tbuckley/cabot-search huggingface dataset:
Imatinib use in chronic phase CML in clinical practice: the UNIC study
Authors: J. L. Steegmann, M. Michallet, E. Morra, D. Marin, G. J. Ossenkoppele, G. Verhoef, T. Kühr, M. Björeman, M. Sterckx, K. Cerri
Journal: Journal of Clinical Oncology (2008)

7077 Background: Imatinib (IM) is widely used to treat CML. The Unmet Needs in CML study assessed real-life treatment of CML. Methods: This cross-sectional study, with retrospective chart review of patients currently treated for CML/Ph+ALL in 8 European countries (enrolled Sept 06-Mar 07), assessed proportions of IM-treated patients and those with resistance/intolerance (primary aims). A secondary aim was to describe dosing patterns. A registry was collected of adults treated for CML/Ph+ALL at participating centers. Case Report Forms (CRFs) were completed for eligible patients. Data were collected at the most recent visit and retrospectively via chart review. Results: CRFs were analysable for 1492 chronic phase (CP) CML patients, of whom 97% had received IM. Of these, 44.6% were IM resistant and/or intolerant (as reported in the medical chart if resistance/toxicity led to a change in or discontinuation of IM use) at some time since IM initiation. 20% stopped and did not restart IM during the study period. 23% stopped IM temporarily due to toxicity (median duration 22 days), of whom ∼30% had >1 such interruption. The most common increase was 400 to 600 mg (33%); most common decrease was 400 to 300 mg (39%). 16% of increases and 14% of decreases were both to and from doses <400 mg. Of the 520 patients with ≥1 dose increase, 17.5% were IM resistant just prior to dose change, of whom 63% were resistant at last observation. Median last IM dose was higher in IM-resistant (600 mg; N=149) vs non-resistant (400 mg; N=1205) patients. 41% of IM-resistant patients had received doses ≤400 mg. Of patients with IM dose increases to 600 and 800 mg, 22% (62/284) and 32% (36/112) had a toxicity post increase, respectively. Conclusions: A notable proportion of IM-treated CP CML patients in this large observational study needed dose modification. Some patients may be receiving suboptimal IM doses. IM-resistant patients received higher IM doses. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb, Novartis Bristol-Myers Squibb Bristol-Myers Squibb, Novartis Bristol-Myers Squibb
The impact of the peak (day 2) C-reactive protein (CRP) on the day 3 and day 4 CRP thresholds associated with infective complications following curative surgery in colorectal cancer.
Authors: Michelle Leana Ramanathan, Paul G. Horgan, Donald C. Mcmillan
Journal: Journal of Clinical Oncology (2013)

595 Background: The postoperative systemic inflammatory response, as evidenced by C-reactive protein (CRP) on day 3 (threshold ~170 mg/L) and day 4 (threshold ~130mg/L), have been reported to be associated with the development of infective complications following surgery for colorectal cancer. The aim of the present study was to assess the impact of the peak, day 2 CRP, on CRP concentrations at day 3 and day 4. Methods: Patients with colorectal cancer who were considered to have undergone elective curative resection were recorded in a prospective database (n=396). CRP was measured preoperatively and on days 1 to 4 postoperatively. Correlations between day 2 CRP and other perioperative CRP concentrations were examined. Results: The majority of patients were 65 or older (67%), male (55%), had colonic tumours (66%), had node negative disease (57%) and were from a deprived area (55%). Day 2 CRP was not associated not with age (p=0.055), sex (p=0.185), deprivation (p=0.103), tumour site (p=0.529) or stage (p=0.395). Day 2 CRP was directly associated with day 1 (r 2 =0.421, p&lt;0.001), day 3 (r 2 =0.617, p&lt;0.001) and day 4 (r 2 =0.315, p&lt;0.001) CRP, but not preoperative CRP (r 2 =0.008, p=0.084). The median day 2 CRP that corresponded with the previously described thresholds (~170mg/L and ~130mg/L at day 3 and 4 respectively) for predicting infective complications was 190mg/L. Similarly, the median day 2 CRP corresponding to the previously described thresholds (~190mg/L and ~140mg/L at day 3 and 4 respectively) for predicting an anastomotic leak was 200mg/L. Conclusions: A day 2 CRP concentration &gt;190 - 200mg/L, was associated with day 3 and 4 CRP concentrations above established CRP thresholds for the development of infective complications. It remains to be determined whether reduction in day 2 CRP concentrations will reduce infective complications following surgery for colorectal cancer.
Impact of liver fibrosis on effects and adverse effects of unresectable colorectal cancer under first line chemotherapy including CPT-11.
Authors: Masashi Yahagi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Ryo Seishima, Hidena Takahashi, Shimpei Matsui, Toru Yamada, Takayuki Kondo, Takehiro Shimada, Mutsuhito Matsuda, Yusuke Yoshikawa, Yusuke Asada, Kiyoaki Sugiura, Yoshiyuki Suzuki, Yuki Tajima, Junpei Nakadai, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

