tbuckley/cabot-search huggingface dataset:
Implications of neuroendocrine tumor and diabetes mellitus on patient outcomes and care: A matched case control study.
Authors: Nina J. Karlin, Heidi E. Kosiorek, Matthew Buras, Kelley Rone, Patricia M. Verona, Kyle Coppola, Curtiss B. Cook
Journal: Journal of Clinical Oncology (2020)

612 Background: The aim of this study was to examine the impact of diabetes mellitus (DM) on survival in neuroendocrine tumor and the impact of neuroendocrine tumor on glycemic control in DM. Methods: Patients with newly diagnosed neuroendocrine tumor with and without DM were matched 1:1 according to age, gender, and year of cancer diagnosis (2005-2017). The file was linked to the electronic medical record to obtain information on DM and neuroendocrine tumor therapies and laboratory results. There were 59 matched pairs (total 118 patients) included in the analysis. We compared characteristics between cases and controls and assessed survival with the Kaplan-Meier method and Cox proportional hazards model. Mixed models compared hemoglobin A1c and glucose levels over time. Results: Median age of patients at diagnosis was 67 (40-86); 41% had stage IV disease. Women constituted 49% of the study population; 22% had pancreatic neuroendocrine tumor and 45% had another GI primary neuroendocrine tumor. No differences in race/ethnicity, marital status, alcohol or tobacco use were detected between cancer patients with and without DM. Mean BMI was significantly different between DM and non-DM patients (31.0 [7.90] versus 26.4 [5.27]); p = 0.011. Among those with DM, mean HbA1c during the year following cancer diagnosis was 7.3%. Mean glucose was significantly different between DM (159.1 [43.5] versus non-DM pts 117 [31.5]); p &lt; 0.001. Median follow-up time was 32.8 (2.4-165.4) months in alive patients. Three year survival was estimated at 72% (95% CI: 60-86%) for DM patients versus 80% (95% CI: 70-92%) in non-DM patients by Kaplan Meier method (p = 0.82 log rank test). Hazard ratio (stratification for matched pairs) = 1.33 (95% CI: 0.56 – 3.16; p = 0.51). Conclusions: DM did not adversely impact survival in patients with neuroendocrine tumor. Neuroendocrine tumor and its treatment did not affect glycemic control. This should be reassuring to oncologists and endocrinologists who treat patients with neuroendocrine tumors and diabetes.
Double Trouble: Concomitant <i>RB1</i> and <i>BRCA2</i> Depletion Evokes Aggressive Phenotypes
Authors: Amy C. Mandigo, Karen E. Knudsen
Journal: Clinical Cancer Research (2020)

Coordinate single- or two copy loss of the BRCA2/RB1 tumor suppressor genes, which reside in close chromosomal proximity, were found to be associated with aggressive prostate cancer and therapeutic resistance. Modeling these events and analyses of human cancers suggest that dual depletion of BRCA2/RB1 may represent a distinct subtype of disease.See related article by Chakraborty et al., p. 2047.
Phase I prospective trial of TAS-102 (trifluride and tipiracil) and radioembolization with 90Y resin microspheres for chemo-refractory colorectal liver metastases.
Authors: Nicholas Fidelman, Chloe Evelyn Atreya, Madeline J Griffith, Marion Alexandra Milloy, Julia C. Carnevale, Pelin Cinar, Alan P. Venook, Katherine Van Loon
Journal: Journal of Clinical Oncology (2020)

