tbuckley/cabot-search huggingface dataset:
Yttrium 90 ibritumomab tiuxetan is safe and effective in older patients with relapsed or refractory NHL
Authors: R. J. Schilder, C. Emmanouilides, K. Vo, T. E. Witzig, I. Flinn, M. Darif, L. Gordon, A. Molina
Journal: Journal of Clinical Oncology (2005)

6562 Background: Age >60 years has been identified as a poor prognostic factor in patients with follicular NHL (FL). Such patients are susceptible to treatment-related complications that may limit treatment options. We evaluated whether the efficacy and safety of the yttrium 90 (90Y) ibritumomab tiuxetan (IT) regimen were affected by patient age. Methods: Integrated analyses of 211 patients with B-cell NHL in 4 clinical trials compared 3 patient groups: group 1, <60 years; group 2, 60–69 years; and group 3, ≥70 years. Median ages were 49, 65, and 75 years, respectively. All patients had bone marrow involvement ≤25%, platelet counts ≥100,000/mm3, and ANC ≥1500/mm3. Results: Most patients had FL (78% in group 1, 62% in group 2, 73% in group 3) and tumors ≥5 cm (56% in group 1, 60% in group 2, 53% in group 3%). All patients had received prior therapy: 1–3 regimens, 74–85%; ≥4 regimens, 15–31%. The majority (94% in group 1, 81% in group 2, 85% in group 3%) had stage III/IV NHL at study entry. Baseline prognostic factors were similar among groups, except that more patients in group 2 (64%) were resistant to their last chemotherapy, compared to groups 1 and 3 (54%, 28%) (P = .01). The regimen was effective and generally well tolerated with no difference in efficacy between age groups. The incidence of hematologic toxicity in patients ≥70 yrs was similar to that in younger patients. Conclusion: Yttrium 90 IT is efficacious in older patients with NHL, including those ≥70 years, achieving high response rates (up to 80%) and durable remissions (>6 years) comparable to those seen in younger patients. Based on its safety profile, the regimen is a suitable treatment for patients who may not tolerate chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BioGen IDEC BioGen IDEC, Genentech, Pharmacyclics BioGen IDEC BioGen IDEC, Genentech, Pharmacyclics BioGen IDEC Inc. to Mayo Clinic, BioGen IDEC, Genentech, Pharmacyclics BioGen IDEC 2001, FDA
Phase II trial of S-1 in combination with gemcitabine in chemo-naïve patients with locally advanced or metastatic pancreatic cancer
Authors: G. Lee, H. Kim, M. Kang, T. Kim, H. Kim, J. Kang
Journal: Journal of Clinical Oncology (2008)

15577 Background: Gemcitabine monotherapy is currently accepted as a standard first-line treatment of unresectable pancreatic cancer. However, the prognosis of patients with unresectable pancreatic cancer still remains dismal. We performed a phase II study of combination chemotherapy with S-1, oral fluorouracil progrug tegafur combined with two modulators, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate, plus gemcitabine in chemo-naïve patients with locally advanced or metastatic pancreatic cancer to evaluate efficacy and toxicity prospectively. Methods: Histologically confirmed locally advanced or metastatic pancreatic cancer were treated with S- 1 80mg/m2/day given orally on day 1–14, and gemcitabine 1250 mg/m2 given as an intravenous infusion on day 1 and 8 of each cycle. Treatment cycles were repeated every 3 weeks. Results: Thirty-two patients were enrolled. 24 (75.0%) were male and 8 (25.0%) were female and the median age was 63.5 years (35–75 years). Twenty-nine patients (90.6%) had metastatic disease. Three patients (9.4%) had locally advanced disease. No complete response was observed and partial response was observed in 14 patients (44.0%, 95% CI; 26.6–60.9%). Stable disease was observed in 8 patients (25.0%), and 8 patients (25.0%) had progressive disease. The median time to progression was 5.41 months (95% CI, 4.37–6.45 months), and the median overall survival was 8.35 months (95% CI, 6.18–10.5 months) after the median follow-up duration of 14.0 months (range, 0.7–28.3 months). A total of 114 cycles of chemotherapy was delivered. The actual administered median dose-intensities were 789 mg/m2/week for gemcitabine (range: 357–833 mg/m2/week; relative dose intensity (RDI), 94.7 %) and 353 mg/m2/week for S 1 (range: 160–373 mg/m2/week; RDI, 94.6 %). Grade 3–4 hematologic toxicities included neutropenia (9, 28.1%), thrombocytopenia (5, 15.6%), febrile neutropenia (3, 9.4%) and anemia (2, 6.3%) and Grade 3 non-hematologic toxicities included diarrhea (5, 15.6%), mucositis (4, 12.5%), and asthenia (3, 9.4%). Conclusions: The combination chemotherapy of S-1 and gemcitabine showed promising antitumor activity and manageable toxicity profiles in patients with locally advanced or metastatic pancreatic cancer. No significant financial relationships to disclose.
Incremental costs of chemotherapy—Pharmacoeconomic results from the prospective adjuvant AGO-WSG intergroup EC->DOC trial comparing an anthracycline-docetaxel sequence to CMF in node-positive breast cancer
Authors: V. R. Jacobs, M. Braun, N. Harbeck, S. Wagenpfeil, D. Sattler, R. Bernard, W. Kuhn, A. Ihbe-Heffinger
Journal: Journal of Clinical Oncology (2008)

583 Background: Taxane-based adjuvant chemotherapy is the current standard for patients with node-positive breast cancer. Compared to the older standard CMF or anthracycline containing regimens, the increase in efficacy is significant but modest. Next to clinically relevant side effects, the implementation of taxanes is associated with a relevant burden on health care resources. In the present study, we compared a modern taxane-based sequential regimen (4 x epirubicin/cyclophosphamide followed by 4 x docetaxel q21, EC->DOC) to the low-priced and less toxic CMF in patients with primary node-positive breast cancer with special consideration of costs and resource consumption. Methods: Data on chemotherapy application and resource consumption were obtained between 2/2000–5/2002 alongside the prospective, randomized, multicenter phase III WSG-AGO Intergroup EC->DOC trial (1999–2005) comparing EC->DOC to CMF or FEC. Total costs were presented from hospital provider perspective. Results: A cohort of 110 patients from 38 study centers receiving a total of 1,047 chemotherapy-cycle days was analyzed. The mean patient age was 52.4 years. Mean costs for the EC->DOC group (n=54) totaled EURO 8,459 per patient (95% CI: EURO 7,785–9,132) with costs for cytostatics being the largest burden (EURO 5,673; 67%). Staff costs for drug application and pharmacy services including transport averaged out EURO 1,357 (16%), average basic hospital costs were EURO 414 (4.9%) and EURO 376 (4.4%) for diagnostic effort and port or catheter insertion. Hospitals spent EURO 354 (4.2%) on supportive drugs, administration devices and infusion bags. Rehospitalization (n=7) due to chemotherapy toxicity accounted for EURO 313 (3.7%). In contrast CMF was significantly less expensive (-41.2%) with mean costs of EURO 4,973 (95% CI: EURO 4,706–5,240). Conclusions: Our results picture a substantial budget increase attributable to introduction of taxanes to adjuvant chemotherapy of early breast cancer. The provided data will allow health economic evaluations in the context of modern individualized chemotherapy strategies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Brain metastasis from esophageal cancer: Changing pattern of failure?
Authors: Jonathan Ben Ashman, Dawn E. Jaroszewski, Naresh P. Patel, David Fleischer, William G. Rule, Rahul Pannala, Francisco Ramirez, Louis Lanza, Harshita Paripati, Kristi L. Harold, Douglas Faigel, Helen J. Ross
Journal: Journal of Clinical Oncology (2013)

134 Background: Brain metastasis (BM) is an uncommon site of failure in patients (pts) with esophageal cancer (EC) with reported rates between 1-6%. EC pts are living longer with the wider adoption of trimodality therapy and, as with other malignancies, this may change the patterns of failure. We evaluated the incidence and outcomes of BM in EC at Mayo Clinic in Arizona. Methods: A retrospective review identified pts who developed BM from cancer of the esophagus or gastroesophageal junction. A total of 321 patients treated for stage I-IV EC (adenocarcinoma, n = 273; squamous, n = 46; small cell, n = 2) were identified between 1997 and 2012. Fisher’s exact test was used for comparisons. Actuarial survival was calculated using Kaplan-Meier analysis. Results: BM developed in 13 pts (4%), all of whom had adenocarcinoma. Nine pts initially presented with T3 and/or node-positive disease. Four pts presented with metastatic disease to other sites, but only 1 of this group was diagnosed with BM at initial presentation. The median time from initial diagnosis to BM detection was 12 months (range 0-40). All pts were symptomatic at diagnosis. BM was solitary in 6 pts, multiple in 6 pts, and unknown in 1 pt. The posterior fossa was involved in 9 pts. The brain represented the first site of failure in 9 pts. Treatment included surgical resection (n = 5), stereotactic radiosurgery (n = 4), and whole brain radiotherapy (n = 9). Median overall survival was 24 months from initial diagnosis and 5 months from BM detection. Among pts with adenocarcinoma, 3/119 (2.5%) were diagnosed between 1997-2006 compared to 10/154 (6.5%) between 2007-2012 (P = 0.1). Conclusions: The brain remains an uncommon site of failure among pts with EC. A recent series reported an incidence of BM in 13% of pts, raising the possibility of a changing failure pattern. In our series, BM was detected in only 4% of pts. Our study is suggestive of a trend towards increased incidence of BM in more recent years, although it did not reach statistical significance and could be a consequence of the retrospective nature of the study. Both series found BM limited only to pts with adenocarcinoma, and a possible association has been reported between HER-2 overexpression and BM in EC. Therefore, BM in EC may be an interesting area for future study.
Global metabolic profiling of clear cell renal cell carcinoma.
Authors: A. Ari Hakimi, Chung-Han Lee, Justin R. Cross, Zhen Li, Yang Chen, Bruce Neri, Victor E. Reuter, Robert John Motzer, Paul Russo, James Hsieh
Journal: Journal of Clinical Oncology (2013)

379 Background: Recent data has suggested that metabolomic profiling in various cancer states may lead to novel biomarkers and innovative therapeutic strategies. We profiled the metabolome of 140 clear cell renal cell carcinomas (ccRCC) and matched normal tissue of various clinical stages. Methods: In collaboration with Metabolon, Inc., 140 clinically annotated tumors were subject to three global metabolic profiling mass spectroscopy platforms. Demographic, clinical, and pathologic data were recorded and patients were grouped into local, locally advanced and metastatic categories using clinical and pathologic criteria. Welch’s paired two sample t tests were used to identify biochemicals that differed significantly between the tumor and normal tissue groups (p value ≤0.001). Supervised clustering using random forest analysis was performed to identify metabolites that differentiated tumors and normals, as well as those associated with tumor progression. Results: A total of 877 biochemicals (including 300 unnamed metabolites) were identified. Several known cancer metabolic pathways were found to be altered consistent with the Warburg effect including accelerated glycolysis and pentose phosphate pathway (PPP), increased lipogenesis, elevated polyamine production, altered nitrogen handling, cell membrane metabolism, inflammation, and oxidative stress. Interestingly, several novel unexpected pathways were found to be altered and associated with disease progression including alterations in the 2-hydroxyglutarate pathway (2HG). 2HG levels were increased over 6 fold in tumors compared to normal and increased further with respect to disease progression (p = 0.019, q = 0.055). Several promising biomarker candidates were identified as well. Conclusions: We provide the first report of large scale metabolomic analysis of ccRCC, revealing several known and novel alterations to cancer-specific metabolic pathways. Investigation of novel pathway biology and biomarker validation in blood and urine samples is currently underway.
Adjuvant treatments in pancreatic cancer: Preliminary data of a pooled analysis.
Authors: F. Drudi, D. Tassinari, C. Castellani, F. Carloni, C. Santelmo, E. Tamburini, M. Fantini, M. Papi, L. Gianni, A. Ravaioli
Journal: Journal of Clinical Oncology (2011)

4042 Background: To assess the role of adjuvant treatments (AT; chemotherapy [AC] and/or chemo-radiotherapy [ACR]) in radically resected pancreatic cancer. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 1966 to 2010 was independently performed by two authors (DT and FD) All the randomized phase III trials investigating the role AT in radically resected pancreatic cancer were considered eligible and included into the pooled analysis. 5-year-survival rate in patients treated with AT was the primary end point of the trial, 5-year-survival rate of patients treated with AC and ACR, and the 5-year-survival number needed to treat (NNT) of AT, AC and ACR were the secondary ones. Heterogeneity between the trials was analysed using the I2 test; the outcome analysis was performed using a random effects model with an alpha error of 5%. Results: The outcomes of 2,410 patients enrolled in 12 trials were compared in the pooled analysis. 1,337 patients were treated with AT (1,008 with AC and 329 with ACR), and 1,073 were enrolled in the control arm (no adjuvant treatment) . Low to moderate heterogeneity between the trials was documented both for AT (I2=29.8%, p=0.153) and AC (I2=48.2%, p=0.051), but not for ACR (I2=0%, p=0.773). A significant improve in 5-year-survival rate was observed for AT and AC (odds ratio of 0.62, p=0.001 and 0.63, p=0.021 respectively), but not for ACR (odds ratio=0.92, p=0.71), with an 5-year survival NNT of 14 (p=0.001), 15 (p=0.021) and 125 (p=0.71) respectively for AT, AC and ACR. Conclusions: Our data confirm that adjuvant chemotherapy improves the 5-year survival rate in radically resected cancer patients; nevertheless, the modest 5-year survival rate of treated patients and the high 5-year survival NNT observed both for AT and for AC seem to suggest the need of further data and further trials to definitively recommend AC for all the patients with radically resected pancreatic cancer.
Recommendations for the delivery of focal tumor ablation services.
Authors: Sherrie Hertz, Cassandra McKay, Jonathan Wang, Fulvia Baldassarre, Amanda Wong, Deanna Langer, John Kachura, Julian Dobranowski
Journal: Journal of Clinical Oncology (2016)

106 Background: The objective of this work was to develop recommendations for the organization and delivery of focal tumor ablation services. New, minimally-invasive ablation technologies such as radiofrequency ablation (RFA), microwave ablation (MWA), and transcatheter arterial chemoembolization (TACE) offer treatment options for patients with a variety of cancers. These emerging therapies can improve patient care (minimize side-effects, offer more rapid recovery with comparable or enhanced outcomes) compared to traditional approaches. However, they are often resource intensive, necessitating a planned system-level approach to ensure appropriate access to high quality services while optimizing care and resource utilization. Methods: This work was led by an Advisory Committee with regional, clinical, administrative and patient representatives and was based on best available evidence, current practice in Ontario, Canada, and guidance from other jurisdictions and experts in the field. A variety of data sources (clinical, system, provider), consultation with external stakeholders and consensus building supported the final recommendations. Results: Thirteen recommendations were developed. Clinical criteria are detailed for RFA for liver, kidney and lung tumors and TACE for hepatocellular carcinoma. MWA is not recommended for lung, liver or kidney tumors. System recommendations include infrastructure (capital equipment, multidisciplinary management and case conference review), the importance of volume-related expertise, and oversight for funding and collaborative planning. Results were broadly disseminated through 12 stakeholder groups connecting with over 40,000 individuals. Conclusions: A systematic approach to understanding opportunities and challenges for focal tumor ablation therapies resulted in multi-level recommendations spanning clinical criteria through to quality oversight. These recommendations will support improvements in care delivery in daily practice and at the system level.
Treatment patterns and health care resource utilization of metastatic colorectal cancer (mCRC) patients who received bevacizumab or cetuximab in second-line regimen.
Authors: H. Yang, A. P. Yu, Y. Yim, E. Yu, E. Wu
Journal: Journal of Clinical Oncology (2011)

525 Background: Targeted therapies such as bevacizumab (BV) and cetuximab (CX) are important treatment options in mCRC. Real-world treatment patterns and resource utilization of mCRC patients (Pts) receiving BV and CX in second-line (2L) treatment are not well studied. Methods: Pts with mCRC were identified from the PharMetrics pharmacy and medical insurance claims database (2002-2009). Included Pts received BV or CX in 2L therapy. 2L was defined as change in therapy from first-line (1L) at least 4 weeks after 1L initiation. Healthcare resource utilization and costs were evaluated during the 6 months following 2L start. Results: A total of 2,188 Pts were included in the analysis, including 1,808 2L BV Pts and 380 2L CX Pts. Demographic and baseline characteristics were similar between groups. Pts' mean age was 61 years and 56% were male. Among all study Pts, 34.1% and 2.7% received BV and CX in 1L, respectively. 60.1% of Pts received oxaliplatin-based regimens in 1L. In 2L, irinotecan and oxaliplatin containing regimens were most commonly used. During the 6 months period following 2L therapy start, BV vs. CX Pts incurred significantly lower risk-adjusted total costs (difference: -$10,231, p=0.020) and inpatient costs ($-3,681, p&lt;0.001). Mean targeted therapy cost was significantly higher for CX ($33,425) than BV ($23,622) (-$10,260, p&lt;0.001). BV Pts incurred significantly less inpatient visits (0.5 vs. 0.7, p&lt;0.001) compared to CX Pts and shorter duration of total hospital stay (3.6 vs. 5.6 days, p=0.007). Conclusions: In 2L treatment of mCRC Pts in the real world setting, BV was most used with oxaliplatin- and irinotecan-based regimens, whereas CX was commonly used with irinotecan-based regimens. Overall, less healthcare resource utilization and costs were observed in patients treated with 2L BV compared to 2L CX. Use of BV in 2L treatment of mCRC was associated with lower number of claims for targeted agents, lower healthcare costs and fewer hospitalizations than CX. [Table: see text] [Table: see text]
PSA patterns during off-time treatment period in patients undergoing intermittent androgen deprivation: Is PSA doubling time reliable in every case?
Authors: Rafael Sanchez-Salas, Dominique Prapotnich, Alexandre Ingels, Fabien Olivier, Mehdi Fhima, Patrick Descamps, David Stephane, Fernando P. Secin, Eric Barret, Marc Galiano, Francois Rozet, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2014)

150 Background: Indicators such as prostate-specific antigen (PSA) nadir after the first on-treatment period (ONTP), off-phase interval duration and PSA doubling time (PSADT) were interpreted as potentially predictive, regarding outcomes of intermittent androgen deprivation (IAD). From actual PSA measurement data recorded on patients undergoing IAD during their off-treatment period (OFTP), we conducted a systematic analysis aimed at screening indicators and finely assessing their relevance as predictive candidates. Methods: Between 1992 and 2012, 727 patients with PC were selected for IAD at our institution. Three hundred ten patients had biochemical recurrence (BCR) after local treatment, 172 showed metastatic disease. ONTP consisted of three-month dose injections of gonadatropin-releasing hormone (GnRH) agonist combined with daily oral androgen receptor antagonist. OFTP was indicated when PSA was less than 4 ng/ml. Criteria for resumption of hormonal therapy were PSA more than 20 ng/ml or clinical symptoms. We tested two basic patterns of PSA behavior-exponential and power law (a&lt;1) and combinations of them, on 597 patients with at least one completed OFTP based on four visits or more (population of the study). Results: We identified 597 patients with a total of 1,573 OFTPs. Median follow-up was 12,2 months (3,0-132,6). Median age at initiation was 76,7 (56,7 to 88,5); 811 OFTPs (51,6%) fitted with a pure exponential (r=0,01), whereas the other part (48,4%) followed more complex patterns (power law or two-steps or linear pattern). Mean cancer specific survival duration was 77,4 months (13,5 to 179,8). 5- and 10-year PC survival rate were respectively of 89,3% and 65,2% (CI 95%). Conclusions: Some OFTPs do not present an exponential pattern behavior: logarithmic calculation of PSADT is not suitable. PSADT determination should be adapted to the nature of the OFTP pattern. Through identification and analysis of the different types of OFTP, it is expected to improve the forecast of clinical outcomes.
Final results of a phase II trial of trabectedin (T) in triple-negative, HER2-positive, and BRCA1/2 germ-line-mutated metastatic breast cancer (MBC) patients (pts).
Authors: K. L. Tedesco, J. L. Blum, A. Goncalves, J. Lubinski, C. R. C. Osborne, P. Lardelli, J. C. Tercero, A. Florez, F. A. Holmes, S. Delaloge
Journal: Journal of Clinical Oncology (2011)

1125 Background: Single-agent T has shown antitumor activity in pts with pretreated MBC. Preclinical data suggested T displays increased activity in cell lines having intact nucleotide excision repair (NER), evidenced in particular by XPG expression or homologous recombination repair (HRR) deficient MBC. Final results of the multicenter phase II trial of T in metastatic breast cancer patients are presented. Methods: T was given at 1.3 mg/m2 as a 3-hour intravenous infusion every three weeks, to pts with pretreated progressive MBC. Group A: triple negative (TN); Group B: HER-2 overexpressed (HER-2+); and Group C: BRCA1/2 mutation carriers. Endpoints were objective response rate by RECIST per independent radiological review, duration of response, progression free survival (PFS), safety and pharmacogenomics. Results: A total of 122 pts (median [med] age 51; ECOG 0/1, 49/51%) were enrolled (A: 50, B: 37, C: 35). For all groups, med number of prior chemotherapy regimens was 3 (1–9) and med number of T cycles administered was 3 (1–22). The most frequent grade 3-4 laboratory disorders were neutropenia (51.7%) and ALT elevations (40.5%). Fatigue (50.1%), nausea (44.9%) and vomiting (24.6%) were the most common AEs, mild-moderate in the vast majority of pts. Tissue samples from 44 pts were collected for RNA expression analysis (XPG, ERCC1, BRCA1). High XPG was associated with longer PFS: 3.7 mo (95% CI, 2.6-5.6) vs 1.6 mo (95% CI, 1.3–3.1), p=0.0093. Conclusions: T demonstrated efficacy in HER2+ and in BRCA1/2 mutation carrier pts with pretreated progressive MBC. Safety profile was tolerable and manageable. RNA overexpression of XPG may identify those MBC pts with highest chance of response to T treatment among these subgroups of breast cancer pts. Efficacy data as per external review. Group Pts n Best response n (%) PFS med (mo) PFS4 % (95% CI) TN 43 5 SD ≥4 mo (11.6) 2.2 18.7 (5.8-31.5) HER2+ 34 4 PR (11.8) 3.3 41.8 (23.5-60.1) BRCA1/2 mutation 29 4 PR (13.8) 3.3 38.9 (19.5-58.4) Months, mo; PFS4, PFS at 4 mo; PR, confirmed partial response.