tbuckley/cabot-search huggingface dataset:
Randomized phase III study of adjuvant chemotherapy for node-positive early breast cancer (BC) patients (pts) comparing epirubicin plus cyclophosphamide followed by docetaxel (EC-T) versus epirubicin plus docetaxel followed by capecitabine (ET-X): Efficacy analysis of the GEICAM/2003-10 trial.
Authors: Begoña Bermejo, Amparo Ruiz, Manuel Ruiz Borrego, Nuria Ribelles, Alvaro Rodriguez-Lescure, Montserrat Munoz-Mateu, Sonia Gonzalez, Mireia Margeli, Agust Barnadas, Manuel Ramos Vazquez, Sonia del Barco, Lourdes Calvo, Cesar Mendiola, Carmen Crespo, Cesar Augusto Rodriguez, Eduardo Martinez, Maria Isabel Casas, M Carmen Camara, Eva Maria Carrasco, Miguel Martin
Journal: Journal of Clinical Oncology (2013)

1027 Background: X is an active drug in metastatic breast cancer. GEICAM/2003-10 is an adjuvant trial investigating the integration of capecitabine into an epirubicin and docetaxel containing regimen for node-positive early breast cancer pts. Methods: Pts aged 18-70, with T1-T3/N1-3 operable BC were eligible. HER2+ pts were initially allowed. In October 2005, after 803 pts were included in the trial, the study was amended to exclude them. Pts were stratified by site, menopausal status, number of axillary nodes (1-3, 4-9, &gt;9) and hormonal receptor status and randomized to receive EC (90/600 mg/m 2 x4) followed by T (100 mg/m 2 x4) or ET (90/75 mg/m 2 x4) followed by X (1,250 mg/m 2 BID, d1–14, x 4) all every three weeks. The primary endpoint was DFS. The trial was designed to detect an absolute 5-y DFS increase of 7% (72% EC-T, 79% ET-X); a sample size of 1,184 evaluable pts (592 per arm) was required to detect this difference (a=0.05, β=80%). Assuming a drop-out rate of 17%, 1,382 pts were required. The first analysis of DFS was planned after 290 events. Results: Between February 2004 and February 2007, 1384 pts (EC-T 669, ET-X 715) were randomized. Patient characteristics were balanced between arms, median age was 51, 84% of pts were HR positive and 11% HER2 positive; 66, 25 and 9% had 1-3, 4-9 and &gt; 9 nodes respectively. The median relative dose intensity was 99% for EC, 99% for T, 99% for ET and 94% for X. The most frequent grade 3-4 toxicities (&gt;5% in either arm) with EC-T vs. ET-X were neutropenia (19% vs. 10%) with 7% febrile neutropenia in both arms, hand-foot syndrome (2% vs. 20%), fatigue (13% vs. 11%), diarrhea (3% vs. 11%), stomatitis (6% vs. 5%) and vomiting (5% vs. 5%). After a median follow-up of 6.6 years and 292 events, the proportion of patients disease free at 5 years is 86% and 82% with EC-T and ET-X (HR for relapse 1.314, 95% CI: 1.042 – 1.657); log-rank p-value=0.0208. Overall survival was not different between treatment arms (HR 1.113, 95% CI: 0.809 – 1.531); log rank p-value=0.511. Conclusions: DFS has been in favour of EC-T in pts with node-positive early BC. Clinical trial information: NCT00129935.
Catholic Social Teaching and the Duty to Vaccinate
Authors: Paul J. Carson, Anthony T. Flood
Journal: The American Journal of Bioethics (2017)

Since the last century, vaccination has been one of the most important tools we possess for the prevention and elimination of disease. Yet the tremendous gains from vaccination are now threatened by a growing hesitance to vaccinate based on a variety of concerns or objections. Geographic clustering of some families who choose not to vaccinate has led to a number of well-publicized outbreaks of vaccine-preventable diseases. Of note is that some of these outbreaks are centered within some Christian religious groups that increasingly avoid vaccination due to moral concerns, fears about safety, or doubts about the necessity of vaccines. We argue from the perspective of Catholic social teaching on why there is a moral duty to vaccinate.
The Elastin Microfibril Interfacer-1 (EMILIN-1) Is a Ligand for CD49d in Chronic Lymphocytic Leukemia Cells
Authors: Erika Tissino, Dania Benedetti, Riccardo Bomben, Michele Dal Bo, Tiziana Vaisitti, Silvia Deaglio, Davide Rossi, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Gianluca Gaidano, Giovanni Del Poeta, Alberto Zamò, Paola Spessotto, Roberto Doliana, Antonella Zucchetto, Alfonso Colombatti, Valter Gattei
Journal: Blood (2012)
Treatment of HIV positive anal cancer patients with chemoradiation
Authors: J. M. Hwang, A. Rao, E. Shieh, J. Yao, M. Tome
Journal: Journal of Clinical Oncology (2006)

