tbuckley/cabot-search huggingface dataset:
Efficacy and safety of dose-dense modified TCF regimen (TCF-dd) in metastatic or locally advanced gastroesophageal cancer (GEC).
Authors: Laura Toppo, Gianluca Tomasello, Wanda Liguigli, Margherita Ratti, Rossana Poli, Federica Negri, Alessandra Curti, Marco Vismarra, Mariangela Maltese, Roberto Delfrate, Maddalena Donini, Chiara Colombi, Matteo Brighenti, Stefano Panni, Bruno Perrucci, Silvia Lazzarelli, Rodolfo Passalacqua
Journal: Journal of Clinical Oncology (2013)

4112 Background: TCF is a standard first line option for GEC. The Norton-Simon hypothesis suggests that chemotherapy efficacy can be enhanced by decreasing intervals between cycles. We previously reported on the high activity of TCF-dd in GEC (Tomasello 2010). The aim of this study is to investigate the efficacy and safety of this intensified dose-dense regimen in a single-center large cohort of patients (pts). Methods: 150 pts with measurable or evaluable GEC, PS 0-2, with adequate organ function, treated in our center from 2004 to 2012 received TCF-dd: Docetaxel (60-85 mg/m2 d 1), Cisplatin (50-75 mg/m2 d 1), l-Folinic Acid (100 mg/m2 d 1-2), 5-FU (400 mg/m2 bolus d 1-2, and 600 mg/m2 as a 22 h continuous infusion d 1-2), plus Pegfilgrastim 6 mg d 3, every 14 days. Pts aged ≥ 65 years received the same schedule with a dose reduction by 30%. Analysis was based on the intention to treat population. Results: At a median follow-up of 44 months, 128 pts were evaluable for response, all for survival. Median age 65 (range 31-81), M:F 112:38. 17 pts (11%) with locally advanced inoperable GEC, 133 pts (89%) with metastatic GEC. Metastatic sites: liver 40%, peritoneum 31%, bone 14%, lung 12%. A median of 4 cycles (range 1-7) per patient was administered. 33% required a dose reduction. 33% were treated without any delay. 10 CR, 74 PR, 24 SD and 20 PD were observed, for an ORR of 66% (95% CI 57-74). Median OS was 13 months (95% CI 9.7-14.2). Most frequent grade 3/4 toxicities: neutropenia (34%), asthenia (28%), thrombocytopenia (17%), hypokalemia (16%), diarrhea (11%), febrile neutropenia (10%), anemia (9%), and stomatitis (4%). 11 pts (7%) [7 metastatic, 4 locally advanced] became operable after TCF-dd and underwent surgery. We identified 12 metastatic pts (8%) with overall survival &gt; 3 years and 7 (5%) still maintaining a long lasting CR at the time of the current analysis. Conclusions: TCF-dd in GEC is very active and may be an option for conversion therapy. Toxicity can be relevant and requires a careful monitoring.
Context matters for attractiveness bias
Authors: Juwon Lee, Glenn Adams, Yexin Jessica Li, Omri Gillath
Journal: Behavioral and Brain Sciences (2017)

Abstract To fully understand the attractiveness bias, we propose that contextual factors or affordances should be integrated into the mating-based evolutionary account of Maestripieri et al. We review examples highlighting the role of contextual factors in the perception of attractiveness and in attractiveness bias. These suggest contextual factors differentially afford the development of preference for attractive others into observed habits of mind.
Downsizing after palliative systemic chemotherapy with weekly high-dose 5-fluorouracil (5-FU) as a 24h-infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with metastatic adenocarcinomas of the stomach or the gastro-esophageal junction followed by secondary metastatic resection
Authors: K. Koucky, F. Boxberger, H. Albrecht, G. Maennlein, K. Wolff, N. Ostermeier, C. Schildberg, H. Golcher, W. Hohenberger, E. G. Hahn, A. Wein
Journal: Journal of Clinical Oncology (2009)

