tbuckley/cabot-search huggingface dataset:
Spectrum of HIV/AIDS-associated cancers in south India.
Authors: Shruti Prem, Geetha Narayanan, Jayaprakash Puthuveettil, Jayasree K, Vijayalakshmi K
Journal: Journal of Clinical Oncology (2014)

e12534 Background: India harbors the second largest number of HIV patients in the world.The aim of this study was to study the cancer pattern in patients diagnosed with HIV and cancer in south India. Methods: We included patients diagnosed with HIV and cancer over a ten year period from 1999-2009 at the Regional Cancer Centre, Thiruvananthapuram. We used the gender specific proportions of each cancer site for the year 2005 as per our Hospital Cancer Registry to estimate the expected number of various cancers among HIV positive cancer patients during the period 1999-2009. The observed number of site-specific cancers was divided by the expected number to obtain the proportional incidence ratio (PIR). Results: We studied 77 patients with HIV and cancer. There were no cases of Kaposi’s sarcoma. 42 (54.5%) patients had AIDS defining cancers and 35 (46.5%) had non-AIDS defining cancers. NHL was the commonest malignancy seen overall (39 patients) and DLBCL was the commonest subtype (17 patients). The top 3 cancers in males were NHL (n=33), oral cancers (n=7),carcinoma lung (n=3) and soft tissue sarcoma (n=3). In females the top 3 cancers were NHL (n=6),carcinoma breast (n=5) and invasive cervical cancer (n=3). The PIR was markedly increased for NHL ( PIR in males-21.3, 95%CI20-22.8, PIR in females- 17.7, 95% CI15.8-20 ). In males the PIR was also increased for penile carcinoma (PIR-2.83, 95% CI 2.4-3.3) and Hodgkin’s lymphoma (PIR-3.96, 95% CI 3.3-5.2). In females the PIR was also increased for carcinoma thyroid (PIR-27.8, 95% CI 14.5-339),carcinoma vagina (PIR-3.6, 95%CI 3.1-4.2),carcinoma pancreas (PIR-5.1, 95% CI 4.2-6.3) and AML (PIR-2.6, 95%CI 2.4-2.96) but the number of patients with these four diagnoses was very small. Conclusions: The absence of Kaposi's sarcoma and the increased proportion of NHL and non-AIDS defining cancers among HIV infected patients indicates a different spectrum of HIV associated malignancies in south India than reported in the West. This may be due to the predominantly hetero-sexual mode of HIV transmission seen in India and the low prevalence of HHV-8 virus in the general population. The increased incidence of NADCs like oral cancers may be due to co-existing risk factors like smoking and alcohol use which were common among patients in our study.
Oncologists’ priorities for breast cancer follow-up.
Authors: Heather B. Neuman, Nicole Steffens, Amye Tevaarwerk, Nora Jacobson, Maureen Smith, Caprice Christian Greenberg
Journal: Journal of Clinical Oncology (2014)

e20602 Background: Wide variation exists in the roles of medical, radiation, and surgical oncologists in breast cancer follow-up, which can lead to both duplication and gaps in care. Understanding each discipline's priorities in follow-up could provide insight into the observed variation and identify opportunities for improving care quality. Methods: We used qualitative content analysis to explore medical, radiation, and surgical oncologists' perspectives on what is most important for them to provide during follow-up. We purposively sampled providers (n=35) whose practices ranges from 10%-100% breast patients and varied in years of experience (mean 14 years). Results: Surgical and radiation oncologists focused on local-regional assessments, including both recurrence and treatment side effects (skin toxicities, lymphedema, cosmesis). Other priorities included coordination of imaging and other oncologist visits. In contrast, medical oncologists highlighted assessment of distant disease (symptoms) and side effects of ongoing drug therapy. Conclusions: Follow-up priorities differed by oncology discipline. Understanding how oncologists prioritize aspects of follow-up can direct development of guidelines that delineate follow-up roles and responsibilities by discipline, thereby improving quality. Priorities Representative quotes Local-regional Recurrence Surgical: "I feel strongly that my job is to perform a good breast examination. I think an operated breast needs to be followed for life by a surgeon." Side-effects of completed treatment Radiation: "I think that the main benefit for radiation oncology staying involved is that a lot of patients don't know what is or isn't a radiation side-effect and many non-oncologists don't know either, so I spend a lot of time talking about what might be side-effects." Systemic Recurrence Medical: "Because, really what's happening is you have a surgical, radiation, and medical oncologist all evaluating for local recurrence. And then you only have the medical oncologist examining for systemic recurrence, so why not just have one person do all of it?" Side-effects of ongoing treatment Medical: "But I always explain to the patient, if they're taking a medication from me, then I will at least have to see them once a year."
