tbuckley/cabot-search huggingface dataset:
Phase II study of chidamide (CS055), a new subtype-selective oral histone deacetylase inhibitor, in patients with relapsed or refractory peripheral T-cell lymphoma.
Authors: Yuan-Kai Shi, Mei Dong, Xiao-Nan Hong, Wei-Jing Zhang, Ji-Feng Feng, Jun Zhu, Li Yu, Xiao-Yan Ke, Hui-Qiang Huang, Zhi-Xiang Shen, Yun Fan, Wei Li, Xie-Lan Zhao, Lu-Gui Qiu, He Huang
Journal: Journal of Clinical Oncology (2013)

8525 Background: Chidamide (CS055) is a new benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10. Chidamide has shown well-tolerated and favorable PK profiles in patients (pts) with advanced solid tumors and lymphomas. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL). Methods: 102 PTCL pts were enrolled. In the exploratory trial, pts were randomized to receive chidamide 30mg or 50mg twice per week for 2 weeks, followed by 1 week of rest. In the pivotal trial, chidamide was administered 30mg twice per week w/o drug-free holiday. The primary endpoint was overall response rate (ORR). Responses were assessed using IWC criteria. Results: In the exploratory trial, 19 pts were enrolled with 9 and 10 to the 30mg and 50mg arms, respectively. ORR was 11.1% (1 CR) in the 30mg arm and 40.0% (1 CR, 1 CRu, 2 PR) in the 50mg arm. One pt in the 50mg arm experienced drug-related grade 4 thrombocytopenia. In the pivotal trial, 83 pts were enrolled. Most pts were stage III (35.2%) or IV (45.9%). 23 pts (29.1%) had confirmed responses out of 79 evaluable pts in the pivotal trial (8 CR, 3 CRu, and 12 PR). Responses of 19 pts (24.1%) maintained for ≥12 weeks. ORR with 27.8% was obtained by the Independent Review Committee. 68 pts (81.9%) experienced at least 1 AE in the pivotal trial, with 52.9% of AEs ≤ grade 2. The most common AEs were thrombocytopenia (50.6%), leucocytopenia (39.8%), neutropenia(21.7%), and fatigue (9.6%). 1 pt had a grade 3 QTc prolongation. 7 pts (8.4%) experienced at least one SAE, in which a grade 4 thrombocytopenia was considered to be drug-related. 2 pts with responses (CR) have received chidamide for &gt; 43 months w/o evidence of cumulative toxicity. Conclusions: Chidamide as an oral single agent had significant and durable activity in pts with relapsed or refractory PTCL. Toxicities with the therapy were generally tolerable and manageable. The overall differences in pathological subtypes of pts enrolled and clinical profiles between chidamide and the two existing drugs, pralatrexate and romidepsin, will be discussed. Clinical trial information: ChiCTR-TNC-10000811.
Recurrent genetic alterations in primary central nervous system lymphoma of immunocompetent patients.