e15585 Background: Due to the positive experience with combined AIO plus irinotecan (iri.) in a phase II trial (Möhler M et al, Br J Cancer 2005), this combination has been applied as first-line treatment in our department since 1999. Methods: 76 chemonaive patients (pts.) with histologically proven metastatic adenocarcinomas of the stomach or AEG tumours (tum.) (UICC IV), deemed to be non-resectable by the Interdisciplinary Tumour Board (ITB), were enrolled from 08/99 to 12/08. Chemotherapy (chemoth.) schedule: iri. (80 mg/m 2 i.v. as 1h-infusion (inf.); d1, 8, 15, 22, 29, 36, qd 57) followed by 5-FU (2000 mg/m 2 i.v.) with sodium folinic acid (500 mg/m 2 ; d1, 8, 15, 22, 29, 36, qd 57) as 24h-inf. via port-a-cath. After downsizing the patients were again presented at the ITB. In 16 out of 76 pts. (21%) a secondary (sec.) metastatic resection (res.) with curative intent was taken into account. This collective is presented here evidencing the efficacy of this interdisciplinary procedure in palliative (pall.) treatment of gastric cancer. Results: Last date of evaluation: Dec/31/2008; median age: 58,7 years; men/women: n=12/4; res. of the primary tum. prior to pall. chemoth.: yes/no: n=2/14, ECOG 0/1: n=5/11; primary tum. localisation: AEG tum.: n=7; gastric carcinoma: n=9, elevated CEA yes/no: n=5/11, elevated CA19–9 yes/no: n=5/11. Number of metastatic localisations: 1/2/3: 69%/19%/12%, chemoth. application: total number:267; average value/patient:17 cycles altogether: 46, median cycles/pt.: 3, higher grade tox. (grade 3–4): anaemia 4%; diarrhea 2%, vomitus 2%, fever/infection 2%; response: PR 32%; SD 56 %; PD 6%; not evaluable 6 %; tum. control (PR, SD) 88 %; sec. res.: R0: 82 %; R1: 6 %, R2: 6 %; RX: 6%; gastrectomy with peritonectomy (R0): n=4 (25%), gastrectomy with lymph node dissection (D4,R0): n=6 (38%); HIPEC: n=4 (25%); 1-year survival:81%, 2-year survival: 44%, 3-year survival: 25%; deceased pts.: n=9 (56%), NED 19% (n=3). Conclusions: In our trial curative resections could be achieved in 82 % of the pts. During a follow-up of 20 months a NED status could be documented in 19% of the patients. No significant financial relationships to disclose.
Model-based estimates of tumor growth inhibition (TGI) metrics to predict for overall survival (OS) in first-line non-small cell lung cancer (NSCLC).
Authors: Laurent Claret, Pierre Mancini, Bernard Sebastien, Christine Veyrat-Follet, Rene Bruno
Journal: Journal of Clinical Oncology (2013)

e19049 Background: A survival model using change in tumor size at week 8 from baseline (CTS) (Clin Pharmacol Ther 86:167-174, 2009) was used to predict OS of the motesanib phase III study in NSCLC (Clin Pharmacol Ther 92:631-634, 2012). However CTS may not fully capture treatment effect on OS. We investigated other TGI metrics to predict OS using historical phase III data. Methods: Various TGI metrics, CTS, time to growth (TTG), and tumor growth rate (G), were estimated using two longitudinal tumor size models (Clin Cancer Res 17:907-917, 2011, PAGE 21 [www.page-meeting.org/?abstract=2328], 2012, JCO in press, 2013) developed from phase III data (1218 1st-line patients with NSCLC treated with doxetaxel (D) plus cisplatin (Cs) or carboplatin (Cb) or vinorelbine (V) plus Cs) (J Clin Oncol, 21:2016-3024, 2003). TGI metrics and baseline prognostic factors were assessed in univariate Cox and multivariate parametric survival models. Alternative models were qualified by simulating OS distributions in 1000 replicates of the phase III study and checking that observed OS distribution belongs to the 95% prediction intervals. Results: In a univariate analysis all TS metrics were strong predictors of OS (p&lt;0.0001). TTG and G were similar and much better than CTS (likelihood ratio test). OS was best described by a log-normal distribution and the influence of the covariates was assessed based on linear regression of the logarithm of OS (days). Parameter estimates of the best multivariate model are shown in the Table. The model was qualified in predicting OS distributions in the 3 arms (D+Cs, D+Cb, V+Cs). Conclusions: With further external validation, this model could be used to analyze longitudinal NSCLC tumor size data and their relationship to OS, in phase II studies of new agents and support end-of-phase-II decisions. [Table: see text]
A retrospective survival analysis of whole brain radiotherapy (WBRT) for brain metastases at Mount Vernon Cancer Centre (MVCC)
Authors: P. J. Mulholland, M. Assoku, P. Sasieni
Journal: Journal of Clinical Oncology (2009)

