tbuckley/cabot-search huggingface dataset:
Oxaliplatin (OX) and leucovorin (L) combined with protracted-infusion fluorouracil (F) and radiation (XRT) in locally advanced esophageal cancer (LAEC): A multicentric phase II study
Authors: V. Chiarion-Sileni, L. Corti, R. Innocente, R. Cavina, I. M. Brunetti, A. Ruol, J. Pigozzo, G. L. de Salvo, A. Santoro, E. Ancona
Journal: Journal of Clinical Oncology (2005)

4071 Background: to evaluate activity and feasibility of FOXL concomitant with XRT in patients (pts) with unresectable LAEC. Methods: pts with histologically proven LAEC, unresectable for T or N extension, not previously treated, were enrolled. FOXL therapy consisted of OX 60 mg/m2 infused over 2h on days 1, 8, 15, 29, 36, 43, 50, 57, followed by L 20 mg/m2 over 1h, and F 200 mg/m2 for 24 hours on days 1–22 and 29–64. XRT, 1.8 Gy in 25 fractions (frs), started on day 29. Downstaged pts underwent either surgical operation (SO) or received brachiterapy (XBRT) 15 Gy in 3 frs. Primary end-point was 1-year PFS. We here report the feasibility, ORR, % of R0 resections, and pCRs in the first 45 pts, out of 52 currently enrolled, since they had sufficient time to complete the planned treatment (PT). Results: 45 pts were enrolled from November 2002 to July 2004, median age 58 (range: 40–73), male:female 36:9, ECOG PS 0/1: 12/33, scc/ad: 38/7; cervical/thoracic/distal: 2/29/14, dysphagia Grade (G) 2/3/4: 15/10/6. Stage at presentation was as follows: T2N1 (2), T3N1 (30) T4 (9) M1a (4). Thirty-two (71%) pts have received the eight planned wks of FOXL; 9 pts interrupted therapy due to toxicity and 2 for PD. 44 pts started XRT and 40 (83%) completed the whole PT. Major toxicity included: leukopenia G3–4: 9% neutropenia G3–4: 13%, anemia G3–4: 4%, thrombocytopenia G3–4: 7%, DVT G3: 7% (always catheter related), mucositis G3–4: 13% diarrhea G3–4: 16%, neuropathy G3: 2%. Three pts died prematurely: 2 for toxicity and 1 for a massive esophageal bleeding. We recorded 22 PRs and 4 CRs (ORR: 65%). SO was attempted in 27 (60%) pts and was radical in 22 (81% of resected, 51% of treated). pCR was recorded in 6 (22% of operated on) pts. Three pts with negative post-treatment endoscopy and biopsy refused surgery. There were two postoperative deaths: one due to myocardial failure and one to ARDS. Conclusions: After 8 weeks of FOXL and concurrent XRT, a radical resection in more than 50% of initially unresectable LAEC pts, with modest toxicity, was possible. With these findings confirmed after a longer follow-up, a phase III comparison to cisplatin-containing chemoradiotherapy should be considered. No significant financial relationships to disclose.
Evaluation of PTEN and TMPRSS2-ERG abnormalities in prostate cancer by FISH and immunohistochemistry to address intra- and intertissue heterogeneity and disease progression.
Authors: A. M. Joshua, A. Evans, J. Squire, M. Yoshimoto, O. Ludkovski, S. Tan, A. Dobi, B. Furusato, G. Petrovics, S. Srivastava, I. Sesterhenn
Journal: Journal of Clinical Oncology (2011)

4651
PD-L1 expression in non-clear cell renal cell carcinoma.
Authors: André P Fay, Marcella Callea, Kathryn P. Gray, Thai Huu Ho, Jiaxi Song, Ingrid Carvo, Megan E. Lampron, Melissa L. Stanton, David F. McDermott, Michael B. Atkins, Gordon J Freeman, Michelle S. Hirsch, Sabina Signoretti, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2014)

