tbuckley/cabot-search huggingface dataset:
A phase II study of gefitinib in combination with S-1 plus carboplatin as first-line triplet chemotherapy for patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations.
Authors: Akihiro Tamiya, Motohiro Tamiya, Takeshi Nakatani, Takayuki Shiroyama, Kanako Kitai, Taisuke Tsuji, Naoko Morishita, Naoki Omachi, Kazuhiro Asami, Norio Okamoto, Hidekazu Suzuki, Kyoichi Okishio, Tomoya Kawaguchi, Tomonori Hirashima, Shinji Atagi
Journal: Journal of Clinical Oncology (2014)

e19095 Background: Gefitinib (GEF), shows dramatic clinical activity against advanced non small cell lung cancer (NSCLC) in patients harboring epidermal growth factor receptor (EGFR) mutations. As there are currently no evidence based studies to support the use of GEF in combination with platinum doublet therapy for patients with NSCLC, we designed a phase II trial to examine the clinical benefits and safety of first-line GEF, carboplatin (Cb), and S-1 triplet chemotherapy in patients with advanced NSCLC harboring EGFR mutations. Methods: This trial was designed as a multicenter, single arm, phase II study of Cb, S-1, and GEF for advanced NSCLC harboring EGFR mutations. Patients received 4 courses of Cb (area under the curve = 5) on day 1, 80 mg/m2 of S-1 on days 1-14, and 250 mg of GEF every day in 4 week cycles, followed by 80 mg/m2 of S-1 on days 1–14 and 250 mg of GEF every day in 4 week cycles until disease progression or unacceptable toxicity was observed. The primary endpoint was the 1-year progression free survival (PFS) rate, and secondary endpoints were response rate (RR), PFS, overall survival (OS), and safety. Results: 35 patients were enrolled between May 2011 and July 2013. The median observation time was 15.1 months. The RR was 85.7%, and the disease control rate was 97.1%. The 1-year PFS rate was 69.4%, and the median PFS was 17.6 months (95% confidence interval, 15.2–20.1 months). The median OS was not achieveded. Major adverse events grade ≥3 included leucopenia (in 8.7% of patients), neutropenia (17.1%), anemia (5.7%), and thrombocytopenia (14.3%), and major non-hematological adverse events ≥grade 3 included febrile neutropenia (2.9%), increased levels of aminotransferase (20.0%), and diarrhea (14.3%). Toxicities characteristic of GEF exposure included diarrhea (in 77.1% of patients), dermatitis acneiform (80.0%), and stomatitis (54.3%). No patient was diagnosed with interstitial lung disease. Conclusions: First-line triplet chemotherapy of S-1, Cb, and GEF was effective and well tolerated in chemotherapy-naïve patients with advanced NSCLC harboring EGFR mutations.
Gaps in supportive and survivorship care for lung cancer patients.
Authors: Tara Perloff, Jennifer C. King, Maureen Rigney
Journal: Journal of Clinical Oncology (2017)

