tbuckley/cabot-search huggingface dataset:
Randomized phase III trial of FOLFOX versus XELOX as adjuvant chemotherapy in patients with early-stage colorectal adenocarcinoma.
Authors: Dimitrios G. Pectasides, George Papaxoinis, Ioannis Xanthakis, George Kouvatseas, Vassiliki Kotoula, Nikolaos Xiros, Epaminondas Samantas, Pavlos Papakostas, George Klouvas, Ioannis I. Varthalitis, George E. Pentheroudakis, George Fountzilas, Dimitris Bafaloukos
Journal: Journal of Clinical Oncology (2014)

3617 Background: The aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC). Methods: Patients were assigned to oxaliplatin 85 mg/m2 as a 2-h iv infusion (d1), given concurrently with leucovorin 200 mg/m2, followed by 5-FU 400 mg/m2 as an iv bolus (d1) and 5-FU 2400 mg/m2 as a 46-h iv infusion (d1 & d2) every 14 d for 12 cycles (group A, FOLFOX6) or oxaliplatin 130 mg/m2 as a 2-h iv infusion (d1) and capecitabine 1000 mg/m2 per os (d1-14) every 21 d for 8 cycles (group B, XELOX). Primary endpoint was disease-free survival (DFS). Tumors were classified as MMR proficient (pMMR) or MMR deficient (dMMR) according to MLH1, PMS2, MSH2 and MSH6 protein expression. KRAS exon2 and BRAFV600E mutational status was also assessed. Results: Between 2005 and 2008, 439 patients were enrolled with 414 being eligible. Of the latter, 201 were randomized to FOLFOX and 213 to XELOX. Most common grade 3-4 toxicities were neutropenia (13.8% with FOLFOX vs 4.4% with XELOX, p<0.0001) and sensory neuropathy (3.2% with FOLFOX vs 2.1% with XELOX, p=0.25). Vomiting was more frequent in the XELOX group (1.6% vs 0%, p=0.017). After a median follow-up of 74.7 months, 3-year DFS was 79.8% (95% CI 76.5-83.4) in the FOLFOX group and 79.5% (95% CI 75.9-83.1) in the XELOX group (p=0.78). Three-year OS was 87.2% (95% CI 84.1-91.1) in the FOLFOX and 86.9% (95% CI 83.4-89.9) in the XELOX group (p=0.84). Overall, 34 of the 308 available tumors (11.0%) were dMMR, 104 of 306 (34.0%) KRAS mutant and 15 of 306 (4.9%) BRAF mutant. Multivariate analysis showed that primary site in the left colon, earlier TNM stage and the presence of anemia at diagnosis were associated with better DFS and overall survival (OS), while grade 1-2 tumors were associated with better OS. Finally, in the left colon only, dMMR tumors were associated with shorter OS (N=208, p=0.016 for interaction) and KRASmutated tumors were associated with shorter DFS (N=209, p=0.123 for interaction). Conclusions: The FOLFOX and XELOX regimens did not differ significantly in their efficacy as adjuvant treatment in high-risk CRC patients. A significant interaction was found between primary site location and MMR status with respect to OS. Clinical trial information: ACTRN12610000509066.
Delays in the diagnosis and treatment of women with lung cancer: A systematic analysis.
Authors: Wolfgang M. Brueckl, Heide Wagner, Manfred Wagner, Gunther H Wiest, Joachim H Ficker
Journal: Journal of Clinical Oncology (2015)