2068 Background: The primary purpose of this retrospective study was to determine the survival of patients with brain metastases following WBRT with regards to the influence of tumor type, age &lt; 65 versus ≥ 65 (RPA RTOG prognostic factor) and recency of treatment date. Methods: From treatment records we identified 1,926 patients with brain metastases from solid tumors who were treated with WBRT at MVCC between February 1992 and March 2008. Dates of death were sourced from records at MVCC, the Cancer Registry and GP practices. Results: We obtained dates of death for patients with lung (n=804), breast (n=457), colorectal (n=129), skin (n=119), kidney (n=82), and unknown primary (n=124) cancers. 42 patients were excluded from analysis as their tumor types were unspecified. A heterogeneous group of 169 patients with a variety of other primary tumor types were also excluded from our primary analyses. 22% of the patients died within the first month following WBRT and only 2.4% remained alive at 2 years. Log-rank analysis of age &lt; 65 versus ≥ 65 demonstrated improved survival for the former for the colorectal, lung, and skin tumor types (p = 0.0048, 0.0001, and 0.0456 respectively). This relationship did not reach significance for the breast, unknown primary, and renal cancer groups (p = 0.14, 0.13, and 0.06 respectively). With the exception of colorectal cancer, the analysis of the effect of treatment date on survival did not reveal recent improvements in survival for patients with brain metastases. An improvement in survival was experienced by the colorectal subgroup treated after March 2006 (HR= 0.51 95% CI 0.27- 0.96). Conclusions: Our data validate age as an important prognostic factor for many tumor types with notable exceptions for as yet undetermined reasons. Metastasis to the brain is a late stage feature of colorectal malignancy. The survival of the majority of patients undergoing WBRT for brain metastases is poor and with the possible exception of colorectal cancer, has not improved over the last decade. [Table: see text] [Table: see text]
Relationship between level of lymph node metastasis (LNM) and survival in head and neck squamous cell carcinoma (HNSCC).
Authors: Yan Xing, Jianjun Zhang, Heather Lin, Erich M. Sturgis, Adam S. Garden, Kathryn A. Gold, J. Jack Lee, William Nassib William
Journal: Journal of Clinical Oncology (2013)

6087 Background: Evidence from small cohorts suggests that level of LNM predicts survival in patients with HNSCC. This study sought to investigate the prognostic value of level of LNM in a large populational database and contrast it with the current AJCC classification of lymph node involvement. Methods: SEER registry was queried for patients with stage I-IVB HNSCC of oral cavity (OC), oropharynx (OP), larynx (LAR) and hypopharynx (HP) diagnosed from 2004 to 2009 (N=39,699, median follow-up 2.3 years). Each anatomic group was divided into 3 subgroups based on level of LNM (no LNM, LNM to levels 1-3, 4 or 5), and 4 subgroups based on AJCC classification (N0, N1, N2, N3). Overall survival (OS) in each subgroup was computed (Kaplan-Meier method) and compared (log-rank test). Concordance statistics (C-index) were used to assess the accuracy of LNM classification by level vs AJCC in predicting OS. Results: Both AJCC and level of LNM-based classifications predicted OS in patients with OC, LAR, and HP cancers. For OP, neither AJCC nor level of LNM-based classification predicted OS as expected (lower OS for N0 vs N1/2 or levels 1-3/4) (Table). The performance of level of LNM-based classification was comparable to AJCC N staging for OC, LAR and HP. Conclusions: Level of LNM is a prognostic factor for OC, LAR and HP HNSCC. Classification by level of LNM reached similar accuracy as AJCC N staging in predicting OS for OC, LAR and HP. Neither classification is satisfactory for OP, illustrating the need to refine the staging system in this subgroup. [Table: see text]
Long-term safety of BLP25 liposome vaccine (L-BLP25) in patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: C. Butts, H. Anderson, A. Maksymiuk, D. Vergidis, D. Soulières, Y. Cormier, M. Davis, E. Marshall, M. Falk, G. Goss
Journal: Journal of Clinical Oncology (2009)