32 Background: Clinical guidelines increasingly recommend an expansion of multidisciplinary care for oncology patients to include supportive and survivorship care. Despite recommendations, lung cancer patients may not access these services due to implementation challenges among health care delivery systems. Our study goal was to assess treatment and care planning from the perspectives of lung cancer patients and caregivers. Methods: A Community Needs Assessment survey was electronically distributed to lung cancer patients and caregivers. 820 people responded, including 471 patients and 349 caregivers. The overall completion rate was 72.6%. The survey assessed the patient’s care team, values-based discussions in care planning, discussions regarding palliative care, and survivorship care planning. Demographic information was collected to determine if patterns of care correlated with geographical or socioeconomic factors. Results: Less than 50% of patients reported having a conversation about their values and care goals with their treatment team before determining their treatment plan. Less than 30% of patients reported a mental health professional, social worker, palliative care specialist, or nurse navigator as part of their care team. Although research shows a survival benefit to lung cancer patients receiving palliative care, only 26.9% of active patients had discussed palliative care and 20.13% reported receiving it. For caregiver reported data, the patients receiving care had more advanced cancer and had often not survived. Of those who had completed treatment and survived more than 5 years beyond diagnosis, only 22% of patients and 15% of caregivers reported having a survivorship care plan. Conclusions: The majority of lung cancer patients and caregivers reported having not received palliative care, survivorship care plans, psychosocial support, or values-based discussions with their oncologist. Respondents were technology enabled and generally health literate indicating that these problems could be more widespread in rural, lower socioeconomic areas where lung cancer is common. Addressing these problems in health care delivery could positively impact the survivorship of lung cancer patients and their families.
Digitalized multiparametric analyses of tumor stroma for identification of low perivascular PDGFBR expression and low vessel density as independent prognosis markers for stage IV CRC.
Authors: Artur Mezheyeuski, Maja Bradic Lindh, Bengt Glimelius, Per Pfeiffer, Elin Kure, Tone Ikdahl, Eva Skovlund, Halfdan Sorbye, Kjell Magne Tveit, Kristian Pietras, Helgi Birgisson, Jan Mulder, Tormod Kyrre Guren, Anna Portyanko, Arne Ostman
Journal: Journal of Clinical Oncology (2014)

e14525 Background: Tumor progression and metastasis are regulated by the tumor stroma (TS), suggesting a largely unexplored prognostic significance of its features. The aim of this study was to perform a multi-parametric analysis of colorectal cancer (CRC) stroma to explore digitally quantified TS characteristics Methods: A tissue microarray with 247 primary stage IV CRC tumors from the phase III NORDIC-VII study was used. Tumors samples were subjected to four double-stainings (CD34 and either ASMA, PDGFbR, Desmin or Ki67). Digital images were collected and subjected to image analyses yielding values for 18 different TS characteristics Results: For each case, values were obtained from 18 different TS metrics, related to marker-defined subsets of fibroblasts and pericytes perivascular cells (PC), and to vascular characteristics such as vessel size, total and size-categorized vessel density (VD) and endothelial cell proliferation We identified strong positive correlations between PDGFbR expression in PC and in fibroblast-rich TS compatible with a common cell-of-origin of these cells. PC coverage was not associated with vessel size implying independent control of these aspects of angiogenesis. Desmin status in PC was independent of ASMA- and PDGFbR-status suggesting that desmin marks a distinct set of PC. Concerning prognostic relevance, the two strongest associations were observed for low PC PDGFbR expression (median OS 19.7 mo for low PC PDGFbR (N=81) vs. 28.8 mo for high PV PDGFbR (N=81); HR=1.8; 95% CI 1.2-2.7; log-rank p=0.008) and low total VD (median OS 18.3 mo for low VD (N=123) vs. 27.6 mo for high VD (N=124); HR=1.7; 95% CI 1.2-2.3; log-rank p=0.001). Both markers remained prognostically significant in multivariate analysis including alkaline phosphatase level, WHO performance and BRAF mutation status: HR=1.8; 95%CI 1.1-2.8; p=0.011 and HR=1.8; 95% CI 1.2-2.8; p=0.009 for PC PDGFbR and total VD respectively. Conclusions: A generic procedure for multi-parametricdigitalized TS characterization have been generated and used to uncover independent prognostic significance of primary tumor VD and PC PDGFbR expression in stage IV CRC
FALSOS NEGATIVOS DEL CRIBADO DE CÁNCER COLORRECTAL MEDIANTE TEST DE SANGRE OCULTA EN HECES Y COLONOSCOPIA COMO PRUEBA DIAGNÓSTICA
Authors: G Ibáñez-Sanz, M Garcia, F Rodríguez-Moranta, J Gómez-Matas, G Binefa, I Padrol, L Benito, N Milà, JB Gornals, V Moreno
Journal: Endoscopy (2015)

