tbuckley/cabot-search huggingface dataset:
Association of higher lung dose received during total body irradiation for allogeneic hematopoetic stem cell transplantation in children with acute lymphoblastic leukemia with inferior progression-free and overall survival: A report from the Children’s Oncology Group.
Authors: Natia Esiashvili, Xiaomin Lu, Stephen Hunger, Thomas E. Merchant, Patrick Andrew Brown, Donna Ann Wall, Stephan A. Grupp, Michael Pulsipher
Journal: Journal of Clinical Oncology (2015)

10030 Background: Lung shielding is not standardized during total body irradiation (TBI) preparative regimens for hematopoietic stem cell transplantation (HSCT), leading to differences in pulmonary radiation dose received by patients. We examined the relationship between lung radiation dose and transplant-related mortality (TRM), relapse-free (RFS) and overall survival (OS) in children and adolescents undergoing TBI-based HSCT for acute lymphoblastic leukemia (ALL) on Children’s Oncology Group trial ASCT0431. Methods: The lung radiation dose received during TBI (1200 or1320 cGy given bid in 6 or 8 fractions) was analyzed in relation to the following variables: total TBI dose, TBI dose per fraction, TBI dose rate, TBI fields, patient position during TBI, pulmonary toxicity, acute graft versus host disease (GVHD), veno-occlusive disease (VOD), TRM, donor type, minimal residual disease (MRD) levels, RFS and OS. Results: From a total of 143 enrolled, 109 patients had lung doses available for analysis. Patients treated with lateral fields were significantly more likely to receive lung doses ≥ 800cGy (p < 0.001). Patients receiving lung dose ≥ 800cGy had higher rates of relapse or TRM (p = 0.034), a trend for higher rates of death (p = 0.078). There was no significant association between lung dose and rates of reported pulmonary toxicity (p = 1.000). In univariate analysis, lung dose ≥ 800cGy, grade IV vs. grade I-III GVHD, VOD, pulmonary toxicity, MRD, higher disease risk group and unmatched donor types were associated with significantly inferior RFS and OS. Multivariate analysis identified lung dose ≥ 800cGy to be significantly associated with inferior RFS (HR 1.9; p = 0.031) and OS (HR 2.1; p = 0.023) while controlling for risk group and donor type. Conclusions: Analysis of ASCT0431 data showed that lung irradiation dose ≥ 800 cGy as part of TBI was associated with inferior RFS and OS. While understanding the mechanisms underlying these results requires more research, reducing the lung dose to 800cGy for TBI regimens administering > 1200cGy is recommended. Clinical trial information: NCT00382109.
Prognostic impact of renal insufficiency (RI) at diagnosis in patients with chronic lymphocytic leukemia (CLL).
Authors: Paolo Strati, Kari G. Chaffee, Sara J Achenbach, Susan L. Slager, Susan M. Schwager, Timothy Call, Nelson Leung, Tait D. Shanafelt
Journal: Journal of Clinical Oncology (2015)

7084 Background: Renal function has a well-established prognostic role in patients with some hematological malignancies, such as multiple myeloma. However, its impact on survival in patients with CLL hasn’t been explored. Methods: We used the Mayo Clinic CLL database to identify all patients diagnosed with CLL between 01/1995 and 11/2014 using the 2009 iwCLL criteria and seen at our center prior to treatment. Patients for whom we could not calculate a baseline creatinine clearance (Cr-Cl) due to missing creatinine/weight or who were missing baseline complete blood count (CBC) (n = 466) were excluded from final analysis. Renal insufficiency (RI) was defined as Cr-Cl < 45 mL/min calculated with the Cockroft-Gault equation. Logistic regression was used to determine which factors predicted RI. Fisher’s exact test was used to compare treatment types by RI. The Kaplan-Meier method was used for the survival analyses. Results: The final analysis included 1268 patients. Of these, 87 (7%) had RI at diagnosis. Factors significantly associated with RI on univariate analysis (UVA) were age > 65 years, female sex, hypertension (HTN), hemoglobin < 11 g/dL, and Rai stage III-IV. Factors associated with RI on multivariate analysis (MVA) were age > 65 years, female sex, HTN, and advanced Rai stage. Of the 506 patients who required treatment, 25 had RI. Type of first treatment differed between patients with and without RI (p < 0.001); patients with RI were more likely to receive alkylator-based therapy (48% vs 15%) and less likely to receive purine analogue-based CIT (8% vs 44%). Median overall survival (OS) was 124 months, 59 months for those with RI, 132 months for those without RI (p < 0.001). Baseline characteristics (age, sex, HTN, diabetes, CBC, CD49d, CD38, ZAP70, IGHV mutation status and FISH) as well as RI were associated with OS on UVA. Conclusions: RI is relatively frequent at time of CLL diagnosis (7% of cases) and has a profound influence on therapy selection among patients requiring treatment. RI at time of CLL diagnosis is associated with overall survival.
Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early stage breast cancer (NCT01372579).
Authors: Virginia G. Kaklamani, Elisha Hughes, Kalliopi P. Siziopikou, Kirsten Timms, Victor Abkevich, Cara Solimeno, Anne-Renee Hartman, Jacqueline Jeruss, Caitlin Meservey, Borko Jovanovic, Irene B. Helenowski, Seema Kahn, Kevin P. Bethke, Nora Hansen, Regina Uthe, Steven Rosen, Kent Hoskins, Jamie Von Roenn, Sarika Jain, William John Gradishar
Journal: Journal of Clinical Oncology (2015)

