tbuckley/cabot-search huggingface dataset:
Pathologic complete response (pCR) to predict patients’ survival in luminal breast cancer.
Authors: Qian Wang-Lopez, Fabrice Kwiatkowski, Catherine Abrial, Marie-Ange Mouret-Reynier, Pascale Dubray-Longeras, Isabelle Van Praagh-Doreau, Nina Radosevic-Robin, Xavier Durando, Frederique Penault-Llorca, Philippe J. M. Chollet
Journal: Journal of Clinical Oncology (2013)

e11615 Background: Gene expression studies have demonstrated that breast cancer can be divided into three major subgroups : Luminal, Human Epidermal Growth Factor Receptor-2 (HER2) over-expression and Oestrogen negative (ER-). Luminal breast cancer is well known for its better prognosis compared with the other types. Conversely, response is less effective by pCR criteria after chemotherapy. This work aimed to evaluate if pCR could still be considered as a surrogate marker in luminal subgroup according to immunohistochemical classification : Hormonal receptor positive and HER2 negative (HR+HER2-). Methods: All 132 luminal early breast cancer patients treated by neo-adjuvant chemotherapy (NAC), in our institution from 2001 to 2007 were included in this study. NAC treatment comprised anthracycline alone, taxotere alone or sequential use of these two drugs. Survival curves have been established according to the Kaplan-Meier’s method. Comparison of curves were performed in using Log-rank test. The median of follow-up was 102 months (range 59 – 142 months) in October 2012. Results: Median age was 53.5 (range 34–78) years and median initial tumor size was 4cm (range 1-10). Objective response rate was 65% (86 patients), of which 8% (10 patients) had a complete response after 6 courses. One hundred and six (80%) underwent breast conservation surgery. Seven patients (5%) and ten patients achieved pCR (8%) according to Chevallier and Satatloff’s classification, respectively. Twenty patients did relapse and 18 patients died. At 10 years, Disease-free survival (DFS) and overall survival (OS) rate was 81% and 84%, respectively. All pCR patients, regardless of classification, did not relapse. However, the patients who achieved a pCR had not a significant difference in DFS and OS compared to the patients who did not. Conclusions: pCR was not a surrogate marker after a relatively short survey of 100 months for luminal breast cancers, who have generally late relapses. However, sixty five percent of patients had &gt;50% reduction in primary tumor and 80% of patients had a breast conservation. Further studies are needed to identify new markers able to predict patients’ survival.
Prognostic factor and outcome of 32 patients with classic and iatrogenic Kaposi sarcoma: A monoinstitutional experience.
Authors: Pasquale Rescigno, Giovannella Palmieri, Lucia Nappi, Carlo Buonerba, Piera Federico, Margaret Ottaviano, Elide Matano, Davide Bosso, Tania Policastro, Michela Izzo, Giuseppe Di Lorenzo
Journal: Journal of Clinical Oncology (2013)

e21500 Background: Classic Kaposi Sarcoma (CKS) is a rare and mild form of the disease that primarily affects men, older than 50 years in the endemic areas. Iatrogenic KS (IKS) is associated with the use of steroids, immunosuppressive agents in patients with autoimmune diseases, inflammatory disorders, or organ transplantation. We have conducted a retrospective analysis from January 2008 to December 2012 for CKS and IKS to evaluated outcomes and potential prognostic factors in this rare disease. Methods: Patients with histologically proven KS lesions of the skin and negative HIV-1/2 were enrolled. In some cases diagnosis was completed by immunohistochemical tests for HHV-8 staining. Eligible patients received different systemic chemotherapy for disease at stage IIb and in all variants of stage III and IV, according Mediterranean KS staging. Results: 32 cases of non-AIDS KS were identified in this study. Mean age at diagnosis of the group was 70 year-old. Approximate male/female ratio was 2:1. 78.2% of cases was classic KS. All patients received systemic chemotherapy containing one of this agent: alkaloid of vinca, taxane, pegylated lyposomial doxorubicin. Ten patients (31.5%) experienced a partial response, a complete response was achieved in 4 patients (12.4%) and stability in 16 cases (50%). Two patients (6.2%) developed multiple local recurrences. PFS was 11.7 months while OS resulted 28.5 months. At multivariate analysis nodular lesions were related to lower PFS compared to macular lesions (HR: 2,5817, 95% CI 1,2911 to 5,1624; p: 0,0049), and HHV8 status (positive vs. negative) had a statistically significant correlation with a worse response to treatment (HR: 5,0289 95% CI 1,6540 to 15,2901; p: 0,0046). Conclusions: Classic and iatrogenic KS patients appears less aggressive, mostly limited to the skin and well-responsive on local or systemic therapeutic strategies. Our data show as positivity to HHV8 and nodular lesions correlate with a worse response to treatment.
Molecular profiling of resected esophageal cancer and its correlation with clinical outcome.
Authors: Tomoya Yokota, Masakuni Serizawa, Ayumu Hosokawa, Kimihide Kusafuka, Keita Mori, Toshiro Sugiyama, Yasuhiro Tsubosa, Yasuhiro Koh
Journal: Journal of Clinical Oncology (2014)

