tbuckley/cabot-search huggingface dataset:
Carboplatin (PA) and pegylated liposomal doxorubicin (CA; PACA regimen) in patients with advanced ovarian cancer in late (>6 months) relapse (AOCLR): Survival results of a GINECO phase II trial
Authors: J.-M. Ferrero, B. Weber, D. Lepille, H. Orfeuvre, M. Combe, F. Mayer, B. Leduc, H. Bourgeois, D. Paraiso, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2004)

5022 Background: The combination of carboplatin and paclitaxel is more active than carboplatin alone in treatment of patients (pts) with AOCLR, but with much greater frequency of severe neurological toxicity and alopecia (ICON4 trial, Lancet, 2003). The GINECO initiated a phase II trial to investigate the efficacy and tolerance of Caelyx (CA) and carboplatin (PA) in platinum- and taxane- pre-treated AOCLR pts. Methods: From 04/00 to 03/01, 105 pts with AOCLR received a q4w schedule of CA (30 mg/m2, d1) followed by PA (AUC 5 mg.ml-1.mn, d1). Results: The median age of pts was 61 years (range, 23–79); 47% had performance status 1–2; 66% had serous histology; 54% had measurable disease; and 86% had CA-125 levels >40 IU/ml. 60% of pts had received 1 previous line of chemotherapy and 40% had received 2. On study, pts received a median of 6 cycles (range, 1–10). Hematologic toxicity was NCI grade 3–4 neutropenia (23% of 592 cycles), anemia (4%) and thrombocytopenia (8%). Febrile neutropenia occurred in 3% of pts. G-CSF, red blood cell and platelet transfusions were required in 16%, 12%, and 3% of pts, respectively. Dose reduction and course delay were observed in 7% and 20% of cycles, respectively, mainly due to slow hematological recovery. Non-hematological toxicities were few, including grade 2–3 nausea/vomiting (32%), alopecia (12%), grade 3 fatigue (8%), grade 2 palmar-plantar erythrodysesthesia (11%), and grade 2–3 mucositis (12%). The overall response rate is 63% (65/105 pts) including 38% with complete response. Median progression-free survival is 9 months. Despite poorer performance status, a greater number of previous chemotherapy treatments including paclitaxel, and more pts who had relapsed within 12 months, the 31.1-month median overall survival of pts treated with PACA compares favourably with that of pts treated with PA and paclitaxel in the ICON4 trial. Conclusions: The PACA regimen is well tolerated with a low incidence of alopecia and neurotoxicity, induces prolonged survival in AOCLR pts, and deserves further evaluation in AOC. No significant financial relationships to disclose.
Dose-intensified chemotherapy and additional Docetaxel may improve inflammatory breast cancer patients outcome over two decades: Results from Institut Curie protocols 1977–1987 and two consecutive French multicenter trials Pegase 02 (1995–96) and Pegase 05 (1997–99)
Authors: T. Palangie, P. Viens, H. Roché, P. Beuzeboc, V. Dieras, T. Dorval, J.-Y. Pierga, V. Mosseri, B. Asselain, P. Pouillart
Journal: Journal of Clinical Oncology (2004)

848 Background: Standard anthracycline based chemotherapy had improved survival of inflammatory breast cancer. New modalities have been developed over the past 10 years including sequential high dose chemotherapy and newer drugs such as taxanes. Methods: We analyzed a first (G1) of patients uniformly treated with conventional chemotherapy in our institution and compared to a second group (G2) receiving sequential HDC and a third group (G3) with HDC + docetacel G1: 223 pts (1977–1987) were treated at the Institut Curie on 3 consecutive protocoles with conventional doxorubicine based CT G2: 95 pts (1995–96) were enrolled onto the multicenter trial Pegase 02 consisting in four 3 weekly cycles of doxorubicine 75mg/m2 associated with CPM (6g/m2 at C1; 3g/m2 atC2) and 5FU 3g/m2 at C3 and C4 G3: 54 pts (1997–99) accrued in Pegase 05 multicenter trial received four 3 weekly cycles of D75mg/m2 + CPM 6g/m2 at C1; CPM 3g/m2 at C2, C6 and C7; docetaxel 100mg/m2 q 2W was administred at C3, C4 and C5 Median survival 3 year OS and DFS were compared between the 3 groups. Conclusions: These results suggest some benefit from dose intensified CT in term of MSV, 3Y OS and DFS. Additional docetaxel seems to inprove 3Y OS and DFS Statistical significance in survival curves will be shown at the ASCO meeting. The impact of Taxotere is currently assessed in the randomized multicenter trial Pegase 07. No significant financial relationships to disclose.
