tbuckley/cabot-search huggingface dataset:
Development of an evidence-based clinical pathway for patients undergoing pancreaticoduodenectomy.
Authors: Alice Chia-chi Wei, Katharine Sarah Devitt, Mahrosh Ahmed, Beverly Barretto, Anna Kacikanis, Steven Gallinger
Journal: Journal of Clinical Oncology (2014)

130 Background: Pancreas cancer is the 4th cause of cancer death. Surgical resection is the optimal treatment. But pancreaticoduodenectomy (PD) is complex with high perioperative morbidity. Complications following PD have a negative effect on quality of life and survival. Clinical pathways (CPW) are quality improvement (QI) tools that standardize the processes of care. Our aim was to develop and implement an evidence-based CPW for PD in the province of Ontario, Canada. Methods: A CPW following PD was developed using the Knowledge-to-Action framework. All 9 high volume Hepato-Pancreato-Biliary (HPB) centers in Ontario were invited to participate in a needs assessments workshop to promote awareness and early agreement for a CPW. Enthusiasm for a CPW was confirmed. End user input was incorporated into a multidisciplinary CPW. Barriers and enablers to implementation were assessed. Evidentiary support for CPW elements was integrated into the final product. An active implementation strategy that addressed key barriers was developed to promote CPW adoption and adherence. Pilot testing was undertaken. CPW uptake, compliance, and impact on clinical outcomes were evaluated. Pilot results were used to design the final CPW product and implementation strategy. Results: The needs assessment confirmed variability of perioperative processes at all sites. Participants expressed interest for a CPW and consensus was obtained on essential CPW components. During a 15 month pilot phase, 83/122 (68%) of eligible patients were initiated on CPW. Subjects able to achieve the goals of the CPW had a shorter length of stay (7 vs 11 days), lower in-hospital complications (9, 22% vs 19, 45%) and readmission (6, 15% vs 11, 26%) compared to those who were unable to achieve CPW targets. The majority of CPW users reported that the CPW was easy to use (26, 93%) and did not adversely affect workload (20, 71%). Pilot data were used to finalize the strategy used to implement the CPW at all Ontario HPB centers. Conclusions: We report that introduction of a standardized CPW for complex cancer surgery is possible with early engagement of stakeholders. Initial results suggest that this standardized approach is safe and positively impact quality of surgical care.
Novel solution to achieve “80% by 2018” <i>Two-Man</i> colonoscopy performed by primary care physicians with expert back-up: Compliance and capacity without diluting quality.
Authors: Stephen Carroll Lloyd
Journal: Journal of Clinical Oncology (2016)

544 Background: The American Cancer Society (ACS) supports 80% by 2018. We have an innovative solution to address barriers: compliance and capacity without diluting quality. Methods: The “gold standard” test is a high-quality colonoscopy. To improve compliancewe leverage the primary care physician (PCP) through navigators. The existing colonoscopists are saturated while screening only half. Quality, as reflected in the protective benefit, is called into question by large-scale studies. An estimated 7% of CRCs are diagnosed as “interval cancers.” occurring in patients compliant with screening. Results: First, when the PCP invites the patient, their “butts” show up! Compliance in our study more than doubled and exceeded the ACS 80% by 2018 goal. We present an update to the initial study (de Groen, NEJM 2014) adding 15,000 more consecutive cases and 4 years to the database; incidence dropped (83%) as did mortality (89%). This is the first large study to demonstrate no diminution of protection in the right colon! Our hypothesis is that the two-man technique simplifies visualizing the mucosal surface. The continual availability of an “expert” to “mentor and monitor” was sufficient to supervise 30 PCPs and thus augment capacity (4,000 cases rather than 1,000 cases per year per expert). With the average cost of $250,000 per case of advanced CRC, the savings are more than double the screening costs. Conclusions: The inclusion of the PCP in CRC screening addresses the barriers: enhanced compliance, augmented capacity without any diminution in quality. The PCP provides capacity needed to screen the underserved (more than half of the at risk population not “up to date” with screening colonoscopy). Rather than taking patients from traditional providers, the model has excelled in identifying the underserved. To achieve 80% by 2018 will require 6,000,000 additional annual screening colonoscopies but would prevent 100,000 cases of CRC and 25,000 deaths. At the current rate, 30,000 PCP colonoscopists could meet this demand. Utilizing PCPs using the team colonoscopy approach could one day result in near elimination of deaths from “the preventable cancer.”
Effect of time windows in analysis of health-related quality-of-life (HRQOL) outcomes.
Authors: C. Quinten, C. Coens, J. Maringwa, F. Martinelli, J. Ringash, D. Osoba, B. B. Reeve, M. King, C. S. Cleeland, H. Flechtner, C. Gotay, E. Greimel, M. J. B. Taphoorn, J. Weis, J. Schmucker-Von Koch, H. Schmoll, A. Bottomley
Journal: Journal of Clinical Oncology (2011)

