tbuckley/cabot-search huggingface dataset:
Baseline cognitive functions among elderly patients with localized breast cancer.
Authors: Florence Joly, Marie Lange, Natacha Heutte, Aurélie Daireaux, Chantal Rieux, Johan Le Fel, Olivier Rigal, Vincent Roy, Jean-Emmanuel Kurtz, Benedicte Clarisse, Benedicte Giffard, Francis Eustache, Sabine Noal
Journal: Journal of Clinical Oncology (2013)

9510 Background: Cognitive deficits (CD) were reported among patients receiving chemotherapy (CT) for cancer, but could also be observed before treatment. Elderly patients were poorly studied although they are more prone to present age-related CD and CD onset or enhancement during CT. This study assessed baseline cognitive functions among elderly localized breast cancer (LBC) patients before adjuvant treatment therapy. Methods: Episodic memory, working memory, executive functions and information processing speed were assessed with neuropsychological tests. Validated questionnaires were used to assess subjective CD, anxiety, depression and fatigue before adjuvant treatment. Geriatric assessment was also realized. Objective CD were defined as a score less than 1.5 standard deviation (SD) of normative data on &gt;2 tests, or less than two SDs on &gt;1 test. Significant subjective CD (evaluated by the FACT-Cog) were defined when the 4 subscales below the first tercile distribution. Results: Results concern 123 elderly LBC (71±4 years): planned treatment included CT and radiotherapy (RT) for 61 patients and RT only for 62 patients. Characteristics are as follows: mastectomy (28%), stage (I: 60%, II: 27%, III: 13%), positive hormonal receptor (88%) and positive Her2 (17%). Before any adjuvant treatment, objective CD were observed in 40% of patients (46% in CT group, episodic memory mainly impaired and 37% in RT group, executive functions and information processing speed mainly impaired). No relation was observed between cancer stage, geriatric frailty and objective CD. Twenty nine percents of patients presented fatigue, 6% anxiety and 10% depression. These variables were not related to objective CD but they were related to subjective CD. Conclusions: More than 40% of elderly LBC patients presented objective CD before any adjuvant therapy that is higher than observed among younger patients. It is important to take account in the decision making of adjuvant treatment in elderly patients. Clinical trial information: NCT01333735.
Efficacy of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with wild-type KRAS exon2 metastatic colorectal cancer previously treated with bevacizumab within 6 months.
Authors: Kaori Hayashi, Seiichiro Mitani, Hiroya Taniguchi, Satoshi Hamauchi, Keiji Sugiyama, Takahiro Tsushima, Kazunori Honda, Akiko Todaka, Toshiki Masuishi, Tomoya Yokota, Yukiya Narita, Nozomu Machida, Shigenori Kadowaki, Akira Fukutomi, Takashi Ura, Yusuke Onozawa, Masashi Ando, Hirofumi Yasui, Kei Muro, Kentaro Yamazaki
Journal: Journal of Clinical Oncology (2017)

800 Background: The ASPECCT study showed panitumumab (Pmab) is non-inferior to cetuximab (Cmab) for chemotherapy-refractory and intolerant wild-type (WT) KRAS exon2 metastatic colorectal cancer (mCRC). In the subgroup analysis, Pmab provided more favorable outcomes than Cmab for patients (pts) previously treated with bevacizumab (Bmab). However, some reports suggested that anti-EGFR antibody (anti-EGFR) efficacy was reduced when received within 6 months of last administration of Bmab. In this study, we aim to evaluate the difference in efficacy between Pmab and Cmab in pts who received prior Bmab and were treated with anti-EGFR after a short interval. Methods: We retrospectively evaluated pts treated with anti-EGFR and irinotecan (IRI) after failure of Bmab, fluoropyrimidine, oxaliplatin, and IRI at two institutions. The main inclusion criteria were WT KRAS exon2 mCRC, ECOG PS 0-2, and no prior administration of anti-EGFR within 6 months after Bmab. Results: From Sep. 2008 to Mar. 2016, 124 consecutive pts met the inclusion criteria (Pmab/Cmab, 30/94). Pts’ characteristics were as follows (Pmab/Cmab): median age (range): 63/62 (38-76/27-82); male, 63%/72%; ECOG PS 0, 43%/27%; PS1, 57%/66%; PS2 0%/7%; tumor in left colon, 87%/76%; histology (por, muc), 10%/16%; ≥2 metastases, 67%/66%; ≥1 subsequent therapy, 73%/63%. Overall response and disease control rates in Pmab/Cmab were 31%/26% and 69%/67%, respectively. In Pmab/Cmab, the median overall survival was 15.8/12.2 months (HR, 0.62; 95% CI, 0.4-0.97; P=0.04) and the median progression-free survival was 6.5/5.5 months (HR, 0.75; 95% CI, 0.49-1.16, P=0.20). The adjusted HR with 10 covariates such as age, gender, PS, tumor location, histology, primary tumor resection, number of metastatic sites, liver limited disease, time from diagnosis of metastasis and initiation date of anti-EGFR plus IRI was 0.61 for PFS (p=0.1) and 0.61 for OS (p=0.04). Conclusions: Pmab plus irinotecan showed favorable outcomes compared with Cmab plus irinotecan in pts with WT KRAS exon2 mCRC within 6 months between the last administration of Bmab and initial anti-EGFR.
Symptomatic BK virus as a significant independent predictor of immune suppression and poor overall survival in allogeneic hematopoietic stem cell recipients.
Authors: Ala Abudayyeh, Amir Hamdi, Heather Y. Lin, Maen Abdelrahim, Gabriela Rondon, Dimitrios P Kontoyiannis, Amanda Leigh Olson, Borje Andersson, Richard E. Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Journal of Clinical Oncology (2015)

