolfi, C. Porta, R. Miceli, N. Zilembo, E. Bajetta
Journal: Journal of Clinical Oncology (2009)

5099 Background: So is an orally active multikinase inhibitor with a well documented activity in advanced RCC. IL-2 is a pleiotropic cytokine with antitumoral activity depending on dose and schedule. The aim of the study is to evaluate the activity and the safety of So and IL-2 association compared to So alone. Methods: In this multicenter, randomized, open label, phase II study, 128 previously untreated metastatic RCC patients (pts) were randomized to receive 400 mg of So, orally given twice daily continuously, in combination with IL-2, 4.5 MIU administered subcutaneously, five times a week for six consecutive weeks any eight weeks (arm A), or So alone (arm B) at the same dose. Therapy continued until progression of disease or unacceptable toxicity. The primary end point was progression free survival (PFS) and the secondary endpoints were response rate, safety and overall survival. Eligible pts had histological diagnosis of RCC, ECOG 0–2, no brain metastases, measurable disease and any Motzer's score. Pts were stratified according to different histotypes and Motzer's score. Results: All pts were enrolled from October 2006 to February 2008. Response rates (all partial responses, PR) were 23 % and 10 % in arm A and B respectively. Overall disease control rates (PR + stable disease SD) were 81 % versus 74 %. Tumour shrinkage was reported in 52 % and 34 % of arm A and B therapies respectively. Median PFS was 38 weeks (range 6–104+) for So + IL-2 and 30 weeks (range 6–102+) for So alone. PFS at 1 year was 31% in the combination therapy versus 22% in arm B. The most common adverse events (AEs) were asthenia, hand foot syndrome, hypertension, fever, diarrhoea and mucositis. AE were usually low or moderate in severity and always reversible and manageable. Grade 3–4 AE were reported in 33% and 22% in arm A and B, respectively. Conclusions: The safety and efficacy data suggest that the association So + IL-2 is safe and feasible and, compared to So alone, improves tumour shrinkage, disease control rate and PFS. [Table: see text]
Diagnostic and prognostic value of serum golgi protein 73 in hepatocellular carcinoma.
Authors: Min Dong, Zhan-Hong Chen, Xiao-Yun Li, Jing-yun Wen, Xing Li, Qu Lin, Xiao-kun Ma, Li Wei, Yan-Fang Xing, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2014)

e15096 Background: Golgi protein 73 (GP73), a membrane protein localized in the type II Golgi complex, is a candidate biomarker for hepatocellular carcinoma (HCC). However, current evidence is conflicting in its diagnostic value as a serum marker for HCC, largely due to the small sample sizes of previous studies. Furthermore, the association between serum GP73 level and prognostic parameters remains unclear. Methods: Serum GP73 levels were measured in 405 patients with HCC, 203 patients with liver cirrhosis, and 98 healthy controls using enzyme-linked immunosorbent assay (ELISA). Its correlation with clinical characteristics was analyzed further. Results: The median serum GP73 levels were 19.59 ng/mL (range, 0–231.17 ng/mL) in patients with HCC, 19.28 ng/mL (range, 0–187.78 ng/mL) in patients with liver cirrhosis, and 0 ng/mL (range, 0–70.42 ng/mL) in healthy controls, respectively. The serum GP73 levels in both HCC and liver cirrhosis groups were higher than those in healthy controls (P < 0.001), whereas no significant difference was found between HCC and liver cirrhosis groups (P > 0.05). The sensitivity and specificity of serum GP73 for HCC diagnosis were 92.21% and 23.62%, compared with 56.14% and 93.71% for alpha-fetoprotein (AFP). In the HCC group, higher serum GP73 levels were significantly associated with larger tumor size (> 5cm) (P < 0.001), multiple tumor nodes (P < 0.001), microsatellite lesions (P < 0.001), vascular invasion (P < 0.001), regional lymph node metastasis (P = 0.011), distant metastasis (P < 0.001) , higher Child-Pugh grade (P < 0.001), more advanced Barcelona Clinic Liver Cancer (BCLC) stage (P < 0.001), and higher serum AFP level (> 400 ng/mL) (P = 0.003). Multivariable statistical analysis revealed that distant metastasis (P = 0.022), Child-Pugh grade (P < 0.001), and BCLC stage (P= 0.033) were positively correlated with higher serum GP73 levels. Conclusions: Serum GP73 detected by ELISA is positively correlated with aggressive tumor features, suggesting that it is a potential prognostic biomarker for HCC. However its diagnostic value is not promising.
Prostate cancer outcomes for African American and caucasian patients undergoing radical prostatectomy.
Authors: Jennifer Cullen, Huai-Ching Kuo, Yongmei Chen, Lauren Hurwitz, Inger L. Rosner, Christopher Porter, Timothy C. Brand, Joseph Sterbis, Sean Stroup, Timothy Rebbeck, Anthony Victor D'Amico, Grace L. Lu-Yao
Journal: Journal of Clinical Oncology (2017)

