tbuckley/cabot-search huggingface dataset:
Intracellular intermolecular relationships of LKB1 in breast cancer.
Authors: Binafsha Manzoor Syed, Andrew R. Green, Ian O. Ellis, Kwok-Leung Cheung
Journal: Journal of Clinical Oncology (2014)

554 Background: The role of liver kinase B1 (LKB1), a serine/threonine kinase, has been described in the development of Peutz Jagher’s syndrome, where a large proportion (45%) of patients have been reported to develop breast cancer in their life time. Cell line studies have also shown a link of LKB1 with the action of oestrogen, metformin and diabetes. This study aimed to analyse the intracellular molecular relationships of LKB1 in older women with early operable primary breast cancer. Methods: Between 1973-2010, a consecutive series of 1,758 older (≥70 years) women with T0-2 N0-1M0 breast carcinoma were managed in a dedicated facility. Of these 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray construction. LKB1 was assessed by indirect immunohistochemistry using Ley37D/G6-ab15095/Abcam (primary antibody) and Envision method (secondary antibody). Tumours having 30% of cells with cytoplasmic expression were considered positive. Results: Positive LKB1 was seen in 318 (78.1%) patients. Such expression was significantly associated with high tumour grade (p=0.01), positive expression of HER2 (p=0.003), Ki67 (p=0.01), VEGF (p=0.002), HER4 (p=0.001), BRCA2 (p=0.01), MDM2 (p<0.001) and negative expression of CD44 (p=0.03). However there was no significant correlation with tumour size, axillary lymph node status, ER, PgR, p53, cytokeratins 5, 5/6, 14, 17, 18 and 19, bcl2, Muc1, EGFR, HER3, MDM4, E-cadherin, and BRCA1. Conclusions: LKB1 showed strong correlations with most biomarkers known to be associated with poor prognosis. Given the evidence from cell line studies mentioned, further studies are required to explore its relationship with clinical outcome and its role as a potential therapeutic target.
Optimal treatment strategy in KRAS wild type (wt) metastatic colorectal cancer (mCRC): Cetuximab plus FOLFIRI followed by FOLFOX4 with or without cetuximab-The <i>Capri</i> trial from the Gruppo Oncologico Dell’Italia Meridionale (GOIM).
Authors: Fortunato Ciardiello, Evaristo Maiello, Salvatore Pisconti, Francesco Giuliani, Carlo Barone, Mimma Rizzo, Roberto Bordonaro, Vincenzo Montesarchio, Saverio Cinieri, Erika Martinelli, Teresa Troiani, Sabina Delcuratolo, Gianni Simone, Nicola Normanno, Antonio Febbraro, Giuseppe Tonini, Giuseppe Colucci
Journal: Journal of Clinical Oncology (2013)

e14565 Background: Cetuximab in combination with standard doublet chemotherapy is an effective treatment in KRAS wt mCRC patients (pts). The present study investigated a treatment strategy of cetuximab in combination with FOLFOX4 as a second line therapy for KRAS wt mCRC pts treated in first line with cetuximab plus FOLFIRI. Methods: KRAS wt m CRC pts were treated in first line with cetuximab plus FOLFIRI and at progression were randomized (1:1) to receive FOLFOX alone (Arm A) or in combination with cetuximab (Arm B). Primary endpoint for each treatment line was progression-free survival (PFS), with secondary endpoints overall survival (OS), response rate (RR), disease control rate and safety. 221 events would be required to statistically differentiate PFS between the two arms with 80% power for the second line treatment. Here we report the results of first line cetuximab plus FOLFIRI treatment. Results: From July 2009, 344 pts were enrolled: 58% males, median age 63 years (range, 20-81 years), ECOG performance status, 0 (85%); 1 (15%); synchronous metastasis (75%). For the 319 evaluable patients, median PFS was 10 months; overall response rate (ORR) was 55% with 47% partial responses (PR), 8% complete responses (CR) and 35% stable disease (SD) for a disease control rate (DCR) of 90%. The most common grade 3/4 adverse events were: skin reactions (15%), diarrhea (9%) and neutropenia (6%). As of January 31 2013, 118 pts have progressed and have been enrolled in second line treatment (58 Arm A; 60 Arm B). Conclusions: The results of first line treatment with cetuximab plus FOLFIRI confirm in a multicenter trial in prospectively selected KRAS wt mCRC pts the efficacy and tolerability of this combination. The randomized second line part of the study is currently ongoing. Multiple gene next generation sequencing to characterize a 24 genes mutation profile is currently ongoing. Clinical trial information: 2009-014041-81.
Incidence, Clinical Features and Outcome of Patients with Differentiation Syndrome in Acute Promyelocytic Leukemia Treated with All-Trans Retinoic Acid (ATRA) Alone Versus ATRA Plus Idarubicin Versus ATRA Plus Arsenic Trioxide.
Authors: Sameer A Parikh, Hagop Kantarjian, Farhad Ravandi, Gautam Borthakur, Stefan Faderl, Amit Verma, Alessandra Ferrajoli, Zeev Estrov, Sherry Pierce, Jorge Cortes
Journal: Blood (2009)
Evaluation of genetic heterogeneity in paired lymph node metastases from melanoma patients using next-generation sequencing (NGS) approaches.
Authors: Giuseppe Palmieri, Antonio Cossu, Corrado Caraco, Paolo Antonio Ascierto, Nicola Mozzillo, Gerardo Botti, Amelia Lissia, Sergio Canzanella, MariaCristina Sini, Antonella Manca, Maria Colombino, Milena Casula
Journal: Journal of Clinical Oncology (2015)

