tbuckley/cabot-search huggingface dataset:
Comparison of 5-FU versus capecitabine in combination with mitomycin or cisplatin in the treatment of anal cancer.
Authors: Irene S. Yu, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2017)

680 Background: Capecitabine is used as an alternative fluoropyrimidine to infusional 5-FU in the non-operative management of anal cancer due to its ease of administration. However, its patterns of use and long-term outcomes in the real world are poorly described. Our objectives were to determine the frequency of capecitabine use, compare the difference in outcomes, and examine the difference in treatment-related adverse events between oral and intravenous fluoropyrimidines. Methods: All anal cancer patients who received either capecitabine or infusional 5-FU as part of their curative intent chemoradiotherapy from 2010 to 2013 at any 1 of 6 comprehensive cancer centers in British Columbia were included. Chi-square and Wilcoxon-Mann tests were used to assess for associations between treatment groups and clinical characteristics and outcomes. Results: A total of 237 patients were identified; median age was 59 (IQR 53-67) years, 71 (30%) were men, 202 (85%) had ECOG 0/1, and 12 (5%) were HIV positive. Median total radiation dose was 54 cGy (IQR 50.4-54.0) and 21 (9%) underwent a colostomy prior to chemoradiation. Baseline characteristics were balanced between the two groups with respect to age, gender, ECOG, and HIV status (all p &gt; 0.05). Overall, 155 patients (65%) received capecitabine. Comparing patients who received capecitabine vs 5-FU, overall (69% vs 74%, p = 0.388) and disease-free survival rates (68% vs 71%, p = 0.637) at 5 years from diagnosis were similar between treatment groups. There were no differences with respect to rates of subsequent colostomy (16% vs 23%, p = 0.185) and abdominoperineal resection (11% vs 12%, p = 0.777). However, patients who received capecitabine were less likely to report adverse effects (51% vs 26%, p &lt; 0.001) than those who underwent 5-FU. The capecitabine group had a lower incidence of stomatitis (6% vs 40%, p &lt; 0.001) whereas the 5-FU cohort reported less frequent hand-foot syndrome (1% vs 8%, p = 0.036). Conclusions: This population-based study demonstrates a preference for capecitabine use in place of 5-FU in the curative management of anal cancer. Survival outcomes are similar between the two treatment groups, but capecitabine may be better tolerated.
Moving forward with interdisciplinary research on attractiveness-related biases
Authors: Dario Maestripieri, Andrea Henry, Nora Nickels
Journal: Behavioral and Brain Sciences (2017)

Abstract In our response, we review and address the comments on our target article made in the 25 commentaries. First, we review and discuss the commentaries that recognized the value of our approach, accepted the main premises and conclusions of our target article, and suggested further avenues for research on attractiveness-related biases. We then respond to commentators who either misinterpreted some parts of our target article or made statements with which we disagree. These commentaries provided us with an opportunity to clarify some aspects of our target article, for example, the fact that we address both the functional significance of attractiveness-related biases and their underlying mechanisms. We provide a rebuttal to two commentaries, in which we are accused of poor scholarship. We conclude our response by addressing two commentaries that discussed the societal implications of the occurrence of attractiveness-related biases in the labor market by briefly discussing the relationship between scientific research and social policy.
Proactive management of egfr TKI's skin rash toxicities:and alternative approach.