4154 Background: Tolerance and outcomes of HIV+ anal cancer patients are questioned, especially since the emergence of High Active Anti-Retroviral Therapy (HAART) in the mid-1990s. Our experience in treating these patients before and during the HAART era is reported. Methods: From 1987–2003, 19 HIV+ invasive anal cancer patients were treated with: 30–60 Gy pelvic RT (2 Gy/d) + Mitomycin C (10 mg/m 2 bolus on d1) + 5-FU (1000 mg/m 2 /d, continuous infusion d1–4 and 28–31). Results: Mean CD-4 count at cancer diagnosis was 311, with 9 on HAART. Mean CD-4 count for HAART was 383 and 247 for non-HAART. Stage distribution: 1 T1, 9 T2, 9 T3, 18 N0, 1 N3. Mean f/u was 40 months. 79% had complete response after chemoRT. 4 had locally persistent disease. There was 1 loco-regional recurrence and 2 distant metastases. 79% of the cohort is colostomy-free. Median OS has not been reached. OS at 2 and 3 years were: 88%and 79%, with 10 Alive and NED, 1 Alive with disease, 3 Dead of disease, 5 Dead from intercurrent disease (all secondary to AIDS). 1.5 year DFS was 74%. Break and CD-4 count &lt; 200 had a statistically significant negative impact on DFS, but not OS. HAART did not affect either factor. 11 had RT break for median of 17 days. There was no Grade 4 skin toxicity. All completed the 2nd 5-FU cycle: 7 had delay (median 7 days) and 3 had dose decrease. There were 6 hospitalizations: 5 neutropenic fevers and 1 perineal abscess rupture. WBC Toxicity: 6-Grade 3 and 2-Grade 4. Platelet Toxicity: 2-Grade 3. Heme toxicity was not affected by HAART or CD4 count &lt; 200. There were no treatment related deaths. Conclusion: HIV+ anal cancer patients have reasonable tolerance and outcomes with chemoRT. CD-4 count &lt; 200 and break were negative prognostic factors for DFS. Our 79% colostomy free survival is similar to RTOG 9208, where suboptimal control was attributed to mandatory RT break. Factors influencing break include heme and skin toxicity. To improve the therapeutic ratio, substitution of Mitomycin-C with Cisplatin, IMRT, and Ethyol are being explored. No significant financial relationships to disclose.
Basic needs of pediatric oncology patients, families, and their psychosocial adjustment.
Authors: Heatherlun Uphold, Amy Peterson, Felicity W. K. Harper, Jennifer Fox, Tanina Foster, Sean Phipps, Jeffrey Warren Taub, Terrance Lynn Albrecht, Louis Penner
Journal: Journal of Clinical Oncology (2013)

e20646 Background: Children are surviving cancer at increasing rates, but dealing with pediatric cancer creates substantial need for services among the families of patients. This study examined the fiscal/material/social needs of families with children in treatment, the relationship between the extent of these needs, and the psychosocial adjustment of primary caregivers. Methods: Participants included 105 pediatric cancer patients (ages 3-12), receiving outpatient cancer treatments at two large children’s hospitals, and their adult caregivers. About one year after treatment began, caregivers completed a questionnaire assessing their fiscal/material/social needs and whether the hospital offered assistance. Caregivers also completed several measures of psychosocial adjustment: satisfaction with life (Diener, 1985), perceived stress (Cohen, 1994), psychiatric symptoms (Derogatis, 1983), and post-traumatic stress symptoms (Weiss, 1996). This non-clinical study is still accruing patients, but it has reached a sample size that is large enough (90% of final sample) to justify data analysis. Results: The top 5 identified needs were: social work services, play activities during treatment, help with insurance to cover their child’s medical care, educational activities to help their child cope, and help obtaining cancer-related medical services. An analysis of the demographic correlates of these needs showed the total number of needs was significantly and negatively correlated with income, and Black families reported more needs than White families; there were no other significant demographic correlates. Total number of needs was significantly associated with caregivers’ psychosocial adjustment. Specifically, total number of needs was negatively correlated with life satisfaction, and positively associated with: caregiver perceived stress, depression, and symptoms of post-traumatic stress. Conclusions: Caregivers of pediatric cancer patients have substantial needs for basic services and the extent of these needs is associated with their psychosocial adjustment. Unmet needs may be a risk factor for patients and families. Programs that address these needs may benefit the adult caregivers and their children.
DPP4 truncated GM-CSF and IL-3 manifest distinct receptor-binding and regulatory functions compared with their full-length forms
Authors: H A O’Leary, M Capitano, S Cooper, C Mantel, H S Boswell, R Kapur, B Ramdas, R Chan, L Deng, C-K Qu, H E Broxmeyer
Journal: Leukemia (2017)
Regional differences in therapy and clinical management of endometrial cancer: Findings of an international survey by the North-eastern German Society of Gynaecological Oncology (NOGGO).
Authors: Robert W. Kraetschell, Christina Fotopoulou, Sean Christopher Dowdy, Keiichi Fujiwara, Nobuo Yaegashi, Domenica Lorusso, Sven Mahner, Thomas J. Herzog, Antonio Casado Herraez, Ignace Vergote, David S. Miller, Christian Marth, Marco Johannes Battista, Werner Lichtenegger, Jalid Sehouli
Journal: Journal of Clinical Oncology (2013)

