tbuckley/cabot-search huggingface dataset:
Platelet counts (PLT) at baseline and on treatment as predictor for progression free survival (PFS) in patients with advanced malignant pleural mesothelioma (MPM): EORTC 08052 study.
Authors: Rabab Mohamed Gaafar, Sanjay Popat, Jan P. Van Meerbeeck, Paul Baas, Dean Fennell, Athanasios G. Pallis, Baktiar Hasan, Mary O'Brien
Journal: Journal of Clinical Oncology (2013)

7585 Background: PLT values at baseline are considered as a negative prognostic factor in several different tumor types (lung, colorectal, renal and endometrial cancer) in both early and advanced disease settings. This is an exploratory analysis of PLT (baseline and changes during treatment) and their value in predicting PFS and overall survival (OS) in patients with stage IV MPM treated with cisplatin/bortezomib in the context of a single-arm phase II trial (EORTC 08052). Methods: Patients participating in the clinical trial were chemo-naïve with histological proven MPM and PS 0/1 (cisplatin 75 mg/m 2 d1 and bortezomib 1.3 mg/m2 on d1, 4, 8, 11 q3wks). PLT analysis was pre-planned in the protocol and was recorded at baseline and at each cycle. Nadir of change in PLT was recorded at 8 and 18 weeks according to predefined cut off points (median PLT value). The association of the PLT with PFS and OS was analyzed. Results: 82 patients from EORTC-08052 study were analyzed with 1394 records of PLT. The cut off point for baseline was median PLT 374x10 3 /mm 3 . We confirmed that patients with baseline PLT less than median had longer PFS compared to patients with counts higher than median (median PFS: 5.7 vs. 3.7 months [mo]; HR: 0.55; 95% CI: 0.34-0.88; p: 0.012). There was also a trend towards higher OS for patients with baseline PLT values less than median (median OS: 14.8 vs.10.6 mo; HR: 0.62; 95% CI: 0.38-1.02; p: 0.059). The median decrease of PLT values at 8 wks of treatment was 243 x10 3 /mm 3 . Patients with decrease lower than median had higher PFS (median PFS: 7.5 vs. 5.7 mo; HR: 2.2; 95% CI: 1.3-3.8; p: 0.003) and a trend towards higher OS (median OS: 14.9 vs. 10.6 mo; HR: 1.6; 95% CI 1-2.7; p: 0.06). Changes at 18 weeks had no prognostic value. Conclusions: Besides low baseline PLT values we observed that a decrease in PLT at 8 weeks (but not 18 weeks) during treatment could predict PFS and to less extent OS. Validation of this observation is planned.
Logistic Regression Diagnostics
Authors: William J. Meurer, Juliana Tolles
Journal: JAMA (2017)

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The forgotten children.
Authors: Chris Kuo, Paul Kent, Jeff Ording
Journal: Journal of Clinical Oncology (2017)

188 Background: The “forgotten children” of pediatric cancer are the siblings. There is a dearth of literature published on the effects of cancer on the siblings’ psychosocial state. Despite significant improvements made in the survival of pediatric cancer patients, the psychosocial health of the siblings remains the same. We hope to shed light on siblings, as well as recognize the emotional and psychological toll they endure as the “forgotten children.” Methods: Selective, narrative review of psychosocial consequences of being the siblings of children with cancer was performed from January 1980 through October 2016 using key words: pediatrics, oncology, psychosocial care, siblings, forgotten children, psycho-oncology, bereavement, caregivers. Results: Compared with siblings of children with other chronic illnesses, siblings of children with cancer endure more emotional distress and adaptive difficulties. From the moment the diagnosis is given, until their sibling’s death, siblings of children with cancer are unmoored. Throughout the cancer trajectory, they are isolated from support systems both inside and outside the family. They experience a wide spectrum of emotional turmoil from intrusive thoughts (anger, unworthiness, jealously, fear, loneliness or guilt), to post-traumatic growth (appreciation of life, desire to pay back society, greater self-knowledge). Since 1990s, various qualitative and quantitative studies have been published for siblings of children with cancer, but little has changed since these reports. Siblings continue to be the “forgotten children” in the family and their needs remain unmet. Siblings endure various distresses throughout the different stages of cancer trajectory. The complexity of the roots of their distress requires meticulous attention to dissect and unravel. Conclusions: Research on the psychosocial well-being for siblings of children with cancer remains limited. Consistencies with screening and supportive interventions continue to be lacking. A standardized screening tool with early interventional services should be implemented. Additionally, interdisciplinary awareness of the siblings’ psychosocial issues should be increased in order to shed light to their invisibility. The goal is to remember the “forgotten children.”
Molecular evaluation of primary tumor (PT) and synchronous liver metastasis in colorectal cancer (srLmCRC) patients after cetuximab-based chemotherapy.
Authors: Daniela Adua, Annalisa Altimari, Elisa Gruppioni, Giorgio Ercolani, Fabiola Lorena Rojas Llimpe, Francesca Di Fabio, Michelangelo Fiorentino, Antonio Daniele Pinna, Carmine Pinto
Journal: Journal of Clinical Oncology (2014)