Authors: Maria RITA Migliorino, Serena Ricciardi, Danilo Rocco, Ciro Battiloro, Livia De Pietro, Gabriella Fabbrocini, Alberto Fulvi, Maria Concetta Romano
Journal: Journal of Clinical Oncology (2015)

e19050 Background: EGFR tyrosine kinase inhibitors (EGFR-TKIs) are commonly associated with a large number of skin adverse events. Strategies to manage those adverse effects are essential to increase patients ‘compliance, quality of life, and overall outcome of the treatment.Through a proper and early management, egfr-tkis may provide a less toxic treatment option for patients suffering from advanced nsclc Methods: Between January 2014 and January 2015, 31pts with common EGFR mutation (exon 19 and 21) were treated with TKIs, 24 with irreversible inhibitors and 7 with reversible.Skin’s toxicity of each patient is carefully monitored every 30 days in our DH through periodic checks carried out by our multidisciplinary team- which includes a dermatologist- in order to prevent skin-toxicity grade G3-4.The inflammation and the alteration of the corneum stratum was treated with water- free unguents, made from vegetable oil (containing no mineral oil (petroleum) or steroids) as well as antibiotic local cream. We use oral antibiotic and steroid only very occasionally.Skin’s toxicity was evaluated according to the System of CTCAE 2014.We evaluated the skin’s toxicity of our patients from the beginning to the end of the Tkis treatment, as well as its modifications over the course of time. Results: Rash has appeared in all pts within 2 wks as of the beginning of the treatment. G3 skin toxicity was detected in 3% of the pts treated with irreversible TKI and in 1% of the other group. No pts had to stop the treatment for more than 3 days because of dermatological toxicity. Conclusions: This study has demonstrated that the proactive dermatological treatment could reduce the percentage of treatment suspension and skin’s toxicity grade. Strategies to improve the management of egfr-tki-related adverse events should improve clinical outcomes, compliance, and Qol in patients with advanced nsclc.
Clinical outcomes of early-stage ampullary carcinoma: A single institutional experience.
Authors: Ashish Manne, Sushanth Reddy, Peng Li, Carlo M. Contreras, John Christein, Selwyn M. Vickers, Martin Heslin, Rojymon Jacob, Thomas N. Wang, Anup Kasi, James Posey, Ravi Kumar Paluri
Journal: Journal of Clinical Oncology (2017)

456 Background: Ampullary carcinoma [AC] is a rare malignancy associated with favorable prognosis among pancreatobiliary tumors. Pancreaticoduodenectomy [PDY] is considered to be curative for early stage cancers. The role of adjuvant chemotherapy [CT] or combination chemoradiation [CRT] remains uncertain for stage I/II. In this analysis we reviewed our institution’s experience with AC. Methods: From 2005 to 2015, 62 patients with stage 1 and 2 AC with at least one year follow up after PDY were reviewed. Clinical and pathologic factors and disease status were obtained from chart review. The patients’ demographical and oncological characteristics are summarized. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival. Kaplan-Meier method and log-rank was used to compare the time-to-events. Results: Adjuvant treatment was administered in 61%: CT (32%), CRT (29%) 39% surgical alone. The median overall survival [OS] for the study cohort is 60 months with 3 yr OS at 58% and 5 yr OS at 50%. Recurrence noted in 21% of patients. About half of patients surviving five years were alive at 10 years. Lymph node [LN] metastases (57%) predicted worse PFS (HR 2.29, 95% CI (1.13-4.61), p = 0.021) but did not significantly affect OS (HR 1.2, 95% CI (0.84-3.61);p = 0.13). There were no postoperative deaths following surgery.Peri- pancreatic extension [PPE] (20%) and peri-neural invasion [PNI] (16%) was also found to be determinants for poor OS. Current data did not suggest lympho-vascular invasion (24%) predict OS (HR 1.20, 95% CI (0.49, 2.96);p = 0.63 or PFS(HR 1.45 (0.65, 3.20),p = 0.36). When compared to surgery alone adjuvant CT or CRT had no statistically significant difference in terms of PFS (p = 0.53) or OS (p = 0.96). Conclusions: The use of adjuvant treatment may be most useful at improving long-term disease control in patients with high-risk features; however, no significant difference between CT and CRT was demonstrated in our series. This could be due to small sample size and needs further validation in larger cohort. PDY with regional lymphadenectomy is appropriate for early-stage AC, but worst outcomes seen in patients with PPE, PNI and LN involvement.
Does presence of chronic obstructive pulmonary disease (COPD) influence clinical behavior in patients with early-stage non-small cell lung cancer (ESNSCLC)?