Survival trends in patients diagnosed with metastatic prostate cancer: A nationwide analysis.
Authors: John Thomas Helgstrand, Nina Klemann, Birgitte Grønkaer Toft, Ben Vainer, Klaus Brasso, James D. Brooks, Peter Iversen, Martin Andreas Røder
Journal: Journal of Clinical Oncology (2017)

171 Background: The risk of prostate cancer (PCa)-death in men diagnosed with metastatic (M+) PCa is high. During the past decade, new life-prolonging therapies have been approved for the treatment of advanced PCa. Even though demonstrated in randomized clinical trials, the impact of these advancements on mortality of men with newly diagnosed M+ PCa has not been described in a nation-wide setting. Methods: In the Danish Prostate Cancer Registry (DaPCaR), all men diagnosed with M+ PCa in Denmark from 1995 to 2011 were identified. Patients were grouped according to the year of diagnosis; 1995-2000, 2001-2005 and 2006-2011. In a competing risk setting, the 5-year cumulative incidences of PCa, other-cause, and overall death were calculated. Multivariate cause-specific Cox analysis was performed. Results: A total of 1,892 (1995-2000), 2,329 (2001-2005), and 2,653 (2006-2011) men were included (total: 6,874). Patient characteristics at diagnosis showed essential differences as median age and median PSA decreased by 1.0 year (74.1 to 73.1) and 134 ng/mL (276 to 142), respectively, in the period studied. The 5-year PCa-specific mortality decreased by 17.0% from 72.8% (1995-2000) (95%CI: 70.8% – 74.8%) to 55.8% (2006-2011) (95%CI: 53.9% – 57.7%), p &lt; 0.0001. The 5-year other-cause mortality increased by 5.7% from 11.4% (95%CI: 9.9% – 12.8%) to 17.1% (95%CI: 15.6 – 18.6), p &lt; 0.0001. The risk of PCa-death decreased for patients diagnosed in 2000-2005; HR: 0.69 (95%CI 0.61-0.79) and for patients diagnosed in 2006-2011; HR: 0.53 (95%CI 0.47-0.61) compared to patients diagnosed in 1995-2000, when adjusting for age, PSA, and Gleason score (GS) in the statistical analysis. Conclusions: A significant reduction in 5-year PCa-specific mortality was observed in a nationwide cohort of patients diagnosed with M+ PCa since 1995. Changes in age and PSA at diagnosis suggest that lead-time introduced by increased PSA use may have affected the results. However, in multivariate analysis, a significant reduction in hazard of almost 50% was observed when adjusting for age, PSA, and GS. Only minor changes in other cause mortality were found, which suggests that the improvement to a large extend can be credited to improved management of men with advanced PCa.