110 Background: Clinical efficacy of Yttrium-90 ( 90 Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC) is limited by extrahepatic disease progression. TAS-102 (trifluride and tipiracil) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. We aimed to evaluate the safety of the combination of TAS-102 and 90 Y resin TARE in a Phase I dose-escalation trial. Methods: Adult patients with bilobar liver-dominant chemo-refractory mCRC were treated with sequential Y90 resin TARE (body surface area dosimetry) in combination with TAS-102 (20mg/m 2 , 27mg/m 2 , and 35mg/m 2 ) in 28-day cycles according to 3+3 dose-escalation design. Beginning with cycle 3, TAS-102 was administered as monotherapy until disease progression or development of intolerable toxicity. Primary objectives were to determine maximum tolerated dose (MTD) of TAS-102, to assess toxicity, and to establish safety of TAS-102 in combination with 90 Y TARE. Results: A total of 14 patients (10 women, 4 men) have been treated to date. Among 9 patients enrolled in the dose-escalation phase, no dose limiting toxicities were observed. The MTD of TAS-102 in combination with Y90 was 35mg/m 2 , which was selected for the dose expansion phase. Severe adverse events (AEs) included: neutropenia (46%); anemia (23%); and thrombocytopenia (8%), which were attributed to TAS-102. All other AEs were mild and transient. At least one follow-up imaging study has been obtained for 13 patients, and 10 patients have completed trial participation. Disease control rate in the liver was 100%. Conclusions: The combination of TAS-102 and 90 Y TARE for patients with liver-dominant mCRC is safe and consistently achieved disease control within the liver. Severity and incidence of AEs is within the expected range of TAS-102 and 90 Y TARE monotherapy. A dose-expansion phase with planned enrollment of 12 patients is ongoing. Clinical trial information: NCT02602327.
Radiation as a single modality treatment in localized pancreatic cancer.
Authors: Walid Labib Shaib, Katerina Mary Zakka, Asser Shahin, Fares Yared, Jeffrey M. Switchenko, Christina Wu, Mehmet Akce, Olatunji B. Alese, Pretesh R. Patel, Mark William McDonald, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2020)

703 Background: Locally advanced pancreatic cancer (LAPC) is managed with multimodality therapy. A subset of patients with LAPC are not good candidates for aggressive treatment. The aim here is to evaluate the outcomes of single modality radiation therapy for LAPC using the National Cancer Database (NCDB). Methods: Data was obtained between years 2004 and 2013. Pancreatic ductal adenocarcinoma (PDAC) patients with unresectable local disease were identified excluding patients who received chemotherapy or surgery. Univariate and multivariable analyses identified factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used for patient characteristics and overall survival (OS). Results: A total of 6,590 patients were included; 480 (6.9%) received radiation therapy only and 6470 (93.1%) received no treatment. Mean age was 73.5 (range, 28‐90) years, with the majority being White (N = 5685; 83.2%) and female (N = 3779; 54.4%). Poorly differentiated histology and tumors ≥ 4 cm ( &gt; T3 stage) accounted for 47.8% and 52.7%, respectively. The median dose of radiation was 39.6 Gy. Stereotactic body radiation (SBRT) was given in 64 patients and external-beam/Intensity modulated radiotherapy (IMRT) in 416 patients. Charlson-Deyo score of +1 was seen in 34.4% of patients who received no treatment, 32.8% of patients who received SBRT and in 29.8% of patients who received external-beam IMRT. Radiation therapy was associated with improved OS compared to no treatment in univariate and multivariable analyses controlling for sex, Charlson-Deyo score, age, tumor size, amongst other covariates. Median OS for patients who received SBRT, external-beam/IMRT or no radiation was 8.6, 6.7 and 3.4 months; respectively (P &lt; 0.001). There is a significant difference in 12-month OS for the SBRT cohort (31.9%; 95% CI 20.9%-43.5%) compared to patients who received no radiation (15.1%; 95% CI 14.2%-16.0%), similarly seen on multivariable analysis (HR 0.50; 95% CI 0.38-0.65; P &lt; 0.001). Conclusions: The current study is the first to evaluate the efficacy of radiation as single modality therapy in LAPC. The results suggest a potential benefit for radiation therapy alone, in comparison to no treatment.
Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial
Authors: David A. Reardon, Annick Desjardins, James J. Vredenburgh, Donald M. O'Rourke, David D. Tran, Karen L. Fink, Louis B. Nabors, Gordon Li, Daniela A. Bota, Rimas V. Lukas, Lynn S. Ashby, J. Paul Duic, Maciej M. Mrugala, Scott Cruickshank, Laura Vitale, Yi He, Jennifer A. Green, Michael J. Yellin, Christopher D. Turner, Tibor Keler, Thomas A. Davis, John H. Sampson
Journal: Clinical Cancer Research (2020)

Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma.In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2.Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07-0.45; P < 0.0001).Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.See related commentary by Wick and Wagener, p. 1535.
金複合体オウラノフィンのマウスしゅようモデルを用いてのin vivo抗しゅよう活性およびin vitroの細胞毒性 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Mirabelli C K, Johnson R K, Sung C M, Faucette L, Muirhead K, Crooke S T
Journal: Cancer Research (1985)
Stereotactic radiotherapy (SRT) in oligometastatic (OM) colorectal cancer (CRC): Can we improve systemic therapy (ST) free interval?
Authors: Daniel Moore Freitas Palhares, Renata Reis Figueiredo, Katia Regina Marchetti, Allan Andresson Lima Pereira, Marcela Alves Teixeira, Luiza Faria, Brenda Pires Gumz, Rafael Gadia, Gustavo Dos Santos Fernandes
Journal: Journal of Clinical Oncology (2020)

154 Background: Metastatic colorectal cancer is common disease that is treated mainly with systemic chemotherapy with or without target therapy combined with local therapies when feasible. Patients with OM-CRC may benefit from local treatments, classically surgery, but more recently SRT is also showing to be effective. We aimed to access the benefit of SRT in patients (pts) with OM-CRC that where not candidates for surgery. Methods: This retrospective study evaluated all the pts with CRC from a single institution that did SRT for OM-CRC. SRT was done with 3D or IMRT/VMAT planning and daily volumetric image. 1-10 fractions were delivered aiming to keep BED &gt; 100Gy10. Dose was decreased as necessary to respect the constraints and minimize toxicity. Progression free survival (PFS) was analyzed from SRT to first progression or death, ST-free survival (STFS) from SRT to the beginning on next ST line or death. Results: We evaluated 32 consecutive pts from Sep/2014 to Jul/2019. Forty-six courses of SRT where performed. Mean age was 56 ± 13y, 60% female and 65% had colon cancer. 52% had metastatic disease after radical treatment. 63% were off ST by the time of the SRT. SRT treatment sites were lung and liver in 28%, bones and lymph nodes 13%, and CNS 11%. 72% of pts had only 1 treated lesion and 70% did 1 SRT course. Most commonly used regimens were 3 x 10-18Gy (35%), 4 x 10-12Gy (15%) and 5 x 7-10Gy (22%). 37% of treatments had BED≥100Gy 10 and 78% were done with IMRT/VMAT. With a median follow-up of 16.1m (IQR 8.2-32.7), the median PFS was 5.4m (95% CI 4.1-11.0) and STFS was 12.7m (95% CI 0.8-24.5). Patients with multiple SRT courses had longer interval between disease progression and starting the next ST line (median 2.2 vs 12.4m). Pts that where on ST holidays before SRT had higher STFS (HR = 0.24 95% CI 0.1-0.6, p = 0.001) probably due to selection bias (lower disease volume). The 3y OS was 71%, median was not reached. Conclusions: Local treatment with SRT for OM-CRC showed to be feasible and safe with promising PFS and OS that deserves further investigation. The median STFS superior to a year suggests that SRT can influence OM-CRC treatment positively, possible impacting quality of life and even treatment costs.
尿中8-イソプロスタグランジンF 2α は高血圧症の酸化ストレスの有用なマーカーである | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Okumura T, Fujioka Y, Kimura M, Kawasaki D, Naitoh Y, Morimoto S, Masai M, Sakoda T, Tsujino T
Journal: Circulation (2004)
The comparisons of the outcomes between surgical resection and proton beam therapy for single primary hepatocellular carcinoma.
Authors: Shunsuke Tamura, Yukiyasu Okamura, Teiichi Sugiura, Takaaki Ito, Yusuke Yamamoto, Ryo Ashida, Katsuhisa Ogi, Shigeyuki Murayama, Katsuhiko Uesaka
Journal: Journal of Clinical Oncology (2020)

482 Background: There are many treatment choices for hepatocellular carcinoma (HCC). Proton beam therapy (PBT) is considered a treatment option for HCC. The purpose of this study was to compare surgical resection (SR) and PBT in order to clarify the prognostic factors for operable HCC based on a single institution’s database. Methods: Patients with single primary nodular HCC ≤ 100 mm without vessel invasion on pretreatment imaging were divided into the SR group and PBT group. In the PBT group, the patients with unresectable HCC due to their liver function and/or performance status (PS) were excluded. Results: There were 314 and 31 patients who underwent SR and PBT, respectively. The median survival time in the SR group was significantly better than in the PBT group (104.1 vs. 64.6 months, p = 0.008). Regarding the relapse-free survival (RFS), there was no significant difference between the SR and PBT groups (33.8 vs. 14.0 months, p = 0.099). Conclusions: In RFS, the PBT group and the SR group were comparable. However, the PBT group was significantly worse than SR group in overall survival. SR may therefore be favorable as an initial treatment for HCC compared to PBT. Clinical trial information: 1856.
Sodium valproate: Sanofi is indicted in France for failing to warn adequately about birth defects
Authors: Clare Dyer
Journal: BMJ (2020)