e19664 Background: Patient reported HRQOL collection in randomized controlled trials (RTC) requires questionnaire completion at specific time points. Our aim was to assess whether HRQOL scores differ depending on the relative timing of completion. Methods: In a retrospective analysis of an EORTC 3-arm RCT of 498 colon or rectum cancer patients comparing 5-FU 24 continuous infusion (Arm A), 5-FU 24 continuous plus leucovorin (LV) (Arm B) and 5-FU bolus plus LV (Arm C), HRQOL was measured as a secondary endpoint at baseline and on each of the 12 scheduled chemotherapy cycle dates using the EORTC QLQ-C30 questionnaire. A ‘time window’ variable was created to indicate when the questionnaire was completed relative to scheduled date and defined as ‘before’ (up to 10 days), ‘on’ (on cycle date), and ‘after’ (up to 10 days). Sensitivity analyses were performed extending the time window to 20 to 30 days. HRQOL mean scores were calculated using a linear mixed model including treatment, cycle number, treatment-by-cycle interaction, and the time window variable. Results: Patient baseline characteristics were balanced across the three treatment arms. The analysis was limited to the first five cycles yielding a total of 753 questionnaires. Only for Arm C were significant (p<0.05) HRQOL mean score differences (Δ) reported. Compared to HRQOL mean scores ‘on’ the scheduled cycle data, the ‘before’ HRQOL scores were worse for physical functioning (Δ=3.05; p=0.0003) and fatigue (Δ=5.85; p=0.0055) and the ‘after’ HRQOL mean scores were worse for nausea and vomiting (Δ=2.45; p=0.0326) and physical functioning (Δ=2.33; p=0.0110). Similar results were reported during the sensitivity analysis. HRQOL mean score differences were well below the 10 points seen as clinically meaningful. Treatment arm comparisons between arms did not significantly change by the inclusion of the time window variable. Conclusions: These results suggest that HRQOL mean scores may differ depending on the relative timing of the questionnaire completion and may vary depending on the treatment arm. In our study HRQOL scores specifically differed, with regard to relative timing, for cancer patients receiving 5-FU bolus infusion. Our findings however should be further explored in settings.
Perioperative chemotherapy with S-1 plus oxaliplatin (SOX) for stage III colorectal cancer patients.
Authors: Naoya Aisu, Yoichiro Yoshida, Akira Komono, Teppei Yamada, Daibo Kojima, Toshiyuki Mera, Syu Tanimura, Yuichi Yamashita
Journal: Journal of Clinical Oncology (2016)

603 Background: Neoadjuvant chemotherapy (NAC) has a potential to increase the curative resection rate and reduce the recurrence rate. The purpose of this study was to evaluate the safety and efficacy of S-1 plus oxaliplatin (SOX) regimen as neoadjuvant (4 courses) and adjuvant (4 courses) for the treatment of patients with Stage III colorectal cancer (anyT and N+). Methods: We have treated patients with Stage III colorectal cancer undergone operation after NAC (SOX 4 courses) and adjuvant chemotherapy (SOX 4 courses) at Fukuoka University Hospital. SOX regimen (S-1 80 mg/ m 2 : day1~14 and oxaliplatin 130 mg/m 2 : day1) was administrated every 3 weeks. The primary endpoint was response rate and safety. Results: Of the 21 patients enrolled between September 2012 and December 2014. The median age was 62 years (range, 43–87), and 57% were female. Eastern Cooperative Oncology Group performance status scores were 0, 1, and 2 in 50%, 40%, and 10% of the patients, respectively. The patients received median 4(1-4) courses of NAC and median 4(0-4) courses of adjuvant chemotherapy. The cumulative median dose of oxaliplatin was 1204 (210-1841) mg/body. In NAC, 4 patients required treatment interruption because of the toxicity [grade2 gastrointestinal bleeding (n = 1), grade 3 thrombocytopenia (n = 2), and grade4 ileus (n = 1)]. A complete response according to Response Evaluation Criteria in Solid Tumors ver.1.1 was observed in a patient (4.8%) and a partial response was observed in 15 patients (71.4%) and a stable disease was 5 patients (23.8%). The response rate and tumor control rate were 76.1% and 100%. Curative resection was performed in all patients. No perioperative complications more than grade3 as Clavien Dindo classification was observed in all patients. The observed adverse events of Grade 3 or higher were thrombocytopenia (n = 4), neutropenia (n = 3), diarrhea (n = 1), and ileus (n = 1). Conclusions: Perioperative chemotherapy with SOX is safe and effective. Further studies are warranted to confirm the safety and efficacy of this method. A single-arm phase II trial of perioperative chemotherapy (SOX) and operation for stage III colorectal cancer patients (FUTURE1104 SOS3).
Potential curability of cladribine in selected patients with hairy cell leukemia
Authors: D. Sigal, R. W. Sharpe, C. Burian, A. Saven
Journal: Journal of Clinical Oncology (2008)