Authors: Alberto Gonzalez, Ahmed Idbaih, Blandine Boisselier, Anne Jouvet, Marc Polivka, Clovis Adam, Dominique Figarella-Branger, Catherine Miquel, Anne Vital, Herve Ghesquieres, Remy Gressin, Vincent Delwail, Luc Taillandier, Oliver L. Chinot, Pierre-Louis Soubeyran, Emmanuel Gyan, Sylvain Choquet, Carole Soussain, Karima Mokhtari, Khê Hoang-Xuan
Journal: Journal of Clinical Oncology (2012)

2023 Background: Little is known about the molecular pathogenesis of primary central nervous system lymphoma (PCNSL) in immunocompetent patients. Our objective was to identify the genetic changes involved in PCNSL oncogenesis and evaluate their clinical relevance. Methods: Twenty nine and four newly diagnosed, HIV-negative PCNSL patients were investigated using high-resolution single nucleotide polymorphism (SNPa) arrays (Infinium Illumina Human 610-Quad SNP array-Illumina; validated by real-time quantitative polymerase chain reaction) and whole-exome sequencing respectively. Molecular results were correlated with prognosis. Results: All PCNSLs were diffuse large B-cell lymphomas, and the patients received high-dose methotrexate-based polychemotherapy without radiotherapy as an initial treatment.SNPa analysis revealed recurrent large and focal chromosome imbalances that target candidate genes in PCNSL oncogenesis. The most frequent genomic changes were (i) 6p21.32 loss (79%), corresponding to the HLA locus; (ii) 6q loss (27-37%); (iii) CDKN2A homozygous deletions (45%); (iv) 12q12-q22 (27%); (v) chromosome 7q21 and 7q31 gains (20%). Sequencing of matched tumor and blood DNA samples identified novel somatic mutations in MYD88 (L265P hot spot mutation) and TBL1XR1 in 38% and 14% of the cases, respectively. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis showed that 6q22 loss (p=0.006 and p=0.01), and CDKN2A homozygous deletion (p=0.02 and p=0.01) were significantly associated with shorter progression free survival and overall survival. Conclusions: Our study identified novel genetic alterations in PCNSL, such as MYD88 and TBL1XR1 somatic mutations, which would both contribute to the constitutive activation of the NFkB signaling pathway and represent potential promising targets for future therapeutic strategies.
Advanced soft-tissue sarcoma in patients over age 75: Patterns of care and survival.
Authors: Delphine Garbay Decoopman, Mary Louise Keohan, Angela Cioffi, Robert G. Maki, Binh Bui Nguyen, Antoine Italiano
Journal: Journal of Clinical Oncology (2012)

10057 Background: There are no data regarding the management and the outcome of elderly patients (pts) diagnosed with advanced soft-tissue sarcoma (STS). Methods: The charts of pts aged ≥ 75 years and diagnosed with metastatic and/or unresectable STS between 1990 and 2011 at Memorial Sloan Kettering (New York) and Institut Bergonié (Bordeaux, France) were reviewed. Results: 189pts were included.Median age was 79 years (range 75-93).160 pts (84.5%) had metastatic disease. The most frequent histological subtype was leiomyosarcoma (n=57, 30%). The median age-adjusted Charlson comorbidity score was 10 (range 5-17). 120 pts (63.5%) received systemic therapy whereas 69 pts (36.5%) were managed with best supportive care (BSC) only. Pts who received BSC only were more likely ≥ 80 years old (58% versus 38%, p=0.01) and with performance status (PS) ≥ 2 (35% versus 14%, p=0.01). Single agent and combination therapy were delivered in 87 (72.5%) and 33 (27.5%) cases respectively. 67 pts (56%) received a 1 st -line anthracycline-containing regimen. The median progression-free survival of pts treated with systemic therapy was 4 months (95% CI: 2.5-5.5). 21 pts (17.5%) had to stop 1 st line treatment because of toxicity. On multivariate analysis, age ≥ 80 years, PS ≥ 2, and single-agent therapy were significantly associated with poor PFS. 51 pts received one or more further lines of therapies. At the time of analysis, 170 pts (90%) had died. 96% of deaths were related to the disease. The median OS for the entire cohort of pts was 9.6 months (95% CI: 7.3-12). The 1-year and 2-year OS rates were 43% (95% CI: 36–50), and 22% (95% CI: 16–28), respectively. The median OS of pts managed with systemic therapy and BSC were 12.5 months (95% CI: 8.4-16.6) and 5.1 months (95% CI: 3.7-6.5), respectively (p=0.02). However, on multivariate analysis, PS ≥ 2 and age-adjusted Charlson score ≥ 10 were the sole independent factors significantly associated with OS. Conclusions: A high proportion of elderly pts with advanced STS were considered unfit for chemotherapy. The OS of STS pts ≥ 75 years who were managed with systemic therapy seems similar to that of younger pts. Further efforts are needed to better define the optimal care for fit and unfit elderly pts with advanced STS.
Utility of PET-CT to evaluate retroperitoneal lymph node metastasis in high risk endometrial cancer.
Authors: Mostafa Atri, Zheng Zhang, Farrokh Dehdashti, Wui-Jin Koh, Shamshad Ali, Robert S. Mannel, Katherine Moxley, Paul DiSilvestro, Michael Pearl, Stephen Duane Watkins King, Marie Plante, xunClare Zhou, Michael Gold
Journal: Journal of Clinical Oncology (2015)

5524 Background: To assess if PET-CT improves accuracy of CT to detect lymph node (LN) metastasis in high risk endometrial cancer. Methods: This was a prospective HIPAA compliant ACRIN/GOG multicenter trial. Patients underwent contrast enhanced PET-CT followed by pelvic and abdominal lymphadenectomy. Seven independent blinded readers reviewed PET-CT and CT only images in different sessions at least one month apart. Region correlation was performed between pathology and review results for abdomen (right and left para-aortic, right and left common iliac) and pelvis (right and left external iliac and right and left obturator) regions. Abdomen and pelvic regions were combined, respecting laterality, to calculate accuracy values at participant level. Reference standard was pathology of surgically removed LNs. Reader average sensitivities/specificities of PET-CT vs CT were compared with generalized linear mixed models. Reader average AUCs were compared with Obuchowski’s method. Fleiss’ kappa was used to assess reader agreement. Results: A total of 207 patients had PET/CT and pathology proof in the abdomen from 215 patients enrolled between January 2010 and June 2013.Twenty-three of 207 patients had metastasis to abdominal LNs. All 23 abdominal positive and 26 randomly selected abdominal negative patients were used for reader study. Reader study cases were from 36 to 81 years old (mean; 62.7±9.6). Cancer stages were: I = 30, II = 14, III = 5; sixteen endometrioid, 17 serous, 6 carcinosarcoma or MMT, 6 mixed epithelial carcinoma, and 4 others. Three were 5 grade 2, 20 grade 3, and 24 unknown. Mean sensitivities of PET-CT/CT alone in abdomen were 0.65 (CI:0.57,0.72)/0.50 (CI:0.43,0.58) (p = 0.01) and in pelvis 0.65 (CI:0.57,0.72)/0.48 (CI:0.41,0.56) (p = 0.004). Corresponding mean specificities were 0.88 (CI:0.83,0.92)/0.93 (CI:0.89,0.96) (p = 0.11) and 0.93 (CI:0.86,0.96)/0.89 (CI:0.82,0.94) (p = 0.27). Mean AUCs were 0.78 (CI:0.66,0.89)/0.74 (CI:0.63,0.86) (p = 0.39) and 0.82 (CI:0.71,0.92)/0.73 (CI:0.63,0.84) (p = 0.02). Agreement for PET/CT was 0.81in both abdomen and pelvis. Conclusions: Addition of PET to diagnostic CT significantly increased diagnostic accuracy to detect LN metastasis in abdomen and pelvis. Clinical trial information: ACRIN6671GOG0233.
Prognostic determinants of adrenocortical carcinoma in adults.
