tbuckley/cabot-search huggingface dataset:
Trabectedin plus pegylated liposomal doxorubicin (PLD) prior to subsequent platinum chemotherapy in patients with platinum-resistant (PR) recurrent ovarian cancer (ROC): Results from OVA-301 follow-up.
Authors: Nicoletta Colombo, Antonio Casado, Consuelo Fernandez, Ignace Vergote
Journal: Journal of Clinical Oncology (2014)

5551 Background: OVA-301, a randomized phase III study of trabectedin plus PLD (n=337) vs. PLD alone (n=335) in patients with ROC demonstrated a statistically longer progression-free survival (PFS) in the combination arm (median PFS: 7.3 vs. 5.8 months; HR: 0.79; p=0.0190) (Monk, JCO 2010). However, among PR patients PFS (4.0 vs. 3.7 months) and overall survival (OS; 14.2 vs. 12.4 months) were not statistically different (Monk, EJC 2013). Based on in vitro (D'Incalci, AACR 2013) and clinical (Casado, ASCO 2013) data, trabectedin may lead to an increased sensitivity to subsequent platinum even in PR patients. Methods: An exploratory analysis of OS, counted from the administration of trabectedin/PLD or PLD until death, was performed in PR patients retreated with third-line platinum after OVA-301. Results: Overall, 59 PR patients with a median age of 55 years (range 26-79) were analyzed. Similar proportions of patients in each arm received subsequent platinum (trabectedin/PLD: 27/115, 23.5%; PLD: 32/117, 27.4%). Both in trabectedin/PLD (55.6%) and PLD (68.8%) arm most had serous-papillary histology and a median progression-free interval of 4.5 (range 0.7-6) and 4.2 (range 1.1-5.9) months, respectively. A median of 6 trabectedin/PLD cycles (range 1-20) and 5 PLD cycles (range 1-9) was given. Trabectedin/PLD resulted in a 42% risk reduction of disease progression or death compared with PLD (median PFS: 5.6 vs. 5.0; p=0.062). Patients with PR ROC treated with trabectedin/PLD, followed by the subsequent reintroduction of platinum achieved a 38% decrease in the risk of death compared with PLD (median OS: 22.2 vs. 15.50; p=0.078). Besides, patients pretreated with trabectedin/PLD who received a platinum salt had a 7.8-months longer median OS than those retreated with a non-platinum regimen (median OS: 22.2 vs. 14.4; p=0.055). Conclusions: Our results hypothesize that the intercalation with trabectedin/PLD prior to subsequent platinum retreatment may contribute to prolong PFS with apparent sensitization of the PR patients to allow further platinum retreatment which could ultimately lead to longer survival. Clinical trial information: NCT00113607.
Adjuvant radiotherapy (RDT) plus cisplatinum (Cis) and cetuximab (Cet) in resected head and neck squamous cell carcinoma.
Authors: Frederic Peyrade, Christian Righini, Jocelyn Gal, Karen Benezery, Benjamin Lallemant, Herve Le Caer, Alexandre Bozec, Philippe Follana
Journal: Journal of Clinical Oncology (2014)

6042 Background: Adjuvant RDT-chemotherapy is the standard for resected head and neck squamous cell carcinomas (SCCHN) with adverse histological prognostic factors (AHPF). Despite this treatment, half of the patients will relapse. Cet can enhance radiotherapy activity for patients (pts) with unresectable SCCHN. Thus, we conducted a phase II clinical trial to investigate a combination of Cis, Cet and RDT in resected SCCHN with AHPF. Methods: Pts with resected M0 SCCHN and at least one of the following (positive margin and/or N+>1, and/or extracapsular extension and/or vascular embolisms and/or perineural disease) were enrolled. They received a radiotherapy (2.0 Gy per day, 5 days a week for 7 weeks) with Cet (400 mg/m2 at D- 8 before RDT followed by 250 mg/m² weekly for 7 weeks) and Cis 75 mg/m² every 3 weeks. The primary objective was Disease Free Survival (DFS). Results: From March 2008 through January 2011, 45 pts were included. The median follow-up was 27 months (95% IC: 26-34 months). The median age was 57 years (range 28 - 71). Tumor location was oral, oropharyngeal and hypopharyngeal in 47%, 45% and 8% respectively. All of patients had at least one adverse prognostic factor mainly >1 N+ (82% of cases). 71% of patient received the all treatment as planned. The 2-year disease free survival was 60% [95% CI: 46-77%]. Median DFS has not been reached yet. The two-year OS was 78.9% [95% CI: 67.5-92.1%]. 86 % of patients presented at least one toxicity > Grade II according to NCI-CTCAE 3.0 classification. Grade 3-4 mucositis, dermatitis inside and rash outside radiotherapy fields were observed in 52%, 50% and 29% of pts respectively. 23 pts (52%) had a grade III/IV lymphopenia. Treatment was definitively discontinued because of toxicities in 6 cases. Conclusions: In patients with SCHNC with AHPF, the association of treatment with Cet, Cis and RDT appears to be safe and effective, comparing favorably with conventional RDT-Cis. Further protocols clinical investigations are justified to compare these two regimens in such a setting. Clinical trial information: NCT00875849.