18010 Background: Hairy cell leukemia (HCL) is an uncommon, chronic B-cell lymphoproliferative disorder associated with pancytopenia, splenomegaly, and recurrent infections. Cladribine as a single seven-day continuous intravenous infusion achieves an overall response rate of 98%, and complete response rate of 91%. Follow-up studies have documented minimal residual disease (MRD) in at least 50% of complete responders and continued clinical relapses, with 108 months median follow-up (range, 86–172). This suggests that all complete responders are at continuous risk for relapse. With twenty-year follow-up now available in some patients, we sought to determine if any patients were without MRD and potentially cured of HCL after a single seven-day course of cladribine. Methods: The Scripps Clinic cladribine phase II database of 379 patients was screened for patients who are alive, in a continuous hematologic remission, and received only a single seven-day course of cladribine. Patients agreed to undergo complete blood counts (CBC) and bone marrow aspiration and biopsy (BM). BM samples were analyzed for morphologic evidence of HCL and for MRD by flow cytometry to detect monoclonal B-cells with HCL phenotypic characteristics. Immunoglobulin heavy chain gene rearrangement studies were performed in some patients. Results: Of the 379 patients screened, we had accurate contact information on 75 patients; 20 patients met inclusion criteria and agreed to undergo CBC and BM. Patient characteristics: 17 males and 3 females; median age, 53 years (range, 39 to 75); median pretreatment duration, 2 years (range, 0.1 to 12.3); median duration following cladribine treatment, 17 years (range, 11 to 20). Prior to cladribine, 13 patients were untreated; 10 had undergone splenectomy, interferon, or chlorambucil. All patients had a normal CBC. Of these 20 patients, 9 patients had no evidence of MRD on BM; 7 patients had MRD; 4 patients had morphological evidence of HCL. Conclusions: Cladribine can potentially cure HCL in a subset of patients. Patients with MRD or even morphologically demonstrable disease can remain asymptomatic with normal blood counts up to twenty years after a single course of cladribine. No significant financial relationships to disclose.
Survival outcomes in elderly patients with plasma cell myeloma: The three-decade Eastern Cooperative Oncology Group (ECOG) experience.
Authors: E. L. Campagnaro, S. J. Jacobus, H. Uno, M. M. Oken, R. A. Kyle, S. V. Rajkumar, P. R. Greipp, D. H. Vesole, M. Weiss, R. Fonseca, H. M. Lazarus
Journal: Journal of Clinical Oncology (2011)