Authors: Zhenyu Ding, Ming-Feng Zhang, Chun Wang, Hui Huang
Journal: Journal of Clinical Oncology (2014)

e15615 Background: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Prognostic factors of ACC were lacking in part owing to the paucity of the disease. This study was to investigate the clinical features and prognostic factors of adult patients with ACC. Methods: The adult patients (≥18 years) with ACC between 1st Jan. 1992 and 31st Jan. 2013 in West China Hospital were retrospectively analyzed. All patients need to be confirmed pathologically. The Kaplan-Meier and Cox proportional hazards regression models were used for survival analysis. Results: During this period, totally 94 patients were diagnosed with ACC. Among them, 77 patients with full records were enrolled and analyzed. The median age was 44 years (range 23–79). The patients were grouped according to the stages [9 (11.7%) cases, 27 (35.1%) cases, 38 (49.4%) cases and 3 (3.9%) cases in stage I-IV respectively] with an average diameter of the tumors of 10.3 cm (3-40 cm). 39 patients (50.6%) died (30th Sept 2013), with a median survival of 42 months. The age (≤45y vs. >45y; p=0.004), the tumor size (≤7.5 cm vs. >7.5 cm; p=0.043), staging (I–II vs. III–IV; p=0.000), clinical symptom (accidental vs. symptomatic; p=0.028), resection modality (laparotomy vs. laparoscopy; p=0.037), resection margins (positive vs. Negative; p=0.001), anemia (p=0.015), hypoproteinemia (p=0.032), and lactate dehydrogenase(p=0.008) were found to be associated with survival. In multivariate regression analysis, male patients (HR, 1.174; 95% CI 1.504–6.964; P=0.003) with advanced stage (HR, 1.435; 95%CI 1.925–9.155; P<0.000) and hypoproteinemia (HR, 0.819; 95%CI 1.064–4.837; P<0.034) seemed to have poor prognosis. Conclusions: ACC is a rare disease. The optimal treatment and prognosis remained largely obscure, and future large-scale prospective clinical study is warranted.
Randomized phase II crossover trial exploring the clinical benefit from targeting EGFR or VEGF with combination chemotherapy in patients with non-resectable biliary tract cancer.
Authors: Lars Henrik Jensen, Eva Fernebro, John Ploen, Jakob Eberhard, Jan Lindebjerg, Anders Kristian Moeller Jakobsen
Journal: Journal of Clinical Oncology (2015)

4071 Background: Non-resectable biliary tract cancer (BTC) is chemosensitive but there are no clear signals of effect from inhibiting any specific molecular target. The most promising targets are EGFR and VEGF. This trial evaluated the effect of adding panitumumab or bevacizumab to chemotherapy in a crossover design. Methods: Eligible patients with biopsy proven non-resectable BTC, 18+ years (y), KRAS wild-type and performance status (PS) 0-2 were randomized 1:1. Patients in arm A received panitumumab 6 mg/kg + gemcitabine 1,000 mg/m2 + oxaliplatin 60 mg/m2 on day 1 and capecitabine 1,000 mg/m2 b.i.d. on days 1-7 of a 2 weeks cycle. In arm B the chemotherapy was similar but added bevacizumab 10 mg/kg on day 1. At progression patients crossed over to bevacizumab in arm A and to panitumumab in arm B with the same chemotherapy backbone. The primary endpoint was the fraction of patients with PFS at six months (PFS6m). Secondary endpoints were PFS and overall response rate (ORR) both before/after crossover, overall survival (OS), toxicity, translational analysis and of second line treatment. Results: Three centres recruited 88 patients with a median age of 66 y (range 35-84). Selected base line characteristics were PS 0 (n = 23), 1 (n = 47), 2 (n = 18) and 73 metastatic/15 locally-advanced disease. Cases of grade > 2 toxicity were equal with more skin toxicity in arm A and more hypertension and infection in arm B. PFS6m in arm A/panitumumab was 43% (95%CI 29-58) and in arm B/bevacizumab 55% (95%CI 40-70). ORR was 46% (95%CI 30-62) in arm A and 18% (95%CI 6-31) in arm B. Median PFS was 6.1 m (95%CI 5.8-8.1) vs 8.2 m (95%CI 5.3-10.6) and OS 9.5 m (95%CI 8.3-13.3) vs 12.3 m (95%CI 8.8-13.3) in arm A vs B. OS was 17.7, 9.5 and 5.6 m in PS 0, 1 and 2, respectively. As a phase II study, comparisons between treatment arms were exploratory and revealed no differences in PFS6m (p = 0.39), median PFS (p = 0.13) or OS (p = 0.47), but ORR was superior in arm A (p = 0.01). Conclusion: Signals of clinical benefit with respect to PFS and OS were equal for targeting EGFR and VEGF, but ORR was higher with EGFR inhibition. This might have implications for potentially resectable disease in the neoadjuvant setting. Clinical trial information: NCT01206049.