Introducción: Es importante conocer los factores relacionados con un test de sangre oculta en heces inmunológico (TSOHi) negativo, especialmente para reducir la proporción de lesiones diana no detectadas (adenoma de intermedio/alto riesgo (AIR/AAR) y cáncer colorrectal (CCR)).
Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary cancer after failure of gemcitabine plus cisplatin: Retrospective analysis of 321 patients.
Authors: Jihoon Kang, Bumjun Kim, Changhoon Yoo, Jaewon Hyung, Kyu-Pyo Kim, Baek-Yeol Ryoo, Heung-Moon Chang
Journal: Journal of Clinical Oncology (2017)

425 Background: In advanced biliary tract cancer (BTC), the role of 2 nd line chemotherapy after failure of 1 st line gemcitabine plus cisplatin (GEMCIS) has not been established. Fluoropyrimidine(FP)-based regimens are widely used as 2 nd line treatment in clinical practice. We retrospectively analyzed the efficacy of 2 nd line FP-based chemotherapy in patients(pts) with advanced BTC after failure of GEMCIS. Methods: Histologically confirmed advanced BTC pts who received 1st line GEMCIS at Asan Medical Center between December 2010 and June 2016 were identified. Among 748 pts treated with GEMCIS, 331 patients (44%) subsequently received 2nd line chemotherapy and FP-based regimens were used in 321 pts (97%). Results: The median age was 60 years (range, 27-82) and 57% of pts were male. Intrahepatic cholangiocarcinoma(IH-CCC) (44%) was the most common type, and followed by extrahepatic cholangiocarcinoma (32%). Most pts (n = 289, 89%) had metastatic/recurrent disease at the time of 1 st line treatment. FP alone and FP plus platinum combination were used in 255 pts (79%) and 66 pts (21%), respectively. In pts with measurable disease, response rate (RR) was 3% (8/301) and disease control rate was 47% (142/301). After a median follow-up of 27.6 months (0.9-70.4 months), the median progression free survival (PFS) and overall survival (OS) were 1.9 months (95% CI, 1.6-2.2) and 6.5 months (95% CI, 5.9-7.0). RR was significantly higher in pts with combination of FP and platinum compared to FP alone (8% vs 1%, p = 0.009). However, there were no statistically significant differences in terms of PFS (p = 0.43) or OS (p = 0.88) between two groups. In the multivariate analysis for OS, IH-CCC, initially metastatic disease and elevated CA 19-9 level at the time of 1 st line treatment, and time-to-progression at 1 st line GEMCIS &gt; 4 months were independent poor prognostic factors. Conclusions: In this analysis, FP-based regimen showed modest efficacy as 2 nd line chemotherapy for advanced BTC patients after failure of 1 st line GEMCIS. Combination of FP and platinum was not associated with improved survival outcomes compared to FP monotherapy, despite of higher RR.
Role of Plasminogen Activator Inhibitor Type 1 (PAI 1) its GenePolymorphism and Urokinase-type Plasminogen Activator (uPA) andUrokinase Plasminogen Activator Receptor (uPAR) in Tumor Tissuein Colorectal Carcinoma Patients
Authors: Jana Halámková, Igor Kiss, Zdeněk Pavlovský, Zbyněk Čech, Jiří Tomášek, Štěpán Tuček, A. Svobodník, L. Hanáková, Mojmír Moulis, Miroslav Penka
Journal: Annals of Oncology (2008)
Living with and beyond cancer: What can be achieved by multi-organization collaboration.
Authors: Nicola Cunningham, Susannah Jane Stanway, Theresa Wiseman, Claire Taylor, Jillian Louise Noble, Natalie Doyle
Journal: Journal of Clinical Oncology (2017)