3624 Background: Molecular heterogeneity among PT and LmCRC is not yet defined. Next Generation Sequencing (NGS) in clinical practice could increase the change of identifying multiple molecular driver alterations calling for therapy. This study evaluates mutations in PT and sLmCRC exon2 KRAS wt patients who underwent chemotherapy (CT) containing cetuximab. Methods: Genomic analysis was conducted in 7 sLmCRC pts: before CT on a PT biopsy, after CT on a PT surgical specimen and all srLmCRC. A total of 54 lesions were examined. DNA libraries were generated using the Ion AmpliSeq Colon and Lung Cancer Panel including 22 mutated genes (KRAS, EGFR, BRAF, PIK3CA, AKT1, ERBB2, PTEN, NRAS, STK11, MAP2K1, ALK, DDR2, CTNNB1, MET, TP53, SMAD4, FBXW7, FGFR3, NOTCH1, ERBB4 , FGFR1, FGFR2) and sequenced on a Ion PGM system Results: A partial response was achieved in all pts, with a median PFS of 11 months (4-15). Molecular analysis of genes correlated with target therapy is shown in the following table (K=KRAS; N=NRAS; P=PIK3AC; M=MET; m= -; wt= + ). Pt 1 showed heterogeneity in PT before and after CT with KRASm clonal selection and related expression of the mucinous pattern; in srLmCRC: 5/9 KRASm exon2, 1/9 PIK3CAm exon20, 2/9 KRASm exon2 and PIK3CA exon20. In pt 7 NRASm exon2 was identified in PT before and after CT; differences in srLmCRC: 3/5 no mutation, 1/5 NRASm exon2, 1/5 PIK3CAm exon20. The other cases showed rare mutations: SMAD4 (pt 2), TP53 (pts 2,5,6,7), FBXW7 (pt1). Conclusions: Our preliminary data suggest a potential role for NGS in the evaluation of biological drug resistance affecting future sequential treatments strategy CT regimen Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Folfiri/Cet Folfiri/Cet Folfiri/Cet Folfoxiri/Cet Folfiri/Cet Folfiri/Cet Folfoxiri/Cet PFS (months) 15 4 14 14 8 11 10 K N P M K N P M K N P M K N P M K N P M K N P M K N P M PT pre-CT - - - - - - - - - - - - - - - - - + - + - - - - - + - - PT post-CT + - - - - - - - - - - - - - - - - + - + - - - - - + - - srLmCRC n.1 + - - - - - - - - - - - - - - - - + - + - - - - - + - - srLmCRC n.2 - - + - - - - - - - - - - - - - - + - + - - - - - - - - srLmCRC n.3 + - - - - - - - - - - - - - - - - - + - srLmCRC n.4 + - - - - - - - - - - - - - - - - - - - srLmCRC n.5 + - - - - - - - - - - - - - - - - - - - srLmCRC n.6 + - - - - - - - - - - - srLmCRC n.7 + - + - - - - - - - - - srLmCRC n.8 + - - - - - - - - - - - srLmCRC n.9 + - + - - - - -
Remote Control of Cellular Functions: The Role of Smart Nanomaterials in the Medicine of the Future
Authors: Giada Graziana Genchi, Attilio Marino, Agostina Grillone, Ilaria Pezzini, Gianni Ciofani
Journal: Advanced Healthcare Materials (2017)

The remote control of cellular functions through smart nanomaterials represents a biomanipulation approach with unprecedented potential applications in many fields of medicine, ranging from cancer therapy to tissue engineering. By actively responding to external stimuli, smart nanomaterials act as real nanotransducers able to mediate and/or convert different forms of energy into both physical and chemical cues, fostering specific cell behaviors. This report describes those classes of nanomaterials that have mostly paved the way to a "wireless" control of biological phenomena, focusing the discussion on some examples close to the clinical practice. In particular, magnetic fields, light irradiation, ultrasound, and pH will be presented as means to manipulate the cellular fate, due to the peculiar physical/chemical properties of some smart nanoparticles, thus providing realistic examples of "nanorobots" approaching the visionary ideas of Richard Feynman.
Usability of evaluations of the relationship between efficacy and toxicity in the development of anticancer drugs
Authors: B. I. Nilsson
Journal: Journal of Clinical Oncology (2004)