424 Background: Programmed death-1 (PD-1) receptor negatively regulates T cell-mediated responses.PD-1 ligand (PD-L1) is aberrantly expressed in clear cell renal cell carcinoma (ccRCC) and is associated with worse prognosis. Levels of PD-L1 expressions in non-ccRCC and its association with clinicopathological features and survival are unknown. Methods: Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 97 patients with chromophobe (CHR), papillary (PAP), translocation Xp11.2 (TrL) RCC and oncoytoma (ONC) and were included in the analysis. PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). The assay was validated using FFPE cell line controls known to be positive or negative for PD-L1 expression by flow cytometry. PD-L1 tumor positivity (PD-L1+) was defined as ≥5% tumor cell membrane staining. For PD-L1 expression in immune cells, a combined score based on the intensity of infiltrate and percentage of positive cells was used. Baseline characteristics including stage/grade, and survival data were collected. Comparisons between PD-L1 expression and clinicopathological features were evaluated using chisq or wilcoxon rank sum tests. Cox model tests for association of PD-L1 expression with OS in univariate and multivariable analysis. Results: Among 97 patients, 12 (12.4%) were considered PD-L1+ in tumor cells: 2/36 (5%) of CHR RCC, 5/50 (10%) of PAP RCC, 3/7 (43%) of TrL RCC, and 2/4 (50%) of ONC. PD-L1 positivity in tumor cells was significantly associated with higher stage (p=0.026) and grade (p=0.046), as well as lower OS on univariate (p=0.02) but not multivariate analysis (p=0.29). On the other hand, PD-L1 positivity by immune cells was observed in 50 (51.5%) patients: 13/36 (36%) of CHR RCC, 30/50 (60%) of PAP RCC, 6/7 (86%) of TrL RCC, and 1/4 (25%) of ONC. PD-L1 positivity in immune cells did not correlate with stage (p=0.7), grade (p=0.1) or OS (p=0.8). Conclusions: PD-L1 expression is variable in non-ccRCC and depends on histology and tumor vs. immune cells scoring. Only PD-L1 positivity in tumors cells was associated with aggressive features. Patients with non-ccRCC should not be automatically excluded from trials of agents that target the PD-1/PD-L1 pathway.
Lymph node metastasis in patients with early pathologic T-stage rectal cancers: What does local excision leave behind?
Authors: Maria C. Russell, Yj Chiang, Barry W. Feig, George J. Chang, Miguel A. Rodriguez-Bigas, John Michael Skibber, Ryaz Chagpar, Janice N. Cormier, Y. Nancy You
Journal: Journal of Clinical Oncology (2012)

537 Background: As the interest in local excision (LE) for rectal cancer increases, the risk of residual nodal disease and local failure must be considered. We utilized a nationwide cancer registry to establish incidence and predictors of nodal metastasis in early pathologic T stage rectal cancers. Methods: Early path T stage rectal cancers (1998-2007) were identified from the National Cancer Database (NCDB), including pT1-2 tumors in patients not receiving neoadjuvant therapy (NT), or ypT0-2 tumors after NT. Proctectomy was performed in 22,416 (74.7%) and LE in 7,589 (25.3%) without NT. After NT, 7,481 (96.1%) underwent proctectomy and 300 (3.9%) LE. Nodal metastasis rates were calculated from proctectomy patients. Factors associated with nodal metastases were analyzed among those with ≥12 nodes assessed. Results: The incidence of nodal positivity was 12.5% for pT1 and 26.8% for pT2 tumors. Among those with ≥12 nodes examined, these rates increased to 16.9% and 28.6% respectively. After receiving NT, nodal positivity rates were 8.6% for ypT0, 12.9% for ypT1, and 21.4% for ypT2 tumors. These rates increased to 13.5%, 16.9% and 28.3% respectively when ≥12 nodes examined. In multivariate analysis, female sex, age &lt;50, higher T stage, higher histologic grade, mucinous/signet-ring features, and more than 12 nodes examined were all significantly associated with nodal metastases in both groups ( Table ). Conclusions: Among rectal cancers of early path T stages, the risk of nodal metastasis increases with higher path T stage and with greater number of nodes examined, regardless of receipt of NT. These findings must be carefully deliberated, given the current interests in expanding the role of LE based on pathologic T stage of rectal cancer. [Table: see text]
Metabolic abnormalities associated with wt loss during chemo-RT of HN cancer
Authors: A. Lin, S. Jabbari, F. Worden, C. Bradford, T. Teknos, D. Chepeha, M. Schipper, S. Urba, G. Wolf, A. Eisbruch
Journal: Journal of Clinical Oncology (2005)