4046 Background: The tumor related gene profiling in esophageal cancer remains unknown and requires further investigation in order to promote efficient and rapid development of molecular-target agents. The aim of this study was to evaluate the expression level and mutations of tumor related genes in resected esophageal cancer and to assess correlation of the profiling with clinical outcome. Methods: 135 consecutive patients with esophageal cancer who underwent esophagectomy at Shizuoka Cancer Center and Toyama University between October 2002 and November 2011 were analyzed. Protein expression of MET, EGFR, ALK and HGF was determined by Automated QUantification Analysis. Copy number of EGFR, PIK3CA, MET and FGFR1/2 was analyzed by real time PCR. The translocation of ALK gene and mutations of tumor related genes were evaluated by fluorescence in situ hybridisation and TruSeq Amplicon Cancer Panel, respectively. Prognostic factors associated with survival were identified by multivariate analyses using the Cox proportional hazards model. Results: Overall, heavy smoking was significantly associated with high HGF expression (p=0.03938), but was not an independent prognostic factor. After adjustment for clinical features by multivariate Cox regression analysis, high expression of ALK was associated with poor OS in patients without neoadjuvant therapy (HR 4.589, p=0.0102). The translocation of ALK gene was present only in 1 patient. High expression of MET was associated with poor OS in patients with neoadjuvant therapy (HR 5.68, p=0.043). Mutations in p53 and PIK3CA were present in 73% and 13%, respectively. The frequency of mutations in APC, BRAF, ERBB4, VHL, KRAS and EGFR was less than 10%. PIK3CA amplification was observed in 2%. Conclusions: High expression of ALK and MET may be prognostic factors for resected esophageal cancer. Esophageal cancers with high expression level of ALK and MET might be possible candidates for ALK and MET targeting therapies.
Elevated interleukin-6 levels correlation with anemia, symptom burden, and neurocognitive deficit in cancer patients receiving chemotherapy: Effects of darbepoetin-alfa administered once per cycle for prevention of anemia
Authors: S. Vadhan-Raj, C. Bueso-Ramos, J. Trent, S. Patel, X. Zhou, R. S. Benjamin, C. A. Meyers
Journal: Journal of Clinical Oncology (2007)

19505 Background: Chemo-naïve sarcoma pts experience severe anemia during chemotherapy (CT) with adriamycin and ifosfamide (AI) resulting in PRBC transfusions (Tx) in &gt;90% of pts. Anemia has a negative impact on quality of life (QOL) and neurocognitive (NC) functions (fx). Preclinical studies suggest that treatment with erythropoietic stimulating agent (ESA) may protect NC fx. The purpose of this study was to evaluate the effects of darbepoetin (Initial dose 500mcg) administered once per cycle on prevention of anemia, transfusions, symptom burden and NC fx. Methods: Pts underwent assessment for neuropsychological tests, symptoms (MDASI), and quality of life (QOL). To determine if NC deficits and Hb were correlated to cytokine levels, serum IL-1, IL-6, and TNF were measured at baseline, after 3 cycles and completion. Results: Baseline median hemoglobin (Hb) was 13.2 g/dL (n=49); however, significantly more NC deficits and symptoms were seen in pts as compared to normal. Interestingly, serum IL-6 levels were significantly elevated as compared to normal at baseline and during treatment (p&lt;0.001), and were negatively correlated with baseline Hb (p=0.003) and significantly associated with NC deficits, QOL and symptoms. Of 45 pts that received &gt; 1 cycle of CT, 38% avoided PRBC Tx. Pts with higher baseline Hb had less sadness and shortness of breath (p&lt;0.01). Pts with higher Hb nadir had lower tingling/numbness (p=0.006). Pts who avoided transfusions had less distress (p=0.032), less sadness (p=0.01), and better motor fx (p=0.005). Conclusions: These findings suggest that cancer pts can have NC deficits prior to CT. Prevention/early intervention with ESA may avoid transfusions, reduce symptom burden, and NC deficit. Significant correlation of anemia, symptoms, and NC deficit with elevated IL-6 levels suggest that anti-IL-6 treatment may improve response to ESA and NC functions. [Table: see text] No significant financial relationships to disclose.
Circulating tumor DNA (ctDNA) and correlations with clinical prognostic factors in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Daniel Khalaf, Matti Annala, Kevin Beja, Gillian Vandekerkhove, Muhammad Zulfiqar, Daygen L. Finch, Conrad D. Oja, Joanna Vergidis, Martin Gleave, Alexander William Wyatt, Kim N. Chi
Journal: Journal of Clinical Oncology (2017)