556 Background: Liver dysfunction is one of the irritating adverse effects in chemotherapy for colorectal cancer. Polymorphisms of UGTIA1, which is related to metabolism of CPT-11 in the liver, cause severe adverse events. In addition, long-term induction of CPT-11 may involve steatohepatitis. Thus, it is critical to surrogate liver dysfunction in chemotherapy including CPT-11. In this current study, we evaluated whether NAHLD fibrosis score (NFS) which is liver fibrosis marker of nonalcoholic steatohepatitis, is feasible for predicting the effects and adverse events of chemotherapy including CPT-11 for colorectal cancer. Methods: From January 2007 to May 2013, of 118 patients who were diagnosed with unresectable advanced/recurrent colorectal cancer in our hospital, we retrospectively analyzed 89 patients who underwent first line chemotherapy including CPT-11. We statistically analyzed the value of the pretreatment NFS on response rate (RR), progression-free survival (PFS), and hematologic or non-hematologic toxicity of chemotherapy including CPT-11. Results: The median NFS was -1.302 (range=-5.158 to 2.62). Multivariate analysis revealed that NFS was an independent negative predictive marker for RR (coef -0.373 (-0.712 to -0.035), p = 0.031), although no contribution of NFS was observed to PFS (coef 0.958(0.786|1.168), p=0.672). In terms of the adverse events, high value of NFS is an independent risk factor in hematological toxicity (coef 0.93 (0.20 to 1.65), p = 0.012), while not in non-hematological toxicity (coef 0.198 (-0.218|0.613), p=0.351). Conclusions: The pretreatment NFS might be a feasible for predicting response and hematological toxicity in first line chemotherapy including CPT-11 against colorectal cancer.
Predicting acute small-bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation: A comparison of peritoneal space versus small-bowel loop contouring techniques.
Authors: Robyn Banerjee, Santam Chakraborty, Ian Nygren, Richie Sinha
Journal: Journal of Clinical Oncology (2012)

673 Background: In lieu of contouring individual small bowel loops, the peritoneal space (PS) has been suggested as a possible surrogate volume for predicting small bowel toxicity. A dose-volume relationship for the PS has not been firmly established. The aim of this study was to determine whether contours of the PS better predict significant acute small bowel toxicity in neoadjuvant rectal cancer patients when compared with contours of individual small bowel loops. Methods: A standardized contouring method was developed for the PS and retrospectively applied to the radiation treatment plans of sixty-seven patients treated with neoadjuvant chemoradiotherapy for rectal cancer. All patients had locally advanced disease, no evidence of metastases, and received concurrent radiation and infusional 5-Fluorourocil chemotherapy. Dose-volume histogram (DVH) data was extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression was carried out for both contouring methods. Results: Grade ≥ 3 small bowel toxicity occurred in 16% (11/67) of patients. Volumes of the contoured small bowel loops correlated with grade ≥ 3 toxicity at each 5 Gray (Gy) dose level from 5 to 45 Gy, with the greatest area under the curve (AUC) measuring .964 (p=.000) associated with the volume receiving at least 25 Gy (V25). Volumes of the contoured PS predicted toxicity from 5 to 40 Gy, with the greatest AUC also at the V25 and measuring .896 (p=.000). Logistic regression analysis demonstrated a less than 15% risk of acute grade ≥ 3 toxicity was associated with a V25 of 215 cc for the small bowel and 710 cc for the PS. Conclusions: DVH analysis of peritoneal space volumes predicts grade ≥ 3 small bowel toxicity in neoadjuvant rectal cancer patients, suggesting the peritoneal space is a reasonable surrogate for contouring individual small bowel loops. However, contouring individual small bowel loops is a more sensitive method for predicting toxicity at each dose increment. For both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving at least 25 Gy (V25).
AHOD0031: A Phase III Study of Dose-Intensive Therapy for Intermediate Risk Hodgkin Lymphoma: A Report From the Children's Oncology Group
Authors: Debra l Friedman, Suzanne Wolden, Louis Constine, Lu Chen, Kathleen M McCarten, T. J Fitzgerald, Pedro De Alarcon, Allen R. Chen, Robert Hutchison, Peter Ehrlich, Nathan L. Kobrinsky, Meghan Higman, Shirley Hogan, Lorna Roll, Tanya Trippett, Cindy Schwartz
Journal: Blood (2010)
Surgical strategy for borderline resectable pancreatic body cancer.
Authors: Hiroki Yamaue, Ken-Ichi Okada, Masaji Tani, Manabu Kawai, Seiko Hirono, Motoki Miyazawa, Atsushi Shimizu
Journal: Journal of Clinical Oncology (2014)

271 Background: The indications for distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) in pancreatic carcinoma remain controversial. Moreover, the incidence of delayed gastric emptying (DGE) is high in patients undergoing distal pancreatectomy with DP-CAR. Methods: Fifty-two consecutive patients with pancreatic cancer who underwent distal pancreatectomy, including 36 standard distal pancreatectomies (standard DP) and 16 DP-CAR were reviewed. To determine the incidence of DGE, 37 consecutive patients who underwent DP-CAR were evaluated for the incidence of DGE, including 23 patients with left gastric artery (LGA)-resecting DP-CAR (conventional DP-CAR) and compared it with 14 patients who underwent distal pancreatectomy with preservation of the LGA (modified DP-CAR). Results: The estimated overall 1- and 2-year survival rates after standard DP / DP-CAR were 81/81% and 52/53%, and the median survival times were 32/25 months, respectively, with no significant difference comparing standard DP. There were no differences in the mortality rates and the incidence of each complication between the two groups except for delayed gastric emptying. In the conventional DP-CAR group, the LGA were involved in 20 patients (87.0%). The ISGPS grades were: no DGE = 43%, grade A = 26%, B = 13% and C = 17% in the conventional DP-CAR group, and no DGE = 93%, grade A = 7%, grade B/C = 0% in the modified DP-CAR group. The R0 rate was higher in the modified DP-CAR group (79%) compared to the conventional DP-CAR group (43%) (p=0.048). On multivariate analysis, resection of the LGA was an independent risk factor for increased incidence of DGE. Conclusions: DP-CAR was a feasible and safe procedure, similar to standard DP. Modified DP-CAR significantly reduced the incidence of DGE in comparison to conventional DP-CAR.
Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents: Analysis of growth signaling pathways expression and clinical outcome.
Authors: J. Mora, C. de Torres, E. Rodriguez, T. M. Cardesa, E. de Alava, O. Cruz
Journal: Journal of Clinical Oncology (2011)

9560 Background: Overall survival (OS) rates of patients with localized Ewing sarcoma family of tumors (ESFT) are >80% when treated with the MSKCC P6 protocol. However, it has been associated with a 5.8% incidence of secondary leukemias. A modified P6 (mP6) protocol with reduced exposure to chemotherapy is presented. The correlation between clinical outcome and the expression of proteins involved in active growth signaling pathways was explored. Methods: Thirty-one newly diagnosed ESFT patients were enrolled onto this phase II, single-arm, non-randomized protocol. A paraffin-embedded tissue array of 45 specimens was stained with the antibodies against c-KIT, AKT, p- AKT, p-mTOR, IGF-1R, IGFBP-3, MAPK, p27KIP1, and p70S6 kinase. Immunohistochemical staining was correlated with patient OS. Results: Twenty-four patients had loco-regional disease and 7 had metastases. The 4-year event-free survival (EFS) rate for patients with localized tumours is 83% and OS is 92%. The 3-year EFS rate for patients with distant metastases is 28% and OS rate is 42%. None of the patients experienced tumour progression before remission. All relapses occurred within 2 years from the end of treatment and local relapses (n=3) happened in patients who did not receive radiation therapy. No secondary malignancies have been observed, median follow-up of 4.3 years. In the univariate analysis only p-mTOR and p27KIP1 showed statistical significance to predict survival. A positive stain for p-mTOR (HR of 4,74 [95% CI (57, 121)]) was significantly (log-rank test, p=0,029) associated with better OS. Also, a positive stain for p27KIP1 (HR 6,87 [95% CI (77, 136)] was significantly (log-rank test, p=0,009) associated with better OS. Multivariate analysis show p-mTOR (HR: 5.57 with 95% CI: 0.7 to 44; p= 0.104) and p27 (HR: 3.2 [95% CI (1.02,10.2)] p=0.047) expression as independent prognostic factors of outcome. Conclusions: In this study, the mP6 protocol produced a complete remission rate of 83% at 4 years in non-metastatic ESFT reducing the risk of secondary malignancies. In our series, p-mTOR and p27KIP1protein overexpression were independently associated with better survival.
IL-6 Induced CD45RO, RB Translocation to Lipid Rafts in Myeloma Cells.
Authors: Fu-Jun Li, Naohiro Tsuyama, Hideaki Ishikawa, Masanori Obata, Saeid Abroun, Shangqin Liu, Kenichiro Otsuyama, Xu Zheng, Zi Ma, Yasuko Maki, Michio M. Kawano
Journal: Blood (2004)
Adjuvant chemotherapy in patients with resectable cholangiocarcinoma.
Authors: Kosin Wirasorn, Thundon Ngamprasertchai, Narong Khantikaew, Ake Pakkhem, Piti Ungarereevittaya, Jarin Jindaprasert, Aumkhae Sookprasert
Journal: Journal of Clinical Oncology (2013)