8021 Background: Successful treatment of plasma cell myeloma (PCM) includes cytotoxic chemotherapy, high-dose chemotherapy with autologous stem cell transplant (ASCT), immunomodulatory drugs and proteasome inhibitors. Landmark papers by Kumar et al and Brenner et al in 2008, and Turesson et al in 2010, showed significant gains in median overall survival (OS) of PCM patients but these gains were attributed primarily to age < 65 years. Marginal improvement seen in older patients did not reach significance. We examined outcome for patients treated on frontline ECOG protocols over the past 33 yrs to assess whether there has been survival improvement in elderly patients. Methods: We reviewed 4 phase III study data for previously untreated PCM patients. ASCT regimens were excluded. OS was analyzed using Kaplan-Meier and group differences were tested using 2-tailed log-rank test. Cohorts were identified based on date of accrual to clinical trial: A 1988-1993, B 1994-2000, and C 2001-2006. Results: 1,528 patients were treated (Table). 727 (48%) were > 65 yr. 358 pts (23%) were age 70-79 yr and 48 pts (3%) were > 80 yr. For all pts, 5 yr probability of OS was significantly better in cohort C (51%) as compared to cohorts A (31%) and B (29%), respectively (p<0.0001). For pts > 65 yr, this effect on OS still was seen but substantially diminished (39% on C versus 26% on A and B, p=0.012), while in the younger cohort effect is more pronounced (63% on C, 35% on A and 32% on B). Conclusions: OS in elderly PCM pts has improved but OS gains still lag behind younger PCM pts. Increased comorbidity, treatment-related toxicity, physician/patient biases, and differences in disease biology in elderly patients are all possible contributing factors to worse outcomes. In-depth review of these variables may contribute to improved design of future clinical trials for elderly PCM pts. Accrual period Pts <65 yr Pts ≥65 yr No. Median OS (0.95 CI) [yr] No. Median OS (0.95 CI) [yr] A 1988-1993 371 3.7 (3.4, 4.1) 282 3.3 (2.9, 3.9) B 1994-2000 100 3.5 (2.9, 4.1) 93 3.0 (2.6, 3.8) C 2001-2006 330 7.4 (6.2, NA)* 352 3.7 (3.3, 4.9)** * Comparing C to A+B, p≤.001 ** Comparing C to A+B, p=.012
Association of PTEN protein loss with upgrading of prostate cancer from biopsy to radical prostatectomy.
Authors: Filipe LF Carvalho, Tamara L Lotan, Sarah B. Peskoe, Jessica Hicks, Jennifer Good, Helen L. Fedor, Elizabeth B Humphreys, Misop Han, Elizabeth Platz, Jeremy Squire, Angelo DeMarzo, David M. Berman
Journal: Journal of Clinical Oncology (2014)

127 Background: Active surveillance is increasingly recommended for men with low-risk Gleason Score 3+3=6 (GS 6) prostate cancer. Yet, approximately one-third of patients with GS 6 cancer on biopsy are upgraded to higher GS at radical prostatectomy (RP). Previous studies have shown that clinical-pathologic parameters (age, prostate-specific antigen [PSA], prostate volume, extent of disease) are weak predictors of GS6 tumor upgrade. Our goal was to investigate the utility of PTEN as a molecular marker to predict upgrading in GS 6 biopsies. Methods: In a retrospective case-control study, 71 patients with GS 6 tumors on needle biopsy that were upgraded to GS 7 or higher cancer at RP (cases) were compared to 103 patients whose GS 6 tumors on needle biopsy were not upgraded at RP (controls). The most extensively involved needle core biopsy from each case was immunostained and scored for PTEN protein loss using a previously validated immunohistochemical (IHC) assay and binary scoring system. Confirmatory fluorescence in situ hybridization (FISH) was used to assess for PTEN gene deletion in biopsies with PTEN protein loss. The correlation of upgrading with PTEN loss and with clinical-pathologic variables was assessed by logistic regression. Results: Patients with upgraded cancers were older than controls (61.8 vs. 59.3 years), had higher mean pre-operative PSA levels (6.53 vs. 5.26 ng/mL), and a higher fraction of biopsy cores involved by tumor (0.42 vs, 0.36). However, of all pathologic variables, PTEN protein loss by IHC was most predictive of upgrading. Overall, PTEN protein loss was found in 18.3% (13 out of 71) of upgraded cases compared to 6.8% (7 out of 103) of controls (p=0.02). In the cases with PTEN protein loss, FISH confirmed homozygous PTEN deletion in 90% (9 out of 10) of upgraded tumors compared to 67% (4 out of 6) of interpretable not upgraded controls. On multivariate analyses, even after adjusting for age, preoperative PSA, clinical stage and race, GS 6 tumors with PTEN protein loss on biopsy were significantly more likely to be upgraded at RP compared to those without PTEN loss with odds ratio (OR) = 3.04 (1.08-8.55; p=0.035). Conclusions: In prostate needle biopsies, PTEN IHC may help distinguish men with low risk cancer from men with intermediate or higher risk cancers.
Dynamic contrast-enhanced ultrasonography (DCE-US) with quantification for the early evaluation of hepato cellular carcinoma treated by bevacizumab in phase II
Authors: B. Benatsou, N. Lassau, L. Chami, S. Koscielny, A. Roche, M. Ducreux, D. Malka, V. Boige
Journal: Journal of Clinical Oncology (2008)