186 Background: Sequencing of ctDNA is a minimally invasive method to study somatic DNA alterations. Quantitation and characterization of ctDNA may correlate with tumor burden and poor risk clinical features, but this is unproven in mCRPC. Methods: We performed deep targeted sequencing of 73 mCRPC-related genes in plasma ctDNA from 136 treatment naïve mCRPC patients. Fraction of ctDNA was determined by quantifying somatic mutant allele frequency and the deviation from heterozygosity for germline single nucleotide polymorphisms at regions of somatic copy number alterations. Baseline clinical factors were correlated with ctDNA fraction and genomic aberrations. Results: ctDNA could be quantified in 86/136 (63%) patients. Increasing fraction correlated with elevated ALP (chi 2 , p &lt; 0.001), LDH (p &lt; 0.001) and presence of liver metastasis (p = 0.01). Patients with any one of these factors were more likely to have a ctDNA fraction ≥ 40% (67% vs 36% of patients with neither factor, p = 0.001) and less likely to have unquantifiable ctDNA (26% vs 49%, p = 0.006). A decreased ctDNA fraction was associated with metastases only to lymph nodes (p = 0.012). Among the most frequently aberrant genes were Androgen Receptor (AR), p53, RB1, and PTEN, present in 38%, 30%, 23% and 22% of patients, respectively. Aberrations were associated with poor prognosis factors, including: AR and p53 alterations, which both correlated with presence of liver metastasis (p = 0.020 and p = 0.004 respectively), elevated LDH (p = 0.001, p &lt; 0.001), and presence of ≥ 10 bone metastasis (p = 0.018, p = 0.017); PTEN deletion which correlated with elevated ALP (p &lt; 0.001), elevated LDH (p = 0.001), ≥ 10 bone metastasis (p = 0.009) and time to CPRC of &lt; 12 months (p = 0.021); and RB1 correlated with ≥ 10 bone metastasis (p = 0.009). Conclusions: We found an association between poor prognostic factors and increasing ctDNA fraction in patients with mCRPC. Genomic aberrations, particularly alteration in AR, p53 and PTEN, correlated with poor prognostic factors. These data show that clinical factors may help predict ctDNA yield in patients with mCRPC, and also provide insight into the role of deleterious genetic alterations.
The Greek participitation to IDEA (International Duration Evaluation of Adjuvant Chemotherapy) study of 3 versus 6 months of adjuvant chemotherapy in stage III colon cancer: Patients’ characteristics and safety analysis.
Authors: John Souglakos, Ioannis Boukovinas, Stylianos Kakolyris, Nikolaos Ziras, Nikolaos E. M. Androulakis, Alexandros Ardavanis, Nikolaos K. Kentepozidis, Michael Vaslamatzis, Athanasios Athanasiadis, Athina Christopoulou, Paris Makrantonakis, Aristidis Polyzos, Dimitrios Mavroudis, Anastasia Mala, Aggeliki Kalisperi, Spyros Xynogalos, Ioannis I. Varthalitis, Charalambos Kouroussis, Efthimios Prinarakis, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2017)

740 Background: The International Duration Evaluation of Adjuvant (IDEA) collaboration was established to prospectively analyze data from six randomized trials to assess whether a 3-month course of oxaliplatin/fluoropyrimidines (FU)-based adjuvant chemotherapy (CT) is non-inferior to the 6-month current standard treatment in stage III colon cancer (CC). The primary endpoint of IDEA was 3-year disease-free survival. The accrual goal for the Greek IDEA study was 1.000 patients. Methods: Greek IDEA randomized patients with stage III colon cancer between 3 months (arm A) and 6 months (arm B) of adjuvant CT with modified (m) FOLFOX6 or XELOX (depending on physician/patient choice). Toxicity was graded during treatment and follow-up using NCI-CTCAE v3.0. Results: From May 2009 to October 2015, 708 patients were randomized in Greek centers either to arm A (n = 354, 50%) or to arm B (n = 354, 50.%). 297 (41.9%) patients received mFOLFOX6 and 411 (58.%) XELOX. The median age was 67 years (20-75) and 579 (81.8%) of them had PS 0. The patients’ population was balanced for the major risk factor between the two arms: N1/N2 disease (68.1/31.9% vs. 68.9/31.1 for ARM A and B, respectively), obstruction (4.5% vs. 2.5 for ARM A and B, respectively) and perforation (5.1% vs. 6.2 for ARM A and B, respectively). Overall, 96.9% and 89.5% of patients completed 3 months (arm A) and 6 months (arm B) of CT, respectively. Median oxaliplatin dose was 505 mg/m 2 in arm A and 738 mg/m 2 in arm B. Toxicity profiles were comparable between the two arm and the two fluoropyrimidines backbones with a total incidence of Grade 3/4 adverse events 18.9/4.4% and 19.7/5.1% for mFOLFOX6 and XELOX, respectively. Grade 2/3-4 peripheral neuropathy during the study was similar between arm A (33.9/4%) and B (38.7/3.7%). Conclusions: Both mFOLFOX6 and XELOX were safe. More patients completed the scheduled treatment in the 3-arm schedule.
Modeling post-progression survival in patients with HER2-positive metastatic gastric cancer.
Authors: Dong Woo Chae, Joo Hoon Kim, Chan Kim, Hong Jae Chon, Choong-kun Lee, Hyo Song Kim, Minkyu Jung, Hyun Cheol Chung, Sun Young Rha, Kyung Soo Park
Journal: Journal of Clinical Oncology (2015)

e15020 Background: The aim of this study is to 1) model the temporal course of maximum tumor diameter (MTD) of HER2+ metastatic gastric cancer patients enrolled into 1stline chemotherapy trials, and 2) predict post-progression survival (PPS) using MTD model parameter estimates. Methods: Data were obtained from 46 HER2+ metastatic gastric cancer patients who received systemic treatment with trastuzumab containing regimen. Analyses proceeded under the assumption that the tumor can be represented by 3 regions, the necrotic core (net cell loss), the quiescent middle zone where neither growth nor death takes place, and the proliferative surface (net cell growth), as its size increases.At the first step, the time course of MTD was modeled using a mixed-effect model within NONMEM, and then PPS using a Cox proportional hazard model within R, based on uncorrelated parameters newly created from the principle component analysis of MTD model parameter estimates obtained at the first step. Results: A predictive model of PPS using variables related to tumor cell kinetics (MTD model) and patient age was successfully constructed. PPS is shorter the higher the baseline MTD/tumor growth rate, and lower the patient age. Patient weight was found to be inversely correlated to tumor death rate constant. MTD was best described by a 3-compartment model for net cell loss, quiescent and net cell growth compartments, with model parameters as follows: baseline tumor MTD (BASE), tumor growth rate constant (KG), tumor death rate constant (KD), and zone migration rate constant (KM). BASE was significantly affected by ECOG score and liver metastasis, and KG by histologic grade. Interestingly, KD was also affected by weight inversely. In the analysis of PPS, PC1 (first principal component) that mainly represents BASE and KG was found as a significant predictor (p = 0.0029), and age as a significant risk factor (p = 0.024). With each unit increase of PC1, PPS was reduced by 37%, and with each year increase of age, PPS was increased by 6%. Both MTD and PPS model predicted data well Conclusions: This work demonstrates the feasibility of applying a model-based approach to predict tumor growth and post-progression survival associated.
Bendamustine-Based (BeEAM) Conditioning before Autologous Stem Cell Transplantation: Result of a French Multicenter Study of 386 Patients from Lysa Centers
Authors: Sylvain Chantepie, Emmanuelle Tchernonog, Frederic Peyrade, Marie-Virginie Larcher, Momar Diouf, Luc Mathieu Fornecker, Roch Houot, Thomas Gastinne, Carole Soussain, Sandra Malak, Olivier Tournilhac, Caroline Delette, Ahmad Ibrahim, Anne-Claire Gac, Jean-Pierre Vilque, Mohamed Amine Bekadja, Rene-Olivier Casasnovas, Remy Gressin, Arnaud Jaccard, Benjamin Carpentier, Reda Garidi, Bachra Choufi, Stéphanie Guidez, Adrian Tempescul, Adrien Chauchet, Emmanuel Gyan, Ibrahim Yakoub-Agha, Krimo Bouabdallah, Eric Durot, Gandhi Damaj
Journal: Blood (2016)
Mind-body medicine epigenetic technique (MET), cognitive flexibility, and brain-derived neurotrophic factor (BDNF) gene expression.
Authors: Francisco Ventura Munoz
Journal: Journal of Clinical Oncology (2017)

172 Background: This is a pilot study update on the potential of MET to up-regulate BDNF gene expression with breast cancer patients assessed with high cognitive flexibility. MET is a technique developed to manage chronic stress and anxiety. BDNF gene expression is associated with learning and memory. Cognitively flexibility is defined as the ability to focus and sustain attention. It also implies vivid imagination and holistic thinking. Methods: The selection process for the study participants was nonrandom. The following was the eligibility criteria. 1. Inclusion Criteria: Breast Cancer, Stages II, III 2. Exclusion Criteria: Cognitively impaired, weak or ill. The study utilized two groups. Each group was assigned two research participants. Group One received one session of MET. Group Two received two sessions of MET. Each MET session was approximately 25-35 minutes in duration. Blood samples were taken at baseline and post-MET sessions to provide evidence in gene expression changes. For Group Two, the post-MET session blood draw was done 7 days after baseline. 1. Primary Endpoint: To determine whether MET can up-regulate BDNF gene expression. 2. Secondary Endpoint:To determine whether there is a correlation between up-regulated BDNF gene expression and cognitive flexibility. The blood samples were sent to genomics labs at the Children’s Hospital of Los Angeles and the University of Nevada Las Vegas for mRNA extraction and microarray analysis. The gene expression was measured by DNA microarray results using the “PrimeView gene chip” and “Partek Genomics Suite” statistical software. Results: One participant from Group 1 evidenced a biologically significant up-regulation of BDNF gene expression. This participant was assessed with high cognitive flexibility. One major limitation of these findings is the statistical insignificance of the results due to the small number of participants. Conclusions: This pilot study evidenced the up-regulation of BDNF gene expression potentially due to MET and provided evidence for the potential correlation of BDNF gene expression and cognitive flexibility. This study also provided a foundation for a larger study with more participants.
Tracking emerging <i>KRAS</i>, <i>BRAF</i> and <i>EGFR</i> mutations through ccfDNA in colorectal cancers treated with EGFR blockade.
Authors: Takeshi Yamada, Goro Takahashi, Takuma Iwai, Kouki Takeda, Michihiro Koizumi, Seiichi Shinji, Akihisa Matsuda, Yasuyuki Yokoyama, Hiroyasu Furuki, Keisuke Hara, Satoshi Matsumoto, Keiichiro Ohta, Uchida Eiji
Journal: Journal of Clinical Oncology (2017)

547 Background: Epidermal growth factor receptor (EGFR) blockade can achieve considerable tumor shrinkage in patients with metastatic colorectal cancer (CRC). However, most patients who benefit from EGFR blockade acquire resistance within a year through emerging KRAS, BRAF or EGFR ( S492R) mutations. We have shown that patients with KRAS or BRAF mutations in circulating cell-free DNA (ccfDNA) do not respond favorably to EGFR blockade. In this study, we aimed to detect acquired resistance to EGFR blockade early by using ccfDNA to track emerging KRAS, BRAF and S492R mutations during chemotherapy. Methods: We enrolled 24 patients with metastatic CRC and no KRAS mutations in their primary tumors who were to be treated with systemic chemotherapy that included EGFR blockade. We purified ccfDNA from 1 mL of serum from each patient before they started chemotherapy. We also extracted ccfDNA from these patients every 2–3 months until disease progression. We detected nine KRAS, BRAF (V600E) and S492R mutations using digital polymerase chain reaction. Results: We detected KRAS mutations in ccfDNA of three patients before chemotherapy (12.5%; 3/24). The response rate was 83% (20/24); the four non-responders comprised the three with KRAS mutations and the other with BRAF mutations in their ccfDNA before chemotherapy. All patients with no KRAS or BRAF mutations in their ccfDNA before chemotherapy responded to the chemotherapy (20/20). Of these 20 initially responsive patients, 12 (60%) acquired resistance. We detected emerging KRAS mutations in the ccfDNA of eight of these 12 patients (67%) prior to relapse, six of them having multiple mutations. Five of these patients had mutations in codon 61 and one had solo codon 61 mutations. We also detected BRAF mutations in five patients; none had solo BRAF mutations. Four patients had S492R mutations; none had solo S492R mutations. Conclusions: If KRAS or BRAF mutation do not detected in primary tumor, EGFR blockade has no beneficial effect in patients with KRAS or BRAF mutations in their ccfDNA prior to commencing chemotherapy. Emerging KRAS, BRAF or S492R mutations that were undetectable before starting chemotherapy are associated with acquired resistance to EGFR blockade.