59 Background: The London Cancer Alliance (LCA), created in 2011, is an integrated cancer system consisting of 14 NHS organisations serving a population of 5.7 million. The multi-professional Survivorship Pathway Group has 18 members including a service user. The purpose of the group is to provide expert clinical leadership for the development and implementation of the pathways to imbed the Recovery Package (Holistic needs assessment (HNA)/care plan, treatment summaries, health and well-being events, cancer care reviews), treatment and management of the consequences of cancer into standard practice of cancer care. Methods: Data is collected quarterly for each NHS organisations’- HNA and care plan, treatment summaries, health and well-being events against defined metrics. Data Collection is in its fourth year. To support the implementation, guidelines have been developed, support and information provided and educational fora run. Results: The number of HNAs completed within 31 days of diagnosis from 487 to 2646 (an increase of 543%) and for HNAs completed within 6 weeks of completing treatment from 185 to 905 (an increase of 489%) (RM Partners Overall 2016) since Q2 2013/14 until Q2 2015/16. The group have mapped service availability across the LCA and developed robust survivorship pathways for lymphedema, complementary services, sexual consequences, GI consequences, onco-fertility, allied health professional rehabilitation and health and wellbeing events. Guidelines have also been developed and published on survivorship, lymphoedema, health and well-being events, gastro-intestinal and sexual consequences, complementary therapies, developing patient information leaflets, gaining patient and carer feedback. Furthermore, over 15 fora have been run on diverse topics. Conclusions: Collaborative working across London organisations has proved to be feasible and productive. The impact of the group has been demonstrated through the significant uptake in implementation of the Recovery Package. Future directions include an improvement in collection of HCP agreed data sets, the embedding of treatment summary templates into Trust cancer data systems, and further role out of electronic HNA.
Adverse effects of ADT on cognitive function and dementia for men with prostate cancer: A meta-analysis and systematic review.
Authors: Maxine Sun, Alexander Cole, Nawar Hanna, Adam S. Kibel, Toni K. Choueiri, Paul L. Nguyen, Quoc-Dien Trinh
Journal: Journal of Clinical Oncology (2017)

150 Background: Nearly 50% of men diagnosed with prostate cancer may receive treatment with some form of androgen deprivation therapy (ADT). While some side effects of ADT are well acknowledged, the specific impact of ADT on cognitive function is uncertain. Our objective was to perform a systematic review and meta-analysis assessing the impact of ADT on overall cognitive decline, and the risks of Alzheimers, Parkinson’s disease. Methods: Relevant studies were identified through search of English language articles indexed in PubMed Medline, PsycINFO, Cochrane Library and Web of Knowledge/Science. First, we assessed rates of cognitive decline in five cohorts from three studies. Second, we assessed rates of Alzheimer’s or Parkinson disease using three large retrospective studies. A pooled-analysis was conducted using a meta-analysis. Weighted averages were reported as odds ratios (OR) with 95% confidence intervals (CI) using RevMan and a DerSimonian and Laird random-effects model. The heterogeneity test was measured using the Q-Mantel-Haenszel ( P&lt; 0.10 was considered of significant heterogeneity). Results: With respect to overall cognitive decline (defined as scoring 1.5 standard deviations [SD] in two or more objective cognitive tests), patients receiving ADT had higher odds of overall cognitive decline than patients with prostate cancer not treated with ADT or health controls (OR: 2.03, 95% CI: 1.42–2.90). Furthermore, men with a history of ADT for prostate cancer had higher odds of developing Alzheimer’s and Parkinson dementia compared to men with prostate cancer not treated with ADT (OR: 1.32, 95% CI: 1.27–1.37). Conclusions: Men receiving ADT for prostate cancer performed significantly worse on measures of overall cognitive function. Additionally, results from the three large observational trials included suggest men exposed to ADT for prostate cancer have higher rates of Parkinson/Alzheimer’s compared to men without ADT.
RETRACTION
Authors: David Hsu, Bala Balakumaran, Chaitanya Acharya, Vanja Vlahovic, Kelli Walters, Katherine Garman, Carey Anders, Richard Riedel, Johnathan Lancaster, David Harpole, Holly Dressman
Journal: Journal of Clinical Oncology (2010)

The authors wish to retract this article because they have been unable to reproduce the experiments demonstrating a capacity of a cisplatin response signature to validate in either a collection of ovarian cancer cell lines or ovarian tumor samples.Because these results are fundamental to the conclusions of the paper,
Usefulness of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy to predict prognosis of advanced biliary tract cancer.
Authors: Kyoung Min Cho, Hyunkyung Park, Do-Youn Oh, Tae Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2017)

416 Background: Systemic inflammation is known to promote carcinogenesis in biliary tract cancer (BTC). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicative of systemic inflammation. We evaluated the clinical significance of systemic inflammation measured by NLR and PLR in patients with advanced BTC. Additionally, we also co-analyzed the dynamics of NLR and PLR during chemotherapy. Methods: We reviewed 554 patients with advanced BTC receiving palliative chemotherapy. NLR and PLR were obtained before initiation of palliative chemotherapy. Changes in NLR, PLR were obtained by subtracting the initial value from the value obtained after progression of chemotherapy. Results: Higher systemic inflammation status also had relation with a primary tumor site ( p = 0.044) and higher levels of CEA ( p = 0.041). The ROC cut-off values of NLR and PLR for predicting overall survival (OS) were 3.8 and 121, respectively. Patients with a high NLR or PLR had worse OS independently in multivariate analysis (7.10 vs. 10.23 months, p &lt; 0.001; 8.43 vs. 11.87 months, p = 0.001, respectively). High NLR with increased NLR after chemotherapy is associated with worse OS and progression-free survival (PFS) ( p = 0.014, p= 0.020 respectively). Results are similar for PLR. Conclusions: Systemic inflammation represented by NLR and PLR, predicts the OS of patients with advanced BTC who are receiving palliative chemotherapy. In addition, considering NLR/PLR with a dynamic change of NLR/PLR during chemotherapy might help to predict a more accurate prognosis.
Phase I trial of AZD1775 (MK1775), a wee1 kinase inhibitor, in patients with refractory solid tumors.
Authors: Khanh Tu Do, Deborah Wilsker, Priya Balasubramanian, Jennifer Zlott, Woondong Jeong, Scott M Lawrence, Robert J. Kinders, Jerry Collins, Alice P. Chen, James H. Doroshow, Shivaani Kummar
Journal: Journal of Clinical Oncology (2014)