3055 Background: The BLP25 liposome vaccine (L-BLP25, Stimuvax) is an investigational innovative therapeutic cancer vaccine incorporating immunoadjuvant monophosphoryl lipid A and synthetic MUC1 lipopeptide in a liposomal delivery system. In an open-label phase IIb study in 171 pts with stage IIIB/IV NSCLC randomized to best supportive care (BSC) alone (n=83) or BSC + L-BLP25 (1000 μg lipopeptide) (n=88), L-BLP25 pts received weekly vaccinations for 8 weeks (wks) and could continue maintenance vaccinations every 6 wks from wk 13. Results were encouraging (Butts et al, JCO 2005) and a remarkable number of pts received prolonged treatment (tmt). As a result a global phase III study (START) has been initiated. Methods: Safety results for 16 pts from the phase IIb study treated for ≥2 years with L-BLP25 are reported. Results: In these 16 pts (median age 57.5 years, ECOG PS: 0 in 5/16 [31%] and 1 in 11/16 [69%]), there were more females (56% vs 44% [9/16 vs 76/171]) and locoregional stage IIIB disease at entry (81% vs 38% [13/16 vs 65/171]) vs the phase IIb study population. Pts received L-BLP25 for 2.0–7.7 years and 10 pts were treated for &gt;5 years. Compliance with tmt was good: almost all (96%) maintenance vaccinations were given every 6 wks according to the tmt schedule. L-BLP25 was well tolerated: the most common tmt-emergent adverse events (TEAEs) were cough (n=12, 75%), fatigue (n=12, 75%), and dyspnea (n=11, 69%). The pattern of TEAEs did not change significantly over time and there was no rise in the incidence of TEAEs with increasing time on tmt. Among the most common TEAEs in years 1, 2, and &gt;2 were nausea (44, 19, and 38%), fatigue (56, 18, and 38%), chest pain (38, 31, and 31%), and cough (38, 25, and 31%). Twelve pts (75%) had tmt-related TEAEs (grade 1/2 in 11/12 pts [92%] and grade 3 in 1/12 [8%]): the most common were injection-site reactions. The occurrence of tmt-related TEAEs decreased with increasing tmt duration. There was no evidence of any TEAEs related to autoimmunity. Analysis of laboratory data did not indicate any long-term renal, liver, or other toxicity. Conclusions: Long-term use of L-BLP25 was without any identifiable safety issues. In particular, there was no evidence of autoimmune reactions with prolonged use. [Table: see text]
Examining gemcitabine and docetaxel for recurrent NMIBC.
Authors: Niv Milbar, Max Kates, Meera Chappidi, Mark Schoenberg, Trinity J. Bivalacqua
Journal: Journal of Clinical Oncology (2017)

322 Background: BCG relapsing/unresponsive patients who are poor surgical candidates or prefer bladder preservation vs. radical cystectomy (RC) may be offered intravesical therapies. Often in the literature, a “recurrence” after these therapies includes low-grade (LG) lesions, though stage progression and RC may be more meaningful outcomes for therapeutic efficacy. Including LG endpoints may make 2 nd line therapies appear less efficacious. 2 nd line intravesical Gemcitabine (GEM) with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). Our objective was to evaluate JHH experience with GEM/DOCE, and to address whether LG vs high-grade (HG) recurrence endpoints influenced outcomes. Methods: 33 patients who received full induction courses of GEM/DOCE since 2011, per the protocol adapted from Michael O’Donnell at U. Iowa, were identified in the IRB-approved JHH NMIBC database. Multivariable logistic regression determined factors associated with recurrence. Cox proportional hazard models evaluated risk factors for all-grade recurrence-free survival (AG-RFS) and HG recurrence-free survival (HG-RFS). Results: Median AG-RFS was 7.6 months with 42% 1-year and 27% 2-year AG-RFS. Median HG-RFS was 17.5 months with 57% 1-year and 44% 2-year HG-RFS. No adverse effects of GEM/DOCE were observed. There were 5 LG recurrences, 11 HG recurrences, and 3 progressions. Of these, 7 patients had RCs. Within initial LGTa presentation, 80% (4/5) had LG and 20% (1/5) had HG recurrence. Within initial HG-NMIBC presentation, 46% (13/28) had HG recurrence. Only in univariable cox models, LGTa presentation showed increased risk of AG-RFS (HR 3.18, 95% CI 1.08-9.40, p=0.036), but comparable HG-RFS (HR 0.32, 95% CI 0.04-2.47, p=0.275). Conclusions: GEM/DOCE is a well-tolerated alternative to immediate RC for highly selected patients with HG-NMIBC. As anticipated, including LG recurrence as an endpoint for RFS made GEM/DOCE appear less efficacious. However, since standard of care for LG recurrence is further intravesical therapy, this endpoint may not be appropriate, as its recurrence often does not result in RC or worse cancer outcomes. Future studies of 2 nd line therapies for NMIBC should identify HG endpoints based on clinically meaningful outcomes.
Biliary tract cancer in a Moroccan medical oncology unit.
Authors: Nezar Bouyahia, Sami Aziz Brahmi, Amine Mohammed Chad, Khaoula Daoudi, Fatima Zahra Hijri, Adil Ibrahimi, Khalid EL Haoudi, Khalid Maazaz, Samia Arifi, Mellas Nawfel, Omar El Mesbahi
Journal: Journal of Clinical Oncology (2012)