40 Background: A disproportionate burden of prostate cancer (CaP) incidence and mortality is observed for African American (AA) versus Caucasian (CA) patients in the US. Potential underlying reasons for racial disparity include biology, comorbidity profiles, access to health care, adherence to follow-up care and/or treatment aggressiveness. This study examined CaP progression and overall survival (OS) among AA and CA patients undergoing radical prostatectomy (RP). Methods: This retrospective cohort study examined men enrolled in the Center for Prostate Disease Research (CPDR) Multi-Center National Database between January 1, 1990 and December 31, 2014. Patients with biopsy-detected CaP without metastasis and treated with RP within 12 months of CaP diagnosis were eligible. Biochemical recurrence (BCR) was defined as a PSA value of &gt; = 0.4 ng/mL followed by a subsequent increase. PSADT was categorized as &lt; 3, 3-8.99, 9-14.99, and &gt; = 15 months. Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis were used to examine BCR and OS. Results: A total of 6,785 patients were eligible; 21.5% self-reported as AA and 78.5% self-reported as CA. Median follow-up time was 6.1 years. Comparable distributions of pathologic features at RP and adjuvant treatment over time were observed across race but several comorbid conditions were more common in AA patients including cardiovascular disease, hypertension, diabetes, and other cancer types. In race-specific unadjusted Kaplan Meier analyses, PSADT was an important predictor of BCR and OS for both AA and CA patients (Log rank p &lt; 0.0001 for all KM models). In multivariable analysis, a greater odds of BCR over time was observed for AA versus CA patients (HR = 1.28, CI = 1.11, 1.48, p = 0.0009) after adjustment for D’Amico risk stratum, comorbidity, pathological features, and PSADT. PSADT was a critical predictor of BCR, with worst outcomes at extreme comparison of PSADT categories: HR &lt; 3 vs. &gt; = 15 months= 41.5, CI = 33.6, 51.3, p &lt; 0.0001). Conclusions: In a large racially diverse, longitudinal cohort with equal health care access, there was a striking relationship between PSADT and time to BCR for each racial group and poorer outcomes for AA versus CA patients.
Survival and long-term follow-up of the phase I trial of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with previously treated advanced non-small cell lung cancer (NSCLC).
Authors: Julie R. Brahmer, Leora Horn, Scott J. Antonia, David R. Spigel, Leena Gandhi, Lecia V. Sequist, Vindira Sankar, Christoph Matthias Ahlers, Jon M. Wigginton, Georgia Kollia, Ashok Kumar Gupta, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2013)

8030 Background: The immune checkpoint receptor programmed death-1 (PD-1) negatively regulates T-cell activation. Nivolumab, a PD-1 receptor blocking antibody, was evaluated in a phase 1 study in pts with various tumors including NSCLC (Topalian et al, NEJM 2012;366:2443). Methods: Pts with ≥1 prior chemotherapy regimen received nivolumab (1-10 mg/kg IV Q2W) for ≤12 cycles (4 doses/8W cycle) or until discontinuation criteria were met. We report initial overall survival (OS) and updated safety and response data for NSCLC pts. Results: 127 pts evaluable for safety received nivolumab at 1, 3, or 10 mg/kg as of July 2012. Common drug-related AEs were decreased appetite (9%), anemia (8%), diarrhea, nausea, and pruritus (7% each). The most common G3/4 AEs were fatigue, pneumonitis, and elevated AST (2% each). Two drug-related deaths from pneumonitis occurred early in the trial and led to increased monitoring without further deaths from pneumonitis. Median OS (mOS) across all dose cohorts was 9.2 mo and 9.6 mo for squamous (sq) and non-sq NSCLC, respectively. mOS was not reached at the 3 mg/kg dose (phase 3 dose) for either histology. Sustained OS was observed, with 44%/ 41% and 44%/ 17% of pts (sq/non-sq) alive at 1 and 2 years, respectively (Table). Prolonged ORs occurred in both histologies (Table). Conclusions: In this long-term follow-up of a phase I trial, nivolumab had an acceptable safety profile and showed an encouraging sustained OS benefit across histologies in previously treated advanced NSCLC. Follow-up through a Feb 2013 data cut (≥1 yr follow-up for all pts) will be provided at presentation. Clinical trial information: NCT00730639. [Table: see text]
Nabrax: Neoadjuvant therapy of breast cancer with weekly single-agent nab-paclitaxel—Final efficacy and biomarkers analysis of GEICAM 2011-02 trial.
Authors: Miguel Martin, Silvia Antolín, Antonio Anton, Arrate Plazaola, Elena García-Martínez, Miguel Angel Seguí, Pedro Sanchez-Rovira, José Palacios, Lourdes Calvo, Carmen Esteban, Enrique Espinosa, Angel Guerrero, J. Norberto Batista, Ana Maria Arance, Agust Barnadas, Eva Maria Carrasco, César Rodríguez-Martín, Rosalia Caballero, Maribel Casas, Jose Ignacio Chacon
Journal: Journal of Clinical Oncology (2014)

1051 Background: Nanoparticle albumin bound paclitaxel (nab-P) administered weekly showed superior efficacy compared to every 3-weeks docetaxel in a randomized phase II study in first line metastatic breast cancer (Gradishar JCO 2009). We present a phase II trial designed to evaluate the activity and safety of weekly nab-P as neoadjuvant treatment of early stage breast cancer patients (pts) with positive estrogen receptors (ER) and negative HER2. Methods: Stage II-III breast cancer pts were included and treated with nab-P weekly (150 mg/m2) on days 1, 8 and 15 every 4 weeks for 4 cycles. Following chemotherapy, pts underwent surgery and adjuvant therapy under the investigator criteria. The primary objective was to determine the percentage of pts with poor response (Symmans residual cancer burden –RCB– class III centrally determined). The study hypothesis was that the RCB III rate will drop from 33% (historical controls treated with docetaxel in the same population, Martin BCRT 2011) to 16% with nab-P. Secondary objectives included good pathological complete response (Symmans RCB class 0+I), objective response rate (ORR), breast conserving surgery (BCS) rate, safety and molecular subtypes and biomarkers (Ki-67, Cav-1, SPARC analyzed in a central lab) correlation with response. The safety and treatment administration analysis was reported previously (Martin SABCS 2013). We report here the efficacy and correlation between RCB 0+I and subtypes/biomarkers from the pre-treatment tumor samples. Results: 83 pts were recruited (81 evaluable). Median age was 47 years, 64.2% were premenopausal; most pts were stage II (35.9% IIa and 33.3% IIb). Central pathological response is currently available for 74 pts (7 pending). RCB III rate was 25.7% and RCB 0+I rate was 27%. The ORR by MRI was 76.5% and the rate of conversion to BCS was 40%. In the univariate analysis we found Ki67>20% and high expression of Cav1 in stroma to be correlated with RCB 0+I. Conclusions: Our study was unable to show the pre-specified efficacy hypothesis. However the RCB 0+I rate is encouraging taking into account docetaxel activity (13.3%) in this population; nab-P merits further evaluation in randomized trials. Clinical trial information: NCT01565499.
A phase II study of biweekly paclitaxel and S-1 (SPA) as first-line combination therapy in patients with metastatic or locally advanced gastric cancer.
Authors: Haiping Jiang, Yulong Zheng, Jiong Qian, Xiaochen Zhang, Haibo Mou, Peng Zhao, Chenyu Mao, Yi Zheng, Yao Wang, Lan Fang Yu, Jing Deng, Weijiang Fang, Nong Xu
Journal: Journal of Clinical Oncology (2014)

e15051 Background: Paclitaxel and S-1 are both effective anti-tumor agents in advanced gastric cancer. However, the continuous administration of S-1 for three weeks or more can result in unacceptable toxicities. Therefore, an alternative treatment schedule (one-week administration followed by a one-week rest) is warrant for testing in order to allow continuation of the therapy. We evaluate the efficacy and safety of biweekly paclitaxel and S-1(SPA) as first-line combination therapy in patients with metastatic or locally advanced gastric cancer. Methods: Forty-four Chinese patients(pts) have been included. 33 were male and 11 were female. Median age was 60 years (24-78). 90.1% had ECOG 0 and 1 and. 9 (20.4%) had locally advanced disease and 35 (79.6%) metastatic disease. Pts were administered intravenously paclitaxel at a dose of 120 mg/m2 on day 1 and oral S-1 twice daily (BSA < 1.25 m2, 80 mg/day; 1.25 < or = BSA < 1.50 m2, 100 mg/day; 1.50 m2< or = BSA, 120 mg/day) on days 1-7 followed by a drug-free interval of 1 week every 14-day cycle. A total of 277 chemotherapy cycles were administered, with a median of 6 cycles per patient (range 1-12), and 19 (43.2%) pts received up to seven cycles. 34 pts (77.2%) received second-line treatment. Results: Of the 44 eligible pts, the ORR was 38.6% with PR in 17 pts, SD in 20 pts s and PD in 6 pts. The median PFS and median OS were 5.2 months (95% CI: 4.08-6.39 months) and 12.2 months (95% CI: 8.81-15.60 months) , respectively, The major hematological toxicities were grade 3 leucocytopenia in 2 pts (4.5%), grade 3 neutropenia in 14 pts (40.9%) and grade 4 in 4 pts (9.0%). Two pts (4.5%) suffered grade 1 febrile neutropenia. The grade 3/4 nonhematological toxicities, such as nausea, vomiting, alopecia, diarrhea, neurological toxicity and fatigue accounted for 4.5%, 6.8%, 4.5%, 2.2%, 2.2% and 6.8%, respectively. Conclusions: Biweekly paclitaxel and S-1(SPA regimen) combination therapy had promising activity with acceptable toxicities. SPA regimen was easy to implement and more patients received second-line chemotherapy. A well-designed randomized phase III study is needed to compare this regimen with other S-1-based combination treatments. Clinical trial information: 85705844.