Natural History of Patients with Multiple Myeloma Refractory to Elotuzumab and Outcomes of Subsequent Therapy with Anti-CD38 Monoclonal Antibodies
Authors: William Varnado, Megan Helena Jagosky, Zhubin Gahvari, Saurabh Chhabra, Ujjawal H Gandhi, Arjun Lakshman, Elizabeth McGehee, Ridhi Gupta, Ehsan Malek, Mark A. Fiala, Joshua Mansour, Barry Paul, Alyssa Barnstead, Saranya Kodali, Neppalli Amarendra, Michaela Liedtke, Kelly N. Godby, Yubin Kang, Ankit Kansgra, Emma C. Scott, Elvira Umyarova, Parameswaran Hari, Ravi Vij, Saad Z. Usmani, Robert Frank Cornell, Shaji K. Kumar, Natalie Scott Callander, Luciano J Costa
Journal: Blood (2018)
Abstract 16875: Trends in Uncontrolled Hypertension, Coronary Heart Disease and Stroke Mortality, and Million Heart Events Among Us Adults From 1999-2014: Difference Between Age Groups
Authors: Yuling Hong, Cathleen Gillespie, Matthew Ritchey, Lawrence Fine, Barbara Bowman
Journal: Circulation (2016)

Introduction: Hypertension (HTN) is the leading risk factor for cardiovascular disease (CVD). Control of HTN can effectively reduce fatal and non-fatal CVD events. The age disparity in trends of HT...
Risk factors for cancer-related venous thromboembolism in ambulatory patients.
Authors: Chiara Alessandra Cella, Michele Arcopinto, Florian Lordick, Chiara Carlomagno, Elide Matano, Katja Muehlberg, Dario Bruzzese, Roberto Moretto, Laura Attademo, Lucia Raimondo, Haiko Schloegl, Alfonso De Stefano, Maren Knoedler, Gertraud Stocker, Maria Gabrecht, Sabino De Placido
Journal: Journal of Clinical Oncology (2014)

e20625 Background: The awareness of venous thromboembolism (VTE) burden in ambulatory cancer patients is growing. Due to the heterogeneity in the individual risk profile, predictive risk scores have been proven to be useful in the identification of high-risk patients for targeting thromboprophylaxis. The first validated risk score, the Khorana score, identified four factors resulting in an increased risk for cancer patients to develop VTE. In our study, we tried to identify additional factors associated with VTE to improve the prediction of high-risk patients. Methods: We performed a prospective, observational study in 544 ambulatory patients (56 ± 12 SD y, BMI 27 ± 5 kg/m?, 382 female [70 %]) with solid tumors and ongoing antineoplastic treatments. Tumor sites were breast n=216 (40 %), colo-rectal n=115 (21 %), gyn/uro n=76 (14 %), pancreas n=45 (8 %), gastric n=22 (4 %), lung n=15 (3 %) and others tumors n=55 (10 %). In 264 (52 %) patients there was metastatic disease. We screened for VTE with ultrasound of the upper and lower extremities and correlated cancer-, treatment- and patient-related conditions with the incidence of VTE. Results: We found a VTE incidence of 10 % (n=54), over a median follow up of 10.1 months. According to Khorana score, 51 % of patients (n=247) belonged to the low-risk (score=0), 44 % (n=213) to intermediate-risk (score=1-2) and 6 % (n=27) to high-risk (score?3) class. Odds Ratio for intermediate risk was 1.18 (95% CI 0.65-2.15, p=.588) and 2.66 (95% CI 1.14-6.17, p=.030) for high-risk patients. In our analysis we identified previous VTE (p<.001), metastatic disease (p<.001), vascular/lymphatic compression by the tumor (p=.002), edema of extremities (p=.005), surgery in last 6 months (p=.003) and presence of central venous catheters (p=.013) to be additional significant risk factors for VTE. Conclusions: Khorana score showed a good predictive value for VTE in ambulatory cancer patients. We found other clinical conditions to be associated with VTE events. These data could implement the existing predictive scores with new clinical risk factors, and refine the decision making in the oncologic clinical practice.