2503 Background: Wee1 tyrosine kinase phosphorylates and inactivates Cdk1, causing G2 cell cycle arrest in response to DNA damage. AZD1775 is a novel inhibitor of Wee1 kinase with single-agent anti-tumor activity in preclinical models. Objectives of this study were to establish the safety, toxicity, maximum tolerated dose (MTD) of single agent AZD1775; determine the pharmacokinetics (PK) of AZD1775; evaluate for target modulation in paired tumor biopsies. Methods: Eligible adult patients (pts) had refractory cancers that had progressed on standard therapy; ECOG PS 0-2; adequate organ function. Dose level (DL) 1 was 225 mg BID x 5 doses, q 21d cycles. Dose escalation: 225 mg (DL 2) or 300 mg (DL 3) BID x 5 doses for 2 wks, q21d cycles; 3 + 3 design. Blood sampling for PK and circulating tumor cells (CTCs) occurred on C1D1 and C1D3. Tumor biopsies at MTD were performed at baseline and C1D3 (2-5 hrs post-drug) and were evaluated for pTyr15-Cdk to assess target modulation. Results: 18 pts treated; median age 54; median # of prior therapies 4; cancer dx (#pts): sarcoma (8); NSCLC (2); head and neck (3); fallopian tube (1); cervical (1); granulosa cell tumor (1); breast (1); appendiceal cancer (1). One pt with BRCA mutated head and neck cancer had a confirmed PR. Common toxicities were myelosuppression and diarrhea. Two DLTs occurred at DL 3: 1 pt had Gr 4 myelosuppression, developed pneumonia, and died; a second pt had SVT. At the MTD of DL 2, average Cmax was 1650 nM on D3; total exposure on D3 was 2-3 fold higher than on D1. Reduction in phosphorylated Tyr15-Cdk levels was shown in 3 of 5 paired tumor biopsies; quantitation of γH2AX, a DNA damage marker, is ongoing in CTCs and tumor biopsies. Conclusions: This is the first single-agent trial of AZD1775 in pts with refractory solid tumors. MTD was established at 225mg BID x 5 doses/week, 2 of 3 wks, with evidence of antitumor activity in a pt with BRCA mutated head and neck cancer. Accrual is ongoing for BRCA+ pts. The accumulation of drug on the BID regimen is consistent with a t1/2 of ~ 24 hrs, which supports a QD schedule for future trials. Target modulation was demonstrated in paired tumor biopsies. CTCs were isolated from 2 pts with non-epithelial cancers. Analysis of tumor biopsies and CTCs for γH2AX is ongoing. Clinical trial information: NCT01748825.
Does higher number of lymph nodes (LNs) excised during radical prostatectomy (RP) improve biochemical relapse-free survival (bRFS) in patients with pT2-3a/pN0 prostate cancer?
Authors: Steven Neema Seyedin, Darrion L Mitchell, James Kyle Russo, Sarah L Mott, Jessica Parkhurst, Mark C Smith, John Michael Buatti, John Morgan Watkins
Journal: Journal of Clinical Oncology (2017)

61 Background: In published series of extended pelvic LN dissection (LND), an association between higher number of LNs resected and both higher rate of occult LN disease discovery and long-term bRFS (for pN0) was observed. Despite this, practice patterns of LND extent (and associated number of LNs examined) vary, with the majority being limited to local nodal sampling. It remains unclear whether the LN yield correlates with bRFS in this context. The present investigation examines whether the number of LNs examined at RP is associated with bRFS. Methods: Patients with clinically localized prostate cancer, initial PSA &lt; 30, and pT2-3a/N0 disease at RP were retrospectively identified for inclusion. Those who received pre-RP or adjuvant radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences. Results: From 2002 to 2010, 672 patients were eligible for this analysis. The median age was 61 yrs (range, 43-76). Most patients had cT1c (83%), Gleason Score (GS) 4-6 (63%), and were low risk by D’Amico classification (56%), with median PSA of 5.6 ng/dL (0.9-28.0). At RP, 213 (32%) patients had positive margins (M+). At a median follow-up of 82 months, 140 patients (21%) experienced PSA failure with estimated bRFS of 81%/76% at 5/8 years. Univariate analysis identified GS ³ 7 (biopsy or RP), intermediate/high risk, M+, higher percentage of biopsy cores involved, and performance of LND as adversely associated with bRFS (all p &lt; 0.01). Of 446 patients (66%) who had LN sampling , 396 had a specific number of LNs reported (median 5; range 1-24, with single outlier case [33] excluded for statistical analysis). A higher number of LNs excised was not associated with bRFS for the entire cohort (HR = 0.99, p = 0.60), or for any biopsy GS subgroup (GS4-6 HR = 0.92, GS7 HR = 1.00, GS8-10 HR = 0.11). Conclusions: In the context of limited LND, this study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2-3a/pN0 prostate cancer managed with RP alone, either in the entire population or with stratification by GS.
Results of Salvage Autologous Stem Cell Transplantation (ASCT) for Relapsed Multiple Myeloma (MM) in the Era of Novel Agents: Outcome of Patients (Pts) Receiving Prior Bortezomib (BTZ)-Based Therapy
Authors: Sara Farshchi Zarabi, Esther Masih-Khan, Christine Chen, Vishal Kukreti, Anca Prica, Rodger Tiedemann, Suzanne Trudel, Donna Reece
Journal: Blood (2016)