The pharmaceutical giant Sanofi has been charged in France with failing to adequately warn pregnant women that its epilepsy drug Depakine (sodium valproate) carries a risk of birth defects.

Prosecutors have issued the indictment for aggravated deception and unintentional injuries after a three year investigation initiated by an organisation representing families of victims. The move does not necessarily mean that a trial will go ahead as the charges could yet be dropped.

The anticonvulsant, marketed around the world under various names including in the UK as Epilim, has been on the market since …
Analysis of hematologic adverse events (HeAEs) in trifluridine/tipiracil (FTD/TPI)-treated patients (pts) with or without renal/hepatic impairment (RI/HI): Pooled safety analyses from TAGS and RECOURSE.
Authors: Ben George, Eric Van Cutsem, Howard S. Hochster, Robert J. Mayer, Atsushi Ohtsu, Alfredo Falcone, Takayuki Yoshino, Toshihiko Doi, David H. Ilson, Hendrik-Tobias Arkenau, Karim A. Benhadji, Lukas Makris, Josep Tabernero, Kohei Shitara
Journal: Journal of Clinical Oncology (2020)

145 Background: FTD/TPI has shown clinical benefit and consistent safety in pretreated pts with metastatic colorectal cancer (mCRC) and metastatic gastric or gastroesophageal junction cancer (mGC/GEJC) in the phase 3 RECOURSE and TAGS trials, respectively. HeAEs were the most frequent AEs with FTD/TPI treatment. Methods: Pts in this analysis received ≥1 FTD/TPI dose in the TAGS and RECOURSE trials. Subgroups included pts with normal renal function (nRF; CrCl ≥90 mL/min), mild RI (CrCl 60–89 mL/min), moderate (mod) RI (CrCl 30–59 mL/min), normal hepatic function (nHF) and mild HI (total bilirubin &lt;1.5 X ULN, or AST &gt;ULN). Results: FTD/TPI was administered to 868 pts in the overall pooled population (OPP; n=335, TAGS [mGC/GEJC]; n=533, RECOURSE [mCRC]); 52%, 36%, and 11% had nRF, mild and moderate RI, and 66% and 33% had nHF and mild HI, respectively. Frequencies of any-cause grade (gr) ≥3 HeAEs were similar across subgroups and the OPP, except for gr ≥3 anemia and gr ≥3 leukopenia, which were higher with mod RI (table). In the OPP, most gr 3/4 neutropenia events occurred within the first 2 cycles (median time to onset [mTTO], 49 d). Median time to resolution (mTTR) was 8 d. Gr 3/4 neutropenia TTO and TTR in most subgroups were consistent with the OPP, except with mod RI (mTTO, 29 d). HeAE management and correlative efficacy analyses will be presented. Conclusions: In this pooled analysis of pts with mCRC and mGC/GEJC, HeAEs with FTD/TPI in pts with mild to mod RI and mild HI were manageable and not largely different from those in the OPP. Clinical trial information: NCT02500043 and NCT01607957. [Table: see text]
Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis
Authors: Surbhi Sidana, Eli Muchtar, M. Hasib Sidiqi, Dragan Jevremovic, Angela Dispenzieri, Wilson Gonsalves, Francis Buadi, Martha Q. Lacy, Suzanne R. Hayman, Taxiarchis Kourelis, Prashant Kapoor, Ronald S. Go, Rahma Warsame, Nelson Leung, S. Vincent Rajkumar, Robert A. Kyle, Morie A. Gertz, Shaji K. Kumar
Journal: American Journal of Hematology (2020)

We evaluated bone marrow minimal residual disease (MRD) negativity in 44 patients with light chain (AL) amyloidosis using next generation flow cytometry (sensitivity ≥1 × 10-5 ; median events analyzed: 8.7 million, range: 4.8 to 9.7 million). All patients underwent MRD testing in 2 years from start of therapy (median: 7 months). The overall MRD negative rate was 64% (n = 28). The MRD-negative rate after one-line of therapy was 71% (20/28). And, MRD negative rates were higher with stem-cell transplant as first-line therapy (86%, 18/21) vs chemotherapy alone as first-line treatment (29%, 2/7), P = .005. The MRD negative rate amongst patients in complete response was 75% (15/20), and in very good partial response, 50% (11/22). There were two patients in partial response/rising light chains (with renal dysfunction) who were MRD negative. There were no differences in baseline characteristics of MRD negative vs MRD positive patients, except younger age amongst MRD-negative patients. Patients with MRD negativity were more likely to have achieved cardiac response at the time of MRD assessment, 67% (8/12) vs 22% (2/7), P = .04. Renal response rates were similar in both groups. Progression free survival was assessed in the 42 patients achieving CR or VGPR. After median follow-up of 14 months, the estimated 1-year progression free survival in MRD negative vs MRD positive patients was 100% (26 patients, 0 events) vs 64% (16 patients, five events), P = .006, respectively. MRD assessment should be explored as a surrogate endpoint in clinical trials and MRD risk-adapted trials may help optimize treatment in AL amyloidosis.
Low Erythrocyte Glutamine-to-Glutamate Ratio: A Novel Biomarker of Hemolysis and Pulmonary Hypertension in Sickle Cell Disease.
Authors: Claudia R. Morris, Jung Suh, Ward Hagar, Sandra Larkin, D. Anton Bland, Martin Steinberg, Elliott Vichinsky, Mark Shigenaga, Bruce Ames, Frans Kuypers, Elizabeth Klings
Journal: Blood (2007)
Reponse to Cabazitaxel in the Postchemotherapy Setting in Crpc Patients Previously Treated with Docetaxel and Abiraterone Acetate
Authors: L. Albiges, S. Le Moulec, Y. Loriot, M. Gross Goupil, T. De La Motte Rouge, A. Guillot, K. Fizazi, C. Massard
Journal: Annals of Oncology (2012)
Impact of cachexia in advanced NSCLC patients treated with PD-1 inhibitor.
Authors: Hitomi Jo, Hidehito Horinouchi, Shigehiro Yagishita, Yuki Shinno, Yusuke Okuma, Tatsuya Yoshida, Yasushi Goto, Noboru Yamamoto, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2020)

44 Background: Cancer cachexia is known to a multifactorial catabolic syndrome and is observed 15-40% in general cancer population with worse prognosis. A recent study suggested a shorter survival period in non-small cell lung cancer (NSCLC) patients with a higher pembrolizumab clearance associated with cachexia. We here conducted analyses for the clinical impact of cachexia in advanced NSCLC treated with pembrolizumab. Methods: We evaluated consecutive advanced NSCLC patients who received pembrolizumab between March 2017 and December 2018 at the National Cancer Center Hospital. Cachexia was defined as a body weight loss &gt;5% over the past 6 months or &gt;2% in patients with a BMI &lt;20 kg/m2 at the start of treatment. Information on patient age, sex, performance status, histology, driver mutation status, smoking status, disease stage, treatment line, and PD-L1 tumor proportion score were recorded. The overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were investigated according to the presence of cachexia. Univariate and multivariate analyses were performed. Results: A total of 157 NSCLC patients received pembrolizumab during the study period. Of these, 134 patients with information for body weight were included in the final analysis. Patients with cachexia accounted for 35% (47 out of 134) of this cohort. The ORR was 38% among the patients with cachexia and 35% among those without cachexia. The median PFS was significantly shorter for the patients with cachexia than for the patients without cachexia (median PFS, 4.2 months vs. 7.1 months; hazard ratio, 1.63; 95% confidence interval, 1.06 – 2.53; P = 0.02). The median OS was significantly shorter for the patients with cachexia (median OS, 8.6 months vs. NR; hazard ratio, 1.83; 95% confidence interval, 1.03-3.25; P = 0.04). The presence of cachexia was independently associated with a shorter PFS in a multivariate analysis. Conclusions: The presence of cachexia was significantly associated with a shorter PFS and OS in our study cohort. Screening for cachexia may help to identify patients who are more likely to achieve a durable response.