e17740 Background: Unfortunately, lung cancer often is diagnosed at a late stage. Delays in diagnosis and initiation of treatment might contribute to the poor prognosis of most patients. The aim of this study was to assess delays in predefined time intervals (TI) between first symptoms and start of treatment and to analyze potential causes for those delays. Furthermore these TIs were correlated with clinical and pathological criteria. Methods: Unselected patients with lung cancer at our institution were interviewed using a standardized and previously validated 35 item questionnaire. Clinicopathological data were taken from the clinical records. Delay and gender was the primary endpoint of this study. Results: First results of this ongoing prospective study: n = 50 patients were studied (34% female, 20% SCLC, 4% never smokers, 62% ex-smokers). Co-morbidities and lung cancer symptoms were present in 96% and 98%, respectively. The median time intervals were: TI1 (from first symptom to general practitioner (GP)) 3d (range:0-100d); TI2 (GP-specialist) 2.5d (r:0-1470d); TI3 (specialist-hospital admission) 8d (r:0-170d); TI4 (hospital-histological diagnosis) 8d (r:0-130d); and TI5 (diagnosis-treatment) 17.5d (r:0-90d); with a median delay symptom-treatment (TI6) of 85d (r:13d-1529d). There was a significant difference in TI2 between women and men with women having a longer delay (mean 65.2 d (95% CI 2.01-128.46) vs 18.2 d (95% CI 1.89-34.55) in male); p = 0.04. Self-reported reasons for these delays were many time restraints due to “occupation” or “family”. Heavy smokers ( > 40 py) had a significantly longer TI6 (p = 0.47). Updated results will be presented. Conclusions: Knowledge about time delays and their reasons is of utmost importance to establish a speedy initiation of treatment in lung cancer. Our data suggest that sometimes women presenting with potential symptoms of lung cancer are not suspected of having lung cancer by their GPs. Further studies are needed to confirm these findings and to establish the reasons for this delay in women.
Updated analysis: A retrospective cohort study evaluating the safety and efficacy of regorafenib in patients with metastatic colorectal cancer—HGCSG1401.
Authors: Yumiko Ota, Satoshi Yuki, Kazuaki Harada, Shuntaro Yoshida, Yasushi Tsuji, Yoshimitsu Kobayashi, Kazuteru Hatanaka, Hiroyuki Okuda, Takahide Sasaki, Masayoshi Dazai, Jun Konno, Tomoyuki Ohta, Takuya Honda, Atsushi Ishiguro, Osamu Muto, Yasushi Sato, Sosuke Kato, Kei Onodera, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2017)

778 Background: The CORRECT trial revealed the safety and efficacy of regorafenib (REG) for patients (pts) with colorectal cancer including Japanese. REG was approved in Japan in March 2013. However, there are few studies exploring the efficacy and safety of REG in a large number of patients, particularly in daily practice. Methods: We analyzed 173 pts who received REG from May 2013 in the multi-institutional retrospective study (HGCSG1401). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR), and Kaplan-Meier method for progression free survival (PFS) and overall survival (OS). Results: Patients’ characteristics were as follows; male/female 98/75, median age 66 (range 29-87), ECOG PS (0/1/2/3) 58/96/18/1, KRAS Exon2 wild/mutant 98/74 (1 patient ; KRAS Exon2 status was not tested). The initial starting dose was 160 mg (n = 145, 83.8%), 120mg (n = 22, 12.7%), and 80mg (n = 6, 3.5%) respectively. Dose reductions were required in 73 pts (42.2%); 38 pts (22.0%) discontinued therapy due to AEs. The common ≥ grade 3 AEs ( ≥ 15%) were palmar-plantar erythrodysesthesia syndrome (n = 48; 27.7%), hypertension (n = 34; 19.7%), proteinuria (n = 24; 19.2%) and AST increased (n = 24; 13.9%). RR and disease control rate (DCR) were 1.3% and 29.6%, respectively. Median PFS and median survival time (MST) were 2.1 and 6.3 months. In an analysis on relationship between ECOG PS (PS 0-1 vs. PS 2-3) and efficacy, median PFS was 2.3 vs. 1.2 months (HR 3.598, p &lt; 0.001), and MST was 7.0 vs. 2.1 months (HR 4.751, p &lt; 0.001). Conclusions: The efficacy of REG in pts with PS 0–1 was similar to the previous report; however, REG was not effective in patients with PS 2–3. In adverse events, hypertension and liver dysfunction were expressed more frequently than previously reported. We will continue the analysis of the factors associated with liver dysfunction and prognostic/predictive factors.
Effective sequence of endocrine therapy for ER-positive and HER2-negative metastatic breast cancer.
Authors: Tomofumi Osako, Reiki Nishimura, Yasuyuki Nishiyama, Rumiko Tashima, Mamiko Fujisue, Masahiro Nakano, Yasuo Toyozumi, Nobuyuki Arima
Journal: Journal of Clinical Oncology (2014)

