tbuckley/cabot-search huggingface dataset:
Comprehensive analysis of variation of tumor infiltrating lymphocytes during neoadjuvant chemotherapy in triple-negative breast cancer.
Authors: Carlos Castaneda Altamirano, Elizabeth Ann Mittendorf, Patricia Arboleda Ezcurra, Sandro Casavilca Zambrano, Maria Teresa Nunez Butron, Yun Wu, Miluska Castillo Garcia, Katerin Ingrid Rojas, Valeria Villegas Bernaola, Carolina Belmar Lopez, Ketty Dolores Cerna, Henry Leonidas Gomez, Julio E. Abugattas Saba, José M. Cotrina, Ana Maria Gonzalez-Angulo, Tatiana Vidaurre
Journal: Journal of Clinical Oncology (2015)

3035 Background: Tumor infiltrating lymphocytes(TIL) have a predictive and prognostic role in Triple Negative Breast Cancer (TNBC).There is little data regarding specific lympohcyte subsets. In this study we evaluated the association between clinicopathologic variables and TIL identified by either H&E (total TIL) or immunohistochemistry (TIL subsets) in TNBC patients receiving neoadjuvant chemotherapy (NAC). Methods: We evaluated stromal TIL in whole sections and in 5 HPF of a 0.6 cm tumor cylinder before and after NAC in a cohort of 100 TNBC patients. Results: Median age:49y,inflammatory(29%),pCR(30%),recurrences(42%),death(45%) and median follow-up(37.5m).TIL percentage by H&E is similar in the whole slide and in the 0.6 cylinder in post NAC homogeneous tumor(ICC = 0.731) but not in post NAC heterogeneous(ICC = 0.065) or preNAC tumor(ICC = 0.017). Quantitative counting and percentage calculating of TIL was significantly correlated in every subset(IHC):CD3,CD4,CD8 and FOXP3 in Pre(r:0.4982-0.6918,p < 0.05) and PostNAC(r:0.5387-0.7733,p < 0.05). The median percentage of total TIL in pre- and post-NAC specimens were 40 and 20%(p < 0.0001), respectively. DFS > 32 m and OS > 41m are associated to higher preNAC TIL by H&E(40 vs 20%,p = 0,007)(40 vs 30%,p = 0.033). Media H&E TIL was not associated with age(40 vs 20%,p = 0.14), inflammatory features of pre-NAC(40 vs 35%,p = 0.64) or pCR in PostNAC samples(20 vs 20%,p = 0.63).TIL in PostNAC samples was not associated to DFS(p = 0.24) nor OS(p = 0.59).The CD4/CD3 ratio tend to be lower in pre-NAC samples with pCR(0.14 vs 0.24, p = 0.06) and lower in post-NAC samples with pCR(0.33 vs 0.07,p = 0.009).The CD8/CD4 ratio was higher in pre-NAC samples with pCR(2.75 vs 0.99,p = 003) and lower in post-NAC samples with pCR(2.09 vs 3.66,p = 0.008). Conclusions: TIL in PreNAC predicts pCR and Survival.TIL in 0.6 cm cylinder differs from whole slide and percentage correlates with absolute TIL calculation.CD4/CD3 and CD8/CD4 ratio evaluated by counting technique appears to predict pCR.
The Role of Microrna-150 in the Prognosis and Transformation of Follicular Lymphoma
Authors: Katerina Musilova, Gabriela Pavlasova, Vaclav Seda, Eva Vojackova, Katerina Cerna, Jana Didi, Robert Pytlik, Vit Prochazka, Zuzana Prouzova, Lenka Zlamalikova, Sarka Pospisilova, Andrew Evans, Clive S Zent, Leos Kren, Marek Trneny, Jiri Mayer, Andrea Janikova, Marek Mraz
Journal: Blood (2016)
Patient perceptions of ovarian cancer, its treatment, and its impact: A qualitative interview study in three European countries.
Authors: Daniel Eek, Matthew Reaney, Carla Ascoytia, Lorie Scrabis, Katarina Halling, Peter Black, Mona L. Martin
Journal: Journal of Clinical Oncology (2015)