5593 Background: We conducted an international survey to evaluate the differences in the systemic, radiotherapeutic and operative management of endometrial cancer (EC) in different regions of the world. Methods: In 2009 avalidated 15-item-questionnaire regarding surgical and adjuvant procedures of EC was sent to all German gynaecological clinics and in 2010 the English adapted questionnaire was set online as well as sent per post in most major gynaecological cancer societies. Results: 316 German institutions and 302 Institutions from 24 countries participated. We combined the different countries into regional groups: Central Europe (CE), southern Europe (SE), Asia and USA/UK. In Asian countries and in CE a lymph node dissection (LND) was performed routinely in 72.8% and in 55.6% of the cases, whereas in the USA/UK and in SE a LND was done mainly in selected cases when specific risk factors such as high-grade or non-endometrioid-histology applied (62.8% and 72.5%) than routinely (p &lt; 0.001). A systematic pelvic and paraaortic LND was performed most frequently in CE 91.0%, in SE 76.9%, in Asia 70.9% and in USA/UK 68.6% (p &lt; 0.001). A systematic LND with the intention of both adequate staging and for therapeutic value was performed in countries of central Europe to 74.6% and in Asia to 67.2%. In USA/UK the LND was seen merely as a staging instrument by 53.5% (p &lt; 0.001). The LND was performed up to renal veins in CE in 86.8%, in Asia in 80.8%, in USA/UK in 51.2% and in SE in 45.1 %. A significant difference war found in the treatment for FIGO stage I (high risk factors (high grade, L1,V1)) and stage II disease between the countries: chemotherapy was applied in 84.8% of the participated centers in Asia,42.3% in SE, 21.2% in CE and only 13.6% in USK/UK (p&lt;0.001).Vaginal brachytherapy was indicated as follows: USA/UK 84.1%, CE 78.8%, SE 78.8%, Asia 5.6% (p &lt; 0.001). Conclusions: There is a large variety in the operative therapy and the clinical management of EC in different regions of the world. Future international prospective trials, will be necessary to improve and harmonize the evidence based treatment guidelines for EC- disease.
Incidence and patterns of phospho insulin growth factor receptor-1 (pIGF-1R) and matrilysin (MMP7) expression in metastatic colorectal cancer (mCRC), and correlation with KRAS status: A prospective evaluation in the PULSE trial—A GEMCAD study.
Authors: Vicente Alonso, Carlos Fernandez-Martos, Marta Martin, Antonieta Salud, Jose Carlos Mendez, Carles Pericay, Hermini Manzano, Javier Gallego, Carlos Horndler, Isidro Machado, Maria Tobeña, Xabier Garcia-Albeniz, Michele Rubini, Pedro Jares, Miriam Cuatrecasas, Joan Maurel
Journal: Journal of Clinical Oncology (2012)