4588 Background: To determine the best quantitative parameters of DCE-US at D3 and 7 for predicting the response at 3 months to bevacizumab in patients with hepato cellular carcinoma (HCC). Methods: Forty-eight patients with HCC, treated with bevacizumab every 2 weeks were prospectively followed by DCE-US. DCE-US was performed before treatment and at day 3, 7, 15, 2 months and every 2 cycles. Contrast uptake was acquired using VRI perfusion software after SonoVue (Bracco) bolus injection. Time-intensity curves (TIC) were determined using linear raw-data from CHI-Q (Toshiba) software. Seven parameters were extracted from the modelized TICs: peak intensity (PI), areas under the curve (AUC), under the wash-in (AUWI), under the wash-out (AUWO), (corresponding all to the blood volume), time to peak intensity (TPI), slope of the wash-in (SWI) (both corresponding to the blood flow), mean transit time. CT-scan were performed before treatment and every 2 months. Patients were separate in good and bad responders according to the clinical benefit after 4 months according the RECIST criteria (good responders = PR+SD). The variation of each functional parameter of DCE-US was calculated between D0 and D3, 7, D15. Results: To date, 42 patients have been followed-up at least 4 months with a maximum of 18 months: 24 were good responders and 18 bad responders. A total of 265 DCE-US were performed. Among 7 parameters: 4 (related to the blood volume) have decreased of more than 30% at D3 and D7 in good responders.(AUC, AUWI, AUWO, PI). Conclusions: Quantitative functional evaluation by DCE-US performed at D 3 and D 8 seems to predict the response at 4 months in patients with HCC treated by bevacizumab The final results including statistical analysis will be presented with a total of 48 patients followed at least 4 months. No significant financial relationships to disclose.
Efficacy and safety of first-line cetuximab + FOLFIRI in older and younger patients (pts) with <i>RAS</i> wild-type (wt) metastatic colorectal cancer (mCRC) in the CRYSTAL study.
Authors: Eric Van Cutsem, Claus-Henning Köhne, Gunnar Folprecht, Silke Guenther, Frank Beier, Demetris Papamichael
Journal: Journal of Clinical Oncology (2016)

647 Background: Pts with mCRC are often older, thus prompting interest in subgroup analyses based on age. Adding cetuximab to FOLFIRI in the first-line CRYSTAL trial improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in pts with RAS wt mCRC. This subgroup analysis evaluated the efficacy and safety of FOLFIRI ± cetuximab within age-defined subgroups from the RASwt population of CRYSTAL. Methods: PFS, OS, ORR, and safety were evaluated in RAS wt pt subgroups in CRYSTAL, defined by age and treatment arm. Older pts were categorized as aged ≥65 y; younger pts were aged &lt;65 y. Among pts ≥65 y, only 26 and 10 pts in the cetuximab + FOLFIRI arm and only 10 and 10 pts in the FOLFIRI arm were aged 70-75 y and ≥75 y, respectively; therefore, an analysis of an older-age cutoff was not performed. Results: Among 367 pts with RASwt tumors, 115 were older and 252 were younger. Baseline characteristics were similar between treatment arms in the younger subgroup; however, in the older subgroup, baseline ECOG status (ECOG=0; 45.9% vs 61.1%) and quality of life (&gt;median; 36.1% vs 51.9%) favored the FOLFIRI arm. This study was not designed to assess differences within and between age subgroups; therefore, interpretation is limited by baseline imbalances and the small number of older pts. Efficacy and safety data are summarized below. Conclusions: In RAS wt CRYSTAL pts, adding cetuximab to FOLFIRI improved ORR, PFS and, to a lesser extent, OS in both older and younger pts. Clinical trial information: NCT00154102. [Table: see text]
Management of Severe Pancreatic Fistula After Pancreatoduodenectomy
Authors: F. Jasmijn Smits, Hjalmar C. van Santvoort, Marc G. Besselink, Marilot C. T. Batenburg, Robbert A. E. Slooff, Djamila Boerma, Olivier R. Busch, Peter P. L. O. Coene, Ronald M. van Dam, David P. J. van Dijk, Casper H. J. van Eijck, Sebastiaan Festen, Erwin van der Harst, Ignace H. J. T. de Hingh, Koert P. de Jong, Johanna A. M. G. Tol, Inne H. M. Borel Rinkes, I. Quintus Molenaar
Journal: JAMA Surgery (2017)

Postoperative pancreatic fistula is a potentially life-threatening complication after pancreatoduodenectomy. Evidence for best management is lacking.