e16550 Background: Ovarian cancer is highly prevalent and associated with mortality. Having a clear understanding of the patient experience, perspectives, needs and priorities is vital for successful management. Methods: Semi-structured qualitative interviews were conducted in France (FR), Germany (DE) and the United Kingdom (UK) with adult women having undergone chemotherapy (ch) for ovarian cancer. Interviews explored symptoms, treatment side-effects and impacts of ovarian cancer. Interviews were audio-recorded, transcribed, and analysed for common themes and descriptive language. Results: A total of55 women participated across the three countries (FR [N = 20]; DE [N = 15]; UK [N = 20]). Mean age was 54 years (range 18−82); mean time since first diagnosis was 4 years (range 0.25−14.0). Significant overlap was reported between symptoms of ovarian cancer and treatment side-effects. The most frequently mentioned symptoms were gastrointestinal (GI) related (30-34% of all symptom expressions across the countries), including bloating, feeling full, and loss of appetite. GI were also expressed as side effects of ch (15-28% of all side-effect expressions). Sleep/energy issues were also frequently reported as both symptoms (12-15%) and side effects of ch (17-26%). Other notable side-effects included hair loss (7-9% of all side-effect expressions), allergic reactions (1-3%), and cognitive dysfunction (1-4%). Pain/discomfort (abdominal pain and pain in the back/side) was reported as a symptom of ovarian cancer (22-25%) and a side effect of surgery (15-23%). Emotional disturbances and limitations in daily functioning are the most frequently mentioned impacts (19-30% of impact expressions). Other impacts (e.g. social activities, relationship impacts, self-perception, sleep difficulties) demonstrated a lower predominance of expression (3-12%). There were few differences by country. Conclusions: This “voice of the patient” study highlights the significant symptom burden of ovarian cancer and the symptom exacerbation associated with chemotherapy. Findings from the current study could be used to develop quantitative patient-reported outcome (PRO) instruments for future research.
Circulating mir-21 and mir-378 are predictive of progression-free survival (PFS) in patients treated with everolimus in metastatic renal cell cancer (mRCC).
Authors: James Lin Chen, Kimryn Rathmell, David F. McDermott, Walter Michael Stadler
Journal: Journal of Clinical Oncology (2012)

4617 Background: The oral mTOR inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and modestly delays RCC progression. We hypothesized that circulating microRNAs, which have been associated with renal cancer and inflammation, may serve as predictive biomarkers to help better define a population more sensitive to treatment. Methods: Plasma from mRCC pts refractory to VEGF inhibition were obtained prior to treatment with standard dose everolimus as part of a clinical trial examining FDG-PET as a potential predictive biomarker. As we were specifically interested in tumor response to drug, only pts who died, remained on trial, or had radiographic progression by RECIST criteria were profiled. Pts who were unable to tolerate drug were excluded. MicroRNAs were extracted and profiled without pre-amplification using Exiqon LNA PCR panels. Crossing point (Cp) values within 5 of the negative control were removed. MicroRNAs must have been present in &gt;90% of samples and varied at least p &gt; 0.10 from mean to be further analyzed. Cox-proportional hazards model and Kaplan-Meier analyses were performed. Results: 28 patients had available plasma and met criteria for profiling. Pt characteristics included: 20 (71%) clear cell histology, median age 57.7 (43 – 76), median number of prior systemic therapies 2 (1 – 3). 103 microRNAs were expressed in at least 90% of all samples. Mir-21 and mir-378 were independently correlated with PFS (FDR: 0.02 and 0.06, respectively). Low circulating plasma mir-21 and mir-378 levels resulted in a median PFS prolongation of 370d vs. 101d (p=0.027) and 368d vs. 106d (p=0.001). Analysis of the clear cell cohort for mir-21 and mir-378 also demonstrated a significant median PFS difference of 350d vs. 173d (p=0.045) and 345d vs. 147d (p=0.004). Conclusions: Elevated levels of circulating mir-21 and mir-378 have been associated with systemic inflammatory states, and in our study are correlated with decreased PFS in mRCC pts undergoing everolimus therapy. Further prospective studies will be required to validate these exploratory results for their potential role as prognostic or predictive biomarkers.
Long-term survival in patients with primary CNS lymphoma: Results from the G-PCNSL-SG1 trial.
Authors: Patrick Roth, Peter Martus, Eckhard Thiel, Agnieszka Korfel, Michael Weller
Journal: Journal of Clinical Oncology (2015)