Cridanimod and progestin therapy in hormone-resistant endometrial cancer.
Authors: Matthew J. Carlson, Koen De Geest, Xiaofang Wang, Kimberly K. Leslie, Donghai Dai
Journal: Journal of Clinical Oncology (2013)

5597 Background: Cridanimod is a novel small molecule that has been shown to increase progesterone receptor (PR) expression in rat endometrium. We hypothesize that cridanimod, in combination with progestin therapy, will increase PR expression and, thus improve survival in a mouse model of advanced, high grade endometrial cancer. Methods: Hec50co cells, established in our laboratory to represent genetically and phenotypically type II endometrial cancer, were injected into the peritoneal cavity of 96 athymic mice. These mice were randomly divided into 6 groups, receiving the following therapies: control (no therapy), medroxyprogesterone acetate (MPA) alone, cridanimod 1mg IM twice a week plus MPA, cridanimod 3mg plus MPA, cridanimod 6mg plus MPA, and adenovirus-mediated PR expression plus MPA. PR expression in tumor tissue and serum interferon (IFN) levels were assayed via Western blot and ELISA, respectively. Results: Kaplan-Meier survival analysis showed that the group receiving MPA plus 6 mg cridanimod twice a week had a significantly longer survival time than the control or MPA alone (62 ± 7.0 days vs 38 ± 5 or 33 ± 3, respectively, p &lt; 0.05). The group with MPA plus 3 mg cridanimod had a significantly longer survival than the group with MPA alone (56 ± 8.0 days vs 33 ± 3, p &lt; 0.05). Western blot analysis showed that PR proteins were substantially higher in xenograft tumors from animals treated with cridanimod at doses of 3mg and 6mg when comparing to the control and MPA alone groups, ELISA data showed significant increases in IFNα and -β in cridanimod-treated mice in a dose-dependent manner. Conclusions: Combined progestin and cridanimod therapy significantly improved survival of mice with high-grade, advanced endometrial cancer. Cridanimod significantly increased PR expression, suggesting that the therapeutic benefit of combined therapy is mediated by up-regulation of PR, which is likely to be mediated through cridanimod induction of IFNα and IFNβ expression. Further investigation is warranted to determine the utility of this promising agent.
Oral health status in Sichuan Province: findings from the oral health survey of Sichuan, 2015–2016
Authors: Wei Yin, Ying-Ming Yang, Hong Chen, Xue Li, Zhuo Wang, Li Cheng, Qiu-Dan Yin, Hong-Zhi Fang, Wei Fei, Fang-Lin Mi, Min-Hai Nie, Tao Hu, Xue-Dong Zhou
Journal: International Journal of Oral Science (2017)

To investigate oral health status in the residents of Sichuan Province, southwest China, a cross-sectional study was performed using the latest Oral Health Survey Basic Methods recommended by the World Health Organization. A multistage stratified random cluster-sampling method was used to enroll participants from the following three groups: children aged 3–5 years, adolescents aged 12 years, and people aged 65–74 years. In these three groups, the mean numbers of teeth that were affected by caries were 3.28, 0.86 and 5.13, respectively, resulting in a prevalence of 63.47%, 37.20% and 83.20%, respectively. Relative to the high rate of decayed teeth, the prevalence of fillings was very low in all age groups (0.97%, 7.24% and 5.43%, respectively). In the 12-year-old adolescent group, only 3.61% had good pit and fissure sealing. In addition, the rate of dental fluorosis was 24.80%, and the Community Fluorosis Index value was 0.39. In the elder group, the community periodontal index was 2.92. The prevalence in the elderly of having lost at least one tooth was 75.54%. Additionally, 4.44% of these participants were edentulous. The incidence of dental prosthesis was 51.75%, the proportion with a removable partial denture, a fixed denture, full dentures, dental implants and an informal fixed bridge was 21.59%, 11.45%, 4.64%, 0 and 16.67%, respectively. In this study, 8.2% of the elderly participants were affected by different types of oral mucosal lesions. Among such lesions, recurrent aphthous ulcers were most prevalent (2.69%) and oral lichen planuses were second (1.6%). The conclusion presented in this survey is that oral diseases, especially dental caries and periodontal disease, are frequent and common in Sichuan province, China. Moreover, the treatment rate is very low, and primary prevention and treatment options are therefore urgently needed in this population. A survey of over 8 000 residents from Sichuan in China found evidence of poor oral health, especially dental caries and periodontal disease. The study, led by Tao Hu and Xuedong Zhou of Sichuan University, looked at teeth, gums and oral mucosa in three age groups: 3–5 years, 12 years, and 65–74 years. The examinations were performed using World Health Organization guidelines designed to promote international comparison. Despite significant improvements in recent years, oral disease in multiple forms was still highly prevalent in all age ranges, with rural areas suffering from poor disease prevention and treatment. The elderly had a particularly high prevalence of disease. The results of the survey provide strong evidence that improvement of oral health requires prioritization by local authorities.
