tbuckley/cabot-search huggingface dataset:
The differences in the stage classification for node-positive colorectal cancer between the United States and Japan: A single institution experience.
Authors: Kiichi Sugimoto, Koichi Sato, Hajime Orita, Hiroshi Maekawa, Mutsumi Sakurada, Tomoaki Ito, Kazuhiro Sakamoto
Journal: Journal of Clinical Oncology (2012)

e14139 Background: In the United States, the stage classification by the number of lymph node metastasis (LNM) is adopted in TNM classification 7th edition. In Japan, the stage classification by the distribution of LNM was modified to that by the number of LNM in order to integrate with TNM classification in Japanese classification of colorectal carcinoma second English edition. We retrospectively examined the possibility of predicting prognosis by the number of LNM and considered the differences between TNM classification and Japanese classification. Methods: Two hundred and seventy-five patients with LNM who underwent curative surgery for colorectal cancer at our department between January 1992 and December 2004 were enrolled in this study. All patients were followed for 5 years after the operation. At first, we calculated cancer-specific survivals according to the number of LNM in order to examine whether the stratifications of prognosis by the number of LNM is appropriate or not. Secondary, clinicopathological factors and survival data were analyzed to determine prognostic factors. Finally, we considered the differences between TNM classification and Japanese classification. Results: When comparing cancer-specific survivals between the patients with the number of LNM of 1 and 2-3 and 4 or more, cancer-specific survivals were well stratified (both; p=0.006). According to the multivariate analysis using clinicopathological factors, invasion depth (T4) (p=0.007, odds ratio=2.230), venous invasion (moderate-severe) (p=0.003, odds ratio=2.577) and the number of LNM (p=0.0002, odds ratio=1.201) were significantly independent prognostic factors. In Japanese classification, there was a significant difference in cancer-specific survivals between Stage IIIa and IIIb (p&lt;0.0001). On the other hand, in TNM classification, cancer-specific survivals in Stage IIIA, IIIB and IIIC were stratified into three groups with significant differences (IIIA vs IIIB; P=0.01, IIIB vs IIIC; p&lt;0.0001). Conclusions: In comparison of Japanese classification and TNM classification, TNM classification seems to be superior to Japanese classification.
Serious adverse events among a population-based cohort of patients receiving first-line chemotherapy for metastatic colorectal cancer (mCRC).
Authors: Raymond Woo-Jun Jang, Katherine Enright, Christopher M. Booth, Kelvin K. Chan, Lingsong Yun, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2012)

e14003 Background: Little is known about the toxicity of first line chemotherapy for mCRC in the general population. We sought to determine the proportion of patients who experienced at least one of the following: a serious toxicity (defined as an emergency department visit or hospitalization) or death within 30 days of receiving chemotherapy. Methods: All patients, age 18 or older, diagnosed with CRC from January 1 2007 to December 31 2009 in Ontario, Canada were identified using the Ontario Cancer Registry. Patient records were linked deterministically to multiple provincial healthcare databases to identify receipt of first-line chemotherapy for metastatic disease and to evaluate Emergency Department (ED) visits, hospitalizations, and deaths. An event was determined to be potentially treatment related if it occurred within 30 days of any cycle of chemotherapy. Results: The cohort contained 2359 patients. Mean age was 62 (range 19-89) and 59% were men. See table below. Conclusions: A significant proportion of patients visit the ED at some point during first line chemotherapy and many are hospitalized. A quarter of all patients had a hospital admission whereby an infectious complication was at least a contributing diagnosis. A significant minority of patients died within 30 days of receiving chemotherapy, raising concerns of either poor patient selection or severe treatment toxicity. [Table: see text]
A phase 1 study of MEDI3617, a selective angiopoietin-2 inhibitor, alone and in combination with carboplatin/paclitaxel, paclitaxel, or bevacizumab in patients with advanced solid tumors.
Authors: David Michael Hyman, Naiyer A. Rizvi, Ronald B. Natale, Deborah Kay Armstrong, Michael J. Birrer, Lawrence David Recht, Efrat Dotan, Matthew Joseph Gribbin, Jennifer T. McDevitt, Fatemeh Tavakkoli, Jennifer McCaffrey, Robert Sikorski, Dominic W. Lai
Journal: Journal of Clinical Oncology (2014)