Smoking history and frequency of somatic <i>KRAS</i> mutations in adenocarcinoma of the lung
Authors: V. A. Miller, G. J. Riely, M. G. Kris, D. Rosenbaum, J. Marks, A. Li, D. Chitale, K. Nafa, W. Pao, M. Ladanyi
Journal: Journal of Clinical Oncology (2007)

7573 Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are more common in patients with adenocarcinoma, especially those who smoked &lt; 15 pack years (py). KRAS mutations are found in ∼25% of lung adenocarcinomas, most commonly in codons 12 and 13 of exon 2 (∼85%) and have been associated with poor prognosis in resected disease [Winton NEJM 2005] and resistance to EGFR tyrosine kinase inhibitors [Pao PLoS Med 2005]. KRAS mutations are uncommon in non-small cell lung cancer histologies other than adenocarcinoma. We sought to determine the association between quantitative measures of cigarette smoking and presence of KRAS mutations in lung adenocarcinomas. Methods: Standard direct sequencing techniques were used to identify KRAS codon 12 and 13 mutations in lung adenocarcinoma specimens from surgical resections between 2001 and 2006 and tumor specimens sent for KRAS molecular analysis in 2006. Surgical specimens were obtained from an institutional tumor bank. Detailed smoking history (age at first cigarette, packs per day, years smoked, years since quitting smoking) was obtained from the medical record and a patient-completed smoking questionnaire. Results: KRAS mutational analysis was performed on 408 lung adenocarcinomas from 242 women and 166 men. Median age was 68 (range 33–89). KRAS mutations were present in 19% (78/408, 95% CI 15 to 23%). The frequency of KRAS mutation was not associated with age or gender. The presence of KRAS mutations was not related to smoking history with 15% (9/61) of never smokers having KRAS mutations compared with 19% (51/275) of former smokers. When compared with never smokers, there was no significant difference in frequency of KRAS mutations for tumors from patients with 1–5 py (5%, p=0.44), 6- 10 py (12%, p=0.99), 11–15 py (25%, p=0.45), 16–25 py (16%, p=0.99), 26–50 py (25%, p=0.129), 51–75 py (20%, p=0.48), &gt;75 py (20%, p=0.47) history of cigarette smoking. Conclusions: While the incidence of EGFR mutations has a strong inverse relationship with the amount of cigarettes smoked, allowing the selective molecular testing for EGFR mutations, the frequency of KRAS mutations cannot be predicted by age, gender, or smoking history. KRAS mutational analysis of all adenocarcinomas is required to reliably identify patients with KRAS mutations. No significant financial relationships to disclose.
Phase II study of NGR-hTNF, a selective vascular targeting agent (VTA), administered as single agent in patients (pts) with colorectal cancer (CRC) refractory to standard regimens
Authors: L. Rimassa, A. F. Sobrero, A. Santoro, V. Andretta, V. Gregorc, F. Sclafani, F. Caprioni, F. Caligaris-Cappio, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2009)

4088 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to an aminopeptidase N/CD13 overexpressed by tumor blood vessels. In preclinical models, NGR-hTNF showed antitumor activity both at low and at high doses. Methods: Pts with CRC resistant/refractory to standard treatments, including biological agents, were treated with low-dose NGR-hTNF given intravenously at 0.8 μg/m 2 as 1-hour infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and 27 pts to be enrolled after first and second stage, respectively. Progression-free survival (PFS) was the primary end-point with reassessment performed q6w. Results: From January to May 2007, 33 pts with radiologically- documented progressive disease after last therapy were evaluated over 111 cycles (range, 1–10). Pts characteristics were: median age: 65 years (range, 53 to 79); M/F 16/17; PS 0/1 26/7. Median number of prior regimens was 3 (range, 2 to 5). Eight pts (25%) were pre-treated with ≥4 lines and 22 (67%) with biological agents. Neither grade 3–4 treatment-related adverse events nor toxicity-related deaths were observed. Main grade 1–2 toxicities per patient were infusion-related chills (47%) and transient blood pressure increase (9%). One partial response (3%) lasting 5 months and 12 stable diseases (36%) were reported. Median PFS was 2.5 months (95% CI, 2.2–2.8). In a post-hoc analysis, no differences in PFS were detected according to baseline characteristics. With a median follow-up time of 18.4 months (95% CI, 18.3–18.5), 11 pts (33%) were still alive. Median overall survival (OS) was 13.1 months and the 2-year OS rate was 22%. In the subset of stable or responder pts, the median PFS and OS were 3.8 months and 15.4 months, respectively. The 6-month PFS rate in the prior-biological and biological-naïve cohorts was 5% and 20%, respectively, whereas 1-year OS rate was 41% and 72%, respectively. Conclusions: Based on the favorable toxicity profile and disease control in heavily pre-treated CRC patients, NGR-hTNF will be further developed in combination with standard chemotherapy. [Table: see text]
Circulating tumor cells enrichment and characterization in <i>ALK</i>-translocation positive lung cancer.