e14041 Background: MMP7 can activate IGF-1R by IGF release due to IGFBP degradation. Activation of IGF-1R can contribute to EGFR resistance by transactivation. We previously described that concomitant expression of p-IGF-1R and MMP7 (Double positive; DP), correlates with poor prognosis, in KRAS WT patients (pts) treated with anti-EGFR compounds (Horndler el al, 2011). Therefore we designed a prospective clinical trial to validate DP as a marker of resistance in KRAS WT pts treated in first-line therapy with FOLFOX-6 plus panitumumab. Methods: mCRC pts in the ongoing prospective PULSE trial (NCT0128833) were prospectively evaluated for p-IGF-1R (p-1316), MMP7 expression and KRAS mutational status. Pts defined as DP should express MMP7 (++ or +++ intensity in &gt;66% of tumor cells) and p-IGF-1R (++ or +++ intensity in &gt;66% of tumor cells). KRAS pts with mutations at exon 2 were excluded. The study was designed to include 40 pts in the two groups (DP vs non-DP) to detect a Hazard ratio difference in PFS of &lt;0.5 (DP vs non-DP) with 80% power. Results: From November 2010 to December 2011, 113 consecutive pts were screened from 24 Spanish Institutions. 54 KRAS WT (40 pts non-DP and 14 DP) have been included. The non-DP arm has being recently closed for inclusion, due to pre-planned complete accrual. Among DP pts, 27% were KRAS WT and 30% KRAS mutant; p=0.63. 48% of cases were positive for p-IGF-1R. Phospho-IGF-1R positive cases had different patterns of staining: peri-nuclear in 76%, 11% nuclear and only 13% membrane-apical staining. These patterns do not differ between KRAS WT; (n=70) and KRAS mutant pts (n=43) (p=0.60). Tumors with positive p-IGF-1R expression, independently of the pattern, have higher MMP7 co-expression (59%) compared with negative cases (13%) (p&lt;0.0001). Conclusions: MMP7 contributes to activate IGF-1R pathway in pts with mCRC. Internalization of the activated IGF-1R, could explain in part, the lack of efficacy of IGF-1R inhibitors in mCRC clinical trials.
A comprehensive prognostic index for patients with CLL.
Authors: Natali Pflug, Jasmin Bahlo, Tait D. Shanafelt, Barbara Eichhorst, Manuela Bergmann, Thomas Elter, Kathrin Bauer, Gebhart Malchau, Kari G. Rabe, Stephan Stilgenbauer, Hartmut Dohner, Ulrich Jäger, Michael Eckart, Georg Hopfinger, Raymonde Busch, Anna-Maria Fink, Clemens M. Wendtner, Kirsten Fischer, Neil E. Kay, Michael Hallek
Journal: Journal of Clinical Oncology (2013)

7015 Background: Besides clinical staging, a number of biomarkers predicting OS in CLL have been identified. The multiplicity of markers, limited information on their independent value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice. We developed an integrated prognostic index using the database of the German CLL Study Group (GCLLSG), which was subsequently validated in a cohort of untreated CLL patients (pts) from the Mayo Clinic. Methods: The analysis was based on a dataset collected between 1997 and 2006 in 3 GCLLSG phase III trials. The external validation was performed on a series of newly diagnosed CLL pts managed at Mayo Clinic. Results: The GCLLSG dataset (1,948 physically fit pts at early and advanced stage; median age: 60 yr (range 30-81); median observation time 63.4 mo) was used as a training dataset. 7 parameters were identified as independent predictors for OS: sex, age, ECOG status, del 17p, del 11q, IGHV mutation status, thymidine kinase and β 2 -microglobulin. By using a weighted grading a prognostic index was derived separating four different pts groups: low risk (score 0 - 2), intermediate risk (score 3-5), high risk (score 6-10) and very high risk (score 11-14) with significant different OS rates (95.2%, 86.9%, 67.7% and 18.7% OS after 5 yr for the low, intermediate, high and very high risk group respectively (p&lt;0.001). This prognostic index was validated in a cohort of 676 newly diagnosed, untreated pts from the Mayo Clinic (median age 61.5 yr (range 32 - 89); median observation time 47.0 mo). The 4 risk groups were reproduced with 98.3%, 95.4%, 75.4% and 10.8% OS after 5 yr. The prognostic index predicts OS independent of Rai/Binet stage and provides accurate estimations regarding time to first treatment (TTF). C-statistic is 0.75. Conclusions: Using a multi-step process including external validation, we developed a comprehensive prognostic index combining clinical, serum, and molecular information into a single risk score for pts with untreated CLL. The prognostic index provides more accurate prediction of both TTF and OS. To our knowledge it is the first prognostic model in CLL to reach the C-statistic threshold (c &gt; 0.70) necessary to have utility at the level of the individual.
Primary tumor location and survival in general population with metastatic colorectal cancer (mCRC).
Authors: Shahid Ahmed, Neha Papneja, Mohamed Elsayed Emara, Riaz Alvi, Tehmina Asif, Dueck Dorie-Anna, Duc Le, Adnan Zaidi, Kamal Haider, Selliah Kanthan, Nayyer Iqbal
Journal: Journal of Clinical Oncology (2017)