3012 Background: MEDI3617 (M) is an investigational monoclonal antibody that inhibits angiogenesis by preventing the interaction of angiopoietin-2 (Ang2) ligands with the Tie2 receptor. Methods: This is a 3+3 dose-escalation (monotherapy [mTx] and combination) study in adults with advanced solid tumors with mTx expansion in platinum-resistant ovarian cancer (prOC) (NCT01248949). Patients (pts) with Karnofsky performance status ≥70, and adequate organ function were treated in 21 or 28 day cycles with M alone or in combination with carboplatin/paclitaxel (CT), paclitaxel (T), or bevacizumab (B). Objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity. Results: As of 22 Jan 2014, 95 pts (median age 61; 54% female) were enrolled: 25 in M mTx dose-escalation, 7 in M mTx prOC dose-expansion, and 63 in combination arms. The maximum tolerated dose was not defined in either mTx or combination arms. In the mTx arms, 72% (n=32) of pts had treatment-related adverse events (trAEs): 63% grade ≤2, 6% grade 3, and 3% grade 4. Non-hematologic grade 3 trAEs in the mTx arms included increased weight (6.3%), peripheral edema (3.1%), lymphedema (3.1%) and pleural effusion (3.1%). The grade 3 peripheral edema and lymphedema that occurred in 2 pts in the prOC expansion arm persisted despite discontinuation of M. In the mTx arms, 3 pts (9.4%) discontinued treatment due to trAEs. Exposure of M approached a linear range beyond 100 mg Q3W or 60 mg Q2W. Circulating serum Ang2 levels were >95% saturated at doses ≥500 mg. Objective responses in the combination arms included 5 partial responses plus 1 unconfirmed in: prOC (1 each in M/B and M/T, 1 unconfirmed in M/CT), renal cell cancer (1 in M/B), cervical cancer (1 in M/B), and lung cancer (1 in M/T). In the mTx arms, 1 unconfirmed partial response in a prOC pt was observed and 7 pts had stable disease for >12 weeks. Conclusions: MEDI3617 alone and in combination had an acceptable safety profile. Combination therapy exhibited signs of antitumor activity across a variety of tumor types. Enrollment in the mTx prOC expansion cohort is ongoing. Clinical trial information: NCT01248949.
Phase II study on the efficacy and safety of lapatinib administered beyond disease progression and combined with vinorelbine in HER-2/<i>neu</i>: Positive advanced breast cancer (CECOG LaVie Trial).
Authors: Christiane Thallinger, Istvan Lang, Cvetka Grasic Kuhar, Rupert Bartsch, Christian F. Singer, Lubos B. Petruzelka, Bohuslav Melichar, Regina Knittelfelder, Thomas Brodowicz, Christoph Zielinski
Journal: Journal of Clinical Oncology (2015)

e11603 Background: This open-label, single-arm, multicenter phase II trial performed by the Central European Cooperative Oncology Group (CECOG) evaluated the efficacy and safety of the combination of vinorelbine and lapatinib in patients with HER-2/neu positive metastatic breast cancer as late-line therapeutic regimen. Methods: Patients with HER-2/neu-positive advanced breast had to be pretreated with lapatinib plus chemotherapy in first or second line for metastatic disease. Patients enrolled in this study were treated with vinorelbine (20 mg/m2i.v. on days 1 and 8), plus lapatinib (1250 mg orally once daily) until disease progression, intolerable toxicity, withdrawal or death. The primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. The study was closed early due to slow accrual. Results: In total, 9 patients were enrolled. 6 patients had endocrine dependent disease. All patients were heavily pretreated and had received at least two lines of prior anti-cancer treatment for metastatic disease. Median PFS was 7.7 months (95%CI 0.56-14.91), median OS was 23.4 months (95%CI 16.61-30.13). Partial response was observed in one of 9 patients, 3 patients had stable disease of >6 months, whereas the remaining 5 patients had progressive disease. Individual patient data are shown in the table below. The majority of reported adverse events (AEs) were grade 1 and 2 in severity; most common AEs were diarrhea (17.9%), neutropenia (8.5%) and leukopenia (6.8%). AEs were consistent with the known lapatinib and vinorelbine safety profiles. Conclusions: The trial was terminated due to poor recruitment. Although limited by the small number of patients the combination therapy of vinorelbine and lapatinib resulted in a median PFS of 7.7 months and might represent a treatment option in heavily pretreated patients with HER-2/neu positive metastatic breast cancer. Individual patient efficacy. Patient No. 1 2 3 4 5 6 7 8 9 PFS, months 1.3 1.2 1.9 7.7 10.0 14.6 12.8 6.3 2.3 OS, months 4.2 2.9 4.9 33.3 24.3+ 20.6 20.7+ 23.4 33.8 ORR, over 6 months SD PD PD PD SD PR SD PD PD
High-dose cytarabine-mitoxantrone versus hyper-CVAD in adult acute lymphoblastic leukemia and Burkitt’s lymphoma: A single center experience of two induction regimens.
Authors: Gurpreet Singh Lamba, Rahul Pawar, Abhishek Marballi, Sang-Joon Lee, Delong Liu
Journal: Journal of Clinical Oncology (2013)