Risk of cancer and use of glucose-lowering medications: The DIABMON project.
Authors: Peter Boyle, Mathieu Boniol, Alice Koechlin, Maria Bota, Chris Robertson, Jay Skyler, Geremia Bolli, Julio Rosenstock, Philippe Autier
Journal: Journal of Clinical Oncology (2014)

e12508 Background: Efficacy of glucose-lowering medications is demonstrated in clinical trials but effectiveness in practice depends on a number of factors including the safety profile. Methods: A systematic evaluation of the published literature has been undertaken to evaluate the effect of such medications on serious adverse events including cancer. Results: No significant difference was found in the incidence of malignancies among rosiglitazone treated patients (SRR=0.91, 95% CI (0.71, 1.16)). In prospective studies, there appears to be an increased risk of bladder cancer among users of pioglitazone when compared to other medications (SRR=1.24, 95% CI (1.05, 1.46)) although the two studies with the best methodology showed no increased risk. Compared to users of other insulins, there is no increased risk of cancer among glargine users in all forms combined (SRR=0.92, 95% CI (0.85, 0.99)) nor in breast cancer (SRR=1.11, 95% CI (0.98, 1.21)), colorectal cancer (SRR=0.85, 95% CI (0.76, 0.95)), prostate cancer (SRR=1.12, 95% CI (0.92, 1.35)), lung cancer (SRR=1.04, 95% CI (0.91, 1.10) nor pancreas cancer (SRR=0.98, 95% CI (0.94, 1.14)). Pancreas cancer has been reported to be increased among users of incretin therapies although few human data are available and more rigorous study is essential. There is no reduction in risk of breast cancer associated with metformin use (SRR=0.96, 95% CI (0.85, 1.08)) even for the longest duration of use (SRR=0.94, 95% CI (0.81, 1.09)). Conclusions: Cancer is a chronic disease which can take many years to develop into a clinical entity from the initial cellular damage. The follow-up time of the studies of glucose-lowering medications is brief by comparison. However, the overall situation regarding an increased risk of cancer with use of glucose-lowering medications appears reasonably reassuring although there are a few specific issues which still require clarification. The need for on-going monitoring is obvious and an on-going project of meta-analyses and their continuous update is on-going in the DIABMON project.
Propensity score matched comparison of persistence and adherence to first-line pazopanib (PAZO) versus sunitinib (SUNI) among advanced renal cell carcinoma (aRCC) patients.