5554 Purpose/Objective: Concurrent chemo-irradiation (chemo-RT) of head and neck (HN) cancer often leads to significant wt loss due to acute mucositis and dysphagia. We studied the metabolic consequences of wt loss during chemo-RT. Materials/Methods: 96 pts with locally advanced HN cancer were treated from 1995–2001 with 1–3 courses of induction cisplatin/5-FU followed with RT (70 Gy over 7 wks) concurrent with cisplatin (100 mg/m2 q3wks) (chemo-RT). Primary sites included larynx (48 pts), oropharynx (40 pts), hypopharynx (3 pts), and oral cavity (5 pts). Stages were III (38 pts) and IV (58 pts). Baseline wt, creatinine clearance, and metabolic laboratory evaluation was obtained prior to initiation of induction chemo and prior to chemo-RT. During the course of chemo-RT, weekly weights and laboratory evaluation were measured. Results: During induction chemo 2% of pts had >10% body wt loss and significant changes were found in BUN (p=0.04), BUN:creatinine ratio (p=0.03), HCO3- (p=0.01), Mg2+ (p=0.004), and albumin (p=0.001). There were no significant changes in wt (p=0.19), creatinine (p=0.93), K+ (p=0.79) or Na+ (p=0.43). During chemo-RT significant increases in BUN, creatinine, BUN: creatinine ratio, and HCO3- as well as significant decreases in wt, Mg2+, albumin, K+ and Na+ (all with p<0.0001) were observed. These changes were all significantly greater than those observed during induction chemo (p=0.001). During chemo-RT, 35% patients had >10% body wt loss. 5% had an increase in creatinine of more than x2 pre-chemo-RT values, all had a wt loss of >10%. There was a significant correlation between % body wt loss and % creatinine and BUN rise during the course of chemo-RT (R=0.40, p<0.0001). Conclusions: Significantly more metabolic alterations were observed during chemo-RT compared with induction chemo, including worsening of kidney function, which was significantly correlated with wt loss. While these findings do not establish a cause-effect relationship, they emphasize the importance of aggressive supportive measures of hydration and nutrition during chemo-RT. No significant financial relationships to disclose.
Progress of small molecular inhibitors in the development of anti-influenza virus agents
Authors: Xiaoai Wu, Xiuli Wu, Qizheng Sun, Chunhui Zhang, Shengyong Yang, Lin Li, Zhiyun Jia
Journal: Theranostics (2017)

The influenza pandemic is a major threat to human health, and highly aggressive strains such as H1N1, H5N1 and H7N9 have emphasized the need for therapeutic strategies to combat these pathogens. Influenza anti-viral agents, especially active small molecular inhibitors play important roles in controlling pandemics while vaccines are developed. Currently, only a few drugs, which function as influenza neuraminidase (NA) inhibitors and M2 ion channel protein inhibitors, are approved in clinical. However, the acquired resistance against current anti-influenza drugs and the emerging mutations of influenza virus itself remain the major challenging unmet medical needs for influenza treatment. It is highly desirable to identify novel anti-influenza agents. This paper reviews the progress of small molecular inhibitors act as antiviral agents, which include hemagglutinin (HA) inhibitors, RNA-dependent RNA polymerase (RdRp) inhibitors, NA inhibitors and M2 ion channel protein inhibitors etc. Moreover, we also summarize new, recently reported potential targets and discuss strategies for the development of new anti-influenza virus drugs.
Prognostic factor of carcinoma of the ampulla of vater after surgery.
Authors: Shinjiro Tomiyasu, Eri Oda, Hiroshi Tanaka, Shinji Ishikawa, Hiroki Sugita, Tetsumasa Arita, Yasushi Yagi, Hiroshi Takamori, Keiichiro Kanemitsu, Masahiko Hirota, Hideo Baba
Journal: Journal of Clinical Oncology (2015)