Authors: Patrick C. Ma, Lihong Yin, Powrnima Joshi, Yan Feng, Barbara Jacobs, Wei Zhang, Marc A. Shapiro, Michael J. McNamara, Nooshin Hashemi, Nathan A. Pennell, Ernest C. Borden, Maciej Zborowski
Journal: Journal of Clinical Oncology (2014)

e19025 Background: Targeted therapy with tyrosine kinase inhibitor (TKI) crizotinib against EML4-ALK (ALK+) non-small cell lung cancer (NSCLC) have impacted cancer therapy as a new paradigm. However, there is still an unmet need to develop affordable and robust technology platforms to assay circulating tumor cells (CTCs), which may form the basis of distant hematogenous metastases. There are relative advantages and pitfalls with various CTC platforms. Methods: We performed pilot studies utilizing two different platforms of CTC detection and enrichment. First, we adopted the CellSearch “positive-selection” platform to profile 11 pts with ALK(+) NSCLC who were treated with crizotinib prospectively. Blood samples were collected (i) pretreatment, (ii) on TKI with CR/PR/SD, and (iii) at disease progression. Second, we evaluated a novel “negative selection” CTCs capture-isolation platform, based on magnetic separation of pan-leukocyte marker CD45+ cells coupled with RBC lysis, to avoid potential bias of predefined CTC criteria. Pilot studies utilizing ALK+ H3122 cell line and ALK+ patients’ blood samples were performed for assay optimization and comparison. Results: Using ALK+ NSCLC patients peripheral blood samples, we demonstrated the presence of the EML4-ALK fusion (variant 1) in QPCR assay from the enriched CTC isolated using the CellSearch platform. Also, CellSearch enumeration in our pilot ALK+ cohort revealed a trend of correlation between the CTC numbers and disease status. The spike-in experiment in “negative selection” CTC platform enriched the spiked H3122 cells by 10,000 fold from the nucleated blood cells. Applying our “negative-selection” CTC assay to a patient with known EML4-ALK variant 1 (EML4-ex13/ALK-ex20) fusion lung cancer during disease progression on crizotinib, we detected the specific EML4-ALK variant 1 fusion in QPCR assay from the CTC enriched “eluate” fraction, but not in the “feed” fraction, whether the CellSearch platform revealed any CTCs or not. Conclusions: Taken together, our pilot CTC study results support the high sensitivity of the unbiased “negative selection” enrichment platform and its potential to empower molecular and genomic determinations in lung cancer.
RESECCIÓN ENDOSCÓPICA MUCOSA APOYADA EN CROMOENDOSCOPIA CON ACÉTICO DE LESIONES EPITELIALES ESÓFAGO-GÁSTRICAS
Authors: D Martínez Ares, B Romero Mosquera, N Quintáns Pinazas, L Cid Gómez, I Martín-Granizo, I Pérez Carballido, P Iglesias Avión, E Feteira, J Hermo Brión, JI Rodríguez Prada
Journal: Endoscopy (2015)

La disección endoscópica submucosa se ha impuesto en Japón como la técnica de elección para la resección de las lesiones epiteliales esófago-gástricas, por mayor tasa de resecciones en bloque y curativas. No obstante es una técnica de complejo aprendizaje, muy laboriosa y con riesgo apreciable de complicaciones. Las técnicas de mucusectomía son menos complejas y más ampliamente extendidas en occidente.
Frequency of surgery in black patients with malignant pleural mesothelioma.