9048 Background: In our previous experience (JCO 2012;30:2522-9), we demonstrated a high consistency of BRAF and NRAS mutations between primary tumors and lymph node metastases in melanoma patients. A subset of paired samples of multiple asynchronous lymph node metastases from that series was here screened mainly using NGS technologies in order to better elucidate the existence of a real genetic homogeneity during clonal expansion to lymph node sites. Methods: Genomic DNA was isolated from frozen tissues of paired asynchronous lymph nodes, ascertained for presence of melanoma metastases (at least 80% of metastatic cells), using standard methods. Specimens from 12 patients were analyzed for mutations in 50 most common cancer genes with the Ion Torrent AmpliSeq Cancer Panel HotSpot.V2 (CHPv2) on the Ion PGM sequencer. All variants detected by NGS were confirmed through PCR-based Sanger sequencing. Paraffin-embedded tumor tissues from the same series were evaluated by fluorescence in situ hybridization (FISH) assays, using probes specific for CyclinD1/EGFR genes or 9p21 locus and correspondent control centromeres. Results: Overall, only one (8%) of the 12 analyzed patients presented discrepancies in mutation patterns between the two distinct lymph nodal metastases developed in different times. In particular, the differences were represented by the BRAF-V600E and the CDKN2A-R80X mutations, suggesting that changes, when occur (though in a limited fraction of cases), they affect the main genes controlling cell proliferation and survival involved in melanomagenesis. No discrepancy was observed by FISH analysis into the same series. Considering the total number of analyzed samples, we detected the following mutations: BRAF-V600E (54% of cases), KDR-Q472H (50%), TP53-P72R (42%), cKIT-M541L (25%), NRAS-Q61R/K (25%). Conclusions: Our findings indicated a very low genetic heterogeneity during lymph node dissemination in melanoma patients, confirming the previously published data. Mutations in BRAF, NRAS, and cKIT genes were further confirmed to play a predominant role in melanoma pathogenesis.
Sentinel lymph node biopsy (SLNB) in melanoma and a simple prognostic score in a prospective cohort with long term follow-up
Authors: F. Nasroulah, A. Gonzalez, J. Kaplan, C. Tajer, J. M. O'connor, M. R. Chacon, M. V. Costanzo, J. P. Sade, M. M. Varela, R. D. Chacon
Journal: Journal of Clinical Oncology (2006)

8058 Background: Outcome of early stage melanoma is related to pathological and clinical findings like SLNB status, but a systematic approach to risk stratification is lacking. Objectives: To assess outcome, and clinico-pathological criteria associated to recurrence and death of patients (pts) who underwent SLNB Methods: From 11/1994 to 5/2005, 286 clinical stages I/II melanoma pts underwent SLNB in our Institution. Median follow up was 38 months. Prognostic factors were analysed with Logranktest and proportional hazard regression. Survival curves with Kaplan-Meier method. A score was derived from coefficients of multivariate analysis and evaluated with ROC curves on 259 pts with complete data. Results: Median age: 48yr; male sex: 54%; median Breslow (Br): 1.8mm. SLNB +: 46 pts (16.1%). Ulcerated: 31%. 5-yr overall survival was 56% in SLNB+ vs 84% in SLNB-, p=0.0002. Five-yr relapse free survival was 52% in SLNB+ vs 73% in SLNB-, p=0.0017. SLNB status, Br, Clark level, Age&gt;50yr, male sex, and ulceration were related to death by univariate analysis, but in multivariate analysis, only SLNB status (HR 2.36), Br (HR 1.66 for each T level of TNM staging) and ulceration (HR 2.35) remained. The score derived from the model was: 5 points (p) for SLNB +; 4p for ulceration; and 0p for Br&lt;1mm, 2p for Br 1–2mm, 4p for Br 2–4mm, and 6p for Br&gt;4mm. Conclusions: SLNB status, Br, and ulceration were, in concordance with literature, statistically significant prognostic factors. This allowed us to build a simple score with good correlation with prognosis (c index: 0.79). This score could be a useful tool for clinical practice and for future clinical trials, but validation in different populations is required. [Table: see text] No significant financial relationships to disclose.
An evaluation of the methodologic quality of clinical practice guidelines and consensus statements in oncology.
Authors: Carmel Maree Jacobs, Ian D Graham, Julie Makarski, Michael Chasse, Dean Fergusson, Mark J. Clemons
Journal: Journal of Clinical Oncology (2014)