270 Background: General rules for biliary tract cancer in Japan were revised and Stage of biliary tract cancer was compliant with the seventh UICC. Carcinoma of the Ampulla Vater (CAV) is relatively good prognosis among the biliary tract cancer, such as lymph node metastasis, pancreatic invasion and perineural invasion has been reported to be prognostic factors. We investigated the validity of TNM-Stage by examining the prognostic factors from the outcome of resection experienced. Methods: To evaluate prognostic factors after surgery based on a series of 70 patients of CAV from 1996 to 2014. Twenty-eight patients received pancreatoduodenectomy (PD), 25 patients received pylorus-preserving pancreatoduodenectomy (PPPD) and 17 patients received subtotal stomach-preserving pancreatoduodenectomy (SSPPD). We reviewed and analyzed the clinicopathologic data, surgical outcomes, recurrence and survival. Results: Actuarial disease-specific survival (DSS) was 65 % at five years. In univariate analysis, pancreatic invasion, lymph node metastasis and duodenal invasion are significantly poor prognosis. In multivariate analysis, pancreatic invasion is the only poor prognostic factor (p = 0.0023, hazard ratio (HR) 5.31 [confidence interval (CI) 1.77-18.9 95%]); lymph node metastasis and duodenal invasion are not significantly different (p = 0.0672 and 0.8769, respectively). Also, in the study of relapse risk factors, pancreatic invasion and lymph node metastasis are significantly different. In TNM-Stage II, those of T3N0, 1 are poor prognosis than T1, 2N1 (p = 0.0334). Conclusions: Pancreatic invasion is an independent poor prognostic and recurrence risk factor. The Stage of Japanese Society of Biliary Surgery has reflect prognosis than TNM-Stage in carcinoma of the Ampulla Vater.
Hodgkin’s Disease (1975-2012): Long-Term Results of a Single Center
Authors: Tiraje Celkan, Gül Nihal Özdemir, Hilal Akı, Hilmi Apak, Alp Özkan, Metin Hallaç, İbrahim Adaletli, Rahşan Özcan, Şefika Arzu Ergen, İnci Yıldız
Journal: Blood (2014)
Modulating bevacizumab resistance: An alternative dosing strategy at progression.
Authors: A. G. Mammoser, N. A. Shonka, J. F. De Groot
Journal: Journal of Clinical Oncology (2011)

e12500 Background: Bevacizumab (BEV) is widely used and prolongs progression-free survival in patients with recurrent glioblastoma. However, all patients ultimately progress on BEV, at which time there is no effective salvage therapy. Preclinical evidence suggests that continuous VEGF inhibition promotes glioma resistance, and that restoration of some VEGF activity may limit glioma invasiveness, although the clinical impact of this approach is unknown. Methods: We present preliminary data on an alternative dosing schedule (5 mg/kg IV q 3-4 weeks), alone or in combination with chemotherapy, initiated in five patients that progressed on standard-dose BEV (SD-BEV; 10 mg/kg IV q2 weeks). Patient outcome from the point of dose adjustment was compared to 21 patients from MD Anderson enrolled in clinical trials of SD-BEV who were transitioned to a non-BEV containing regimen at progression (control group 1), and to published data in patients who continued on a regimen containing SD-BEV after initial progression (Quant 2009; control group 2). Results: Two of 5 patients presented with progressive DWI changes in addition to clinical decline and FLAIR/T2 changes at the time of SD-BEV failure. Improvement in DWI changes occurred following dose modification of BEV. Median OS from the time of SD-BEV failure in control group 1 was 11.7 weeks (0.6 weeks - 71.7 weeks) and 17.6 weeks in patients with glioblastoma in control group 2 (Quant 2009, personal communication), while median OS for patients treated with alternate dose BEV in our cohort was 46.0 weeks (23.9 weeks – 89.6 weeks), with all patients currently alive at the time of writing. Median age was 44, 50, and 48 for each group, respectively. Median number of treatment regimens was 4, 4, and 3, respectively. Conclusions: Survival following BEV progression remains poor despite multiple treatment attempts. In this small case series, OS from the time of SD-BEV failure and the initiation of alternate dosing exceeds that of patients remaining on SD-BEV. Early dose adjustment may prolong overall survival and should be further investigated for the treatment of recurrent BEV-failure glioblastoma.
Changes in regional immunity and metastasis in melanoma.
Authors: A. S. Mansfield, T. Grotz, J. W. Jakub, T. Flotte, L. Erickson, S. Markovic
Journal: Journal of Clinical Oncology (2010)