7025 Symptomatic BK virus as a Significant Independent Predictor of Immune Suppression and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients Background: BK virus (BKV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction and prolonged hospital stays. In this study we looked at all transplant associated variables and the patient’s immune status to evaluate what factors predicted for the risk of BKV viuria. We hypothesized that BKV infection is a marker of poor immune recovery and survival outcomes in HSCT recipients. Methods: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center between January 2004 and December 2012. We evaluated their immune panels and their transplant associated factors. BKV positivity was defined as BKV detection in urine by PCR testing. Overall survival outcome was defined as the time from the day of stem cell infusion to the day of death. Results: We identified a total of 2477 patients with a median age of 52 years. BK viruria was manifest in 25% (n = 629) of the patients. The median time from transplantation to BK viruria development was 42 days. On multivariate analysis, age; female sex; acute GVHD; chronic GVHD; myeloablative conditioning regimen; cord blood transplantation; low CD3, CD4, CD8, and CD56 levels; and a low platelet count were significantly associated with BKV infection with mostly p values of (P < 0.001). In addition, BKV infection was associated with a lower overall survival duration (P < 0.001). Patients with BKV infections were more likely to be immunosuppressed for the first 3 years after transplantation than were patients without BKV infections. Conclusions: This study for the first time reports a significant association between BKV reactivation following allogeneic HSCT and decreased overall survival. In addition, this study provides valuable information on the immune status of HSCT recipients with BKV infections to help us formulate plans for more effective prevention and treatment of this infection.
Urinary incontinence and sexual dysfunction are worse after surgery for prostate cancer, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Radical prostatectomy is associated with a considerable decline in erectile function and urinary continence when compared with external beam radiation therapy (EBRT) or active surveillance for localised prostate cancer, research published in JAMA shows.1

The authors of two new studies concluded that different treatment strategies for localised prostate cancer were associated with distinct patterns of side effects and said that doctors should use this information to help men make informed decisions in line with their individual preference.

The first prospective cohort …
Correlation of plasma TIMP-1 levels and disease-free survival in primary colorectal cancer independent of serum CEA levels
Authors: H. J. Nielsen, N. Brünner, I. J. Christensen
Journal: Journal of Clinical Oncology (2009)