2102 Background: Evaluation of safety and efficacy of anti-cancer drugs is a complex procedure. Here, a tool is presented that may facilitate an overall assessment of the usefulness of a given therapy. Methods: Interindividual variation of Cmax and AUC were assessed for various chemotherapeutic agents via the literature, also including data on correlations between Cmax and AUC and toxicity. A few studies were evaluated for the relation between efficacy and toxicity. Results: Cmax and AUC typically showed a 3–4–fold variation between minimum and maximum value. Toxicity is related to Cmax and/or AUC for several agents. Toxicity is variable between subjects in a given study population because of interindividual differences regarding various pharmacokinetic parameters. Categorizing patients according to grade of toxicity makes it possible to study the relation between toxicity and efficacy. It has been possible in several studies to show differences in response rate or survival depending on grade of toxicity experienced. Conclusions: The dose used in phase II and later may be the optimal dose for less than half of the patients, provided that maximal efficacy is obtained at the highest possible dose. A correlation between toxicity and efficacy is suggestive of biological activity. A finding of a low response rate or a poor survival may be due to genuine lack of activity or to treatment at an inadequate dose. Evaluation of the relation between efficacy and toxicity (ERBET) is analogous to a randomization between active treatment and an inactive control since it is a comparison of two populations with different drug exposure, although retrospective. ERBET represents a biological assignment to different tissue levels of the drug and is in that sense an unbiased comparison. No significant financial relationships to disclose.
INDICACIONES, COMPLICACIONES Y UTILIDAD DE LA ENDOPRÓTESIS COLÓNICA EN LA OBSTRUCCIÓN INTESTINAL POR CÁNCER COLORRECTAL
Authors: M Hernández Tejero, F García Durán, JA Carneros Martín, JM Hernández Atance, D Huerga Álvarez, D Bonillo Cambrodón, A Granja Navacerrada, P Bernal Checa, A Bermejo Abati, B Piqueras Alcol, F Bermejo San José
Journal: Endoscopy (2015)

Introducción: El 10% de pacientes con cáncer colorrectal (CCR) presenta obstrucción intestinal. La utilidad del manejo endoscópico de esta complicación es controvertida.
Randomized, double-blinded study of dacomitinib, an irreversible pan-human epidermal growth factor receptor (HER) inhibitor, versus erlotinib for second-line/third-line therapy of locally advanced/metastatic non-small cell lung cancer (ARCHER 1009).
Authors: Suresh S. Ramalingam, Pasi A. Janne, Tony Mok, Kenneth O'Byrne, Michael J. Boyer, Hui Zhang, Jane Q. Liang, Jim P. Doherty, Ian Taylor, Cecile A. Mather, Joseph P. O'Connell, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2014)

8018 Background: Dacomitinib, an irreversible pan-HER kinase inhibitor, has demonstrated anti-cancer activity in phase 2 studies for patients with EGFR activating mutation and in those with EGFR and K-RAS wild-type (WT) NSCLC. Methods: Patients (pts) with locally advanced/metastatic NSCLC were randomized following progression with 1 or 2 prior chemotherapy regimens to treatment with Dacomitinib (D) (45 mg PO QD) or Erlotinib (E) (150 mg PO QD) with placebo control for both arms. Archived tumor tissue, ECOG performance status (PS) of 0-2, adequate organ function and informed consent were required. The primary endpoint was progression-free survival (PFS) per independent review in the co-primary populations [all patients and those with KRAS WT]. The estimated sample size was 800 pts, using 1-sided stratified log rank test for all pts to detect HR≤ 0.75, at significance = 1.5% with 90% power and to detect HR≤ 0.69 for KRAS WT at significance = 1% with 80% power. Secondary endpoints: overall survival, objective response (OR), safety, and patient reported outcomes. Results: 878 pts with the following baseline characteristics were enrolled; approximate median age of 63 years, 64% males, 76% Caucasians, 90% with PS 0/1, 69% adenocarcinoma and 18% never-smokers. Activating EGFR mutation was present in 41 pts in each arm. Discontinuation for treatment-related toxicity was more frequent with D (8% vs. 4.8%). Diarrhea, stomatitis, paronychia, and mucositis were more common with D. Conclusions: Irreversible EGFR inhibition with Dacomitinib is not superior to Erlotinib in the second-/third-line therapy of advanced NSCLC. Overall survival and outcomes for pts with EGFR mutation are not mature. Clinical trial information: NCT01360554. Population All pts KRAS WT Dacomitinib Erlotinib Dacomitinib Erlotinib N 439 439 256 263 Response rate 11.4% 8.2% 13.3% 11% Median PFS 2.6 m HR 0.941, P=0.229 2.6 m 2.6 m HR 1.022 P=0.587 2.6 m Median OS (95% CI) 7.9 m (6.8,9.0) 8.4 m (7.4,9.7) 8.1 m (6.8,9.5) 8.5 m (7.5,10.2)
Real-world study of imatinib treatment patterns and outcomes among veteran patients with chronic myeloid leukemia.
Authors: Lizheng Shi, Lei Chen, Hari Sharma, Maryna Marynchenko, Eric Q. Wu, Jinan Liu, Heidi Yang, Min Amy Guo, Nancy S. Vander Velde
Journal: Journal of Clinical Oncology (2012)