Outcome parameters in node-negative vulvar cancer: A subset analysis of the AGO Care 1 study.
Authors: Linn Lena Woelber, Julia Kathrin Jueckstock, Felix Hilpert, Petra Neuser, Nikolaus De Gregorio, Severine Iborra, Frank Chen, Anika Habermann, Peter Hillemanns, Sophie Fuerst, Hans-Georg Strauss, Klaus H. Baumann, Falk Thiel, Alexander Mustea, Werner Meier, Philipp Harter, Pauline Wimberger, Lars Christian Hanker, Barbara Schmalfeldt, Sven Mahner
Journal: Journal of Clinical Oncology (2013)

5531 Background: Prognosis of node-negative vulvar cancer is generally favorable compared to node positive disease. However, a small proportion of node-negative pts experience early recurrence with subsequent need for radical interventions. Aim of this analysis was to identify possible prognostic factors in this subset of pts. Methods: The AGO CaRE 1 study was designed as retrospective survey of treatment patterns and prognostic factors in vulvar cancer. Pts with primary squamous-cell vulvar cancer stage ≥1b treated at 29 gynecologic cancer centers in Germany 1998-2008 were included in a centralized database. Results: A total of 1618 pts were documented, 802 were node negative (pN0) after surgical staging and further analyzed. Median age was 66 yrs (21-94); 399 (49.8%) had pT1b, 365 (45.5%) pT2, 36 (4.5%) pT3 and 1 pT4 tumors; in 1 pt tumor stage was unknown. Median tumor size was 20 mm (1–345) and depth of invasion 4 mm (0.75–60). 703 (87.7%) pts had an R0 resection with a minimal margin of 5 mm (0.2–33); there were 46 R1 (5.7%) resections and 53 (6.6%) pts with unknown margin status. 692 pts (86.3%) received a full groin dissection (178 after sentinel node dissection) and in 85 pts (10.6%) only a sentinel node procedure was performed; surgery type was unknown in 25 pts (3.1%). 73 pts (9.1%) underwent adjuvant radiotherapy to the vulva. Median follow-up was 40 months. 169 pts (21.1 %) developed disease recurrence (thereof 111 (65.7%) at the vulva only and 53 (31.4%) at other locations, in 5 cases the localization was unknown) after a median of 17.7 months. 101 pts (12.6 %) died. To assess potential prognostic factors, multivariate analyses were performed including age, stage, tumor size, invasion depth, tumor grade, resection margin, adjuvant radiation, and mode of groin dissection [sentinel vs. full]) showing age as the only consistent prognostic factors for recurrence-free and overall survival. Conclusions: Even in the very large patient cohort of the AGO-CaRE database with more than 800 node-negative pts it was not possible to identify reliable clinicopathologic prognostic factors for node-negative disease. Identification of new biological markers will therefore be necessary to select high risk node negative pts for adjuvant treatment.