2032 Background: Although potentially curable, primary CNS lymphoma (CNS) is still a therapeutic challenge and only a minority of patients survive longer than 5 years. The factors which define the prognosis of PCNSL patients have only been partially elucidated. A more detailed insight into the parameters which promote long-term survival in PCNSL may allow for more patient-tailored therapies. Methods: We analysed the dataset of patients enrolled into G-PCNSL-SG1, the largest phase 3 study performed in PCNSL evaluating the role of whole-brain radiotherapy after high-dose methotrexate-based chemotherapy. Out of 459 patients with sufficient data quality, we identified 89 patients who had survived for five years or more after surgery and diagnosis of PCNSL. This long-term survival (LTS) cohort was compared with two different reference groups: first, patients who had died within one year of diagnosis for any reason (control 1 = C1 patients) and second, all patients who had survived for more than 1 year, but who did not reach a survival of 5 years from diagnosis (control 2 = C2 patients). Patients censored (i.e. alive but without further follow-up) before 5 years of follow-up were excluded. Within the LTS group, survival after 5 years was analysed using the Kaplan Meier method. Results: We compared baseline characteristics and treatment of the 89 patients surviving for 5 years or more with the C1 and C2 control populations. Patients within the LTS cohort were younger and had a higher performance score at diagnosis. Furthermore, they had less frequently multiple tumor manifestations, a better renal function and were less often affected by cardiovascular disease. High-dose methotrexate-based treatment resulted in a higher complete response rate and was associated with less toxicity, particularly a reduced frequency of myelosuppression. Within the group of LTS patients, age at diagnosis was the only prognostic factor for conditional survival from 5 years on. Conclusions: Within this large patient population, survival of 5 years or more was reached by approximately a fifth of the patients. Young and fit patients with single lesions are most likely to survive for 5 years or more following diagnosis of PCNSL.
Modifiable factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients.
Authors: Seok Joon Yoon, Samyong Kim
Journal: Journal of Clinical Oncology (2014)

e20542 Background: Higher caregiver burden is associated with poor quality of life among family caregivers. However, in Korea, very few studies have examined factors associated with caregiver burden. The present study investigated factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients, particularly modifiable factors as a potential target of intervention strategies. Methods: A cross-sectional study using self-administered questionnaires was performed. Sixty-four family caregivers of terminally ill cancer patients who were admitted to the hospice-palliative care unit of a University Hospital in South Korea were included. To identify caregiver burden, the Caregiver Reaction Assessment scale (CRA) was used in this study. Time spent in providing care per day, number of visits per week from other family members, family functioning, and a positive subscale, self-esteem, of the CRA were deemed as modifiable factors. Other socio-demographic, care-giving characteristics of the subjects were non-modifiable factors. Results: Longer time spent providing care per day, fewer weekly visits from other family members, poor family functioning, and low self-esteem were considered as modifiable factors associated with caregiver burden. Low monthly income and being the spouse as the family caregiver were non-modifiable factors. Conclusions: Our study has practical significance in that it identifies modifiable factors that can be used to devise intervention strategies. Developing and applying such intervention strategies for alleviating the factors associated with high caregiver burden could be important for improving the quality of life of both patients and their families.
A longitudinal evaluation of oral mucositis in patients receiving radiation therapy (IMRT) with/without chemotherapy (CTX)
Authors: M. J. Dodd, M. Cho, C. Miaskowski, J. Quivey
Journal: Journal of Clinical Oncology (2009)

e20572 Background: Oral mucositis is a major side effect of RT ± CTX to the head and neck. A variety of instruments and techniques have been used to quantify oral cavity changes during treatment. Few studies have reported on the evaluation of oral mucositis using both subjective and objective methods. A secondary aim in our study testing an innovative mouthwash is to increase our understanding of using subjective and objective methods for measuring oral mucositis, functional status, and weight changes over time. Methods: Patients reported functional status, pain and investigators measured oral mucositis and weight at four times (beginning of RT [T1], onset of mucositis [T2], end of RT [T3], and healing of mucositis [T4]) over a 10 - 15 week period, using the Karnofsky Performance Status [KPS]) and the Oral Mucositis Assessment Scale (OMAS). The OMAS measures researcher-evaluated ulceration/pseudomembrane formation and erythema in specific sites in the mouth, and self-report by patients, rating severity of mouth pain, ability to swallow and chew. Results: Of 51 head and neck cancer patients enrolled, 3 never developed mucositis. Mean days to onset of mucositis was 15.58 (SD 6.85), and mean days to healing of mucositis was 77.86 (SD 40.1). Mucositis pain scores (possible range 0–45) were moderate at T2 (x=6.25, SD 3.5) and T3 (x=12, SD 5.0). Subjective pain, chewing, and swallowing scores were positively correlated with each other (r= .31 - .73, p&lt;.05) and objective oral mucositis scores were positively correlated with each other (r= .49 - .77, p&lt;.01), however, no significant correlations were obtained between the subjective and objective scores. In both the RT-only group as well as the RT+CTX group, weight significantly decreased from T1 to T4, and KPS significantly decreased from T1 to T3. RT+CTX patients showed lower KPS and greater weight loss from T1 to T4 (X=10lbs) compared to the RT-only group (X=3 lbs), but neither was significantly different. Conclusions: During RT+CTX, patients need more supportive care to maintain functional status and avoid weight loss. Lack of correlations between the subjective and objective scores is interesting in that they are measuring something quite different, which may provide some insight into underlying mechanisms. No significant financial relationships to disclose.
Efficacy of the Royal Marsden Score (RMS) to improve the selection patients (pts) considered for participation to dose-seeking phase I trial.
Authors: Veronique Favre, Fatima-Zhora Meniai, Philippe Alexandre Cassier, Carlos Alberto Gomez-Roca, Nicolas Isambert, Stephanie Clisant, Peggy Philippe, Alice Levart, Isabelle Desmoulins, Juliette Bouchet, Jean-Pierre Delord, Nicolas Penel
Journal: Journal of Clinical Oncology (2013)

2548 Background: Selection of pts entering in phase trials remains difficult. An international network of expert centers had validated the efficacy of the RMS as selection tool in such context. Nevertheless, RMS have been developed (Arkenau EJC 2008) and validated (Olmos et al. JCO 2012) in cohorts of already enrolled pts, whereas that the question of eligibility is crucial at the time of screening. We have then implemented and measured the efficacy of the RMS in 453 pts entering in the screening process in 4 expert centers. Methods: We have analyzed pts having signed the PIS/IC. RMS (0 to 3) is sum of the following prognostic factors: LDH&gt;ULN, met. sites&gt;2 and albumin &lt;35 g/L. We have established the rates of enrolled pts, of pts dying within 90 days, of pts having completed PK/PD analysis, with accurate tumor assessment, having to be replaced according to RMS value. Results: Score was as follows: 0 (122/453, 27.0%), 1 (147/453, 32.4%), 2 (79/453, 17.4%), 3 (20/354, 4.4%) &amp; not assessable (84/453, 19.2%). OS according to RMS value were 615, 299, 239 &amp; 136 days (p=0.0001). The rates of 90-day mortality were 5.3%, 12.6%, 26.6% &amp; 41.1% (p=0.0001). The rates of enrolled pts were 79.5%, 77.5%, 60.7% &amp; 50.0% (p=0.001). Among enrolled pts, the rates of pts having completed the PK/PD analysis were 87.6%, 79.8%, 70.8% &amp; 50.0% (p=0.007). Among enrolled pts, the rates of tumor assessment available were 95.8%, 88.6%, 89.5% &amp; 70.0% (p=0.006). The rates of pts having to being replaced 4.1%, 5.2%, 2.0% &amp; 50.0% (p=0.04). The time under study was 118, 81, 56 and 62 days (p=0.005). Conclusions: We confirm that the RMS is a reliable, easily obtained tool for selecting pts in such context. The enrollment of pts with RMS=3 is associated with a high risk of attribution rate &amp; risk to be replaced. The time under study was significantly lower in cases of RMS =[2-3].
Evaluation of microRNA-10b expression as a novel predictive marker of metastases development and patients’ survival in breast cancer.
Authors: Paola Parrella, Raffaela Barbano, Barbara Pasculli, Andrea Fontana, Massimiliano Copetti, Vanna Maria Valori, Maria Luana Poeta, Giuseppe Perrone, Marina Castelvetere, Michelina Coco, Teresa Balsamo, Fabio Pellegrini, Andrea Onetti-Muda, Evaristo Maiello, Roberto Murgo, Vito Michele Fazio
Journal: Journal of Clinical Oncology (2013)

576 Background: MicroRNA-10b was found highly expressed in metastatic breast cancer cell lines and able to generate metastases in mice models. The aim of this study is to evaluate the putative association between miR10b expression and disease progression. Methods: We selectedfrom our tumor bank 150 consecutive breast cancers with at least three years follow up. For each case frozen paired tumor and normal tissue and complete clinical data were available. Pathological examination was performed to ensure that each tumour sample contained more than 70% of cancer cells resulting in 114 samples suitable for RNA extraction. RNA quality was measured and only samples with RIN≥7.0 were analyzed (n=101) by a relative quantification method. Results: miR10b relative expression in tumor to normal samples (RERs) was significantly higher in the subgroup of patients with metastases (median 0.25 IQR 0.11-1.02) as compared with patients without metastases (median 0.09 IQR 0.04-0.29) (P=0.023 Mann Whitney Test). The association between miR-10b RERs and survival was evaluated in the group of patients without metastases at diagnosis (n=90). In univariate Cox regression model, patients with high miR-10b RERs had a higher risk of distant metastases development (HR 4.91, P=0.02) and disease related death (HR 6.02; P=0.01). In a multivariate Cox regression model adjusted for tumor size, lymph node metastases, grade, ER, PgR status, and Ki67 labeling index (n=79), higher miR-10b RERs were still associated with increased risk of distant metastases development (HR18.84; P&lt;0.001) and disease related death (HR 13.39; P=0.003) (Table). Conclusions: We show that in breast cancer patients miR-10b expression is associated with worse prognosis on a short term follow up. These results suggest that miR-10b expression could be used for individual patient’s risk assessment and perhaps as potential therapeutical target. [Table: see text]
Time trend in the survival advantage in phase III trials investigating molecular-targeted agents for advanced non-small cell lung cancer (NSCLC) during the past decade.
Authors: Yuka Kato, Katsuyuki Hotta, Hiroe Kayatani, Toshio Kubo, Kadoaki Ohashi, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2014)

e19084 Background: OS is still a traditional endpoint for assessing efficacy of chemotherapy, though its benefit may be confounded by the effects of post-study therapies. The ASCO draft recommendation proposes clinical trials should aim to improve OS by a minimum of 25% in advanced NSCLC. Few studies, however, have assessed whether treatment outcomes have improved substantially over the years in pts with NSCLC enrolled into the randomized trials investigating molecular-targeted agents. Here, we examined its time trend in the phase 3 setting with a literature survey. Methods: We searched for trials reported between 2003 and 2013. Evaluating molecular-targeted agents and showed the results of OS benefit. The MST ratio and difference in each trial were simply defined as the ratio and difference of MST in the investigational arm to that in the control arm, respectively. Results: In total, 58 trials were identified, evaluating 20 kinds of molecular-targeted agents with 37,171 advanced NSCLC pts. The median MST was 10.9 months (range ; 3.7 – 36.0 months) in the investigational arms and 11.0 months (range ; 3.60 – 39.0 months) in the control arms. The median MST ratio was 1.02 (range ; 0.65 – 1.42). Only three trials (5.2%) showed a 25% or more increase in MST in the investigational arms relative to the control arms in MST, equal to the MST ratio of 1.25 or more. Also, we assessed the time trend in the MST ratio, which unfortunately revealed it neither increased nor decreased significantly over the decade (regression coefficient = -0.002, p = 0.755), suggesting a 0.2%-decline per year. As for the MST difference, it was a median of 0.3 month (range ; -6.1 - 4.6). Similarly to the MST ratio, the slope of MST difference was almost flat over the observed years (regression coefficient = 0.327, p = 0.660; suggesting a 0.3 month-increase per year). Conclusions: Few phase 3 trials assessing molecular-targeted agents have shown a substantial survival benefit over the decade from the viewpoint of both MST ratio and MST difference. This potentially suggests the need for further discovery of novel targets and development of compounds targeting specifically them.
Diffuse intrinsic pontine gliomas—current management and new biologic insights. Is there a glimmer of hope?
Authors: Kenneth J. Cohen, Nada Jabado, Jacques Grill
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies have been undertaken-all of which have had a negligible impact on the natural history of this disease. More recently, improvements in neurosurgical techniques have allowed for the safe upfront biopsy of DIPG, which, together with a wider use of autopsy tissue, has led to an evolving understanding of the biology of this tumor. The discovery of a recurrent somatic gain-of-function mutation leading to lysine 27 to methionine (p.Lys27Met, K27M) substitution in histone 3 variants characterizes more than 85% of DIPG, suggesting for the first time the role of the epigenome and histones in the pathogenesis of this disease, and more unified diagnostic criteria. Along with further molecular insights into the pathogenesis of DIPG, rational targets are being identified and studied in the hopes of improving the otherwise dismal outcome for children with DIPG.