e11504 Background: Sequential endocrine therapy (ET) is recommended for ER positive metastatic breast cancer (MBC). A previous ET, including adjuvant settings, for MBC may have an influence on the effect of the next-line ET. However, the best sequence of ET for MBC is unclear. From the point of view of mechanism of resistance, we hypothesize that changing to different type of endocrine agents (EAs) is more effective than sequencing within the same kind of EAs. To investigate factors affecting effect of ET for MBC, we analyzed clinicopathological factors in relation to the treatment efficacy. Methods: From 2000 December to 2012 December, 149 patients with ER-positive and HER2-negative breast cancer recurred in our hospital. Items investigated were progesterone receptor status and Ki-67 index of primary tumors, disease free intervals, recurrence sites, type of EAs for adjuvant treatment and treatment for MBC, progression free survival (PFS) for each ET. We also focused on changing of ET from an AI to other type of EAs or vice versa. Accordingly, we classified EAs as AIs group (anastrozole, letrozole, exemestane), SERMs or SERDs group (tamoxifen, toremifene, fulvestrant) and a progestin (medroxy progesterone). Results: All the patients had ET after recurrence of breast cancer. Median follow-up time was 37.1 months and median duration of ET was 23.7 months. In the first line ET for MBC, multivariate analysis revealed low Ki-67 index, locoregional recurrence, and changing the type of EAs were significant factors for PFS (high / low Ki67, HR=1.65, 95%CI 1.1-2.5, p=0.02; distant / locoregional, HR=2.3, 95%CI 1.2 - 4.1, p=0.008; different / same agent group, HR=0.62, 95%CI 0.4-0.9, p= 0.04). In the second line ET, multivariate analysis showed that changing the type of ETs was a significant factor for PFS (different / same agent group, HR=0.64, 95%CI 0.4-0.9, p= 0.03). In the third line ET for MBC, multivariate analysis revealed that longer PFS of second line ET was a significant factor for PFS (HR=0.96, 95%CI 0.93-0.98, p= 0.002). In the fourth line ET, there was no significant factor for PFS. Conclusions: In the sequence of ET for ER-positive and HER2-negative MBC, changing the group of the EAs may be helpful for prolongation of survival.
Impact of diabetes and hyperglycemia on outcomes in advanced breast cancer patients.
Authors: Cynthia Mayte Villarreal-Garza, Robin J. Shaw, Fernando Lara-Medina, Ludwing Bacon, Daniel Rivera, Lorena Urzua, Christian Aguila, Rebeca Ramirez-Morales, Enrique Bargallo Rocha, Alberto Alvarado Miranda, Julieta Santamaria-Galicia, Erika Sifuentes, Alejandro Mohar, Luis A Herrera
Journal: Journal of Clinical Oncology (2012)

e12027 Background: Clinical experience and previous studies suggest that women with diabetes and breast cancer (BrCa) have worse outcomes than their non-diabetic counterparts. However, analysis of the contribution of diabetes to BrCa specific mortality is difficult because of the substantial mortality attributed to diabetes alone and because diabetes is commonly associated with adverse prognostic factors specific to BrCa. The purpose of this study was to examine the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent BrCa. Methods: We performed a retrospective analysis of patients with advanced BrCa receiving palliative chemotherapy from 2006 to 2011 at the National Cancer Institute in Mexico, and compared breast cancer-specific mortality in diabetic and non-diabetic patients, as well as in patients that presented hyperglycemia during palliative treatment. Results: A total of 265 patients receiving palliative therapy were eligible for inclusion. Previous diagnosis or detection of diabetes at recurrence was recorded in 40 patients (15%). No difference was observed between diabetic and non-diabetic patients in terms of overall survival (OS). A statistically significant difference in OS was observed between patients without diabetes and diabetics who had hyperglycemia (p=0.003). OS in diabetic patients with proper metabolic control was shown to be superior compared to diabetics with hyperglycemia (p=0.01). Hyperglycemia was identified in 14% of non-diabetics at some point while receiving palliative treatment. For patients that experienced hyperglycemia during treatment or who had a mean glucose level &gt; 130, either in the diabetic or non-diabetic subgroups, a worse outcome was noted compared to normoglycemic patients, with a HR of 1.5 (p=0.029) and HR of 2.04 (p=0.006) for death, respectively. Conclusions: Elevated glucose levels confer a poor outcome in diabetic and non-diabetic patients in contrast with patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians must monitor glucose levels during treatment for advanced BrCa disease, and should take action in order to maintain normal glucose levels.
Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC).
Authors: Raphael Brandao Moreira, Rana R. McKay, Wanling Xie, Daniel Yick Chin Heng, Guillermo de Velasco, Daniel E. Castellano, Andre Poisl Fay, Fabio Augusto Barros Schutz, Connor Wells, JoAnn Hsu, Sumanta K. Pal, Jae-Lyun Lee, Robert J. Motzer, Darren R. Feldman, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2017)