674 Background: Recent evidence from clinical trials suggests that location of the primary tumor in patients with mCRC correlates with differential outcomes and patients with tumors originating in the right side of colon have inferior survival. This large population-based cohort study using individual patient data was performed to confirm this findings in general population with mCRC. Methods: A cohort of 1947 patients who were diagnosed with synchronous mCRC from 1992-2010 was studied. Ascending and transverse colon cancers were defined as right-sided tumors (RT) and remainder tumors were define as left-sided tumors (LT). Cox proportional multivariate analyses were done to determine prognostic significance of primary tumor location and to adjust other prognostic variables including age, Charlson comorbid index (CCI) and WHO performance status (PS) in patients treated with chemotherapy. Results: Median age was 70 years (IQR: 60-78) and M:F was 1.3:1. Mean CCI was 9.7±1.4 and 29% had WHO PS of &gt; 1. 770 (39%) patients had RT and 37% had stage IVb disease. 908 (47%) received chemotherapy and of those 44% received modern chemotherapy. Significant differences were noted between the groups with RT and LT with respect to age, WHO PS, CCI, liver metastases, mucinous tumor, grade, smoking history, and primary tumor resection. Median overall survival of patients with RT was 14 (95%CI: 12.7-15.3) months compared with 20.5 (95%CI: 18.5-22.5) of patients with LT (p &lt; 0.001). On multivariate analysis following variables were correlated with inferior survival: Right-sided tumors, hazard ratio (HR) 1.40 (95%CI: 1.20-1.60); no primary tumor resection, HR 1.60 (95%CI: 1.32-1.90); no metastasectomy, HR 2.40 (95%CI: 1.90-2.90); not using modern chemotherapy, HR 1.52 (95%CI: 1.31-1.80); leukocytosis, HR 1.44 (95%CI: 1.28-1.73); elevated CEA, HR 1.54 (95%CI: 1.30-1.90); WHO PS &gt; 1, HR 1.30 (95%CI: 1.10-1.55); and stage IVb disease, HR 1.50 (95%CI: 1.17-1.86). Tests for interaction were negative. Conclusions: Our results confirm that patients with RT who received chemotherapy have inferior survival independent of other known prognostic variables. Future studies are required to understand underlying pathophysiology.
Phase II trial of erlotinib in advanced pancreatic cancer (PC)
Authors: P. Tang, S. Gill, H. J. Au, E. X. Chen, D. Hedley, M. Leroux, L. Wang, M. J. Moore
Journal: Journal of Clinical Oncology (2009)

4609 Background: The epidermal growth factor receptor (EGFR) is a potentially important target in PC. Benefit from erlotinib (Tarceva), an oral EGFR tyrosine kinase inhibitor has been associated with the presence of a skin rash. The purpose of this study was to determine the efficacy of erlotinib, dosed to achieve a rash, in patients (pts) with PC. Methods: Erlotinib was given at an initial dose of 150 mg/day to eligible pts with locally advanced (LA) or metastatic PC who had progressed or were unable to tolerate gemcitabine-based chemotherapy. The dose of erlotinib was increased by 50mg every 2 weeks (maximum 300 mg/day) until &gt; grade 1 rash (CTCAE v 3.0) or other dose-limiting toxicities occurred. Erlotinib pharmacokinetic (PK) studies were performed. Baseline tumor tissue was collected for analysis of Kras mutations, EGFR by IHC and FISH. The primary endpoint of this two- stage phase II trial was prolonged disease control (PR + SD &gt; 8 wks) with a rate of &gt;20% assumed to be significant . Results: Fifty pts were accrued (median age 61, M:F = 25:25, ECOG 0:1:2 = 5:41:4, LA:Metastatic = 5:45, prior gemcitabine none:adjuvant:palliative = 2:16:35). 47 and 40 pts were evaluable for toxicity and response, respectively. Dose-escalation to 200–300 mg of erlotinib was possible in 9 pts. Most common treatment adverse events (TAEs) of any grade were: rash (35 pts, 74.5%), diarrhea (18 pts, 38.3 %), and fatigue (8 pts, 17%). Grade 3+ TAEs were rash in 2 pts and diarrhea in 2 pts. Best response was SD in 14 pts, 0.35 (95% CI: 0.2–0.5). Prolonged disease control (SD &gt; 8 wks) was observed in 10/40 evaluable pts, 0.25 (95% CI: 0.12–0.38), which met the primary study endpoint. Median TTP was 1.6 mo (95% CI:1.6–2.1), mOS 4.1 mo (95% CI:3.2–7.3), and 6 mo OS rate was 39% (95%CI: 24–61%). PK and correlative data are being analyzed and will be presented. Conclusions: Erlotinib is associated with prolonged stable disease in a subset of pts with advanced refractory PC. Dose escalation in the absence of toxicity is feasible and safe. [Table: see text]