8567 Background: Despite the immunogenicity of melanoma, immunotherapy has not resulted in significant therapeutic improvements. We sought out to determine if differences in regional immune profiles of patients with melanoma existed. We compared sentinel lymph nodes (SLN) for the expression of markers of T cell polarity (CD4, CD8), dendritic cell maturation and costimulatory molecule expression (CD40, CD86, CD123), monocytes (CD14), cytokine expression (IL-10), lymphatic vasculature (LYVE), and vascular endothelial growth factors and receptors (VEGF-C and VEGFR3). Methods: SLN from patients with melanoma who had metastatic involvement (SLN+, n = 8), and from other patients who did not (SLN−, n = 12) were compared with reactive lymph nodes (RLN; n = 10) from patients who presented with lymphadenopathy, and dormant lymph nodes (DLN, n = 10) from patients with breast cancer who had a prophylactic contralateral mastectomy. We used immunohistochemistry to stain these nodes for CD4, CD8, CD14, CD40, CD86, CD123, HLA-DR, IL-10, LYVE, VEGFR3, and VEGF-C. Whole tissue sections were sequentially imaged with high power fields, and the positively-stained areas for each stain of each LN was determined. The expression of each marker was compared between the groups using the Kruskal-Wallis test. A Bonferroni correction was applied due to the multiple comparisons and a p value less than 0.004 was considered significant. Results: There were no differences demonstrated between SLN+ and SLN− in any of the markers that were tested. DLN demonstrated greater expression of CD8 (p < 0.0001), CD86 (p < 0.0001), and VEGFR3 (p < 0.0001) than RLN, SLN+ and SLN−. RLN demonstrated greater expression of CD8 (p < 0.001) than SLN+ and SLN−. SLN+ and SLN− demonstrated greater expression of CD40 (p < 0.0001) than DLN and RLN. No other differences were detected. Conclusions: Changes in regional immunity appeared to precede metastasis in melanoma. Whether there was tumor present in SLN or not, SLN demonstrated a marked decrease in cytotoxic T cells, costimulatory marker CD86, and VEGFR3 than DLN. Furthermore, the control lymph nodes (RLN, DLN) used for comparison can significantly impact interpretation as DLN and RLN significantly varied in their immune profiles. No significant financial relationships to disclose.
The efficacy, toxicity profile and tolerability of cisplatin plus 5-FU versus docetaxel plus carboplatin as induction therapy in locally advanced oral cancer: An experience from a tertiary cancer centre from South India
Authors: K. V. Sajeevan, K. C. Lakshmiah, A. Rani, T. M. Suresh, J. Ankit, K. Saini, S. Tejinder, U. Batra, G. Anupama
Journal: Journal of Clinical Oncology (2008)