Authors: Satomi Yamamoto, Tomoya Kawaguchi, Taro Tamura, Kazuhiro Asami, Kyoichi Okishio, Shinji Atagi, Hyungeun Yoon, Akihide Matsumura, Shigeki Shimizu, Masanori Kitaichi, Minoru Takada, Kazuto Hirata
Journal: Journal of Clinical Oncology (2013)

e18530 Background: CDPD and lung cancer sometimes occurs simultaneously. COPD has been recognized as an inflammatory disease and may potentially affect biology of the accompanying tumor. It is not fully understood whether presence of CDPD influences clinical characteristics, pathological findings and/or clinical outcomes in patients with ESNSCLC. Methods: Retrospective and consecutive data were collected from the medical records of patients who underwent surgical resections at Kinki-chuo Chest Medical Center, Japan, between January 2009 and December 2010. CDPD status was classified as absence of COPD, stage I and II COPD based on the criteria of Global Initiative for Chronic Obstructive Lung Disease (GOLD). Histology, vascular / lymphatic invasion and the status of epidermal growth factor receptor (EGFR) were determined using the surgical materials. Results: A total of 319 cases was included with median age of 67 (range, 36 - 89). There were 81 cases of relapse and 40 cases of death during the median follow up of 28 months (11 days to 49 months). In the subgroup of non-COPD, stage I and II COPD, the median age, the number of case in gender (male/female), performance status (PS, 0/1), histology (squamous cell carcinoma [SQ] /non SQ), smoking status (never/ever), and EGFR status (wild type/mutant) were 67, 72, 72 (p&lt;0.001) and 105/110, 48/12, 38/6 (p&lt;0.001) and 170/40, 53/7, 27/14 (p=0.029) and 31/184, 12/48, 14/28 (p&lt;0.001) and 89/122, 7/53, 2/39 (p=0.002) and 47/37, 21/3, 9/3 (p=0.013), respectively. No significant difference was observed in disease-free survival (DFS, log-rank p=0.411) and overall survival (OS, log-rank p=0.127) between the patients with and without COPD. In multivariate analysis adjusted for age, gender, PS, histology, smoking status, pathological stage, vascular / lymphatic invasion and EGFR status, presence of COPD did not affect DFS (HR=1.457, p = 0.279) nor OS (HR=0.993, p = 0.990).Conclusions: Although COPD was significantly associated with the elderly, male gender, presence of symptoms, SQ histology, ever smoking, and wild type EGFR, it did not add values of prognostic factors in patients with ESNSCLC.
Prospective study of a 17-GENE RT-PCR-based assay for prediction of high risk pathology at radical prostatectomy.
Authors: Neal D. Shore, Tim Richardson, Steve Rosenberg, Evan Goldfischer, Ruixiao Lu, Alan W Shindel, John Bennett, Lawrence Ivan Karsh, Howard Korman, Phillip G. Febbo, Bela Stephen Denes
Journal: Journal of Clinical Oncology (2017)

36 Background: A biopsy-based 17 gene tissue-based RTPCR assay (Oncotype Dx Genomic Prostate Score, GPS) has been validated in retrospective cohorts as a predictor of adverse pathology and biochemical recurrence in prostate cancer (PCa) patients who underwent radical prostatectomy (RP). The National Comprehensive Cancer Network (NCCN) recommends that men with pathologic Gleason Score (pGS) &gt; 8, pT3+, and/or Lymph Node positive disease (i.e. high risk surgical pathology, HRSP) consider adjuvant therapy after RP. We report herein on GPS at biopsy as a predictor of HRSP in men presenting with clinically low-risk PCa. Methods: As part of an ongoing observational study of GPS (N = 1200), we performed an exploratory analysis in men who elected RP as initial disease management. Descriptive statistics were reported. Binary logistic regression was performed to determine the association between GPS and HRSP. The odds ratio (OR) per 20 GPS units and 95% confidence interval (CI) were reported. All analyses were conducted with SAS 9.4. Results: Of the 1,200 patients enrolled in the study, 150 (21 sites) selected RP for initial management; 122 (19 sites) had biopsy and surgical pathology data available for analysis.Median age was 63 (range 50-79) years, with 38% &gt; 65 yrs. There were 72 (59%), 39 (32%), and 11 (9%) patients who had NCCN Intermediate-, Low-, and Very Low-Risk disease, respectively Median GPS was 30 (IQR 20-40, range 8-82). Biological risk (GPS+NCCN) differed from NCCN risk in 28 cases (23%). At surgery, 29 /122 (24%) of patients had HRSP; of these, 1 had NCCN Very Low-, 8 had Low-, and 20 had Intermediate-Risk cancer at diagnosis. GPS was a significant predictor of HRSP (OR per 20 GPS units: 2.1; 95% CI: [1.2, 4.0]; p-value 0.02). No other clinical factor was significantly associated with HRSP. GPS remained significant after adjusting for NCCN risk group (OR per 20 GPS units: 2.0; 95% CI 1.1-3.8, p = 0.03). Incorporation of GPS increased the AUC for prediction of HRSP from 0.57 (NCCN alone) to 0.65 (NCCN + GPS) Conclusions: GPS derived from biopsy tissue is an independent predictor of HRSP. This information may be valuable in treatment planning for men with clinically low risk PCa who are at risk for HRSP.
Pregnane X receptor is associated with unfavorable survival and induces chemotherapeutic resistance by transcriptional activating multidrug resistance-related protein 3 in colorectal cancer
Authors: Yan Dong, Zhe Wang, Gan-feng Xie, Chong Li, Wen-wei Zuo, Gang Meng, Cheng-ping Xu, Jian-jun Li
Journal: Molecular Cancer (2017)

Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but the regulatory mechanism is poorly understood.Oxaliplatin (L-OHP) content in tumor cells was analyzed by mass cytometry. The roles of PXR on cancer cell proliferation, apoptosis and tumor growth with L-OHP-treated were investigated by MTS, colony formation, flow cytometry and xenograft tumor assays. Luciferase reporter, Chromatin-immunoprecipitation and Site-directed mutagenesis were evaluated the mechanisms. The PXR and multidrug resistance-related protein 3 (MRP3) expressions were examined by western blot, RT-PCR or immunohistochemistry of TMA. Kaplan-Meier and Cox regression were adopted to analyze the prognostic value of PXR in colorectal cancer (CRC).PXR over-expression significantly increased oxaliplatin (L-OHP) transport capacity with a reduction of its content and repressed the effects of L-OHP on tumour cell proliferation and apoptosis. Conversely, PXR knockdown augments L-OHP-mediated cellular proliferation and apoptosis. Moreover, PXR significantly reduced the therapeutic effects of L-OHP on tumor growth in nude mice. Further studies indicated a positive correlation between PXR and MRP3 expression and this finding was confirmed in two independent cohorts. Significantly increased MRP3 expression was also found in PXR over-expressing cell lines. Mechanistically, PXR could directly bind to the MRP3 promoter, activating its transcription. The PXR binding sites were determined to be at -796 to -782bp (CTGAAGCAGAGGGAA) and the key binding sites were the "AGGGA" (-787 to -783bp) on the MRP3 promoter. Accordingly, blockade of MRP3 diminishes the effects on drug resistance of PXR. In addition, PXR expression is significantly associated with poor overall survival and represents an unfavorable and independent factor for male or stage I + II CRC patient prognosis.PXR is a potential biomarker for predicting outcome and activates MRP3 transcription by directly binding to its promoter resulting in an increased L-OHP efflux capacity, and resistance to L-OHP or platinum drugs in CRC. Our work reveals a novel and unique mechanism of drug resistance in CRC.