1017 Background: Platinum-based chemotherapy has been reported to have efficacy in patients with Triple Negative Breast Cancer (TNBC). Germline BRCA1/2 mutation status has been shown to be predictive of platinum response in patients with metastatic TNBC. In the neoadjuvant setting some, but not all patients with sporadic TNBC also achieve a pathologic complete response (pCR). This study evaluated the efficacy and toxicity of neoadjuvant treatment with carboplatin and eribulin in patients with early stage TNBC, and assessed the role of a HRD (homologous recombination deficiency) test to predict response. Methods: Patients with histologically confirmed early stage TNBC received carboplatin AUC 6 iv every 21 days and eribulin 1.4 mg/m2 day1 and day 8 every 21 days for four cycles. The primary endpoint of the study was pCR, with secondary endpoints including clinical response rate and safety of the combination. Tumor specimens were evaluated for BRCA1/BRCA2 mutations, BRCA1 promoter methylation, and HRD status. Results: A total of 30 patients enrolled in the study. 13 (43.3%) achieved pCR. The combination was safe with mostly grade 1 and 2 toxicities. 28 pre-treatment samples were available for HR deficiency assessment and 26 obtained passing HRD scores. HR deficiency (HRD positive with HRD score ≥ 42), significantly predicted pCR in the full cohort (P = 0.0012) and in the subset of BRCA1/2 wild type patients (P= 0.0018). Conclusions: The combination of carboplatin and eribulin is safe and efficacious in the treatment of early stage TNBC. The use of an HRD test can predict pCR after carboplatin and eribulin treatment in this patient population and with further validation can be used to identify patients beyond those with a germline BRCA mutation who will respond to a platinum-containing regimen. Clinical trial information: NCT01372579.
Incidence of bone metastases among children with cancer in Denmark.
Authors: Rohini Khorana Hernandez, Vera Ehrenstein, Merete Lund Mægbæk, Alexander Liede, Henrik Toft Sørensen
Journal: Journal of Clinical Oncology (2012)

1579 Background: There are no published population-based studies on the incidence of bone metastases (BM) among children with cancer. The current literature is limited to small case series or case reports. Methods: We used the Danish Cancer Registry (DCR) to identify children &lt;18 years old diagnosed with cancer between 1/1/1994 and 12/31/2009. Patients were followed from cancer diagnosis to BM, emigration, death, or end of study (1/1/2011). DCR data were linked to (1) Danish Civil Registration System to obtain information on death and emigration, and (2) Danish National Registry of Patients to identify ICD-10 codes for BM. We estimated incidence rates (IRs) of BM and mortality rates overall and stratified by gender, calendar year, age, and primary tumor type. Results: During the study period, 2,652 children were identified with a first-time diagnosis of cancer, of whom 35 (1.3%) developed BM (mean follow-up of 7.0 years). The IR of BM was 1.9 per 1,000 person-years (95% CI: 1.4 – 2.6); the highest rates occurred in children aged 12 – 17 years and among those with osteosarcoma (Table). Twenty-one (60%) children with BM died during follow-up, yielding a mortality rate of 192 per 1,000 person-years (95% CI: 125 – 295). The median time from cancer diagnosis to BM was 221 days and from BM to death was 283 days. Conclusions: This study represents the first comprehensive examination of BM in children and reveals that BM is a rare event, with median survival of less than one year from diagnosis. [Table: see text]
Palonosetron (PALO) plus 1-day versus 3-day dexamethasone (DEX) with or without aprepitant against delayed nausea (DN): Pooled analysis for 554 women receiving highly emetogenic chemotherapy (HEC).
Authors: Luigi Celio, Flavia Longo, Giovanni Mansueto, Vittoria Lapadula, Francesco Agustoni, Matti S. Aapro
Journal: Journal of Clinical Oncology (2012)

9133 Background: Nausea is more difficult to control than vomiting, because the incidence of the symptom continues to rise over the days after chemotherapy. This post-hoc analysis addressed two questions: 1) Does PALO plus single-dose DEX result in suboptimal control of DN when compared to the same regimen with additional DEX doses? 2) Is the combination of PALO, DEX, and aprepitant a more effective coverage against DN? Methods: The analysis was based upon outcomes in chemo-naïve women (median age =52) with solid tumors (89% breast) enrolled in two Phase III and two Phase II trials of HEC (AC combination or cisplatin). Patients received the following regimens: 1) PALO 0.25 mg plus DEX 8 mg IV on day 1 of chemotherapy (1-day regimen, n=243); 2) the same regimen on the day 1 followed by DEX 8 mg orally on days 2 and 3 (3-day regimen, n=207); or PALO plus DEX plus aprepitant 125 mg on day 1 followed by aprepitant 80 mg on days 2 and 3 (triple regimen, n=104). The pre-specified primary endpoint was the proportion of patients with no DN (days 2-5 after the first cycle of chemotherapy). The two primary comparisons were 1-day vs. 3-day regimen, and triple vs. 3-day regimen, with statistical significance set to the 0.025 level. Results: The 1-day to 3-day regimen comparison was not statistically significant (44% vs. 47.8%; risk difference (RD) = -3.8%, 95% CI (-5.4 to 12.9%), P=0.421 (two-sided chi-square test). The triple to 3-day regimen comparison was also not significant (57.7% vs. 47.8%), RD= +9.9%, 95% CI (-1.9 to 21.3%), P=0.101. More patients receiving triple regimen experienced no acute-onset nausea compared with those administered only DEX (97.1% vs. 51.2%, P&lt;0.0001). Conclusions: This analysis provides evidence that PALO plus 1-day or 3-day DEX yield similar prevention of DN. The addition of aprepitant does not improve the control of DN. Complete results utilizing a multivariable model accounting for risk factors and trial heterogeneity will also be presented.
Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial
Authors: Peter Brocklehurst, David Field, Keith Greene, Ed Juszczak, Robert Keith, Sara Kenyon, Louise Linsell, Christopher Mabey, Mary Newburn, Rachel Plachcinski, Maria Quigley, Elizabeth Schroeder, Philip Steer
Journal: The Lancet (2017)

Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes.
High-dose methotrexate with and without rituximab for the treatment of newly diagnosed primary CNS lymphoma: Johns Hopkins Hospital experience.
Authors: Matthias Holdhoff, Guneet Sarai, Ahmed Abdelaziz, David Bonekamp, Stuart A. Grossman, Xiaobu Ye
Journal: Journal of Clinical Oncology (2013)

2034 Background: The current institutional standard for treatment of patients with newly-diagnosed primary CNS lymphomas (PCNSL) at Johns Hopkins Hospital (JHH) consists of treatment with high-dose methotrexate plus rituximab (hd-MTX/R) every 2 weeks until complete response (CR), progression or unacceptable toxicities. Once CR is achieved, this is followed by monthly treatments for a total of up to one year for consolidation. Prior to 2008, the institutional standard had been treatment with hd-MTX alone. The benefit of adding rituximab to hd-MTX has not been formally evaluated. Methods: This is a retrospective study of HIV-negative adult patients with newly-diagnosed PCNSL treated at JHH with either hd-MTX or hd-MTX/R as initial therapy. Patients were identified using the cancer center registry (1995-2012) and were included if they had received at least one cycle of therapy (intention-to-treat). Primary objectives were CR rate (patients with sufficient imaging data; centrally reviewed) and overall survival (OS, all patients included). Results: A total of 81 patients were analyzed (median age of 65 yrs; 52% male). 54 patients received hd-MTX alone (median age, 65 yrs) and 27 patients received hd-MTX/R (median age, 66 yrs). 37 and 24 patients in the two groups were evaluable for response, respectively. Among these, the CR rate was 51% in patients treated with hd-MTX alone (overall response rate, ORR, 76%) and 79% in patients treated with hd-MTX/R (ORR 96%). The median number of cycles to CR was 5 and 4.5, respectively. Median OS among all patients (both groups combined) was 26 months (95% CI: 11-44). Conclusions: These data show potential clinical benefit from the addition of rituximab to hd-MTX for newly diagnosed patients with PCNSL based on a higher CR rate. Analysis of OS benefit between patients treated with hd-MTX and hd-MTX/R is pending maturation of further survival data.
Discrepancy in bone marrow blast counts between morphology and flow cytometry and its potential clinical implications.
Authors: Weigang Tong, Megan Othus, Vicky Sandhu, Xueyan Chen, Pamela S. Becker, John Pagel, Roland B. Walter, Brent L. Wood, Elihu Estey
Journal: Journal of Clinical Oncology (2015)

e18031 Background: Both bone marrow morphology (MO) and flow cytometry (FC) are traditionally used in characterizing the blast percentage (BP) in patients with newly diagnosed acute myeloid leukemia (AML). We examined how often the 2 methods were discordant in assessing BP, covariates associated with these discrepancies, and whether discrepancies were an independent predictor of outcome. Methods: We reviewed 310 newly diagnosed AML patients that were treated at SCCA/FHCRC from January 2008 to December 2013. We categorized patients as (a) BP by MO > 10% (absolute) higher than BP by FC, (b) BP by FC > 10% absolute than BP by MO,or (c) BP by MO and FC within 10% of each other. We did the same using cutoffs of 20% and 5%, as well as > 1 standard deviation (SD) above or below the regression line. Since the blast percentage reported by flow cytometry is based on the total white blood cells after lysis of erythroid component, we corrected the blast percentage by morphology for the erythroid cells counted. Covariates examined for a relation with discordance and outcome (RFS and OS) by univariate and multivariate analyses were age, gender, cytogenetics, de novo vs. secondary AML, WBC, absolute neutrophil counts, platelet and bone marrow cellularity. Results: In 53% of cases BP by MO and FC were within 10% of each other, in 38% BP by MO was > 10% higher than by FC, and in 9% BP by FC was > 10 higher than by MO. Corresponding figures for the 20% cut-point were 76%, 21% and 2% and for the 5% cut-point 31%, 54% ,and 14%. 69% of cases were within 1 SD of the regression line, 15% were > 1 SD above the line (BP by FC > than by MO) and 15% were below the line (BP by MO > than by FC). None of the above covariates were associated with discordance using the 10%, 20%, 5%, or 1 SD cut-offs. Nor after accounting for these covariates was discordance as defined above associated with differences in relapse-free survival or overall survival. Conclusions: Our study suggests that knowledge of BP by MO (FC) adds little to knowledge of BP by FC (MC) in newly-diagnosed AML. Hence there appears to be no reason to do both MO and FC. Because results with FC are typically available before results from MO, we would argue for use of FC over routine use of MO in patients with newly diagnosed AML.
Metabolic syndrome (MetS) incidence in renal cell carcinoma (RCC) patients.
Authors: Luis Antón-Aparicio, Joaquin Mosquera Martínez, Aurea Molina Diaz, Javier Cassinello Espinosa, Emilio Esteban, Ana Medina, Isabel Santamarina Cainzos
Journal: Journal of Clinical Oncology (2015)

e15587 Background: Renal Cell Carcinoma (RCC) accounts for 2% of all adult malignancies, its remains a very aggressive and often fatal disease, and is increasingly being recognized as a metabolic disease. Established life-style related risk factors for RCC are obesity, hypertension, and smoking, and these risk factors have been estimated to account for up to the half of the cases. It has been linked to certain types of cancer including aggressive urologic cancers involving prostate and bladder. However, less is known about the possible link between MetS and RCC. The aim of this study was to identify the incidence of MetS among RCC patients and to evaluate whether there is any association between the MesT and RCC. Methods: We designed a study that is a representative sample of patients in which adults diagnosed with RCC who has received primary surgery between 2000 and 2014 at a University City Hospital and its surrounding rural communities. This study is pending approval by Institutional CEIC. Histological subtype and nuclear grade were determined according to the 2004 WHO classification and Fuhrman grading system, respectively. Criteria proposed for clinical diagnosis of MetS were provided by the report of AHA/NHLBI. Results: The prevalence of MetS as defined by AHA/NHHLBI was < 45 % among RCC patients. The prevalence was higher among males compared with females. RCC is statistical significantly more prevalent in males than females and male gender < 2 times increased the risk on RCC. We found a statistical significantly association between the presence of MetS (having 3 or more MetS components). Conclusions: RCC is increasingly being recognized as a metabolic disease. In the present study, it was found that the existence of MetS, about 4 fold increased risk fort RCC. As an interesting finding, there was a cumulative effect of MetS components for RCC risk in our study.
Sentinel node biopsy in the initial evaluation of 87 patients with Merkel cell carcinoma.
Authors: Eve Maubec, Amandine Servy, Francoise Boitier, Pierre Emmanuel Sugier, Florent Grange, Sandrine Mansard, Thierry Lesimple, Benoit Couturaud, Sebastien Albert, Xavier Sastre, Eduardo Marinho, Agnes Carlotti, Lydia Deschamps, Angelique Girod, Jamal Kassouma, Astrid Blom, Nicolas Dupin, Beatrice Crickx, Marie-Françoise Avril
Journal: Journal of Clinical Oncology (2014)