e22040 Background: Introduction of independent prognostic markers may play a significant role in future treatment of early stage colorectal cancer (CRC). CEA is still the only recommended (ASCO and EGTM) serological marker in CRC. However, Tissue Inhibitor of Metallo Proteinases-1 (TIMP-1), which is a glycoprotein that acts as an inhibitor of most of the active matrix metalloproteinases, has previously been shown to carry independent prognostic information in patients with primary CRC. The purpose of the present study was to assess the combination of preoperative serum CEA and plasma TIMP-1as prognostic markers in patients undergoing resection for primary CRC. Methods: In the present prospective study serum and plasma samples were collected before surgery from 422 patients with primary CRC stage I-III. CEA was determined in serum by a commercial assay and TIMP-1 was determined in plasma using a thoroughly validated, in-house ELISA. Time to recurrence or death of CRC was registered and the association to serum CEA and plasma TIMP-1 levels were studied in a Cox multivariate model including age, gender, disease stage and tumor location. Hazard ratios and 95% confidence intervals (HR (95%CI)) for disease free survival (DFS) were calculated. Results: An event was recorded in 186 patients, 75 had local recurrence, 103 had a distant metastases (28 of these patients had both local recurrence and distant metastases) and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale (base 2), both serum CEA and plasma TIMP-1 were statistically significant in a multivariable analysis with HR=1.12 (1.03–1.21) and HR=1.51 (1.12–2.04), respectively. Additional calculations of low CEA plus low TIMP-1, high CEA plus low TIMP-1, low CEA plus high TIMP-1 and high CEA plus high TIMP-1 showed that high plasma TIMP-1 levels carried prominent information of poor prognosis independent of CEA. Conclusions: Preoperative serum CEA and plasma TIMP-1 levels were independent predictors of disease free survival for patients with primary CRC. Combination of the two proteins showed that TIMP-1 was a prominent predictor of poor DFS independent of CEA. [Table: see text]
Safety and pharmacokinetics (PK) of cabazitaxel (C) in patients (pts) with hepatic impairment (HI).
Authors: John Sarantopoulos, Alain C. Mita, Aiwu Ruth He, James Lloyd Wade, Chung-Tsen Hsueh, John Charles Morris, Albert C. Lockhart, David Quinn, Jimmy J. Hwang, James Walter Mier, Wenping Zhang, Claudine Wack, Jian Yin, Pierre-François Clot, Olivier Rixe
Journal: Journal of Clinical Oncology (2015)

2538 Background: C studies excluded pts with HI. A Phase I dose-escalation study (NCT01140607) assessed the effect of HI on C PK and safety in pts with advanced solid tumors. Methods: Pts with normal hepatic function (NHF; bilirubin [B] ≤ ULN; aspartate aminotransferase [AST] ≤ ULN), mild (MiHI; B > 1– ≤ 1.5 x ULN or AST > 1.5 x ULN), moderate (ModHI; B > 1.5– ≤ 3 x ULN) or severe (SHI; B > 3–10 x ULN) HI received C dose escalation starting at 25, 20, 10 or 10 mg/m2, respectively. Endpoints were cycle 1 (C1) dose-limiting toxicities (DLTs), safety and PK. Plasma PK were derived by non-compartmental analysis. HI effect was assessed by linear mixed-effects modeling on clearance normalized to body surface area (CL/BSA) and exposure normalized to dose. Results: Pts (43 [6 NHF, 18 MiHI, 12 ModHI, 7 SHI]) had a median age of 60 years (range 18–79); 52% were male; 81% had ECOG performance status 1. Colon and liver tumors were most common (19%; prostate 7%). Maximum tolerated doses (MTD) were 20 (MiHI) and 15 mg/m2 (ModHI). The SHI cohort was discontinued early (first pt treated at 20 mg/m2 died). Median number of C cycles (range) at MTD were: NHF 3 (1–4); MiHI 2 (1–31); ModHI 2 (1–3). In evaluable pts, C1 DLTs were seen in 3/4 NHF, 3/11 MiHI and 1/6 ModHI pts at MTD, and 0/6 SHI pts at 10 and 15 mg/m2. The most frequent DLT was grade 4 febrile neutropenia (FN). The most frequent C-related, grade 3–4 toxicities were neutropenia (42%), FN (16%) and anemia (12%). PK was assessed in 36 pts (6 NHF, 15 MiHI, 9 ModHI, 6 SHI). CL/BSA was lower (geometric mean 13.4 L/h/m2) than typical values (26.4 L/h/m2) in NHF, but similar in MiHI (23.5 L/h/m2) and ModHI (27.9 L/h/m2). CL/BSA in SHI was 18.1 L/h/m2. Compared with MiHI, CL/BSA increased 19% in ModHI (geometric mean ratio 1.19; 90% CI 0.74−1.91), but decreased 23% in SHI (0.77; 0.39−1.53) (39% with erratic PK profiles excluded [0.61; 0.36–1.05]), and AUClast/dose decreased 14% in ModHI (0.86; 0.50−1.46) and increased 17% in SHI (1.17; 0.63–2.14). No change in C free fraction was seen. A pt with cholangiocarcinoma on study had stable disease at cycle 32. Conclusions: Cabazitaxel tolerability was similar in pts with MiHI, ModHI or NHF, and consistent with prior reports. There is no evidence that MiHI or ModHI results in a substantial decline in C CL. Clinical trial information: NCT01140607.
Erratum: The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement
Authors: M A Hussein, F D Vrionis, R Allison, J Berenson, S Berven, E Erdem, S Giralt, S Jagannath, R A Kyle, S LeGrand, R Pflugmacher, N Raje, S V Rajkumar, R L Randall, D Roodman, D Siegel, R Vescio, J Zonder, B G M Durie
Journal: Leukemia (2008)
Efficacy and safety of oral MEK162 in patients with locally advanced and unresectable or metastatic cutaneous melanoma harboring <i>BRAF</i>V600 or <i>NRAS</i> mutations.
Authors: Paolo Antonio Ascierto, Carola Berking, Sanjiv S Agarwala, Dirk Schadendorf, Carla Van Herpen, Paola Queirolo, Christian U. Blank, Axel Hauschild, J. Thaddeus Beck, Angela Zubel, Faiz Niazi, Simon Wandel, Reinhard Dummer
Journal: Journal of Clinical Oncology (2012)