Sequential (ST) versus combination (CT) chemotherapy in older patients (pts) with advanced colorectal cancer (aCRC): A retrospective analysis of the CAIRO study
Authors: J. Doornebal, A. Wymenga, N. Antonini, W. T. van der Graaf, M. Koopman, C. Punt, J. Timmer-Bonte
Journal: Journal of Clinical Oncology (2009)

9542 Background: Although older pts have been underrepresented in clinical trials, studies support the efficacy of chemotherapy in older pts with aCRC. We retrospectively evaluated efficacy, tolerability, and quality of life (QoL, EORTC QLQ C30) of older (group 1: ≥ 70 yrs) vs younger pts (group 2: &lt; 70 yrs) who participated in a randomized phase III trial of ST vs CT in CRC (Koopman et al, Lancet 2007). Moreover, differences between ST vs CT were analyzed in both age groups. Methods: All 803 eligible pts were randomized between ST - 1 st line capecitabine (Ca) 1250 mg/m 2 bid d1–14 (group 1: n = 104/group 2: n = 297), 2 nd line irinotecan (Ir) 350 mg/m 2 d1 (1:63/2:189) and 3 rd line Ca 1000 mg/m 2 bid d1–14 + oxaliplatin 130 mg/m 2 d1 ([CAPOX], 1:34/2:119) - and CT - 1 st line Ca 1000 mg/m 2 bid d1–14 + Ir 250 mg/m 2 d1 (1:95/2:307), 2 nd line CAPOX (1:33/2:165). Cycles were given q 3 weeks. Results: Baseline characteristics, median number of administered cycles and median relative dose intensities were comparable. Group 1 vs 2: Overall survival (OS) and progression free survival (PFS) were comparable (OS: ST: 17.6 vs 16.0 months, HR 1.127 [0.883 - 1.437], CT: 19.8 vs 16.8 months, HR 0.913 [0.708 - 1.178]). A better RR was observed in 1 st line ST for group 1 (30% vs 17%). Grade 3–4 toxicity was more common in 1 st and 2 nd line ST in group 1 (overall grade 3–4 toxicity 54/59% vs 40/43%). However, significant decreases in overall QoL, fatigue, appetite loss, and diarrhea were only reported in CT for group 1. ST vs CT: OS was comparable (1: 17.6 vs 19.8 months; 2: 16.0 vs 16.8 months). A better RR (17% vs 40%) and longer PFS (5.4 vs 7.8 months) were only observed in CT for group 2. Cumulative overall toxicity over all subsequent lines of treatment was worse for ST in group 1 (85% vs 69%). However, significant decreases in overall QoL, symptomatic appetite loss, nausea and vomiting and diarrhea were only reported in group 1 for CT. Conclusions: Older pts derived comparable benefit from both chemotherapeutic strategies compared to younger pts. CT did not result in any benefit in terms of efficacy in older pts. Despite the higher incidence of grade 3–4 toxicities, both efficacy and QoL results support the preference of ST in fit older aCRC patients. No significant financial relationships to disclose.
Prognostic score for Luminal A-like breast cancer patients.
Authors: Caterina Fontanella, Stephan Gade, Gunter Von Minckwitz, Bianca Lederer, Jens U. Blohmer, Serban Dan Costa, Carsten Denkert, Holger Eidtmann, Bernd Gerber, Claus A. Hanusch, Joern Hilfrich, Jens Bodo Huober, Andreas Schneeweiss, Stefan Paepke, Christian Jackisch, Keyur Mehta, Valentina Nekljudova, Michael Untch, Sibylle Loibl
Journal: Journal of Clinical Oncology (2014)

525 Background: Luminal A breast cancer (BC) is considered a subtype with a good prognosis, but some poor prognostic factors can be identified, i.e. advanced stage and/or young age at presentation seem to be associated with higher risk of recurrence after neoadjuvant treatment (NAT). The importance of the progesterone receptor (PR) in Lum A BC prognosis has also been explored. Methods: We evaluated 2,248 patients with Lum A like BC (HER2-/estrogen receptor +/grade1-2) from 6 anthracycline-taxane based NAT trials (plus adjuvant endocrine therapy (ET) and radiotherapy if indicated). Combining tumor stage (AJCC Cancer Staging seventh), PR status, and age at baseline, we generated a score to divide Lum A like BC into 5 groups (Table). We used Kaplan Meier and uni/multivariate Cox regression analyses to explore the effect of the score on disease free (DFS) and overall survival (OS) and to evaluate its interaction with CPS+EG score (Mittendorf EA, JCO 