Authors: Andrea S Wolf, Marlene Camacho-Rivera, Emanuela Taioli, Raja Michael Flores
Journal: Journal of Clinical Oncology (2014)

e17571 Background: We evaluated the role of race in presentation, treatment, and survival of malignant pleural mesothelioma (MPM) in the Survival Epidemiology and End Results (SEER) database. Methods: The SEER database was explored from 1973 to 2009 to identify all cases of pathologically-proven MPM. Age, sex, diagnosis year, stage, cancer-directed surgery, radiation, and vital status were analyzed according to self-reported race (black or white). The association between prognostic factors and survival was estimated using a Cox proportional hazards model. Results: There were 13,046 white and 688 black patients, 1.1 per 100,000 whites and 0.5 per 100,000 blacks annually (age adjusted, p = 0.01). Blacks were more likely to be female, younger, and present with advanced stage and less likely to undergo cancer-directed surgery than whites, even stratified by stage (p = 0.001). On multivariable analysis, younger age and surgery were associated with longer survival for both groups; HR 0.81 (95% CI 0.79-0.83) for younger age and 0.65 (0.61-0.70) for cancer-directed surgery in whites and 0.76 (0.68-0.83) for younger age and 0.53 (0.38-0.73) for surgery in blacks. Female gender [HR 0.82 (0.77-0.88)] and early stage [HR 0.83 (0.76-0.90)] were predictive of longer survival in white, but not black, patients. Conclusions: Surgery was associated with improved survival for both black and white MPM patients. Black patients, however, were less likely to undergo cancer-directed surgery. Early stage was associated with better survival for white, but not black, patients. Increased surgical intervention in black patients with early stage disease may lead to improved survival in MPM. Demographic, treatment, and outcome characteristics among whites and blacks (n = 13,734). Variable Categories Whites (n = 13046) Blacks (n = 688) p-value Sex Female 2887 (22%) 181 (26%) 0.010 Mean age in yr (95% CI) 70.2 (70.0-70.4) 66.6 (65.6-67.6) <0.0001 Overall stage Localized 1449 (11%) 75 (11%) 0.002 Regional 2155 (16%) 91 (13%) Distant 7639 (59%) 450 (65%) Unknown 1803 (14%) 72 (11%) Cancer-directed surgery Yes 3087 (24%) 125 (18%) 0.001 Radiation Yes 1659 (13%) 77 (11%) 0.241 Mean survival in months (95% CI) 15.5 (15.1-15.9) 16.7 (14.5-19.0) 0.899
Impact of treatment prior to allogeneic stem cell transplantation for myelodysplastic syndromes: A study on behalf of the SFGM-TC and the GFM groups.
Authors: Gandhi Laurent Damaj, Alain Duhamel, Marie Robin, Mauricette Michallet, Mohamad Mohty, Stephane Vigouroux, Yves Beguin, Alice Garnier, Bruno Lioure, Jean El Cheikh, Nathalie Fegueux, Jerome Cornillon, Sylvie Francois, Marie Therese Rubio, Anne Huynh, Sophie Park, Jean pierre Marolleau, Frederico Garnier, Pierre Fenaux, Ibrahim Yakoub-Agha
Journal: Journal of Clinical Oncology (2012)

6534 Background: Until the early 2000s, treatment prior to SCT varied according to cytogenetics and % BM blasts and was mainly induction-type chemotherapy (ICT). The role of Azacitidine (AZA) prior to transplant remains uncertain. Methods: 163 consecutive pts (M/F=104/67; age &gt; 18) underwent alloSCT between 2005 and 2009 from sibling (n=96) or HLA- allele-MUD (10/10) (n=67). The SC source was blood (n=142) or marrow (n=21) and conditionings were myeloablative (n=33); nonmyeloablative (n=130). Pts who did not received neither prior ICT nor AZA were excluded since the main objective of this study was to investigate the impact of prior therapy on pts’ outcome. Results: At diagnosis, FAB/WHO was: 24 RA/RARS/RCMD, 52 RAEB-1, 74 RAEB-2, 13 RAEB-t/AML; Cytogenetic: fav (n=93), int (n=32), unfav (n=37). 