Authors: Stacey DaCosta Byfield, Jeffrey T McPheeters, Tanya Burton, Saurabh P Nagar, Michelle Denise Hackshaw
Journal: Journal of Clinical Oncology (2014)

e17646 Background: Clinical trialsshow efficacy and safety for PAZO and SUNIfor aRCC but few studies have examined real world treatment patterns. This study compares persistence and adherence among patients who receive PAZO vs SUNI as first-line therapy for aRCC. Methods: A retrospective study using data from two large US claims databases was conducted. Adults with ≥2 RCC medical claims (ICD-9 189.0, 189.1) and ≥1 claim for PAZO or SUNI from 10/2009 to 7/2012 were included; index date was defined as the first fill date. Patients were continuously enrolled for 2 months before (baseline) and 6 months after (follow-up) the index date with no prior therapy and no other primary cancers. Evidence of drug-related adverse events based on ICD-9-CM codes was also examined. Persistence with index drug was compared using days to discontinuation, estimated level of persistence (ELPT) at 180 days, and proportion of days covered (PDC). Adherence was estimated using medication possession ratio (MPR). PDC was defined by dividing the number of days covered with the index drug by the number of follow-up days. For matched cohort pairs with >1 fill, MPR was defined by dividing the number of days covered with index drug by the number of days between the first and last index fill. Results: Among 97 PAZO and 349 SUNI patients, 84 matched pairs were identified. Both groups were balanced for demographics and clinical characteristics; mean (SD) age 63(9) and approximately 77% male. Fatigue and hypertension were identified in >20% of the matched pairs. Similar persistence and adherence were observed between the matched pairs (see Table). Conclusions: Persistence and adherence to first line PAZO and SUNI for aRCC were similar in the first 6 months after therapy initiation. Further study with larger cohorts and longer follow-up should be examined. PAZO (N=84) SUNI (N=84) p value Mean daily dose, mg (SD) 758 (101) 46 (8) - Days to discontinuation, mean (SD) 133 (63) 140 (56) 0.445 ELPT at 180 days, n (%) 45 (54) 47 (56) 0.732 PDC ≥ 80%, n (%) 44 (52) 47 (56) 0.622 MPR ≥ 80%, n (%)^ 48 (81) 55 (93) 0.071 ^ valid n=59, p <0.05=statistical significance.
Single nucleotide polymorphism of SOD2 to predict survival for Chinese gastric cancer patients received platinum/fluorouracil-based adjuvant chemotherapy.
Authors: Zhi Xu, Meilin Wang, John M. Luk, Jinfei Chen
Journal: Journal of Clinical Oncology (2014)

e15035 Background: The antioxidant enzymes SOD2 and GSTP1are involved in oxidative stress and drug detoxification, which may interfere with the efficacy of anticancer drugs. Here, we investigated the clinical associations of two functional single nucleotide polymorphisms (SNPs) of SOD2 and GSTP1in gastric cancer patients receiving curative surgery and adjuvant chemotherapy. Methods: A total of 740 gastric cancer patients were genotyped for SOD2 rs4880 and GSTP1 rs1695. Two hundred and sixty-two of them received platinum/fluorouracil-based adjuvant chemotherapy. Pearson’s chi-square test, Kaplan-Meier survival and Cox proportional hazards regression analyses were used to examine the relationships between SNPs and clinical outcomes. Results: SOD2 rs4880 CT/CC significantly associated with high grades of invaded depth of tumor and regional lymph nodes metastasis. SOD2 rs4880 CT/CC and GSTP1 rs1695 GA/GG were identified as “risk” genotypes associated with inferior survival. Combined “risk” genotypes predicted the worst clinical outcome, especially for the patients receiving adjuvant chemotherapy (HR, 2.694; 95%CI, 1.405-5.165, P=0.003). Stratification analysis showed the effect of SOD2 rs4880 CT/CC on survival affected significantly for patients with stage III disease (HR, 1.421; 95%CI, 1.077-1.875, P=0.013) or patients receiving adjuvant chemotherapy (HR, 1.903; 95%CI, 1.294-2.799, P=0.001), whereas GSTP1 rs1695 GA/GG strongly affected patients with proximal gastric cancer (HR, 1.449, 95%CI: 1.015-2.068, P=0.041), tumor size larger than 5cm (HR, 1.450; 95%CI: 1.051-2.001, P=0.024), or patients without adjuvant chemotherapy (HR, 1.317; 95%CI: 1.012-1.714, P=0.038). Conclusions: The two functional polymorphisms involved in oxidative stress would affect the survival of gastric cancer patients. SOD2rs4880 could be used as a predictive marker for patients receiving platinum/fluorouracil-based adjuvant chemotherapy.
A phase II randomized, open label study of sipuleucel-T versus sipuleucel-T and tasquinimod in patients with metastatic castrate-resistant prostate cancer (CRPC).
Authors: Roberto Pili
Journal: Journal of Clinical Oncology (2014)

TPS5110 Background: A barrier for cancer immunotherapy is the presence of suppressive cells including myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs). Tasquinimod is a novel anti-tumor agent that has shown clinical activity in patients with CRPC (Pili R et al JCO 2011). A potential target of tasquinimod is the inflammatory protein S100A9, which is associated with the accumulation and function of tumor suppressive myeloid cells. Our preclinical studies showed that combination of tasquinimod with a tumor vaccine in a prostate cancer model significantly enhanced the anti-tumor effects in mice. Compared to single treatment, tasquinimod inhibited MDSC and M2 polarized macrophages. T cell effector functions, including cell-mediated cytotoxicity and IFN-γ production, were potentiated. Taken together, these data suggest that pharmacological targeting of suppressive myeloid cells by tasquinimod induces therapeutic benefit in combination with cancer immunotherapies. Methods: This is a Phase II, open-label, randomized study to assess the immunomodulation of tasquinimod in combination with sipuleucel-T in patients with metastatic, castrate-refractory prostate cancer. 60 subjects will be randomized in a 1:2 ratio to either sipuleucel-T or sipuleucel-T + tasquinimod, respectively. The primary endpoint is change from baseline in immune response, which will be evaluated over time (Weeks 0, 2, 6, 26 and 52) with an IFN-γ ELISPOT assay specific for PA2024. Descriptive summaries of safety assessments and immune response parameters will be generated on a periodic basis. Key secondary endpoints include progression free survival and overall survival. Correlative studies will include assessment of immune response to sipuleucel-T and effects of tasquinimod on the inhibition MDSCs and other immune cells at defined time points post treatment. Blood samples will be analyzed for immune cell sub populations. CD4+, CD4+/Foxp3, CD8+ cells, NK cells will be quantitated by FACS analysis. Additional studies will include assessment of clinical efficacy based on PSA response, response on imaging, and change in circulating tumor cells.
Association between metformin (M) use and survival among non-small cell lung cancer (NSCLC) patients (pts).
Authors: Alice K Fortune-Greeley, Christina D. Williams, Jessica K Paulus, Michael J. Kelley
Journal: Journal of Clinical Oncology (2014)

7568 Background: The antidiabetic drug M may improve cancer-specific survival; however, little is known about the association between M use and survival among NSCLC pts. Methods: We retrospectively identified pts diagnosed with stage I-IV NSCLC from the Veterans Affairs Central Cancer Registry. A diagnosis of type 2 diabetes (DM) within 6 months of diagnosis was obtained from VA administrative data. Anti-DM medication (med) use, including M, was identified using VA pharmacy data. We used Cox proportional hazards regression controlling for age, race, BMI, stage, co-morbidities, HbA1C, and NSCLC treatment to estimate adjusted hazard ratios (AHR) to compare mortality risk among (1) DM pts with M use (2) DM pts with non-M anti-DM med use (3) DM pts with no anti-DM med use and (4) non-DM pts. Results: Between 2001-2008, 51,824 pts were diagnosed with NSCLC, 19% (n=9,982) of whom had a diagnosis of DM. Of the DM pts, 33% (n=3,309) were treated with M, 41.2% (n=4,113) were treated with non-M anti-DM meds, and 26% (n=2,560) were not treated with any anti-DM meds. When compared to non-DM pts, DM pts treated with M had similar survival [AHR: 0.99; 95% CI: (0.96, 1.03)] while DM patients treated with non-M anti-DM meds [AHR: 1.14; 95% CI: (1.10, 1.18)] or who received no anti-DM meds [AHR: 1.10; 95% CI: (1.05, 1.15)] were associated with poorer survival. DM pts treated with M were associated with improved survival compared to DM pts treated with non-M anti-DM [AHR: 0.86; 95% CI: (0.82, 0.91)]. DM pts treated with M had a similar improved survival relative to DM pts treated with non-M anti-DM meds across all stage groups [stage I/II: AHR 0.85; 95% CI: (0.77-0.93), stage III: AHR 0.88; 95% CI: (0.81-0.97), stage IV: AHR 0.86; 95% CI: (0.80-0.99)], including stage IA [AHR 0.83; 95% CI: (0.75-0.93)]. Conclusions: M use in NSCLC pts with DM is associated with (1) similar survival to non-DM pts, and (2) improved survival among DM NSCLC pts. These associations were observed regardless of stage, suggesting a broad anti-NSCLC effect of M or an unidentified confounding factor.
Predictive ability of blood neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in gastrointestinal stromal tumors (GIST).
Authors: Jennifer M. Racz, Michelle C. Cleghorn, M. Carolina Jimenez, Eshetu G. Atenafu, Timothy D. Jackson, Allan Okrainec, Lakshmikumar Venkat Raghavan, Fayez A. Quereshy
Journal: Journal of Clinical Oncology (2014)

10556 Background: The immune response, specifically the neutrophil-to-lymphocyte ratio (NLR), has recently been shown to be prognostic in untreated, primary GIST. Moreover, the platelet-to-lymphocyte ratio (PLR) has been shown to predict outcome in several gastrointestinal tumors; however, no studies have examined its predictive ability in GIST. This study serves to evaluate the prognostic utility of NLR and PLR in patients undergoing surgical resection for GIST. Methods: All patients who underwent surgical resection for primary, localized GIST from 2001 to 2011 were identified from a prospectively maintained database. Demographic profile, clinicopathologic variables, laboratory values and recurrence rates were analyzed. NLR and PLR were both assessed pre-operatively. Survival curves were calculated by the Kaplan-Meier product limit method and compared by the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to identify associations with outcome variables. High/low NLR and PLR were determined using optimization techniques, and defined as ≥2.04/<2.04 and ≥245/<245, respectively. Results: 93 patients were included. On univariate analysis, PLR was associated with recurrence-free survival (RFS) (HR .271, 95% CI .078 – .938, p = .039). PLR was also associated with RFS on multivariate analysis (HR .048, 95% CI .003 – .884, p = .041). Patients with low PLR had 2- and 5-year RFS of 94 and 84%, compared with 57 and 57% in those with high PLR. RFS in patients with mitotic rate ≤5/50 HPF with low PLR was significantly longer than in those with high PLR (p = .007). Similarly, RFS in patients with tumor size <5 cm with low PLR was significantly longer than in those with high PLR (p = .004). NLR was not associated with either RFS (p = .226) or overall survival (p = .994). Conclusions: Although there was no association between NLR and survival, a low PLR was associated with improved RFS, especially in tumors with mitotic rate ≤5/50 HPF or <5 cm. The independent prognostic ability of PLR to predict disease recurrence in these patients suggests that it may play a role in risk stratification schemes when deciding which patents will benefit from adjuvant therapy.
Antileukemic Activity of 8-Chloro-Adenosine (8-Cl-Ado) Is Mediated By Mir-155 Degradation and ErbB3 Binding Protein (Ebp1)-Dependent p53 Activation: A Novel Therapeutic Approach for FLT3-ITD Acute Myeloid Leukemia (AML)
Authors: Ralf Buettner, Le Xuan Truong Nguyen, Bijender Kumar, Corey James Morales, Chao Liu, Lisa S Chen, Tea Pemovska, Ryan Thompson, Ling Li, Dinh Hoa Hoang, Bin Zhang, Lucy Ghoda, Claudia Kowolik, Mika Kontro, Krister Wennerberg, Calum Leitch, Xiaochun Yu, Ching-Cheng Chen, David Horne, Varsha Gandhi, Vinod A. Pullarkat, Guido Marcucci, Steven T Rosen
Journal: Blood (2018)
基底细胞癌中的 SLC7A5、SLC7A7、SLC7A8 和 TDO2
Authors: E. Tina, S. Prosén, S. Lennholm, G. Gasparyan, M. Lindberg, A. Göothlin Eremo
Journal: British Journal of Dermatology (2019)

基底细胞癌 (BCC) 是最常见的非恶性皮肤癌,世界范围内的 BCC 患者数量正在增多。尽管癌症间存在差异,一些癌症的特异性变化可在所有病例中发现。这些变化可能包括肿瘤特异性因子(这些因子可能帮助医生诊断 BCC 或预测其发生)的表达,因此可能导致新的靶向药物的开发。在我们的研究中,我们比较了基底细胞癌与健康皮肤中的基因表达。基因表达是特定基因被激活后产生所需蛋白的过程。基本而言,细胞将表达某些基因,具体取决于细胞将要扮演的角色。此研究的作者使用了微阵列,即一种能够分析单一样本中数以千计基因的分析。在这些结果中,他们发现与氨基酸转运(例如 SLC7A5、SLC7A7 和 SLC7A8)和氨基酸代谢 (TDO2) 相关的基因表达较高值得进一步关注。肿瘤细胞通常依赖能量利用的变化,且需要获得基础组成成分来生长。在比较基底细胞癌与健康皮肤时, SLC7A5、SLC7A8 和 TDO2 基因在肿瘤中显著上调(增高)。作者们未能证实 SLC7A7 的基因表达更高。在比较这四个基因的细胞来源时,他们发现,SLC7A5 和 SLC7A8 蛋白由肿瘤细胞表达,而 TDO2 主要在周围组织和免疫细胞中发现。SLC7A7 蛋白位于颗粒层中,这是皮肤的最外层(称为表皮)中的一薄层细胞。SLC7A7 不太可能与肿瘤发生(癌症发生)有关。综上所述,作者们鉴定出了若干种在 BCC 中有潜在作用的蛋白,这些蛋白可能是特殊药物的潜在靶点,但需要进一步研究。
A systemic inflammation-based prognostic scores (mGPS) to predict overall survival of patients with small cell lung cancer.
Authors: Li Zhang, Ting Zhou, Zhihuang Hu, Xue Hou, Yan Huang, Hongyun Zhao, YuanYuan Zhao, Wenhua Liang, Wenfeng Fang
Journal: Journal of Clinical Oncology (2014)

e18548 Background: Small cell lung cancer (SCLC) has poor prognosis which differs much between patients. Recent studies have shown the combination of C-reactive protein and albumin (The modified Glasgow Prognostic Score, mGPS) had prognostic value in solid tumors. The aim of this study was to examine the role of mGPS in the prediction ofoverall survival in patients with SCLC. Methods: In this retrospective study, we enrolled 460 consecutive patients with pathologically confirmed SCLC from 2009 to 2011 in our cancer center, and 359 of them were eligible for analysis. Each patient was assigned a mGPS of 0, 1, or 2 based on the result of both C-reactive protein and albumin (0 = CRP ≤ 10 mg/L; 1 =CRP >10 mg/L and albumin≥ 35 g/L; and 2 = CRP>10 mg/L and albumin<35 g/L). Other information on patient demographics, performance status (PS), disease stage and overall survival (OS) were collected for univariate and multivariate analyses. Results: Among the 359 patients identified, 304 (84.7%) were men and the median age was 60 (22 to 82). Most of them had a PS score of 0 or 1 (95%) and limited disease (LD) accounted for 54.6%. The mGPS of 0, 1 and 2 was assigned to 66.3%, 30.6% and 3.1% of this population, respectively. The median overall survival was 29.0 months, with 33.4 months for LD and 25.6months for extensive disease (ED)(P<0.001). The overall survival was 30.4 months, 28.2 months, and 14.3 months in group mGPS-0, mGPS-1,and mGPS-2, respectively (P<0.001).Besides, PS score (P<0.001) and disease stage (P<0.001), but not age (P=0.63) or gender (P=0.16), were effective predictors of OS for patients with SCLC. The difference between mGPS groups was independent of PS and disease stage (P<0.001). Conclusions: This study demonstrated that mGPS was an independent predictor of overall survival for patients with SCLC. The assessment of mGPS could assist the identification of patients with poor prognosis and improve clinical management for SCLC patients.
Application of Real-Time PCR for the Detection of BCR-ABL1-like Group in Pediatric Acute Lymphoblastic Leukemia Patients
Authors: Grigory Tsaur, Tatiana Muhacheva, Sergey Kovalev, Alexander Druy, Petr Sibiryakov, Yulia Olshanskaya, Olga Soldatkina, Alexander Popov, Anna Vlasova, Oleg Arakaev, Tatiana Verzhbitskaya, Leonid Saveliev, Larisa Fechina
Journal: Blood (2018)