219 Background: Cholangiocarcinoma patients usually have poor treatment outcome and high mortality rate. The role of adjuvant chemotherapy is controversy. Our study aimed to evaluate benefits of adjuvant chemotherapy in resectable cholangiocarcinoma patients. Methods: A retrospective study included 263 patients who underwent curative resection in Srinakarind university hospital. These patients had pathological report with clear margin (R0) or microscopic margin (R1). Results: There were 138 patients received adjuvant chemotherapy. This group had significantly lower mean age than patients without chemotherapy (57.7 ± 8.5 vs. 60.4 ± 9.0 years, p = 0.01). Level of serum albumin above 3g/dL was more common in adjuvant chemotherapy group than another one (87.7% vs. 79.2%, p = 0.04). Patients who received adjuvant chemotherapy had significantly longer overall median survival time (21.6 vs. 13.4 months, p = 0.01). Patients with combination of gemictabine and capecitabine regimen had the longest survival time (median overall survival time of gemcitabine and capecitabine 31.5, 5-FU and mitomycin 17.3, 5-FU alone 22.2, capecitabine alone 21.6, and gemcitabine alone 7.9 months, p = 0.02). Benefits of adjuvant chemotherapy were likely to be found in patients who had high risk features, i.e. high level of CEA, high level of CA19-9, advanced stage, T4 stage, nodal involvement and R1 margin. Conclusions: Adjuvant chemotherapy may significantly prolong survival time in resectable cholangiocarcinoma patients, particularly the high risk group.
Value of cardiophrenic angle lymph nodes for the diagnosis of colorectal peritoneal carcinomatosis.
Authors: Caroline Caramella, David Malka, Edwige Pottier, Diane Goéré, Valerie Boige, Charles Honoré, Michel Ducreux, Isabelle Borget, Clarisse Dromain, Dominique Elias
Journal: Journal of Clinical Oncology (2013)

372 Background: The radiological diagnosis of peritoneal carcinomatosis (PC) is challenging. Metastases in the cardiophrenic angle lymph nodes (CPALN) have been anecdotally reported in patients with abdominopelvic malignancies. We aimed to assess whether CPALN detected by computed tomography (CT)-scan are associated with PC in patients with colorectal cancer (CRC). Methods: Between 2007 and 2010, 550 patients with CRC, including 165 (30%) with PC, underwent surgery with complete exploration of the peritoneal cavity in our center. We retrospectively reviewed preoperative CT-scans for the presence of CPALN, and assessed the association of CPALN with surgically confirmed PC by univariate and multivariate analyses. Results: CPALN were present in 123 (75%) of the 165 patients with PC, but absent in 263 (68%) of the 385 patients without PC (sensitivity (Se), 0.72; specificity (Sp), 0.68; positive predictive value (PPV), 0.49; negative PV (NPV), 0.85; odds ratio [OR], 3.3; p&lt;0.001). The presence of CPALN was not correlated with the extent of PC, the primary tumor and lymph node status , or the presence, number, size and location of liver metastases. Among the 165 patients with PC, 99 (60%) had visible signs of PC (other than CPALN) on CT-scan; among the remaining 66 patients, CPALN were the only potential sign of CP in 41 (62%), leading to Se, Sp, PPV, and NPV in patients with no signs of CP (other than CPALN) on CT of 0.62, 0.68, 0.24, and 0.92, respectively. Conclusions: The detection of CPALN on CT may be of valuable help for the diagnosis of PC in patients with CRC.
Do oncologists believe new cancer drugs offer good value?
Authors: E. S. Nadler, B. Eckert, P. J. Neumann
Journal: Journal of Clinical Oncology (2005)

6011 Background: The FDA’s approval of bevacizumab (Avastin), cetuximab (Erbitux) and other novel agents has generated debate about the high cost and relative value of new cancer therapeutics. Oncologists play a pivotal role in treatment decisions, yet little is known about their perceptions regarding the cost-effectiveness of these agents, and the degree to which they believe costs matter, or should matter, in their prescribing behavior. Methods: We surveyed 139 medical oncologists at two large academic hospitals. The self-administered questionnaire consisted of 11 questions in four sections. We asked respondents to provide estimates for the cost and effectiveness of Avastin (without referring to published information), and whether they thought the treatment represented good value for the money. We also asked respondents to judge, hypothetically, how large a gain in life-expectancy would be needed to justify a new drug for lung cancer that cost $70,000 per year more than standard care. We used this information to calculate an implied cost-effectiveness threshold for each respondent. Finally, we asked respondents to consider their general views on the role of cost in treatment decisions, and whether they felt there would be a need for future “rationing” in oncology care. Results: 90 oncologists (65%) completed the survey. The implied cost-effectiveness thresholds for the Avastin and hypothetical scenario were roughly $300,000 per quality-adjusted life year (QALY) gained, suggesting that respondents believed that treatments up to $300,000/QALY represented reasonable value for the money. 78% stated that patients should have access to “effective” care regardless of cost, while 71% responded that rising costs would mean greater rationing over the next 5 years. Conclusions: A majority of medical oncologists in an academic medical settings state that cost does not influence their clinical practice, nor should it limit patient access to “effective” care. They also implied that up to $300,000/QALY reflected reasonable value for money. A small subset of oncologists were very sensitive to the cost of prescribed therapy, and believed that such costs should play a role in clinical decisions. No significant financial relationships to disclose.
Investigation of metformin as a radiation sensitizer in pancreatic cancer.
Authors: Jennifer Anne Dorth, Gina Ferris, Johnathan Zeng, Scott Welford
Journal: Journal of Clinical Oncology (2014)

253 Background: Clinical study demonstrates that diabetic patients taking metformin while undergoing chemotherapy and/or radiation for localized pancreatic cancer have improved overall survival compared to diabetics not taking metformin or non-diabetic patients (Sadeghi, Clin Cancer Res 2012). Metformin may act as a radiosensitizer through direct effects on cancer cells and/or indirect effects on the host, such as the inhibition of hepatic gluconeogenesis or inflammation (Pollak, Clin Cancer Res 2012). In vitro study demonstrates that the direct effects of metformin include suppression of mTOR, G2/M cell cycle arrest, and toxicity to cancer stem cells with resultant increase in chemo and radiosensitivity, though some of these studies employed supra-physiologic doses of metformin (1-10mM) instead of physiologic doses (10uM) (Song, Sci Rep 2012; Sanli, IJROBP 2010). Methods: MiaPaCa-2 human pancreatic cancer cells were grown in physiologic (5mM) or supra-physiologic (25mM) glucose media. After exposure to metformin (10uM or 10mM) for 3-7 days in cell culture, phosphorylation of AMPK, a target of metformin, was measured by western blot and radiation survival was determined by clonogenic survival assay. Results: MiaPaCa-2 cells grown in 5mM glucose media with metformin have higher levels of AMPK phosphorylation than those grown in 25mM glucose media or without metformin. Radiation clonogenic survival was similar between cells exposed to any of the treatment conditions, including differences in glucose concentration and/or presence of metformin. Conclusions: MiaPaCa-2 pancreatic cancer cells do not demonstrate enhanced radiosensitivity to metformin in vitro. Future studies will investigate whether K-Ras wild-type cell lines exhibit enhanced radiosensitivity to metformin in vitro and whether metformin acts as a radiosensitizer in vivo.