482 Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component &gt; 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]
Clinical significance of MYC expression in acute myeloid leukemia.
Authors: Maro Ohanian, Hagop M. Kantarjian, Uri Rozovski, Sanam Loghavi, Yang Huh, Lynne Abruzzo, Guillermo Garcia-Manero, Farhad Ravandi, Gautam Borthakur, Franceso Stingo, Peter Hu, Martin H. Nguyen, Patricia S Fox, L Jeffrey Medeiros, Zeev Estrov, Carlos E. Bueso-Ramos, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2014)

7094 Background: MYC, a transcription factor controlling DNA replication, is overexpressed in many cancers, yet rarely investigated in myeloid neoplasms, where its clinical significance is unknown. Objectives:Assess MYC expression by immunohistochemistry (IHC) in bone marrow (BM) of patients (pts) with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute promyelocytic leukemia (APL). Methods: MYC expression by IHC was assessed in BM of pts with AML, MDS, APL, and normal BM. MYC expression showed a distinct nuclear pattern. Cases were considered positive if > 5% blasts were stained. Results: We evaluated BM MYC expression in 220 pts during 2006-2013 (97 mo) with newly diagnosed AML (n=162), previously treated AML (induction failure or relapse) (n=30), MDS (n=19), and newly diagnosed APL (n=11). Median age was 60 yrs (13-88); 56% male. Normal BM (negative controls) showed negligible MYC expression (<5%, n=11). Varying degrees of MYC expression were observed in AML pts with median MYC expression of 20% (range 2-90%) and 50% (range 19-75%) in APL. Median MYC expression across diseases was 20%. MYC expression of >5% was observed in 134 (84%) newly diagnosed AML pts, 22 (73%) previously treated AML, all (n=11) APL, but in only 7 (40%) MDS (p= 0.0001 for difference across groups). High MYC expression correlated with high LDH (rs = 0.390, p<0.0001), WBC (rs = 0.205, p=0.006) and BM blasts (rs 0.341, p=0.0001). MYC levels were similar across karyotypes: trisomy 8 (where MYC resides), complex, and core binding factor. In newly diagnosed AML pts, 105 were screened for NPM1 and 81 for FLT-3 ITD mutations. MYC expression was higher in 21 NPM1 mutated pts (P = 0.04) and in 22 FLT3-ITD mutated pts (P = 0.01). MYC expression strongly predicted survival in newly diagnosed AML. Normal MYC expression (n=26) had a median OS of 28 mo (CI 19-37); those with increased MYC expression had a median OS of 14 mo (CI 10-18) (Log-rank p=0.023). Among normal karyotype (NK) pts median OS was 40 mo (CI 16-63) if MYC <5% vs. 16 mo (CI 9-23) if MYC >5%. The OS advantage was similar with or without mutated FLT3-ITD. Among NK cases of varying MYC levels, MYC rearrangement was not detected by FISH. Conclusions: MYC expression is a strong predictor of survival, particularly in newly diagnosed NK AML.
Predictors of resilience in women treated for breast cancer: A prospective study.
Authors: Barbara Kaye Bennett, Andrew R. Lloyd, Kate Webber, Michael Friedlander, David Goldstein
Journal: Journal of Clinical Oncology (2012)

