tbuckley/cabot-search huggingface dataset:
Is clinical stage T2C prostate cancer intermediate- or high-risk disease?
Authors: Zachary Klaassen, Abhay A Singh, Lauren Howard, Martha K. Terris, William J Aronson, Matthew R. Cooperberg, Christopher L Amling, Christopher J Kane, Lionel Lloyds Banez, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2014)

110 Background: Clinical stage T2c (cT2c) is an indeterminate factor in the algorithm for prostate cancer (CaP) risk stratification. According to the D’Amico risk stratification and the American Urological Association (AUA) guidelines, cT2c is high−risk, whereas the National Comprehensive Cancer Network (NCCN) and EUA classify cT2c as intermediate−risk. Since determining whether cT2c is intermediate- or high-risk has implications for treatment, it is important to define what exact risk cT2c portends. Thus, we sought to assess whether cT2c tumors, without associated other high−risk factors (cT2c not otherwise specified (cT2c−nos)), behave as intermediate− or high−risk by analyzing biochemical recurrence (BCR) after radical prostatectomy (RP). Methods: We retrospectively analyzed 2,759 men who underwent RP from 1988 to 2011 from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Comparisons in time to BCR between cT2c−nos patients and intermediate−risk (prostate-specific antigen [PSA] 10 to 20 ng/ml or Gleason sum (GS) =7 or cT2b), and high−risk (PSA greater than 20 ng/ml, GS 8 to 10, cT3) patients was performed using log−rank test and Cox proportional hazards analyses. Given changes in CaP, we adjusted for year of surgery (continuous) and to adjust for case mix among centers contributing to SEARCH we included a categorical term for center. Results: A total of 99 men (4%) were classified as cT2c−nos. During a median follow-up of 66 months (IQR: 34−101 months), cT2c−nos patients had similar BCR risk as intermediate-risk (p=0.27), but significantly lower BCR risk versus high-risk patients (p&lt;0.001, Figure). After adjusting for year and center and compared to low-risk disease, the HRs for cT2c−nos patients was similar to those with intermediate-risk (HR 1.90 vs. 2.28). When specifically compared to intermediate-and high-risk patients, and after adjusting for year and center, cT2c−nos patients had outcomes comparable to intermediate−risk (p=0.44), but significantly better than high-risk patients (HR 0.55; 95%CI 0.38,0.78; p=0.001). Conclusions: BCR risk for patients with clinical stage T2c was comparable to men who had intermediate-risk disease and significantly better than men with high-risk CaP. These findings suggest men with cT2c disease should be offered treatment options for intermediate-risk CaP.
Durable Event-Free and Overall Survival (EFS/OS) in Mantle Cell Lymphoma (MCL) without Rituximab: Long-Term Follow-Up of a Phase II Trial with Intensive Chemotherapy (CTAP/VMAC) Followed by Autologous Hematopoietic Stem Cell Transplant (aHSCT).
Authors: Andrew M. Evens, Jane N. Winter, Nanjiang Hou, Fred Rademaker, Katalin Kelemen, Beverly Nelson, David Patton, Olga Frankfurt, Stephanie Williams, Seema Singhal, Martin S. Tallman, Steven T. Rosen, Jayesh Mehta, Leo I. Gordon
Journal: Blood (2006)
Conditional survival of patients with esophageal cancer: A SEER database analysis.
Authors: M. Muzaffar, S. Khuder, I. Mohamed
Journal: Journal of Clinical Oncology (2011)

e14597 Background: The standard survival estimates of esophageal cancer as calculated from the time of diagnosis continue to be dismal. Conditional survival may be a more reliable estimate for patients who survive 1 or more years after diagnosis. The aim of the study was to calculate the conditional survival of patients with esophageal carcinoma. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (17) was used to extract data of patients diagnosed with esophageal cancer from 1982-2002. SEER*Stat: Version 6.6.2 software was used to calculate 5 year observed conditional survival (CS) by the life-table method for patients surviving 0-5 years after diagnosis. Age, gender, race, summary stage (excluding unknown/blank status) and grade were used to stratify the conditional survival. Results: SEER identified 30,441 patients of esophageal cancer diagnosed from 1982-2002. The male to female ratio was 2.7:1; average age at diagnosis was 65.6 yrs. The most common site of involvement was lower third segment 46.11% and poorly differentiated carcinoma was the predominantly reported grade (39.21%). The 5-year conditional survival for esophageal cancer increased the most, with an absolute improvement of 11% in patients with distant disease, 8% in Asians/Pacific Islanders,4.6% in patients with age more than or equal to 50 and 6.4% in patients with poorly differentiated cancer, in 5th year after diagnosis. Conclusions: The dataset presented here is one of the few attempts to study conditional survival in esophageal cancer as opposed to other cancers. The estimates of conditional survival improve for all summary stages of esophageal cancer, especially distant disease after surviving more than 1 year after diagnosis. Conditional survival may provide more accurate understanding of patients changing risk of cancer death over time. Conditional survival of esophageal cancer according to summary stage. Months Localized 2,406 Regional 2,906 Distant 3,075 12 97.2% 94.7% 89.2% 24 98.3% 96.6% 94.4% 36 98.4% 98.1% 99.2% 48 99.2% 98.4% 98.9% 60 99.5% 98.4% 100%
Comparison of two bidirectional hyperthermic intraperitoneal chemotherapy (HIPEC) regimens in patients with colorectal peritoneal metastasis.
Authors: Gabriel Glockzin, Michael Gerken, Sven A. Lang, Hans J. Schlitt, Pompiliu Piso
Journal: Journal of Clinical Oncology (2014)

628 Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) became part of many national and international treatment guidelines as an additive therapeutic option for selected patients with colorectal peritoneal metastasis. Multiple HIPEC regimens are used regarding cytotoxic agents, concentration, perfusion time an other parameters and consistent data for standardization is missing. Methods: 32 consecutive patients after complete macroscopic cytoreduction (CC-0/1) and bidirectional HIPEC for colorectal peritoneal metastasis were retrospectively analyzed. Twenty patients received oxaliplatin-based and twelve patients received irinotecan-based HIPEC. Morbidity and toxicity according to CTCAE v4, mortality and 3-year survival rates hava been determined. Results: The overall 3/4 morbidity rate was 34.4 % and the perioperative mortality rate 0 % in both groups (p = 1.000). Median survival was 26.8 months (95 % CI 15.7-33.1 months) in the IRI group and has not yet been reached in the OX group. 3-year survival rates were 65.0 % in the OX group vs. 41.7 % in the IRI group (p = 0.295). Conclusions: Both HIPEC regimens showed comparable morbidity and toxicity. Nevertheless, oxaliplatin-based HIPEC might be preferred due to the not significant positive survival trend. Prospective randomized trials are needed to compare the different HIPEC regimens and to determine the most effective therapeutic approach.
Splenic embolization as an alternative to surgical splenectomy for the restoration of blood counts suitable for effective chemotherapy in gastrointestinal malignancies (GIM).
Authors: Robert de Wilton Marsh, Marc Alonzo, Hector Ferral
Journal: Journal of Clinical Oncology (2016)

396 Background: Chemotherapy regimens used for GIM are often notably myelosuppressive and may also engender hypersplenism. This can result in platelet (plt) and/or absolute neutrophil counts (ANC) too low for the maintenance of required dose intensity or frequency. One successful approach to this problem is surgical splenectomy but this is both morbid and invasive. An alternative strategy uses super-selective embolization of the splenic arterial tree, which is performed as an outpatient, and is far better tolerated. The true efficacy of this technique is uncertain and the optimal patients (pts) for this procedure are not well defined. Methods: Between 11/2012 and 6/2015, pts with ECOG PS 0/1 currently on active therapy for GIM in our clinics, whose plts and/or ANC were consistently below threshold values for appropriate frequency or intensity of therapy, were referred to Interventional Radiology for splenic embolization. Selective catheterization of the splenic artery was achieved via a femoral approach. This was followed by super-selective catheterization of branches of the splenic artery, as distally as possible, with subsequent embolization using Embosphere particles (300-500 micron spheres). All pts received prophylactic IV antibiotics. Results: 10 pts were identified and referred and all were deemed suitable for embolization. The mean plt count prior to the procedure was 73,000 (39,000-167,000) and the mean ANC was 3.5 (1.3 – 5.3). Following one procedure in 9 pts and 2 procedures in 1 pt, the mean plt count rose to 175,000 (55,000-432,000) and the ANC to 7.2 (2.9 – 13.2) immediately, and to a maximum of 253,000 (76,000-511,000) and 9.3 (5.0 – 14.5) within one to two months.Splenic enlargement was noted in 6 pts (mean size 18.3 cm) prior to the procedure and was not present in 4 pts. Following embolization all patients were able to resume chemotherapy with previously effective doses and/or frequency. Conclusions: In our cohort of pts with GIM, splenic embolization was successful at restoring acceptable plt and/or ANC levels for the resumption of effective chemotherapy. Splenomegaly does not appear to be a prerequisite for success.
Sirolimus in combination with tacrolimus for the treatment of resistant chronic graft-versus-host disease
Authors: M. P. Escalón, R. M. Saliba, Y. Hsu, S. Ghosh, C. Ippoliti, C. Hosing, M. J. de Lima, J. L. Neumann, R. E. Champlin, D. R. Couriel
Journal: Journal of Clinical Oncology (2005)

6657 Introduction: Chronic graft versus host disease (cGVHD) remains a major complication in hematopoietic transplant recipients. We conducted a phase II trial of sirolimus in combination with tacrolimus for patients with steroid-refractory cGVHD. Patients and Methods: The median age of the 35 patients was 45 years (19–69). The median number of prior treatments for chronic GVHD was 3 (range 2–6). Chronic GVHD was defined as GVHD present beyond day 100 post-transplantation. The patients were divided into two groups. One group had continuous or recurrent manifestations of acute GVHD (late acute GVHD group). The remaining 23 patients had clinical manifestations of chronic GVHD (true chronic GVHD group). Results: Six patients had a complete remission and 16 had a partial remission for an overall response rate (ORR) of 63%. Skin was the organ most often involved (n= 29) and had an ORR of 65%. Eight patients with sclerodermatous skin involvement responded to therapy (73%). Responses were also seen in patients with GVHD of the lower GI tract (67%), liver (33%), eye (64%), and oral mucosa (75%). Major adverse events related to sirolimus were hyperlipidemia and cytopenias. Median survival was 15 months, and estimated actuarial survival at 2 years was 41% (95% CI 20–61). A significantly worse non-relapse mortality was noted in patients who had a platelet count of less than 100,000/mm3 (p < 0.0001) or late acute GVHD features (p = 0.001). Actuarial survival at 1 year was 25% in the late acute GVHD group, and 76% in the true chronic group (p = 0.0003). Corresponding estimates at 2 years were 12% (95% CI 1–40) and 62% (95% CI 34–80) (p = 0.0005). Non-relapse mortality at 2 years post initiation of therapy was significantly higher in patients with late acute GVHD (75%, 95% CI 49–99%) than in those with true chronic GVHD (35%, 95% CI 17–64%, p = 0.003). Conclusions: The addition of sirolimus to tacrolimus and methylprednisolone was effective for the treatment of resistant chronic GVHD with an ORR of 63%. It was most effective in patients with true chronic features and sclerodermatous skin involvement. Differentiating between late acute GVHD and true chronic GVHD may result in better interpretation of studies intended to target chronic GVHD. No significant financial relationships to disclose.
Association between endoxifen serum concentration and predicted CYP2D6 phenotype in a prospective cohort of patients with early-stage breast cancer.
Authors: V. O. Dezentje, J. den Hartigh, H. Guchelaar, T. Hessing, T. van der Straaten, J. M. Vletter - Bogaartz, R. Vree, E. Maartense, C. H. Smorenburg, H. Putter, A. Dieudonné, P. Neven, J. W. R. Nortier, H. Gelderblom
Journal: Journal of Clinical Oncology (2011)

562 Background: The variance of endoxifen blood levels, unexplained by CYP2D6 genotype alone, may have contributed to the conflicting study results on the relation between CYP2D6 genotype and tamoxifen efficacy. Testing only 4 variant CYP2D6 alleles, possibly causing misclassification into predicted phenotypes, may partly explain the large variance previously demonstrated in 80 patients (R2=.23, Jin Y et al. JNCI, 2005). The objective of this study is to relate CYP2D6 phenotypes to endoxifen serum concentrations in early stage breast cancer patients using tamoxifen. Methods: In The Netherlands and Belgium a prospective study is ongoing, aiming to relate CYP2D6 genotype and endoxifen serum levels to tamoxifen efficacy. In 423 early stage breast cancer patients using tamoxifen, blood samples were collected to determine CYP2D6 genotype by SNP array (Amplichip, Roche) and steady state endoxifen serum levels. We translated the CYP2D6 genotype into an ultrarapid (=UM), extensive (=EM), heterozygous extensive (= hetEM, e.g. *1/*4), intermediate (=IM, e.g.*41/*41) or poor metabolizer (=PM) phenotype. The predicted CYP2D6 phenotypes were related to (log transformed) endoxifen serum concentrations. Results: The median (range) endoxifen level for each phenotype was: UM: 67.7 nM (43.9-83.0); EM: 33.7 nM (7.2-87.3); hetEM: 25.3 nM (6.5-76.3); IM: 15.0 nM (4.6-121.3); PM: 9.1 nM (5.1-27.6). The CYP2D6 phenotypes were associated with endoxifen concentrations (p<.001); 43% of the variance in endoxifen levels was explained by phenotype. The hetEM phenotype was identified as a distinct phenotype with a different mean endoxifen level than the other phenotypes (p<.001). Conclusions: Genotyping with broad CYP2D6 allelic coverage resulted in a clear association between CYP2D6 predicted phenotypes and endoxifen concentrations with improved explained variance of endoxifen levels (R2=.43 vs .23). However, substantial variance in endoxifen remained unexplained by CYP2D6 genotype, indicating that other genetic or non-genetic factors contribute to the variation in endoxifen levels. Heterozygous extensive metabolizers should be considered a distinct CYP2D6 phenotype.
The Outcome of 551 1st CR Transplants in Adult ALL from the UKALL XII/ECOG 2993 Study.
Authors: Anthony H. Goldstone, Hillard J. Lazarus, Sue M. Richards, Mark R. Litzow, Raj Chopra, Alan Burnett, Peter H. Wiernik, Ian M. Franklin, H. G. Prentice, Martin Tallman, G. Harrison, Jill Durrant, Jacob Rowe
Journal: Blood (2004)
TNFα-Induced Apoptosis of Hematopoietic Progenitors Is the Major Cause of Bone Marrow Failure Observed In TAK-1 Knockout Mice.
Authors: Yechen Xiao, Hongling Li, Peter Breslin, Shubin Zhang, Wei Wei, Penelope Cadigan, Manuel O Diaz, Jiwang Zhang
Journal: Blood (2010)
Percentage of CD34 + Cells in a Minimum 500-Cell Count in Bone Marrow Trephines of Patients with Chronic Myeloid Leukaemia Provides the Best Correlation with Aspirate Blast Count.
Authors: Victoria J. Elliot, David Marin, Donna Horncastle, Kay Elderfield, Jane F. Apperly, Irvin A. Lampert, Kikkeri N. Naresh
Journal: Blood (2004)
Serum amyloid α (SAA-1) SNP rs12218 to predict outcome for mCRC patients treated with FOLFIRI and bevacizumab: Data from FIRE-3 trial.
Authors: Martin D. Berger, Sebastian Stintzing, Volker Heinemann, Dongyun Yang, Yu Sunakawa, Yan Ning, Satoshi Matsusaka, Satoshi Okazaki, Yuji Miyamoto, Mitsukuni Suenaga, Jordan David West, Wu Zhang, Nicos Petasis, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2016)

586 Background: The formyl peptide receptor 2 (FPR2) plays a key role in regulating inflammatory processes and host defense by binding a variety of both pro- and anti-inflammatory ligands. As inflammatory mediators may represent a favourable soil for tumor initiation and progression, we hypothesize that genes encoding for FPR2 and its ligands may predict outcome in patients with metastatic colorectal cancer (CRC). Methods: Three hundred and one patients with CRC enrolled in the randomized phase III FIRE-3 Trial and treated with FOLFIRI and Bevacizumab were included in this study. Genomic DNA was extracted from formalin fixed paraffin embedded tissue. Eight functional SNPs in 8 genes (FPR2, ANXA1, ALOX5, ALOX12, ALOX15, SAA1, PLCB3 and PRKCB1) were analyzed by PCR-based direct sequencing. Candidate SNPs and their correlation with outcome were analyzed by uni- and multivariate analysis. Results: The SAA1 rs12218 variant showed significant association with progression-free survival (PFS). Patients harboring any T allele had a significantly longer PFS than those with a CC genotype in both univariate (p = 0.013) and multivariate analysis (p = 0.010). Conclusions: This is the first report demonstrating that the SAA1 polymorphism rs12218 might serve as a predictive marker in patients with metastatic CRC treated with FOLFIRI and Bevacizumab in the first line setting. Targeting SAA1, a proinflammatory ligand of FPR2, might be a promising approach to enlarge our treatment armamentarium against mCRC.
Open-label study evaluating change in chronic low-grade (LG) non-hematologic (heme) adverse events (AEs) in Philadelphia positive (Ph+) CML-CP patients (pts) switched from imatinib (IM) to nilotinib (NL).
Authors: J. E. Cortes, C. B. Miller, J. H. Lipton, L. Busque, L. P. Akard, J. Pinilla-Ibarz, S. Ericson, M. J. Mauro
Journal: Journal of Clinical Oncology (2011)

6615 Background: IM cross-intolerance on NL is rare (4% in the NL registration study). This ongoing study assesses change in chronic LG non-heme AEs when pts are switched from IM to NL. Methods: Pts were eligible after treatment with IM 400 mg/d ≥3 months (mos) and IM-related G 1/2 non-heme AEs persisting ≥2 mos or recurring ≥3 times and persisting despite best supportive care. Pts received NL 300 mg BID. Primary endpoint was change in IM-related LG non-heme AEs after 3 mos on NL. Disease response was monitored and patient reported outcomes measured by Quality of Life (QoL) questionnaire and MD Anderson Symptom Inventory (MDASI)-CML. 23 pts enrolled as of data cut-off (11/30/10) were analyzed. Results: Median time on NL was 3.57 mos. Of 105 baseline IM-related non-heme AEs, 33 were G2, 72 were G1. 15 pts completed cycle 3 by data cut-off; 45 of 75 IM-related AEs improved (30, 7, 3 resolved by mos 1, 2, 3, respectively; 5 decreased from G2 to G1), 27 were unchanged, 3 increased in severity. 20 pts had MMR (3-log reduction of Bcr-Abl) at entry. 3 more pts achieved MMR by data cut-off. 11 pts completed QoL questionnaires. Compared to baseline, 82% reported improvement in QoL over the last 24 hrs at end of cycle (EOC) 3. Mean reduction from baseline in MDASI-CML severity score and interference score, therefore improvement in symptoms, were 1.47 & 1.86 (EOC 1) and 1.45 & 1.33 (EOC 3), respectively. 7 pts were dose reduced for NL-related non-heme AEs; 14 G3 AEs occurred in 6 pts; 10 (increased bilirubin & lipase, dehydration, hypokalemia, hypophosphatemia, arthralgia) were suspected to be NL related. No pt had a G4 AE. Most AEs were managed by brief dose interruption. 1 pt discontinued for hyperglycemia and 1 pt for upper abdominal pain/ oral pain/ headache. Maximum QTcF change from baseline was 37 msec. No QTcF prolongation >500 msec occurred. Conclusions: In this analysis, >50% of pts showed improvement in non-heme IM-related LG AEs after switching to NB. 82% of pts improved in QoL, including 5 of the 6 pts who had G3 AEs. In addition, overall improvement of symptoms, as measured by MDASI-CML, was seen by the reduction of severity scores.
Bone Cancer Guidelines
Authors: J Sybil Biermann, Douglas Adkins, Robert Benjamin, Brian Brigman, Warren Chow, Ernest U Conrad, Deborah Frassica, Frank J Frassica, Suzanne George, John H Healey, Robert Heck, G Douglas Letson, Joel Mayerson, Sean V McGarry, Richard J O'Donnell, Joshua Patt, R Lor Randall, Victor Santana, Robert L Satcher, Richard G Schmidt, Herrick J Siegel, Michael K Wong, Alan W Yasko
Journal: Journal of the National Comprehensive Cancer Network (2007)

Primary bone cancers are extremely rare neoplasms, accounting for less than 0.2% of all cancers. Primary bone cancers show wide clinical heterogeneity and, perhaps most importantly, are often curable. With current multimodality treatment, including multi-agent chemotherapy, approximately three quarters of all patients diagnosed with osteosarcoma are cured. Updates for 2007 include changes in recommendations for treating chondrosarcoma, Ewing's sarcoma, and osteosarcoma. For the most recent version of the guidelines, please visit NCCN.org
A large study of the older cancer patient in the community setting: Initial report of a randomized controlled trial using pegfilgrastim to reduce neutropenic complications
Authors: L. Balducci, J. Tam, H. Al-Halawani, S. Shahin, J. Green, R. Dansey, W. Ershler
Journal: Journal of Clinical Oncology (2005)

8111 Background: There is a paucity of randomized controlled studies in older pts despite that most new cancer diagnoses occur in people ≥ 65 yrs. The increased risks of the older population, which mandate an individualized treatment approach, are obstacles to study accrual. The Geriatric Oncology Consortium (GOC), which includes a cooperative group of community practices, was established to facilitate the study of older cancer pts, thereby reducing the data gap in older pts. This study documents the feasibility of conducting community clinical trials in older pts and addresses age-related increased risk of neutropenia and its complications that may prevent optimal treatment of this special population. Methods: This is a large, prospective, open-label trial in pts ≥ 65 yrs scheduled to receive chemotherapy (CT) Q21 days for lung, breast, or ovarian cancer (solid tumor stratum), or NHL. Pts were randomized to either pegfilgrastim (Neulasta) in first and subsequent cycles, or, no pegfilgrastim in cycle 1 with use in subsequent cycles per MD discretion. Endpoints included incidence of neutropenia (ANC < 1 x 109/L) with or without fever (≥ 38° C), CT dose delays and reductions, hospitalizations, antibiotic use, and quality of life using multiple instruments. Results: A total of 852 pts were enrolled from Jun 02 to Jul 04, with the last subject ending treatment in Nov 04. Approximately 46% lung, 22% breast, 14% ovarian, and 18% NHL pts were treated; 32% had stage 1/2 or limited (SCLC) disease. Mean age was ∼72 yrs (range 65–88) with 34% ≥ 75 yrs. Solid tumor CT included carboplatin with: paclitaxel (29%), etoposide (12%), or docetaxel (10%); and doxorubicin with cyclophosphamide (12%). Over 80% of NHL pts received CHOP-R. Conclusions: This is the largest prospective trial focusing on CT side effects in patients ≥ 65 yrs. The GOC provided an effective platform for the study of older cancer patients, establishing the feasibility of community-based trials in this population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen Amgen