9015 Background: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor. The objective was to determine the role of sentinel lymph node biopsy (SNB) in the management of patients with MCC. Methods: A SNB procedure was proposed to all patients, from 5 hospitals, referred for a MCC without palpable regional lymph node from 1999 to 2013. Features between positive (SNB+) and negative (SNB-) SNB patients (pts) were compared using a Fisher’s exact test. Results: Eighty-seven pts with a F/M ratio=0.85, a median age =74 yrs (31-90 yrs; 63% aged at least 70 yrs), a stage T1 (N=54), T2 (N=30) or T3 (N=3), a location on extremities (56%), head and neck (32%) or trunk (12%) were included. Among pts, 8% were immunosuppressed. The frequency of SNB metastasis (20/83=24% of successful SNB) did not differ significantly in T1 and T2 stages (p= 0.4). 19/20 SNB+ pts had a radical lymph node dissection and additional positive lymph nodes were found in 6/19 (31%) pts. Adjuvant radiotherapy was delivered to the primary tumour site in 71/87 pts and to the involved lymph node basin in 18/20 SNB+ pts. During a median follow-up period of 25 mths (4-158 mths) (25 mths in SNB+ and 23 mths in SNB- pts) recurrence developed in 23% of all pts within a median period of 13 mths (3-115 mths). Fifteen per cent of pts died of MCC. Although higher in SNB+ pts (20% vs 9.5%) the frequency of specific death did not differ significantly in the 2 groups (p=0.19). SNB- pts who did not received radiotherapy to the primary tumour site had a worse course of the disease with more recurrences (42% vs 14%; p= 0.04) and a trend to a higher death rate (25% vs 6%; p= 0.08). Conclusions: SNB positivity is not associated with T stage and is high in T1 stage. All pts without palpable lymph node should be considered for SNB. Negative SNB might predict for better outcome.
Identification of molecular biomarkers of cisplatin-based chemosensitivity in patients undergoing neoadjuvant chemotherapy for muscle-invasive bladder cancer.
Authors: Paras Hemant Shah, Annette Lee, Xinhua Zhu, Thomas Paul Bradley, Manish Arvind Vira, Ilya Korsunsky, Andrew Shih, Oksana Yaskiv, Kozel Kozel
Journal: Journal of Clinical Oncology (2017)

374 Background: Although survival benefit of cisplatin-based neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC) has been demonstrated, a significant proportion of patients do not respond. Identification of chemoresponsive cohorts would avoid morbidity and delayed surgical intervention in patients unlikely to derive benefit. We evaluate the role of miRNA and mRNA expression profiles in initial TURBT specimens of patients who receive neoadjuvant chemotherapy prior to undergoing radical cystectomy. Differences in expression patterns between complete responders (pT0) and nonresponders (pT2 ≤ ) at time of cystectomy may help stratify patients being considered for neoadjuvant chemotherapy. Methods: FFPE tissue was isolated from initial TURBT specimens of patients with clinically localized MIBC treated with cisplatin-based neoadjuvant chemotherapy. Tissue from 9 patients with T2 ≤ disease was compared with specimen from 10 pT0 patients at time of cystectomy specimen. Differential expression of 754 miRNAs and mRNA was analyzed utilizing real time quantitative polymerase chain reaction. miRNA expression profiles were compared between complete responder and nonresponder groups. mRNA in tumor specimen was sequenced from both groups with 76 base pair paired-end reads using NextSeq technology. KEGG Pathway analyses helped identify differential gene expression between complete responders and nonresponders. Results: Significant upregulation of miRNA 1203, miRNA 1304, and miRNA 580 was observed nonresponders versus complete responders. KEGG pathway analysis revealed significant upregulation of the hsa03430 pathway, implicated in DNA mismatch repair, the hsa03420 pathway, implicated in nucleotide excision repair, and the hsa03410 pathway, involved in base excision repair, among pT0 patients. Conclusions: Differential miRNA and mRNA expression within the initial tumor specimen of patients with complete pathologic regression versus progression indicates a possible role in determining-neoadjuvant chemo-sensitivity.