98 pts received prior ICT (ICT-group) and 65 had received AZA, either alone (AZA-group; n=48) or AZA preceded or followed by intensive CT (AZA-chemo-group; n=17). In AZA groups, the drug was started 38 to 941 days from transplant and discontinued 6 to 438 days before transplant with a median number of 4 cycles (range 1-26). Overall, 119 pts were considered responders at SCT (CR, PR, mCR), including 33 (69%) treated with AZA-alone, 9 (53%) with AZA-chemo and 77(78%) with ICT.While there were no differences between AZA-group and ICT-group in terms of OS, EFS, relapse and NRM, having a poor risk cytogenetic and receiving AZA-chemo prior to SCT were, in multivariate analyses, the most important factors that adversely influenced OS with [HR=3.03; 95% CI 1.84-4.96] (p&lt;.0001) and [HR=2.72; 95% CI, 1.38-5.35] (p=.004), respectively. Pts of AZA-chemo group had the same rate of relapse but significantly higher NRM rate (p=.059) than those who received either AZA or ICT alone. Conclusions: With the goal of down-staging underlying disease before allo-SCT, AZA treatment appears to be a valid therapeutic approach, but mainly in pts receiving AZA alone with an outcome at least equivalent to pts receiving ICT prior to SCT. Allo-SCT in pts who required both AZA and chemotherapy had less satisfactory outcomes, possibly reflecting additional toxicity and/or more resistant disease.
GEINOFOTE: Safety and activity analysis of the use of fotemustine (FT) in different schedules in progressive high-grade glioma (HGG) in Spain.
Authors: Pedro Pérez-Segura, Ray Manneh Kopp, Isaac Ceballos, Almudena Garcia, Manuel Benavides, Jose Fuster, M. Angeles Vaz, Juana Maria Cano, Jose Pablo Berros, Marta Covela, Victor Moreno, Maria Teresa Quintanar Verduguez, Jose Maria Garcia-Bueno, Isaura Fernandez, Oscar Gallego Rubio, Patricia Ramirez, Jaime Espinós, Sonia Gonzalez, Sonia del Barco, Silverio ROS
Journal: Journal of Clinical Oncology (2014)

2055 Background: Previous studies showed that FT may be useful as treatment in recurrent high-grade glioma (HGG). The present study evaluate the activity and toxicity of FT in recurrent malignant glioma patients in the clinical setting in Spain. Methods: Patients (age >18 years) with HGG that was progressive (first or second recurrence) after prior standard radiotherapy plus TMZ chemotherapy were eligible for the study. Patients were scheduled to receive FT in different schedules (Addeo vs others). Tumor response was assessed by MRI every 8-12 weeks. The primary end point was safety; secondary points included progression free survival (PFS), overall survival (OS). We analyze the differences between Addeo schedule (A) vs others (O) and 1º recurrence (1ºR) vs 2º recurrence (2ºR) in terms of safety and activity. Results: 114 patients were assessed (84 glioblastoma and 30 grade III glioma); all of them began FT previously Nov 31, 2012. There were 60 males, and the median age was 52.5 years (ranged from 19 to 73). The median KPS was 70 (30-100). Addeo schedule was used in 85 pts (74.6%). FT in first recurrence was used in 51 pts (44.7%) and 58 pts (50.9%) in second recurrence. The median PFS was (A 1ºR / O1ºR/ A 2ºR / O 2ºR) 3.37/2.41/3.04/2.68 months, the median OS was (A 1ºR / O1ºR/ A 2º R / O 2ºR) 5.62/5.59/5.09/3.97 months. The most common toxicities include neutropenia and thrombocytopenia. There were no statistical differences in Grade III or IV toxicities in relation with the type of schedule (A vs O) nor the 1º or 2º R (20%-32.6%). The patients in 1ºR received more frequent A schedule than in 2ºR (86.3% vs 62.1%, p=0.004). No differences between A vs O in terms of clinical benefit, PS improve or less dexametasone use. Time to response: patients in A schedule spent less time to get the better response than patients with O schedules, whenever we use FT (no significant differences). Conclusions: FT has modest activity for recurrent high grade glioma with acceptable toxicity, regardeless the type of schedule. Probably, A get better response in less time than O schedules.