e14726 Background: Biliary tract cancers (BTC) are relatively rare (3% of digestive cancers), they mainly affect older women and are located in the gallbladder in about 70% of the cases. Methods: In this retrospective study, we reviewed 63 cases of BTC admitted in the medical oncology unit of HASSAN II university center between January 2007 and December 2011. The aim of this study is to define epidemiologic, diagnostic and therapeutic aspects of this disease in a Moroccan population. Results: In our study, BTC account for 4,9% of digestive cancers. The mean age of our patients was 58,2 years ranged from 32 to 81 years, female gender represent 69%. The tumors were located in the gallbladder (GB) in 70% of the cases divided into adenocarcinoma (79%) and squamous cell carcinoma (21%). The other locations were hilar cholangiocarcinoma (24%) and intrahepatic cholangiocarcinoma (6%). Magnetic resonance cholangiographic was performed (n=15) and suspected cancer in all cases. Incidental finding of GB cancer at surgery was recorded in 21 patients: intraoperatively in 8 cases or after pathological study in 13 cases. Staging of the disease was divided into localized stage (7%), locally advanced stage (13%) and metastatic stage (80%). A complete surgery in GB cancer was performed in 13 patients, a palliative surgery was done in 20 patients: cholecystectomy (n=7) and biliary drainage (n=13). For metastatic patients (n=44), a palliative chemotherapy was administred as following: combination of cisplatin and gemcitabin (n=18), gemcitabin (n=7), combination of cisplatin and 5 fluoro uracile (n=5), combination of oxaliplatin and gemcitabin (n=3), capecitabine (n=3), FUFOL Mayo clinic (n=2) and combination of capecitabine and oxaliplatin (n=2). While 9% of the patients received supportive care because of their comorbidities and the deterioration of the performans status and liver blood tests. Conclusions: Because of the silent evolution of BTC, the diagnosis is therefore delayed, the prognosis is poor and treatment is usually palliative. Our results are consistent with those of the literature concerning the epidemiological finding and diagnosis aspects.A multidisciplinary approach is recommended to improve the prognosis of patients with BTC.
MGMT promoter methylation as a predictive biomarker for response to radiotherapy versus chemotherapy in malignant astrocytomas in the elderly: The NOA-08 trial.
Authors: Wolfgang Wick, Christoph Meisner, Michael Platten, Matthias Simon, Guido Nikkhah, Kirstin Papsdorf, Michael Sabel, Christian Braun, Guido Reifenberger, Michael Weller
Journal: Journal of Clinical Oncology (2012)

2000 Background: In a few years more than half of the patients with glioblastoma will be older than 65 years of age and thus be classified as elderly. The current standard of care in elderly patients with glioblastoma (GB) or anapestic astrocytoma (AA) is resection or biopsy followed by involved-field radiotherapy (RT). The role of primary chemotherapy is poorly defined. The NOA-08 trial compared efficacy and safety of RT to temozolomide (TMZ) in patients with newly diagnosed AA or GB. Methods: Patients (N=412; 39 AA, 373 GB) &gt; 65 years with a Karnofsky performance score &gt; 60 were randomized to receive RT or TMZ. The primary endpoint was overall survival (OS). The trial sought to demonstrate the non-inferiority of TMZ compared with RT. Results: Patient characteristics in the intention-to-treat population [N=373 (178 patients RT, 195 patients TMZ)] were balanced. All histologic diagnoses (11% AA and 89% GB) were centrally confirmed. Median OS [HR=1.09 (95% CI: 0.84-1.42)] and event-free survival (EFS) [hazard ratio (HR)=1.15 (0.92-1.43)] of TMZ versus RT did not differ between both arms. Non-inferiority of TMZ compared with RT was significant (p&lt;0.05). Extent of resection, but not age or diagnosis of AA were associated with prolonged EFS and OS. DNA repair protein O 6 -methylguanine DNA-methyltransferase (MGMT) promoter methylation in tumor tissue was associated with prolonged OS [HR=0.67 (0.38-1.29)]. Patients with MGMT promoter methylation had longer EFS when treated with TMZ (8.4 months [5.5-11.7] versus RT (4.6 [4.2-5] months) whereas patients without MGMT promoter methylation had longer EFS when treated with RT (4.6 [3.7-6.3] versus 3.3 [3-3.5] months). This effect persisted for OS. Conclusions: NOA-08 demonstrates the non-inferiority of TMZ compared with RT in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ.