tbuckley/cabot-search huggingface dataset:
A two-month cisplatin-epirubicin-paclitaxel (PET) weekly administration is highly effective in large operable breast cancer. Final analysis of a SICOG phase II study
Authors: L. Maiorino, G. Frasci, G. D’Aiuto, P. Comella, R. Thomas, M. Di Bonito, G. Iodice, M. D’Aiuto, M. R. Rubulotta, G. Comella
Journal: Journal of Clinical Oncology (2005)

566 Background: The present study was aimed at defining the antitumor activity of 8 cisplatin-epirubicin-paclitaxel (PET) weekly cycles with granulocyte-colony stimulating factor (G-CSF) support in patients with large operable breast cancer. Methods: Operable breast cancer (T2-T3 N0–1; T>3 cm) patients received 8 preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel 120 mg/m2, with G-CSF (5 microgr./kg days 3–5) support. Results: Sixty-three patients (T2/T3=30/33; N0/N+=8/55) were enrolled. Thirty-one clinical complete (49%), and 30 partial (48%) responses, were recorded, giving a 97% response rate [95% confidence interval, 89–100%]. Breast-sparing surgery was performed in 32/63(51%) patients. At pathological assessment, 28 patients (45%) showed absence of invasive residual disease in breast and 34 (55%) had negative axilla. In 20 women (32%) both breast and axilla were found disease-free. The absence of Estrogen receptors was associated with a higher probability of pCR achievement (ER- vs. ER+= 66% vs. 14%; p=0.00005). A significantly higher pCR probability was also observed in HER2 3+ patients (60% vs. 23%; p=0.01). At a 23-month median follow-up (range; 4–63), only 8 relapses, and 2 deaths have occurred, 5-year projected RFS and OS being 59% and 95%, respectively. Grade 3–4 neutropenia, and anaemia occurred in 24% and 5% of patients, respectively. Emesis, diarrhoea, and mucositis were the main non-haematological toxicities; however, only 9(14%) patients experienced one or more episodes of severe non-haematological toxicity. Peripheral neuropathy was frequent, but never severe. Conclusions: A two-month weekly treatment with PET represents a well tolerated and highly effective approach in large operable breast cancer patients. A randomized study comparing weekly PET with triweekly epirubicin-paclitaxel is underway. No significant financial relationships to disclose.
Prospective study of oncogenic mutations in circulating cell-free DNA (cfDNA) using a multiplex sequencing platform for patient (pt) allocation to phase I clinical trials.
Authors: Michael Ong, Joaquin Mateo, Lorna Pope, Amy Mulick Cassidy, Timothy Anthony Yap, Geraldine Perkins, Ruth Riisnaes, Penelope Flohr, Khin Thway, Sadiya Saeed, Katie Ann Denholm, Helen Nicole Toloui, Kirsty Moran, Jen Kate Lewis, Jesus Corral Jaime, Andrea Biondo, L Rhoda Molife, Stanley B. Kaye, Udai Banerji, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2012)

10525 Background: Studies suggest that tumoral cfDNA can be isolated from plasma and used as a biomarker. Methods: We conducted a prospective study in adult pts with advanced cancer referred for phase I clinical trials Sep09-Dec10 (A: Pilot Phase n=104) and Jan11-Sep11 (B: Expansion Phase n=176). cfDNA and tumor DNA from formalin-fixed paraffin-embedded (FFPE) tissue were isolated, quantified, and analyzed for 238 mutations in 19 oncogenes by the Sequenom OncoCarta Panel 1.0. Mutation data were used for trial allocation when available. Pt data and outcomes were collected. Statistical inferences used Wilcoxon rank-sum and Pearson’s Chi-squared. Results: 280 pts enrolled including breast (60), colorectal (42), ovarian (37), lung (31), and prostate (20); median age 60yrs [23-81]; 93% ECOG PS 0-1. cfDNA in 95% and FFPE in 60% were analyzed. Median time to cfDNA result, trial allocation and consent were 7 [5-14], 6 and 23 d. Median cancer pt cfDNA concentration (ng/ml) (A: 18 [1-1600]; B: 34 [16-1657]) was higher than 20 healthy volunteers (6 [5-13] A: p=0.0001) and higher in metastatic vs locally advanced cancer (A: 21 vs 4 p=0.0006; B: 42 vs 24 p=0.066). Pts with higher than median [cfDNA] had shorter median survival (MST) than below (A: 217 vs 274 d, HR 1.72 95% CI 1.07-2.65, p=0.025; B: MST not reached yet). Mutations were found in 89 pts (32%), including KRAS (11%), PIK3CA (5%), MET (5%), BRAF (4%), and AKT (2%). cfDNA mutations (57 pts, 21.5%) were mainly found above the median [cfDNA] (A: 41 vs 17% χ 2 =6.9, p=0.009; B: 24 vs 11% χ 2 =5.0, p=0.025). Of 155 pts with both cfDNA and FFPE available, 68 had mutations detected: 30 identical in cfDNA and FFPE; 28 in FFPE alone and 10 in cfDNA alone. Overall, 153 pts were treated on a phase I trial; 23 pts had relevant mutation data and received a trial targeting the PI3-Akt-mTOR axis. Conclusions: Higher cfDNA is associated with greater disease burden, worse prognosis, and higher mutation detection rate, suggesting cfDNA is tumorally derived. Moreover, cfDNA can be analyzed for oncogenic mutations in a time-frame suitable for clinical decision making, making it a potentially useful non-invasive adjunct to tumour DNA analysis.
Human Adenylate Kinase 2 Deficiency Inhibits Hematopoietic Cell Differentiation towards Neutrophil and T Lymphoid Lineages.
Authors: Emmanuelle M. Six, Chantal Lagresle-Peyrou, Corinne Demerens-deChappedelaine, Frederic Rieux-Laucat, Andrea Didati, Marie-Claude Stolzenberg, Bruno Cassinat, Christine Chomienne, Alain Fischer, Marina Cavazzana-Calvo
Journal: Blood (2009)
Utilization and effectiveness of adjuvant chemotherapy (ACT) for colon cancer (CC) in the general population.
Authors: James Joseph Biagi, William J. Mackillop, Sulaiman Nanji, Xuejiao Wei, Yingwei Peng, Timothy P Hanna, Monika K. Krzyzanowska, Christopher M. Booth
Journal: Journal of Clinical Oncology (2016)

702 Background: International guidelines recommend ACT for patients (pts) with stage III CC based on level I evidence showing improved survival. For stage II CC ACT is not routinely recommended but may be considered for pts with high-risk features. Here we describe practice patterns and outcomes associated with ACT in a routine population-based setting. Methods: All CC cases treated with surgery in Ontario 2002-2008 were identified using the population-based Cancer Registry. Electronic treatment records were linked to the registry to identify surgical procedures and utilization of ACT. Pathology reports were obtained for a 25% random sample of all cases to obtain details of extent of disease; pts with stage II or III were included in the study population. High-risk stage II was defined as: T4, &lt;12 lymph nodes, poorly differentiated histology and/or lymphovascular invasion. Logistic regression was used to evaluate factors associated with ACT utilization. Cox proportional hazards model was used to evaluate cancer-specific (CSS) and overall (OS) survival. Results: The study population included 2,801 stage III and 2,488 stage II pts (47% of which were high-risk). In the stage III subgroup 66% received ACT, but was 90% among ages 20-49 vs 68% for ages 70-79 (p&lt;0.001). ACT was associated with increased CSS (HR 0.63, 95% CI 0.54-0.73) and OS (HR 0.63, 95% CI 0.55-0.71). Among all stage II pts 18% received ACT but 24% in the high-risk disease subset. ACT utilization was higher in younger patients (51% for ages 20-49 vs. 16% ages 70-79, p&lt;0.001) and varied across geographic regions (range 10-39%, p&lt;0.001). Among all stage II pts ACT was not associated with improved CSS (HR 1.41, 95%CI 1.09-1.82) or OS (HR 1.16, 95%CI 0.94-1.42). Stratified analysis for high-risk stage II disease also did not show benefit to ACT (CSS HR 1.14, 95%CI 0.84-1.55; OS HR 1.02, 95%CI 0.79-1.31). Conclusions: One third of pts with stage III CC in the general population do not receive ACT, with age the strongest predictor of treatment. For stage II pts, ACT utilization varies substantially across age groups and geographic regions. ACT is associated with improved CSS and OS in stage III pts but not stage II pts, including those with high-risk disease.
Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation
Authors: Tetsuichi Yoshizato, Yasuhito Nannya, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Hiromichi Suzuki, Yasunobu Nagata, Yusuke Sato, Nobuyuki Kakiuchi, Keitaro Matsuo, Makoto Onizuka, Keisuke Kataoka, Kenichi Chiba, Hiroko Tanaka, Hiroo Ueno, Masahiro M. Nakagawa, Bartlomiej Przychodzen, Claudia Haferlach, Wolfgang Kern, Kosuke Aoki, Hidehiro Itonaga, Yoshinobu Kanda, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Torsten Haferlach, Yasushi Miyazaki, Keizo Horibe, Masashi Sanada, Satoru Miyano, Hideki Makishima, Seishi Ogawa
Journal: Blood (2017)
Bone Marrow Mast Cells Are Significantly Increased in Patients with Waldenstrom’s Macroglobulinemia, and Their Number Following Therapeutic Intervention Is Dependent on Extent of Response.
Authors: Daniel Ditzel Santos, Mariana Z.A. Chemaly, Olivier Tournilhac, Kelly E. OConnor, Evdoxia Hatjiharissi, Xavier Leleu, Lian Xu, Andrew R. Branagan, Robert J. Manning, Christopher Patterson, Allen W. Ho, Zachary R. Hunter, James M. You, Yu-Tzu Tai, Jeffery L. Kutok, Kenneth C. Anderson, Nikhil Munshi, Steven P. Treon
Journal: Blood (2005)
A phase II trial of low-dose multiagent chemotherapy with gemcitabine, docetaxel, capecitabine, and cisplatin (GTX-C) in patients with metastatic pancreatic cancer.
Authors: Dung T. Le, Daniel A. Laheru, Katrina Purtell, Jennifer N. Uram, Hao Wang, Susie Lawrence, Ellen-Lilly Foreman, Jacob Joseph David, Rose Parkinson, Dionne T Savage, Ross C. Donehower, Zeshaan Rasheed, Lei Zheng, Nilofer Saba Azad, David Cosgrove, Ana De Jesus-Acosta, Ilene Browner, Luis A. Diaz
Journal: Journal of Clinical Oncology (2014)

213 Background: Multiagent chemotherapy with three agents has been shown to delay the emergence of resistance and extend survival in patients with metastatic pancreatic adenocarcinoma. Four drug regimens, even at low doses, may further improve survival by simultaneously targeting multiple non-redundant oncogenic pathways. Methods: A phase II study of GTX-C (capecitabine 500 mg bid on days 1-14, and the combination of gemcitabine 500 mg/m2 (10 mg/m 2 /min), docetaxel 20 mg/m 2 and cisplatin 20 mg/m 2 on days 4 and 11) was initiated in newly diagnosed untreated metastatic pancreatic cancer patients. The primary endpoint was progression-free survival rate at 6 months; the regimen would be considered active if the 6-month PFS rate was &gt;75% and inactive if &lt; 50%. Results: Twenty-nine patients were enrolled and 10 patients remain on GTX-C treatment at the time of this report. All patients were ECOG 0 or 1. Eighty-six percent of patients had evidence of liver metastases and 25% had biliary stents in place at time of study enrollment. Median CA19-9 was 6,159 U/mL (37-154,323 U/mL). Median length of follow-up was 9.0 months. Grade 3/4 related adverse events included: nausea/vomiting (7%), transaminitis (10%), anemia (14%), thrombocytopenia (24%), and neutropenia (55%). However, febrile neutropenia occurred in only 3 patients (10%) and not until cycles 6, 14, and 15. PFS rate at 6 months was 76.4% (95% CI: 54.6% - 88.7%). The partial response (PR) rate was 50%, stable disease (SD) rate was 39% and the disease control rate (DCR) was 89%. CA19-9 declines of &gt;80% occurred in 77% of patients with measurable levels. Estimated median PFS was 8.4 months (95% CI: 6.1-10.6 months) and OS was 13.9 months (95% CI: 10.0-17.2 months) at the time of this submission. Updated results will be reported at GI ASCO 2014. Conclusions: GTX-C is highly active and well-tolerated in patients with metastatic pancreatic cancer and should be tested in a larger, comparative study. Clinical trial information: NCT01459614.
Reactivation of hepatitis B infection among patients with cancer.
Authors: J. Hwang, M. Fisch, H. Zhang, M. Kallen, M. Routbort, L. S. Lal, J. Vierling, M. Suarez-Almazor
Journal: Journal of Clinical Oncology (2011)

9056 Background: Patients with active or occult hepatitis B virus (HBV) infection are at risk for reactivation after chemotherapy. Although studies of selected patients receiving chemotherapy have demonstrated reactivation rates of up to 50%, no large-scale study has ever been conducted in the US to understand the prevalence of HBV reactivation in a general cancer population. Methods: In this retrospective cohort study conducted at a comprehensive cancer center, we used institutional databases and chart reviews to investigate patients with newly diagnosed cancer who received chemotherapy between 1/2004 and 9/2007. Prevalence of HBV infection prior to chemotherapy was determined by testing HBsAg and anti-HBc. Reactivation of HBV infection was defined as: 1) ALT >100 IU/L or a 3-fold rise compared to baseline levels, and/or 2) detectable serum HBV DNA ≤ 6 months after initiation of chemotherapy. Using Chi-square tests of association, patients with reactivation were compared to those without reactivation in terms of demographic characteristics, cancer type, and chemotherapeutic agent. Results: Among 70,737 patients with cancer meeting our criteria, 10,729 received chemotherapy. Of these, 1787 (16.7%) were screened, and 151 patients were found to be positive for HBsAg and/or anti-HBc. Patients with HBV infection had a mean age of 53 years, 33.1% were women, and 47.7% were white. Overall, reactivation occurred in 73 patients (48.3%). Reactivation differed significantly by race (p=0.03): 26.0% of those with reactivation were Asian, compared to 9.0% without reactivation. There were no significant reactivation status associations with age, gender, or chemotherapeutic agent. Reactivation occurred in 39.1% (n=27) of solid tumor patients compared to 56.1% (n=46) of patients with hematologic malignancies (p=0.04). Conclusions: Reactivation occurred in nearly half of patients with HBV infection and cancer receiving chemotherapy; however, screening for HBV infection occurred in only a small percentage of patients. Determining the prevalence of this preventable cancer therapy complication is an essential first step in establishing an evidence-based screening policy for HBV infection in cancer patients.
The impact of immigration status on cancer outcomes in Ontario, Canada.
Authors: Matthew C. Cheung, Craig Earle, Hadas Fischer, Ximena Camacho, Refik Saskin, Baiju Shah, Peter Austin, Simron Singh
Journal: Journal of Clinical Oncology (2016)

285 Background: In the delivery of cancer care, barriers to access could potentially result in inferior outcomes and survival. Although a relationship has been demonstrated between disadvantaged socio-economic status and mortality, the impact of immigration on outcomes is less clear. Methods: Administrative databases were linked to create a cohort of all incident cases of colorectal, lung, prostate, head/neck, breast and hematologic malignancies from Jan 2000 to Dec 2012 in Ontario, Canada. Cases were defined according to immigration status and followed from diagnosis until death (or cancer-specific death). Cox proportional hazards models were constructed to study the impact of immigration status on survival after adjusting for relevant variables. Additional adjusted models studied the relationship of time since immigration on mortality. Results: During the study period, 11,485 cancer cases were diagnosed in recent immigrants (0-10 years in Canada), 17,844 cases in non-recent immigrants (11-25 years), and 416,118 cases in non-immigrants. Following adjustment for relevant predictors by Cox regression, survival was improved for recent immigrants (HR 0.843; 95% CI 0.814-0.873) and non-recent immigrants (HR 0.902; 95% CI 0.876-0.928) compared to non-immigrants. Cancer-specific survival was also better for recent immigrants (HR 0.857; 95% CI 0.823-0.893) and non-recent immigrants (HR 0.907; 95% CI 0.875-0.94) compared to non-immigrants. Amongst immigrants, each year from the original landing in Canada was associated with increased mortality (HR 1.004; 1.000-1.009) and a trend to increased cancer-specific mortality (HR 1.005; 0.999-1.010) that was not statistically significant. Immigrants from all WHO world regions were found to have similar reductions in mortality and cancer-specific mortality. Conclusions: Immigrants to Canada demonstrate a “healthy immigrant” effect, with lower mortality compared to Canadian-born individuals. This benefit appears to diminish over time, as the health of immigrants potentially converges with the Canadian norm. Potential contributors to the benefit include self-selection for immigration, health requirements for entrance, and differences in disease distribution related to ethnicity.
Meta-analysis of cord blood transplantations for indication of leukemia from private umbilical cord blood banks from 1993-2009.
Authors: N. Gottschalk, E. F. Lampeter, V. R. Jacobs
Journal: Journal of Clinical Oncology (2010)

6596 Background: Experimental cord blood (CB) transplantation was initially described in 1972 but became clinically relevant in 1988 after the first CB transplantation in Fanconi anemia. Soon afterwards private blood banks were established to store umbilical cord blood and stem cells individually. Until 11/2009 n = 400 CB transplantations from private cord blood banks including clinical trials are confirmed to be performed worldwide. Leukemia is among several indications CB is used for. For in-depth analysis an evaluation was done for this subgroup. Methods: For the first time a comprehensive meta-analysis with a database was performed covering all known cord blood transplantations n = 400 worldwide from private storage between 1993 and 2009. A variety of parameters were analyzed e.g. disease, age, sex, type of use, HLA status, storage time, CB volume, count of TNC/MNC and country of cord blood transplantation. Results: From 12/1993-11/2009 n = 92/400 indications for all CB transplantations were for leukemia (23.0%). The group was divided in ALL (n = 50), AML (n = 36), CML (n = 3), CLL (n = 1) and not known (n = 2). The age at transplantation was Ø 84 months (n = 90; range 0-600), n = 20 were male, n = 23 were female, the rest n.k. All were allogenic transfers beside one autologue for ALL. HLA status was Ø 5.8 (n = 22; range 3-6), storage time was Ø 18 months (n = 85; range 1-69), CB volume Ø 99 ml (n = 70; range 24-257), TNC/MNC count Ø 9.15 × 108 (n = 57; range 2.44-25.14). Country of CB transplantation was primarily the USA (n = 81; 88.0%), Canada and Germany (n = 2 each; 2.2%), Poland, Malaysia and Singapore (n = 1 each; 1.1%) or n.k. (n = 4; 4.3%). Conclusions: Umbilical cord blood transplantation is a common indication for leukemia usually served by public cord blood banks. This analysis shows that cord blood from private blood banks serves as additional source of stem cells for such indications. Due to limited data published the long-term outcome is not documented. A CB transplant registry for private cord blood banks is suggested to document follow ups and long-term results to confirm identical results to public stem cell sources. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vita34 Vita34 Vita34, Germany
Overall survival and clinical characteristics of BRCA germline/somatic cholangiocarcinoma (CCA).
Authors: Talia Golan, Maria Raitses-Gurevich, Robin Kate Kelley, Andrea Grace Bocobo, Ayelet Borgida, Rachna T. Shroff, Spring Holter, Steven Gallinger, Maeve Aine Lowery, Ghassan K. Abou-Alfa, Daniel H. Ahn, Apurva Jain, Tanios S. Bekaii-Saab, Eitan Friedman, Milind M. Javle
Journal: Journal of Clinical Oncology (2016)

244 Background: Biliary tract cancers (BTC) exhibit a diverse and high frequency of actionable mutations detectable using next generation sequencing (NGS). The Breast Cancer Linkage Consortium reported that BRCA2 mutation carriers are at increased risk for BTC with estimated relative risk of 4.97, (95% CI = 1. 50-16.52). The purpose of this study was to evaluate the clinical characteristics of germline/somatic BRCA1/2mutations in CCA patients. Methods: Multi-center retrospective analysis of patients with germline/somatic BRCA1/2- associated CCA diagnosed between January 2000 and December 2013. Cases were identified from clinical databases at participating institutions. Data including demographics, clinical history, surgical procedures and systemic chemotherapy or radiation were extracted from patient records. Results: Overall, we identified 18 cases including 5 carriers of germline BRCA1/2 mutations (4 BRCA2; 1 BRCA1) and 13 harboring somatic mutations (7 BRCA1; 6 BRCA2) using a NGS panel testing tumor for 'actionable' mutations. One patient presented with two different somatic mutations in the BRCA2gene. Mean age at diagnosis was 60 years (range 36-75), male: females (61.2% vs 38.8%, respectively). Stage at diagnosis: I (n = 4), II (n = 3), III (n = 3) and IV (n = 8). Six patients had extrahepatic CAA; twelve patients had intrahepatic CCA. Prior therapy in 13 patients included platinum-based therapy with one patient receiving prior olaparib. Median overall survival for patients with stage I/II is 34.7 months (95% CI, 7.06-62.9) and for stages III/IV is 25 months (95% CI, 12.02-35.84). Conclusions: BRCA associated CCA may have an enhanced therapeutic sensitivity to DNA damaging agents. This needs confirmation in a larger cohort of patients.
The degree of preoperative hydronephrosis to predict pathologic features and oncologic outcomes in high-grade upper tract urothelial carcinoma.
Authors: Oussama M. Darwish, Laura-Maria Krabbe, Paul H. Chung, Mary Elizabeth Westerman, Aditya Bagrodia, Bishoy A. Gayed, Ahmed Q Haddad, Payal Kapur, Arthur I. Sagalowsky, Yair Lotan, Vitaly Margulis
Journal: Journal of Clinical Oncology (2014)

525 Background: There have been multiple reports implicating the role of hydronephrosis (HN) as a predictor of outcome in patients diagnosed with upper tract urothelial carcinoma (UTUC). However, this was done in mixed populations (low-/high-grade) and degree of HN (DOH) was not taken into account. We evaluated the impact of severity of hydronephrosis on systemic and bladder relapse in patients with UTUC. Methods: We retrospectively reviewed the records of 141 patients with localized UTUC that underwent extirpative surgery. Preoperative imaging was used to evaluate ipsilateral DOH. We analyzed the association between DOH (none/mild vs. moderate/severe), pathological findings and oncological outcomes in high-grade vs. low-grade patients. Bladder recurrence was assessed separately from local or systemic (L/S) recurrence. Results: High-grade UTUC was present in 80% of patients, 35% had muscle-invasive disease (≥pT2), and 29% had non-organ-confined disease. At a median follow-up of 34 months (range, 1-149), 35% of patients experienced intravesical recurrence, 20% developed L/S recurrence, and 17% died of UTUC. No difference in outcomes was seen between patients without HN and mild HN. DOH was none/mild in 55% and moderate/severe in 45% of cases. In patients with high-grade UTUC, moderate/severe HN was associated with advanced pathologic stage (p&lt;0.001) and positive lymph node status (p=0.01). On Kaplan-Meier analysis, DOH was a predictor of L/S recurrence-free survival (RFS) (HR 5.5, p=0.019) and cancer-specific survival (CSS) (HR 5.2, p=0.022) but not intravesical recurrence. On multivariable analysis with preoperatively known factors controlling for grade and tumor location, DOH was independently associated with L/S RFS (HR 2.8, p=0.016) and CSS (HR 2.5, p=0.044). Conclusions: Moderate/severe HN was associated with features of advanced disease and predicted worse oncological outcomes in patients with high-grade UTUC. Since preoperative imaging is a routinely available diagnostic tool, this can serve as a surrogate parameter for advanced disease and can help to counsel patients towards preoperative chemotherapy and radical surgery.