9044 Background: Because a cancer diagnosis may be regarded as a potentially traumatic event with untoward consequences, much research has focussed on negative aspects of cancer diagnosis and treatment, emphasising psychological outcomes. A recent paradigm shift recognises that such a psycho-pathological approach discounts the human capacity for resilience "the ability to maintain relatively stable functioning following an aversive life event" (Bonanno GA Curr Direct in Psychol Science 2005 14(3) 135). Predictors of resilience in women who recovered uneventfully from surgical and adjuvant treatment for early stage breast cancer were investigated in a prospective study. Methods: Validated self-report measures of mood, somatic symptoms, temperament, illness attitudes, and social support were completed post-surgery. Clinical, tumor and treatment details were recorded. At end treatment and subsequently at 1, 3, 6, 9 and 12 months, self-report measures of mood and somatic symptoms were completed. Resilience was defined as: no evidence of protracted psychological or somatic distress in the 12 months following treatment completion. Identified resilient and non-resilient groups were compared and predictors sought by logistic regression. Results: Of 218 women evaluated, 106 (49%) were classified as "resilient." They either reported no clinically significant psychological or other distress post-surgery (34%) and 12months following adjuvant treatment or recovered promptly (15%) and remained well. There were no significant differences in age (52 years); marital status; tumor size; treatment; treatment toxicity (nadir hemoglobin and neutrophil count) or mortality at 5 years post treatment (8 confirmed deaths in each group). Logistic regression identified low neuroticism (temperament or personality trait) as the most significant predictor of resilience. Conclusions: These findings suggest that without any intervention almost half the women treated for breast cancer adapt well to diagnosis and treatment. These outcomes warrant further research, to provide further insight into how individuals cope with major illness and to facilitate development of programs to aid those in whom outcomes are protracted.
Differential impact of sex in young and elderly patients with DLBC: Correlation with rituximab (R) pharmacokinetics.
Authors: Michael Pfreundschuh, Carsten Mueller, Samira Zeynalova, Gerhard Held, Viola Poeschel, Carsten Zwick, Tanja Rixecker, Norbert Schmitz, Niels Murawski
Journal: Journal of Clinical Oncology (2013)

8570 Background: Sex and weight independently influence R clearance in elderly DLBCL pts (Mueller et al., Blood 2012). Methods: We analyzed the impact of sex on R pharmacokinetics and outcome of 1,222 elderly pts of the RICOVER-60, 823 young (18 to 60 years) aaIPI=0,1 pts of the MInT, and 375 aaIPI=2,3 pts of the Mega-CHOEP trials. R pharmacokinetics was determined by ELISA in 33 young and 49 elderly patients. Population pharmacokinetic modeling was performed with nonlinear mixed-effect modeling software (NONMEM VI). Results: R clearance was independent of tumor mass (IPI), but weakly correlated (0.2, R 2 linear=0.045) with increasing age in male, and moderately inversely correlated (-0.5, R 2 linear=0.207) with age in female DLBCL patients, resulting in similar R clearances in young female and male patients (9.88 vs. 10.38 ml/h; p=0.238), but a significantly faster R clearance in elderly males compared to females (10.50 vs 8.25 ml/h; p=0.006). In the RICOVER-60 trial, elderly females had a higher 3-year PFS (68% vs. 61%) and OS (74% vs. 68%) than male pts. due to a greater outcome improvement by the addition of R in females. In a multivariable analysis adjusting for IPI, the hazard for progression in male compared to female pts. was not significantly increased after CHOP (HR=1.1; p=0.348), but was significantly higher after R-CHOP (OR=1.6; p=0.004). In contrast, young males treated in the MInT and Mega-CHOEP trials benefitted as much as females from the addition of rituximab, with a similar hazard for male pts. after CHOP and R-CHOP (HR=1.2) with no significant difference to female patients (HR PFS =1.2, p=0.552; HR OS =1.0; p=0.898). Conclusions: While no differences in R clearance and benefit from rituximab were found in young female compared to male patients, the reduced benefit of adding R to CHOP in elderly male DLBCL pts. who have a shorter rituximab serum half life and hence lower serum levels suggests that this subpopulation is suboptimally dosed when R is given based on body surface area at 375 mg/m 2 . Ongoing studies of the DSHNHL investigate whether higher R doses for pts. with a shorter R serum half life can improve the outcome of the respective patients. Supported by Deutsche Krebshilfe and Roche.