2011), body mass index (BMI≤30/>30kg/m²), pCR (ypT0 ypN0), NAT density (conventional/dose-dense), and duration (24/18/≤12 weeks). Results: Mean DFS and OS decreased from score A to E (DFS: A 106.9 months, B 98.9, C 90.7, D 80.5, E 46.5; p< .001; OS: A 109.9 months, B 107.2, C 100.6, D 91.0, E 57.8; p< .001). Univar. analysis hazard ratios (HR) are displayed below. In multivar. analysis, our score independently predicted DFS (p< .001) and OS (p= .049). No interactions were observed (DFS: score*CPS+EG p= .440, s*BMI p= .347, s*pCR p= .462, s*density p= .350, s*duration p= .590; OS: s*CPS+EG= .734, s*BMI p= .784, s*pCR p= .999, s*density p= .870, s*duration p= .999). Conclusions: Using characteristics available in daily practice before treatment, we developed a score to identify Lum A like BC patients with poorer prognosis, despite NAT and ET, who are candidates for more aggressive NAT or additional postNAT in future studies. SCORE (patients) DFS OS HR 95%CI p HR 95%CI p A (686) I-IIA/PR+/age≥40 1.0 1.0 B (592) IIB/PR+/age≥40 2.1 1.4-3.1 < .001 1.8 1.1-3.0 < .001 C (709) I-IIA/PR-/age≥40 I-IIA/PR+/age<40 IIB/PR+/age<40 IIIA-B/PR+/age≥40 3.4 2.4-4.9 < .001 3.0 1.8-4.8 < .001 D (230) I-IIA/PR-/age<40 IIB/PR-/any age IIIA-B/PR+/age<40 IIIA-B/PR-/any age 5.4 3.6-8.1 < .001 4.8 2.8-8.4 < .001 E (31) IIIC 11.7 6.3-21.6 < .001 10.9 4.8-24.6 < .001
Comparison of two chemotherapy regimens in non-small cell lung cancer patients relapsing after surgery and peri-operative chemotherapy (IFCT-0702 study).
Authors: Denis Moro-Sibilot, Clarisse Audigier-Valette, Patrick Merle, Elisabeth A. Quoix, Pierre Jean Souquet, Fabrice Barlesi, Christos Chouaid, Oliver Molinier, Armelle Lavole, Julien Mazieres, Laurence Baudrin, Franck Morin, Gerard Zalcman
Journal: Journal of Clinical Oncology (2013)

8081 Background: To evaluate the benefit of adding cisplatin or carboplatin (P) to docetaxel (D) chemotherapy (CT) in patients with the first metastatic relapse after perioperative chemotherapy and surgery. Methods: Patients (Pts) with histologically or cytologically confirmed inoperable non-small cell-lung cancer not eligible for curative radiotherapy (local or metastatic relapse), disease progression after perioperative chemotherapy and surgery and PS 0-1. Pts were randomized to D 75 mg/m² combined with cisplatin 75 mg/m² or carboplatin AUC5 every 3 weeks (Arm A) or alone (Arm B). The primary endpoint was progression-free survival (PFS). Results: Due to low accrual the trial was interrupted after inclusion of 88 patients. From November 2007 to August 2012, 68 males and 20 females, median age (range) 61 (41-75), ECOG PS 0/1/ 49%/50%, squamous histology 39%, Arm A and Arm B 44 patients each, were enrolled. Interval from last cycle of perioperative CT ou last cycle of adjuvant CT was ≥ 12 months in 69% of pts. 79.5% of patients received DP full treatment. A non-statistically significant increase in PFS favoring combined CT was observed with a HR of 0.73 (95% CI: 0.46-1.15; p = 0.18), median PFS 8 months vs 5.6. Objective response rate was increased in the P-containing arm; p &lt;10 -4 ). However, overall survival was not improved by the addition of P to D; the HR for death was 0.90 (95% CI: 0.55-1.48; p = 0.68) median OS 15.9 months vs 12.4 months. Overall grade 3/4 toxicity was observed in 36 pts (DP) vs 30 (D) : neutropenia (32 pts vs 26), febrile neutropenia (8 vs 3), non-hematological toxicities (18 vs 6). Conclusions: PFS and OS weresurprisingly longer than expected in this cohort of NSCLC patients with metastasis, and comparable with that observed in historical cohorts of NSCLC treated in first-line. DP resulted in a non significant 27% reduction of hazard of progression as compared to D alone. A reduced statistical power related to a slow and insufficient accrual may explain this lack of significance. Considering survival data and toxicity profile, we suggest that these patients behave like first-line patients and may probably be treated accordingly with a platinum-based doublet. Clinical trial information: NCT00535275.