17017 Background: Oral cancer is a major problem in India. Most of these patients present with locally advanced disease not amenable to upfront surgery. The treatments of these patients are often complicated with underlying malnutrition and toxicity. Chemotherapy is used as an induction treatment in these patients to achieve local control and outcome. Platinum based therapy with 5FU is commonly used. Taxane based regimens are becoming more common now a days with good overall response rate and survival at the cost of more treatment related complications. Methods: A total of60 patients with stage III, IV (without metastasis) squamous cell caner of oral cavity were randomized to receive either 3 cycles of cisplatin 100 mg/m2 day1 and 5 FU 1 gm/m2 day 1–4 continuous infusion or docetaxel 75 mg/m2 and carboplatin with AUC 6 on day 1. Cycles were repeated every 21 days. Patients who responded were subjected to surgery and/or radiotherapy. The aim was to assess the response rate, toxicity profile and tolerability among the two treatment group. Results: There were 30 patients in each treatment group. The pre treatment characteristics and demographic data were comparable in both groups. Conclusions: Induction chemotherapy with docetaxel and carboplatin was associated with better over all clinical response. The tolerability and toxicity profiles were comparable in both groups though there were more hematological toxicity in docetaxel, carbolated group. 5FU, Cisplatin (n) (%) Docetaxel, Carboplatin (n) (%) Total No. of patients 30 30 Median No. of cycles per patient 3 3 No. of patients required dose adjustments 3 (10) 0 (0) Delay in treatment ≥ 1 week 5 (16) 6 (20) Mucositis grade 3,4 ( CTC.v3.0) 6 (20) 5 (16) Febrile neutropenia 4 (13) 6 (20) Thrombocytopenia Grade 3,4 (CTCv3.0) 0 (0) 3 (10) Diarrhoea Grade 3, 4 (CTCv3.00) 2 (6) 0 (0) Overall clinical response 18 (60) 22 (73) No significant financial relationships to disclose.
Impact of population genetic substructure on association studies and risk assessment for melanoma.
Authors: I. Lobach, I. Belitskaya-Levy, J. D. Goldberg, H. Ostrer, R. S. Berman, A. C. Pavlick, R. L. Shapiro, I. Osman, P. Manga
Journal: Journal of Clinical Oncology (2011)

8521 Background: Genetic substructure due to varying allele frequencies between populations can confound association studies. Ancestry informative genetic marker (AIMs) data combined with statistical adjustment can reveal spurious associations and identify population specific risk markers. In melanoma, AIMs may also be risk markers, e.g. pigment genes contribute to melanoma susceptibility and segregate with ancestry. We have thus developed a strategy to adjust for population genetic substructure (PGS) using AIMs, while identifying potentially novel genes associated with melanoma. Methods: 326 melanoma patients and 400 controls of European ancestry from the New York area were studied. Tag SNPs spanning 14 candidate genes and 75 AIMs were genotyped and odds ratios (OR), unadjusted and adjusted for PGS, computed. Results: A PGS model based on all AIMs separated cases and controls, suggesting that some AIMs were associated with melanoma. An algorithm was developed to select AIMs least capable of separating cases and controls to infer PGS and validated using simulations. The resulting model, which was reproduced using 49 additional AIMs, separated Northern (NE) and Southern Europeans (SE) and was used to adjust ORs. Three classes of SNPs were identified 1. Associated before and after PGS correction in both groups (10 SNPs localized to MATP, TYR and ERCC5). 2. Not associated in unadjusted analysis, but significantly associated with melanoma in NEs (6 SNPs localized to XPC, ERCC4, OCA2, ASIP and TYR). 3. Associated with melanoma before but not after adjustment. To determine if AIMs that separate cases and controls can identify novel melanoma genes, we genotyped 16 SNPs localized to 4 genes that house candidate AIMs. Four SNPs at 2 different loci were associated with melanoma (e.g. AIM1: OR=0.35, p=0.01; AIM2: OR=1.77, p=0.03). Conclusions: Our approach demonstrated that ancestry is a significant confounding factor in identifying melanoma susceptibility genes. Melanoma risk markers vary significantly between groups and a DNA based risk assessment model will require adjustment for ancestry. We have also identified potentially novel susceptibility melanoma genes for futher study.