8511 Background: BRAF and NRAS mutations occur in 50-60% and 15-20% of cutaneous melanomas, respectively. MEK162, a selective inhibitor of the kinases MEK1 and MEK2, has shown pre-clinical activity in BRAF and NRAS mutant (mt) melanoma models. This open label, phase II study assessed the antitumor activity of MEK162 in patients (pts) with BRAFV600 and NRAS mt advanced cutaneous melanoma. Methods: MEK162 was administered orally at a starting dose of 45 mg twice daily. Treatment was until unacceptable toxicity, disease progression (PD) or investigator or patient refusal. Tumor response was assessed by CT imaging every 8 weeks (RECIST 1.0) until PD. Results: As of 16 Sept 2011, the full analysis and safety populations comprised 66 pts: 42 BRAF mt and 24 NRAS mt. Median age 58.0 years; 57.6% male; 72.7% WHO performance status 0. All NRAS pts and all but 2 BRAF (1 each stage IIIB and IIIC) pts had stage IV disease, and 87.5% of NRAS pts and 66.7% of BRAF pts had received prior therapy at study entry. Median time from 1st diagnosis to 1st dose of drug was 40.4 months. Median time on study was 10.4 and 8.5 weeks for the BRAF and NRAS arms. Relative dose intensities of 80–&lt;100% were received by 71.4% and 70.8% of pts, respectively. Among 29 BRAF mt and 13 NRAS mt pts evaluable for efficacy, 1 confirmed and 6 unconfirmed partial responses (PRs) and 9 pts with stable disease (SD) were recorded in the BRAF arm and 2 confirmed PRs, 1 unconfirmed PR and 4 pts with SD recorded in the NRAS arm. Common treatment–related adverse events (AEs), all grades (Gs) and all pts, were rash (40.9%), diarrhea (33.3%), acneiform dermatitis (27.3%), creatine phosphokinase (CK) elevation (25.8%), fatigue (18.2%) and peripheral edema (21.2%). Central serous retinopathy-like retinal events (G 1/2 only) were reported in 8 (12.1%) pts (6 G1, 2 G2). All retinal events were reversible. G3/4 AEs in &gt;1pt were diarrhea (4.5%) and CK elevation (15.2%). 5 pts discontinued due to toxicity. 34 pts are ongoing with more responses under current review. Conclusions: MEK162 showed clinical activity and good tolerability in pts with BRAF and NRAS mt advanced melanoma. This is the 1st targeted therapy to show activity in pts with NRAS mt melanoma.
Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) associated with "responsive" malignancies.
Authors: Kurt A. Jaeckle, S. Keith Anderson, Anna Willson, Gerardo Colon-Otero, Tejal Amar Patel, Edith A. Perez
Journal: Journal of Clinical Oncology (2012)

2015 Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent + CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had + CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13+, 30+, 33+, and 180+ wks. 4 pts (24%) lived &gt; 95 wks. Of 11 w/ baseline + CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear = 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.
Awareness and misconceptions of colorectal cancer risk factors among laypersons and physicians.
Authors: Jerome Viguier, François Eisinger, Sebastien Couraud, Lysel Guibaudet, Jean-Yves Blay, Laurent Greillier, Christine Lhomel, Alexis B. Cortot, Jean F. Morere, Xavier B. Pivot
Journal: Journal of Clinical Oncology (2017)