6600 Background: Imatinib (IM) is the most commonly used drug in the treatment of chronic myeloid leukemia-chronic phase (CML-CP) patients (pts). This study investigated the treatment patterns and outcomes for veteran CML-CP pts initiated on IM. Methods: Pts (age &gt;18 yrs) with &gt;1 CML diagnosis codes documented (ICD-9 CM: 205.1x) between 1/1/2000 and 12/31/2010 were identified from the VISN 16 data warehouse. Pts were required to have initiated IM as the first-line therapy in CML-CP. Accelerated and blastic phases (A/BP) were identified based on WHO classification using CBC information. IM dose adjustments were assessed as dose increase from &lt;400 mg to &gt;600mg or from 400-600mg to &gt;800 mg daily. Rates of IM discontinuation (no use of IM for &gt;60 days) and switching to other drug therapy (dasatinib/nilotinib (DS/NL), hydroxyurea, and interferon-alpha) were estimated. Time to discontinuation, progression to A/BP, and survival were assessed using Kaplan-Meier analysis (K-M). Overall survival was measured from IM initiation while survival among pts with disease progression was measured from the date of progression. Results: Among the 137 pts selected, average age was 64.8 yrs and follow-up time was 4.0 yrs. 16.8% of pts had dose increase from &lt;400mg to &gt;600mg and 21.7% of these pts switched to other therapy after dose increase. 13.1% of pts had dose increase from 400-600mg to &gt;800 mg with 22.2% of these pts switching to other therapy later. During the study, 83.8% of the 74 pts who discontinued IM did not use other drug therapies; and 16.2% (12 pts) switched, among which 9 pts took DS/NL. K-M showed that 25.6% and 42.4% pts discontinued IM treatment by year 1 and 2 and 8.1% and 16.0% pts experienced disease progression by year 1 and 2, respectively. Among the 28 patients who had disease progression, 32.1% continued IM use after progression and only 7.1% switched to other therapies (50% switching to DS/NL). The mortality rates were 3.0% and 9.5% by year 1 and 2 after IM initiation, and 21.7% and 42.7% by year 1 and 2 after disease progression, respectively. Conclusions: The majority of IM-treated patients, including patients with disease progression, discontinued IM use without switching to other effective therapies.
Gut Colonization with Carbapenem Resistant Enterobactriaceae (CRE) Adversely Impacts the Outcome in Patients with Hematological Malignancies: Results of a Prospective Surveillance Study
Authors: Sarita Rani Jaiswal, Satyanker Gupta, Amit Sherawat, Seena Vinod, Hensey Jacob, Sajin V Abraham, Anushree Chaturvedi, Suparno Chakrabarti
Journal: Blood (2016)
Genomic profiling of breast cancer in African-American women.
Authors: Raquel Nunes, Lynette Wray, Mihriye Mete, Thomas Godwin, Pia Maarit Herbolsheimer, Karen L. Smith, Lana Bijelic, Marc E. Boisvert, Sandra M. Swain
Journal: Journal of Clinical Oncology (2013)

11054 Background: Molecular profiling of breast cancer (BC) identifies intrinsic subtypes with distinct gene expression and clinical characteristics. In the US, BC is less frequent in African-American females (AAF); however mortality is higher, particularly among younger women. Unfavorable subtypes of BC seem to be more frequent in premenopausal AAF. Methods: Tumor gene expression in AAF presenting with early stage or locally advanced BC was performed using the Symphony platform on fresh and paraffin-embedded tissue (Agendia inc), a microarray-based method which classifies tumors according to prognosis (MammaPrint, MP), molecular subtype (BluePrint, BP) and estrogen receptor (ER), progesterone receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) mRNA levels (TargetPrint, TP). Genomic information is correlated with clinical and pathologic characteristics and Oncotype DX recurrence score (RS) when available. We plan to enroll 100 patients. Results: Results available in 46 patients. Median age 62 years (range 24-100), 20 stage I, 15 stage II, 11 stage III disease. There was no significant association between MP risk and stage, but MP risk was significantly associated with grade 3 disease (p=.006). 9 cancers were triple negative by IHC; using BP, 8 of these were Basal-type and 1 HER2-type. Basal-type was the most common subtype in patients ≤ 40 years old (p &lt; .001). In the 6 cases ER positive by IHC but negative by TP, 3 were Basal-type and 3 were HER2-type.14 patients had Oncotype RS results available: 2 were High Risk by Oncotype and MP; 3 had intermediate RS, 2 of which were High Risk by MP; 9 had a low RS, 4 of which were High Risk by MP. Conclusions: African-American women with stage I to III BC often present with High-Risk disease irrespective of stage. BP classified all young patients (≤40) as Basal-type. Molecular subtyping confirmed the biologic heterogeneity in triple negative and hormone positive tumors. Oncotype RS and MP offered different prognostic information. Follow up will be needed to determine correlation with outcome. Funding: MP, BP and TP test provided by Agendia. Biostatistical support by GHUTTCS-CTSA. [Table: see text]
A phase II multicenter study of the efficacy and safety of sunitinib given on an individualized schedule as first-line therapy for metastatic renal cell cancer.
Authors: Georg A. Bjarnason, Naveen S. Basappa, Jennifer J. Knox, Christian K. Kollmannsberger, M. Neil Neil Reaume, Pawel Zalewski, Robyn Jane Macfarlane, Mary J. MacKenzie, Sebastien J. Hotte, Daniel Yick Chin Heng, Denis Soulieres, Jessie Miller
Journal: Journal of Clinical Oncology (2013)

TPS4594 Background: Retrospective reviews have shown poorer than expected response rate (RR), progression free survival (PFS) and overall survival (OS) in Sunitinib treated (Rx) Renal Cell Cancer (RCC) patients (pts) who experience minimal toxicity. This study is based on an individualized (individ) Rx strategy where dose/schedule modifications (DSM) were done to maximize dose and minimize time off Rx in 172 pts (Bjarnason ASCO-GU 2011). Pts started on 50mg 28 days (d) on/14d off. DSM were done to keep toxicity (fatigue, skin, GI, hematology) at ≤ grade-2. DSM-1 was 50mg 14d/7d with individ increases in d on Rx based on toxicity. DSM-2 was 50mg 7d/7d with individ increases in d on Rx. DSM-3 was 37.5mg continuously with individ 7d breaks. DSM-4 was 25mg continuously with individ 7d breaks.In pts with clear cell histology PFS was inferior (5.8 mo) on the standard 50mg 28d/14d schedule vs. DSM schedules (&gt;14 months, p=0.0002) These data, confirmed in 185 pts at MD Anderson (Jonasch KCA 2012), suggest that pts with minimal toxicity after 28d on Rx may benefit from dose escalation. Methods: A prospective phase II study has opened in 11 centers in Canada. DSM are done as described above. Pts with minimal toxicity after 28d are escalated to 62.5 mg and then 75 mg on a 14d /7d schedule. We expect to dose escalate 25% of pts and maintain another 40% of pts on a 50 mg dose that would otherwise have been dose reduced. The primary objective is the PFS associated with this strategy. Secondary objectives include dose intensity, RR, OS, toxicity, and quality of life. Samples for Sunitinib pharmacokinetics are obtained during the first course and again when the ideal sunitinib schedule has been established. Samples for biomarker and DNA correlative studies are collected. Based on the standard arm of the EFFECT trial (identical eligibility criteria), we assume a median PFS of 8.5 months in pts Rx using standard dosing. We expect pts treated with the indiv dosing will have a median PFS of 14 months. With alpha=0.05, a two-sided, single-arm non-parametric survival test would have over 90% power to detect this difference with a total of 110 pts on study. Study enrollment began in July 2012 with 25 pts currently on study. Clinical trial information: NCT01499121.