e17629 Background: Evidence-based consensus statements (CS) and clinical practice guidelines (PG) are widely available and used to enhance patient care. Despite subtle differences in their definition and purpose CS and PG are often used interchangeably. To assist both authors and journals, appraisal tools such as AGREE II (Appraisal of Guidelines for Research and Evaluation II) have been developed to standardise the formulation of guidance documents. We explored the methodological quality of CS and PG published in 3 commonly read cancer-specific journals from North America and Europe. Methods: Three cancer-specific journals were searched for CS and PG published between January 2005 and August 2013. Each publication was appraised using AGREE II (using the domains; rigour of development and editorial independence) by two independent reviewers. We also evaluated CS and PG using standards from the Institute of Medicine and author guidelines, if available, from each journal. Results: 35 CS and 69 PG were published during the study period. Preliminary results from the first journal analysed show overall CS consistently scored lower than PG with limited AGREE II scores of 40.8% (SD 21.2%) for CS compared to 77.6% (SD 21.8%), for PG (p<0.05) Discrepancy scores for the two reviewers were low. A trend for CS to endorse products marketed by the statement funding source was also seen. Conclusions: Guidance documents such as CS and PG are an essential part of oncology care. Such statements should be subjected to a rigorous development process. It is evident the quality of CS was consistently lower than that of PG. Potential sources of this reduced quality will be explored. Given their lower quality the widespread use of CS should be challenged. Wider use of tools such as AGREE II by CS developers and journal peer reviewers would enable more consistent and evidence-based guidelines to be developed and reported.
Successful removal of an impacted stone in the common bile duct by electric lithotripsy using a needle-knife and a forward-viewing endoscope
Authors: Kinya Fujita, Ko Hasegawa, Takayuki Akamatsu, Takaomi Kasuga, Kazuaki Miyake, Ikuzo Fujii, Sumiharu Morita
Journal: Endoscopy (2017)

Although stones in the common bile duct (CBD) can be endoscopically removed [1] [2], stone impaction in the CBD occasionally occurs as a severe complication [3] [4]. We encountered a case of stone impaction in the CBD after endoscopic papillary balloon dilation (EPBD), which could be successfully treated by electrically cutting the stone using a needle-knife.
The transition from treatment to follow-up care: A critical time for patient navigation.
Authors: Sam Gaster, Rita Sanem, Diane Jones-Larson, Jordan Fiegen, Jamie Arens
Journal: Journal of Clinical Oncology (2017)

83 Background: There are many points of transition in cancer care, and each presents a unique set of challenges for patients and providers (Nekhlyudov, Levit, Hurria, &amp; Ganz, 2014). This includes the transition from treatment to follow-up care, or the transition to survivorship. For patients, challenges include the need for continued support, education, and communication with the cancer care team. For providers, challenges include the management of late- and long-term effects, modification of health behaviors, and coordination with other providers (IOM, 2005). These challenges can be overcome with patient navigation services. However, survivors’ access to these services is not universal. This evaluation describes the implementation and assessment of these services at six regional cancer centers in the Midwest. Methods: Key stakeholders designed a protocol for survivors to receive patient navigation after their transition to follow-up care. These navigation services are provided by nurse and social work navigators, and involve placing outbound calls to survivors. These contacts occur approximately two weeks after survivors receive a survivorship care plan (SCP) and a needs assessment. Results: From August through September 2016, 33 (91.67%) survivors were contacted by patient navigators. Three survivors could not be reached. Twenty-one percent (n = 7) of survivors contacted had not previously received navigation services. However, all survivors contacted received navigation services that would not otherwise been provided. Contacted survivors expressed high satisfaction with the services, and the most common needs addressed were anxiety and fatigue. Conclusions: Results support the value of patient navigation services for cancer survivors. This evaluation describes the successful implementation of a protocol for the continued navigation of survivors after their transition to follow-up care. Results encourage further development and evaluation of this protocol, including its impact on symptom management, health promotion, and care coordination via referrals and the provision of education and resources.
New WHO classification for pancreatic endocrine tumors: Is time to leave the previous one?
Authors: Claudio Ricci, Davide Campana, Marina Macchini, Silvia Vecchiarelli, Giovanni Taffurelli, Sokol Sina, Donatella Santini, Mariacristina Di Marco, Paola Tomassetti, Guido Biasco, Riccardo Casadei, Francesco Minni
Journal: Journal of Clinical Oncology (2012)

e14647 Background: In 2010 WHO released a new classification (NWHO) system for endocrine pancreatic tumours (NETs). The aims of this study was to compare the NWHO and previous one (OWHO) in patients affected by NETs. Methods: From January 1980 to December 2010, 89 consecutives patients underwent surgical intervention for PNETs Data regarding sex, age, presence of symptoms, hormonal status, presence of MEN1, surgical procedure, R status, TNM stage, older and new WHO classification and disease specific survival (DSS) were prospectively collected. Multivariate analysis, including OWHO and NWHO, was carried out to evaluate the independent factors related to DSS. A sensitivity analysis was performed to include patients in which NWHO was impossible to be calculated. Results: Mean age of patients was 54.7 ± 14.2 years. There were 46 (51.7%) female and 43 (48.3%) male. Symptoms were present in 68 (76.4%) patients. Fifty-two (58.4%) patients had non-functioning NETs. Left pancreatectomy was performed in 48 (53.9%) cases, atypical resection in 22 (24.7%), pancreaticoduodenectomy in 12 (13.5%), total pancreatectomy in 2 (2.2%) and palliative surgery in 5 (5.6%). R0/1 resection was carried out in 79(88.7%) cases. According TNM stage there were: I, 27 (30.3%); II 29 (32.6%); III, 22 (24.7%); IV, 11 (12.4%). According OWHO 46 (51.7%) patients had a well differentiated tumours (WDT), 32 (36%) well differentiated carcinoma (WDCa), 11(12.4%) poorly differentiated carcinoma (PDCa). The NWHO was available only in 49 (55.1 %) patients: 20 (22.5%) NET G1, 25 (28.1%) NET G2, 4 (4.5%) neuroendocrine carcinomas (NEC) G3. At multivariate analysis OWHO and R2 status were the only independent factors related to DSS (RR=6.7, p&lt;0.001 and RR 2.0, p=0.018 respectively). OWHO stratifies DSS better than NWHO: RR 0.12 (C.I. 95% 0.01-0.99; p=0.049) and RR 0.16 (C.I 95% 0.16-0.05; p=0.002) comparing WDT vs WDCa and WDCa vs PDCa, respectively. The sensitivity analysis confirmed in two model the superiority of OWHO while in others two we did not find any difference. Conclusions: In our experience OWHO still remains the best prognostic factor to predict DSS in patients with NETs .
A predictive model to identify patients at risk of local recurrence following glansectomy for penile squamous cell cancer (SCC).
Authors: Maarten Albersen, Arie Parnham, Alex Freeman, Raj Nigam, Peter Malone, Asif Muneer
Journal: Journal of Clinical Oncology (2017)

427 Background: Penile preserving surgery for penile cancer is associated with a higher risk of local recurrence (LR). This study developed a predictive model for LR following glansectomy and split skin graft reconstruction . Methods: Retrospective review performed of 177 patients undergoing glansectomy over a 10 year period. The clinicopathological features, LR patterns and cancer-specific survival (CSS) were recorded. Univariate and multivariate logistic regression was used to identify prognostic indicators for LR. The hazard ratio (HR) for LR was estimated using a KM analysis and based on these data we designed a postoperative model for the prediction of LR. Results: The median follow-up period following surgery was 41.4 (1.9-155) months. In total, 9.3 % of the patients developed a LR. Univariate, but not multivariate logistic regression identified perineural invasion (PNI), carcinoma in situ and high grade disease, but not basaloid variant, T stage, lymphovascular invasion and positive resection margins on the specimen to be predictors of LR. A risk model was designed using PNI, CIS and high grade disease in the resected specimen. KM analysis and log rank test revealed no significant differences in LR-free survival between patients with 0 vs 1 or 2 vs 3 risk factors whereas the chance of having local recurrence with 2 risk factors was significantly higher (HR = 5,75; 95% CI 1,43 to 23,15) than with 1 risk factor. A risk stratification model based on a cut-off score of &gt; 1 out of 3 risk factors discriminated well between patients with a high vs low chance of recurrence in a Kaplan-Meier analysis (HR 9.18, 95% CI 3.29 to 25.65 P &lt; 0.001). Indeed, ROC-curve analysis showed an optimal cut-off point of &gt; 1 risk factors with an AUC of 0.77 (P &lt; 0.001, specificity 63%, specificity of 85%) for prediction of LR. Conclusions: Although,LR after glansectomy does not affect the CSS, patients at risk of local recurrence can be identified when &gt; 1 of the factors PNI, CIS and high grade are found on histopathological analysis of the glans. These findings can define the frequency of follow-up and -if validated on pre-op biopsy- potentially be helpful in planning the margins of surgical resection in patients with penile SCC.
Association of head and neck cancer (HNSCC) subgroups defined by HPV RNA status, gene expression patterns, and <i>TP53 </i>mutations with lymph node metastasis and survival.
Authors: Andreas Dietz, Gunnar Wichmann, Marciej Rosolowski, Knut Krohn, Markus Kreuz, Andreas Boehm, Dirk Halama, Dana Holzinger, Michael Pawlita, Jochen Hess, Christoph Engel, Dirk Hasenclever, Markus Scholz, Peter Ahnert, Holger Kirsten, Alexander Hemprich, Christian Wittekind, Olf Herbarth, Markus Loeffler
Journal: Journal of Clinical Oncology (2015)

6046 Background: Classification of HNSCC based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient stratification. Methods: We compared tumors differing in HPV16 DNA and RNA (E6*I) status from consecutively recruited HNSCC patients by gene expression profiling (n = 270, Illumina HT12) and targeted sequencing (n = 226; 50 genes, Ion Torrent). Gene expression was analyzed unsupervised using consensus clustering. Results: HPV16 DNA+RNA+ tumors are molecularly distinct from HPV-negative (HPV DNA-) HNSCC, have elevated expression of cell cycle genes and carry rarely TP53 mutations (3.6%, 1/28). HNSCC without transcriptionally active HPV16 (DNA+RNA-) are similar to HPV DNA- tumors in gene expression and TP53 mutation frequency (47%, 8/17, and 43%, 72/167). We identify four gene expression clusters significantly differing in overall survival (OS; P = 0.04, adjusting for UICC stage, age, tumor site, treatment, pack-years smoked, alcohol use, HPV16 status). One cluster with high expression of immune response genes (IR) contains most (77%, 27/35) HPV16 DNA+RNA+ HNSCC. The IR cluster and disruptive TP53 mutations (TP53mut) are associated with lymph node metastasis (OR = 5.7; CI95% 2.2-18.0; P < 0.001, and OR = 2.6; CI95% 1.2-6.0; P = 0.01) independent of HPV16 status and tumor site. This validates the associations identified by Walter et al. (2013). Consistent with earlier studies, TP53mut has unfavorable prognosis (OS: HR = 2.0; CI95% 1.1-3.6; P = 0.03; PFS: HR = 1.9; CI95% 1.2-3.2; P = 0.01), adjusting for the UICC stage, age, tumor site, treatment, pack-years smoked, alcohol use, HPV16 DNA RNA status. Conclusions: Elucidation of HPV16 E6*I and TP53mut status are required for patient stratification. The IR gene expression cluster and TP53mut in HNSCC are associated with lymph node metastasis.
Pathologic validation of ablation therapy for gastric epithelial neoplasia: comparison of argon plasma coagulations vs. coagulation forceps.
Authors: Byung-Wook Kim
Journal: Journal of Clinical Oncology (2017)

82 Background: Ablation therapy has been introduced as an alternative in the management of gastric epithelial neoplasia. However, most of previous studies were retrospective observational studies and has not been validated pathologically. The aim of this study was to validate the effect of ablation therapy for gastric epithelial neoplasia pathologically. Methods: After ablation therapy either by argon plasma coagulations (APC) or by coagulation forceps for gastric epithelial neoplasia, immediate endoscopic resection for the lesions was performed. Consequent histologic mappings for the lesions were followed for the residual tumors. Factors which can affect the residual tumors were analyzed. Results: Twenty nine patients among 33 patients who underwent APC (87.9%) and 21 patients among 26 patients who underwent coagulation forceps (80.8%) showed residual tumors. Factors such as type of coagulation therapy, size of the lesion, type of the lesion (elevated vs. flat) and coagulation time/cm 2 of the lesion were not associated with complete removal of the lesions. Conclusions: Ablation therapy is inadequate for complete removal of gastric epithelial neoplasia and this therapy cannot replace endoscopic resection. Clinical trial information: KCT0001587.