536 Background: The aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. The colorectal cancer (CRC) screening program is in place and targets the 50-74-yr age group. CRC prevention also relies on increased awareness of known risk factors (behavioral [BRF] or non-behavioral [NBRF]). This analysis focuses on awareness of CRC risk factors among the lay population and physicians. Methods: The 4th nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1463 individuals with no history of cancer (age, 40-75 yrs) was interviewed between June 12 and July 10, 2014. A mirror survey on a representative sample of 301 physicians was conducted between July 9 and August 8, 2014. Interviewees were asked to cite the five main RF for CRC. Results: Heredity/family history of CRC was widely cited by physicians but far less by laypersons (LP) (95.3% vs. 26.1%, P &lt; 0.01). Digestive disorders, age, polyps and Crohn’s disease were also cited as NBRF by 38.2%, 22.9%, 15.3% and 12.3% of physicians, respectively. In comparison, these RF were very rarely cited by LP (5.4%, 1.5%, 1.7% and 0.1%, respectively, P &lt; 0.01). Unhealthy-lifestyle RF were cited by 86.4% and 52.7% of physicians and LP, respectively (P &lt; 0.01): poor eating habits, ranked first for both physicians and LP (80.1 vs 46.8%, P &lt; 0.01), including unbalanced or excessively rich diet (52.8% vs. 41.2%, P &lt; 0.01) and excessive quantities of red meat (12.6% vs. 2.2%, P &lt; 0.01). Among unhealthy-lifestyle RF, after poor eating habits, physicians cited first tobacco (24.3%), then alcohol (19.9%), and lack of exercise (14.6%) as other BRF. These were cited by 12.2% (P &lt; 0.01), 16.0% (NS) and 4.7% (P &lt; 0.01) of LP, respectively. Overweight/obesity was cited by 19.6% of physicians but by only 1.8% of LP. Conclusions: Overall, there is a lower level of awareness of CRC risk factors in lay persons than in physicians. Physicians are generally aware that heredity/family history and unhealthy lifestyle are the major RF for CRC, in line with the widely recognized RF. In contrast, lay persons rank BRF highest, and notably those related to poor eating habits.
Clinical and cost benefit of aprepitant in patients receiving high-dose chemotherapy prior to autologous peripheral blood stem cell transplantation.
Authors: Ayumi Nakamura, Yuki Kojima, Kenji Miyazawa, Shuichi Matsumoto, Chiyoe Kitagawa, Hiroatsu Iida, Tomoki Naoe, Hirokazu Nagai
Journal: Journal of Clinical Oncology (2014)

8610 Background: The clinical benefit of aprepitant has not been elucidated in the patients (pts) receiving high-dose chemotherapy (HD-CT) prior to autologous peripheral blood stem cell transplantation (APBSCT). We retrospectively surveyed the efficacy of aprepitant and the total cost during hospitalization of APBSCT. Methods: All pts received HD-CT at our institute between 2009 and 2013 were registered. We identified a total 38 pts (27 non-Hodgkin lymphomas and 11 multiple myelomas). Thirteen pts received aprepitant and granisetron (aprepitant group) for the prophylaxis of the emesis, whereas, 25 pts received granisetron only (non-aprepitant group). Nausea, vomiting, and appetite loss during were evaluated according to NCI-CTCAE version 4.0. Total costs including hospitalization, and supportive care were calculated from medical records. Results: The incidence of severe nausea (>=grade 3) was 15.4% in aprepitant group and 52.0% in non-aprepitant group (p=0.028). Percentages of pts with appetite loss (>=grade 3) in the aprepitant group were 23.1% in aprepitant group and 72.0% non-aprepitant group (p=0.028). In addition, the median length of total hospitalization from day of HD-CT in aprepitant group and non-aprepitant group were 22 and 29 days (p=0.005), respectively. The time of engraftment of the hematopoietic stem cells from auto-PBSCT and the incidences of infectious events were not significantly different between these groups. Furthermore, in aprepitant group, the mean total costs decreased from $20,204 to $17,256 per patient, respectively. The common causes for reduction of total costs in the aprepitant group were reduction in costs of hospitalization, transfusion, and treatment for infections. Conclusions: Our data indicated that the addition of aprepitant for the prophylaxisis of the emesis decreased the incidence of severe nausea and appetite loss, and might introduce some economic benefits in the total management of HD-CT followed by APBSCT.