A comparative study of ultrasonography and non-contrast computerized tomography of upper abdomen as a screening tool for biliary tract cancer detection in endemic community.
Authors: Teerapat Ungtrakul, Wachara Eamratsameekool, Paiboon Pensuwan, Surachate Siripongsakul, Nisakorn Kijsawat, Akeanong Worakitsitisatorn, Wariya Boonchuay, Sirachat Vidhayarkorn, Sirima Jaroenpatarapesaj, Benyapha Pothijaroen, Kriengkrai Kovingthangkoon, Chantit Poonlaab
Journal: Journal of Clinical Oncology (2014)

4087 Background: Biliary tract cancer is the leading cause of cancer-related death among men and women in the north and northeastern region of Thailand. Over 21 million people in this region are at risk for this type of cancer. However, no reliable test is currently available for its detection at the earliest stage. Despite the suggested use of ultrasonography in some reports, it is still not feasible for implementation as a screening tool across the country due to its high operational dependency and difficult quality control. This study aimed to compare the effectiveness between abdominal ultrasonography (AUS) and computerized tomography of upper abdomen (CT) without contrast for better outcome of detecting biliary tract cancer in the endemic area. Methods: Both male and female participants, aged 50-60 years old, from Phanomphrai district, Roi Et province, Thailand were enrolled. All of them were sent for AUS screening by a mobile imaging unit while CT without contrast was done using a standard protocol at a nearby imaging center. Confirmation of diagnostic studies or tissue biopsy was subsequently performed in the cases with liver nodules or bile duct dilatation. Experienced radiologists proceeded with CT scan and imaging data interpretation through tele-imaging system. Results: Of 839 participants, either liver nodule or bile duct dilatation was found in 54 cases (6%) by US and 44 cases (5%) by CT, respectively. Biliary tract cancer was diagnosed in 7 cases (5 cases of intrahepatic cholangiocarcinoma and 2 cases of extrahepatic cholangiocarcinoma). Five out of 7 cases were successfully treated with a curative intent. In addition, all cases were detected by AUS and CT without contrast, with the sensitivity and specificity of 100% and 94% for AUS and 100% and 95% for CT, respectively. Conclusions: Both CT without contrast and ultrasonography were effective screening tools for the detection of biliary tract cancer at an early stage in the endemic area. Nevertheless, the feasibility, cumulative radiation exposure, false positive rates, and operational costs need to be considered before implementation in the screening.
Relapsed Acute Myeloid Leukemia Is Less Sensitive to Venetoclax + Azacitidine Due to Leukemia Stem Cell Resistance Driven By Fatty Acid Metabolism and Can be Overcome By Pharmacologic Inhibition of CPT1
Authors: Daniel A Pollyea, Courtney L Jones, Brett M Stevens, Shanshan Pei, Angelo D'Alessandro, Rachel Culp-Hill, Diana Abbott, Andrew Hammes, James Dugan, Jonathan A Gutman, Enkhtsetseg Purev, Clayton Smith, Craig T Jordan
Journal: Blood (2018)
Plasma vemurafenib concentrations in advanced <i>BRAFV600</i><sup>mut</sup> melanoma patients: Impact on tumor response and tolerance.
Authors: Elisa Funck-Brentano, Jean-Claude Alvarez, Christian Funck-Brentano, Christine Longvert, Alain Beauchet, Philippe Saiag
Journal: Journal of Clinical Oncology (2014)

9016 Background: Vemurafenib (V), a BRAFV600mut targeted therapy, improves survival in advanced melanoma pts, but tolerance is often poor and resistance frequently occurs. No predictive factor of intolerance or escape is well known. We searched for a relation between plasma V concentration (PVC) and V intolerance or melanoma resistance. Methods: After obtaining informed consent, blood was prospectively collected in 23 successive previously BRAFinh naive pts with AJCC stage IIIc (n=3) or IV (n=20) inoperable BRAFV600mutmelanoma receiving V monotherapy. Blood was harvested when tumor response was evaluated or when toxicity occurred. Tumor response to V was assessed every 2 months blinded to PVC results using RECIST 1.1 and adverse effects were graded using CTCAE 4.0. PVC was measured with liquid chromatography-tandem mass spectrometry (precision: 13%). Herein, we report on PVC at steady state (≥14d after V introduction or dose modification). As V could be continued in slowly progressing pts, samples collected after first melanoma progression were excluded from the response-concentration analysis. All samples were included in the tolerance-concentration analysis, where each adverse event occurrence was linked to the closest sample collected. Wilcoxon rank sum test was used. Results: V was first line systemic treatment for 17 pts. Initial V dose was 960 mgx2/d, reduced by 25% (n=6) or 50% (n=1) for intolerance. 12 pts experienced first progression during study after a mean 35 weeks on V. PVC showed high inter-individual variability (13 to 104 µg/mL, mean 56). Mean PVC was lower at time of first progression (37.8±19.3 µg/mL) compared to PVC found when tumor was considered stable or in complete or partial response (56.9±20.8 µg/mL, p=0,003). 105 samples were included in the tolerance-concentration analysis: PVC tended to be higher when toxicity occurred, without reaching statistical significance. All pts declared high compliance to treatment. Conclusions: PVC at steady state is highly variable, and low PVC was associated with tumour progression, suggesting a new (and simple) path to melanoma resistance to V. This preliminary finding should be confirmed in larger series.
Hepatitis C co-infection in HIV-positive patients treated for lymphoma.
Authors: Ashwin Sridharan, Susanna A Curtis, Justin D Kaner, Santiago Aparo, Stefan K. Barta
Journal: Journal of Clinical Oncology (2014)

8578 Background: While reactivation of Hepatitis B virus (HBV) infection is well described in patients treated for hematological malignancies, less is known about outcomes in patients co-infected with the Hepatitis C virus (HCV). Co-infection with HCV is frequent in HIV+ patients. We aimed to describe characteristics and outcomes of HIV+ patients co-infected with HCV and treated for lymphoma. Methods: HIV+ patients diagnosed with lymphoma between 01/01/1997 - 12/31/2013 at the Albert Einstein Cancer Center were identified. HBV+ alone and PCNSL patients were excluded. Characteristics of HCV+ and HCV- patients were compared using Fisher’s exact, Chi-Square, or Mann-Whitney U tests. HCV reactivation was defined as a 3-fold increase in ALT from baseline or 1-log increase in HCV viral load within 1 year of diagnosis. The association of HCV co-infection with OS was assessed by multivariate analysis adjusting for age, sex, race, CD4 count, presence of cirrhosis, type of lymphoma, stage, LDH, and Charlson comorbidity score (CCS). We compared overall survival (OS) of HCV+ and HCV- patients using the Kaplan-Meier method and log-rank test. Results: 190 HIV+ lymphoma patients were identified. 28% (n=53) were co-infected with HCV, and 8.4% were co-infected with HBV (n=16); 1 patient was co-infected with both HCV and HBV. 50 HCV+HBV-, 107 HCV-HBV- and 1 HCV+HBV+ patients were included in the final analysis. HCV+ patients were older (52 vs. 44, p < 0.001), had higher CCS (13 vs. 11, p < 0.01), and more often cirrhosis (24% vs. 0%, p < 0.001) than HCV- patients. In HCV+ patients, HCV reactivation occurred 33% (n=17) and persisted in 7.4% (n=4) until 1 year after lymphoma diagnosis; none died from liver failure. Median OS in HCV co-infected patients was 59.7 mo vs. 88.6 mo in HCV-HBV- patients (p=0.76). In multivariate analysis, HCV co-infection was not associated with worse survival (HR 0.98, 95% CI 0.54-1.8; p=0.96), while low CD4 count (<100 cell/mm3), NHL subtype, advanced stage, high LDH (>190 U/L), and cirrhosis were independently associated with worse OS. Conclusions: While HCV reactivation is common in co-infected HIV+ patients treated for lymphoma, HCV co-infection did not portend worse OS in our cohort. Our analysis is limited by the small size of the cohort.
Nab-paclitaxel (nab-P) combined with FOLFOX for advanced pancreatic cancer: A phase I study.
Authors: Howard Safran, Kimberly Perez, Kevin Charpentier, Trevor Clark Austin, Kalyan C. Mantripragada, Kenneth D. Bishop, Alise Lombardo, Lindsay Houlihan, Kristen Mitchell, Kayla Rosati, Diane Martel, Lynn Shaw
Journal: Journal of Clinical Oncology (2014)

4123 Background: The contribution of irinotecan to the efficacy of FOLFIRINOX in pancreatic cancer is uncertain. The addition of irinotecan to gemcitabine was not superior to gemcitabine alone in pancreatic cancer, however nab-P demonstrates a survival benefit. This phase I study was designed to evaluate the addition of nab-P to fluorouracil, leucovorin, oxaliplatin (FOLFOX-A). Methods: Patients with metastatic or locally advanced pancreatic adenocarcinoma without prior treatment received oxaliplatin, 85 mg/m2, leucovorin 400 mg/m2 and 5-FU 2400 mg/m2 with 3 dose levels of nab-P (125, 150 and 175 mg/m2) every 2 weeks for up to 12 cycles. Patients with locally advanced disease could receive locoregional therapy after 6 cycles. The maximum tolerated dose (MTD) was established from dose limiting toxicities (DLTs) in the first 2 cycles of therapy. A study amendment, to include an expansion phase allowing a dose reduction of oxaliplatin to 68 mg/m2for patients developing grade 2 neuropathy to facilitate administration of > 10 cycles of FOLFOX-A, was activated after the MTD was determined. Results: 25 patients (pts) have been entered: Dose level 1 (n=6), dose level 2 (N=16), dose level 3 (N=3). The median age was 65 (35-82). Eighteen had metastatic and 7 had locally advanced disease. 15 pts were entered to determine the MTD. DLTs of nausea and fatigue occurred in 2 of 3 pts at dose level 3. Eight of the first 9 pts (89%) who received 10 or more cycles of FOLFOX-A had grade 2 or greater neuropathy including 2 of 9 (22%) with grade 3 neuropathy. None of the pts receiving less than 10 cycles of FOLFOX-A developed grade 2 neuropathy. One patient had grade 3 and one patient had grade 4 neutropenia. Eight of the first fifteen pts (53%) had a partial response. Following activation of the amendment allowing a dose reduction of oxaliplatin for grade 2 neuropathy, 10 additional pts have been enrolled. Conclusions: The MTD of nab-P is 150mg/m2 every 2 weeks with FOLFOX. FOLFOX-A has substantial activity and may represent a promising regimen in pancreatic cancer. Supported by the Davis and Browning families and LIFEcycle. Clinical trial information: NCT01744353.
Efficacy of adjuvant chemotherapy after resection of pulmonary metastasis from colorectal cancer: A propensity score matching analysis.
Authors: Mamiko Imanishi, Yoshiyuki Yamamoto, Yukako Hamano, Takeshi Yamada, Toshikazu Moriwaki, Masahiko Gosho, Yukinori Sakao, Takehiro Okumura, Narikazu Boku, Haruhiko Kondo, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2018)

788 Background: A number of retrospective studies reported that 5-year survival rate was 30-60% in patients who underwent curative resection of pulmonary metastases (PM) from colorectal cancer (CRC), and PM-CRC resection was recommended in clinical practice. Efficacy of adjuvant chemotherapy after resection of PM remains unclear. Therefore, using a large-scale data obtained from patients who underwent R0 resection of PM in Japan, we investigated it with a propensity score-matching analysis. Methods: We retrospectively collected clinical data of 1237 patients who underwent metastasectomy of PM-CRC at 46 Japanese institutions from 2004 to 2008. Excluding non-curative resection, preoperative chemotherapies, extra-thoratic metastases, complications after surgery, and inadequate data, 530 patients’ data (surgery alone 269 and surgery with adjuvant chemotherapy 261) were used for the matching. Patient backgrounds affecting doctor’s recommendation of adjuvant chemotherapy and including commonly reported prognostic factors were adjusted, using a propensity score-matching method. Primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS), respectively. Results: After the matching with propensity-score, 167 patients for each group were selected. Patient backgrounds were balanced between both groups. Adjuvant chemotherapies were fluorouracil alone (67%), oxaliplatine-containing regimen (24%), irinotecan-containing regimen (7%) and others (2%). There were no significant differences between both groups in OS (HR 0.97, 95%CI 0.64-1.46, p = 0.88) and DFS (HR 0.99, 95%CI 0.75-1.32, p = 0.96). Conclusions: A propensity score-matching analysis did not show a survival benefit of adjuvant chemotherapy after resection of PM in patients with CRC. A large prospective observational study with high quality or randomized clinical trial is needed.
Treatment and prognosis in mucosal melanoma: An Anatolian Society of Medical Oncology Study.
Authors: Ozlem Ercelep, Ahmet Siyar Ekinci, İbrahim Vedat Bayoglu, Sernaz Uzunoglu, Arife Ulas, Oktay Bozkurt, Asude Aksoy, Ozge Gumuscay, Sebnem Yaman, Melike Ozcelik, Turkan Ozturk Topcu, Burcu Yapar Taskoylu, Mukremin Uysal, Nuriye Özdemir, Ahmet Alacacioglu, Berna Oksuzoglu, Alper Sevinc, Mahmut Gumus
Journal: Journal of Clinical Oncology (2014)

e20051 Background: Mucosal melanoma is a rare disease that is clearly distinct from cutaneous melanoma in clinical course and prognosis. We aim to evaluate patients with mucosal melanoma of different anatomical sites and describe specific variables that predict outcomes. Methods: The review of 11 cancer center databases identified 60 mucosal melanoma patients was included. All of the patients were resected. Demographic, histopathologic and clinical data were recorded and analyzed. Patients with node positive disease were received adjuvant interferon treatment. Relationships between age, gender, disease localization, T and N stage, lactate dehidrogenase level, performance status, present or absent of ulceration and resection type and survival were evaluated in univariate and multivariate analyses. Results: Median follow-up time was 17 months (range 3-167). Median age was 65 years (range 30-88). Twenty-seven (45%) patients were female. Localization of the disease was head and neck region in 31 (52%), gastrointestinal tract in 23 (38%) and genitourinary tract in 6 (10%). Node positive disease rate was 35%. The median OS time was 35 months (SE:6; 95% CI: 23-47). Three-year OS was 48.6%. The median DFS was 16 months (SE:2; 95% CI: 12-20). Three-year DFS was 29.3%. Younger age, head and neck localization and good performance status were nearly reached a significant level for DFS in univariate analysis (p: 0.075, 0.060 and 0.075 respectively). No correlation between demographic, histopathologic, clinical data and overall survival was found in univariate and multivariate analyses. Conclusions: Current evidence supports totally resection as the best chance of cure. Further studies are needed to complement existing data and to increase our understanding of mucosal melanoma.