7076 Background: This is a retrospective analysis of 111 newly diagnosed adult ALL patients treated between January 1994 and January 2012 at Westchester Medical Center. Methods: Patients received induction chemotherapy with either high dose mitoxantrone and high-dose Ara-c (HDAM, n=62) or Hyper-CVAD (n=49). The patient characteristics are summarized in the table. OS, CR duration and time to recurrence were estimated using the Kaplan-Meier product estimate methods and comparative study was conducted based on Log-rank test. Differences in CR rates by treatment and by prognostic factors were analyzed using Chi-squared test and Fisher’s exact test. Results: The CR rate was 85% in the HDAM group and 84% in the HyperCVAD group. The median OS was 22.7 months (m), (95% CI 15.3-38.3 m) for the entire cohort, 21.4 m (95% CI 13.3 - 35.5 m) for HDAM arm and 26.8 m (95% CI 11.7 - 63.3 m) for HyperCVAD arm. The OS for patients with Philadelphia chromosome positive or t(4,11) was 13.2 m (95 % CI 9.5 – 26.8 m). In an analysis of the entire cohort for differences in CR rates based on prognostic factors, WBC &lt; 10,000 was the only favorable factor toward CR (p=0.049). Other prognostic factors including cytogenetics, cell type, age, LDH, were not statistically significant. Conclusions: HDAM and Hyper-CVAD appear to be comparable in CR induction and overall survival in this single institution retrospective analysis. These two regimens should be compared in a large multicenter randomized study. [Table: see text]
Phase II trial of target-guided personalized chemotherapy in first-line metastatic colorectal.
Authors: Antonio Cubillo, Jesus Rodriguez-Pascual, Fernando López-Ríos, Carlos Plaza, Elena García, Rafael Alvarez-Gallego, Emilio De Vicente, Yolanda Quijano, Ovidio Hernando, Carmen Rubio, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2013)

3543 Background: Chemotherapy (Ch) options for patients (pts) with colorectal cancer (CRC) have increased in the last years. However, there are no validated prospective molecular markers in CRC to select which agents are better to treat any individual case. The aim of this study was to determine the efficacy in terms of progression free survival (PFS) of a biomarker panel to guide treatment selection in this setting. Methods: Treatment naive, ECOG 0-1, metastatic CRC pts were accrued. Pts were prospectively analyzed with a predefined set of 10 molecular targets, including: KRAS, BRAF, and PI3K mutations and Topoisomerase-1(Top-1), ERCC-1, Thymidylate synthase (TS) and Thymidine phosphorylase (TP) expression by inmunohistochemistry ( IHC) performed in a tumor biopsy. Ch combination schema plus Cetuximab (C) or Bevacizumab (B) at standard doses was customized based on: Topo-1 +:Irinotecan (I). Topo-1- and ERCC-1 -:Oxaliplatin(O). Topo-1- and ERCC1 +:investigator option (I or O). TS -:Fluoropyrimidines (FP).TS +:No FP. TP -:5-FU, TP +:Capecitabine. Maintenance C or B treatment was allowed. Primary outcome measure was PFS. Results: 74 pts were accrued and all of them received biomarker guide treatment. All of them began personalized. Interim analysis on 61 pts (38 males, median age 65) showed.Topo-1 + in 33 pts (54%),ERCC-1- in 36( 59%) TS + in 44 (73%), TP – in 61 ( 100%), K-ras nativein 34 ( 55%), BRaf mutated in 2 (3,2%). With a median follow up time of 9,1 months (m). Median PFS (95% CI) is 8,6 (6,2-10,9) m, with a 41,3% (27,4-55,2) 12mPFS . Overall clinical benefit (Response + Stabilizations) was 74,5% (65,6-83,4).Toxicities Grade ≥ 3 included 18% neutropenia, 4,9% asthenia and 3,3% anemia. 12 pts (23%) received loco-regional treatment ( surgery or radiosurgery). Median Overall survival has not been reached. Conclusions: Target- Guided Personalized Ch in first line CRC pts is feasible and results in promising PFS with low toxicity. Update of final results and more detailed data will be presented. Clinical trial information: NCT01453257.
Phase I trial results of PCK3145 in patients (pts) with castrate metastatic prostate cancer (PC)—The US experience
Authors: S. F. Slovin, L. Daigneault, H. Dulude, C. Panchal, J. Richardson, T. Curley, A. Delacruz, M. Fleisher, M. Morris, H. Scher
Journal: Journal of Clinical Oncology (2006)

4650 Background: PCK3145 is a synthetic 15-mer peptide derived from the natural sequence of amino acids of Prostate Secretory Protein (PSCP94), a predominant protein found in seminal fluid. Its expression in PC is down-regulated in pts with metastatic disease and is believed to be a signal transduction inhibitor via multiple pathways in carcinogenesis. Recent data from a phase IIa trial in Great Britain demonstrated safety and suggested reduction in MMP-9 levels, an enzyme involved in angiogenesis, tumor invasion and metastasis. A phase I trial was performed to assess dosing and dosing schedule, pharmacokinetics, safety and impact on MMP-9 levels in pts with castrate metastatic PC who have failed multiple therapies including hormones and chemotherapy. Methods: Two cohorts of 10 pts received either 7.5 mg/m 2 twice weekly or 15 mg/m 2 weekly, respectively. Pts were treated for 4 weeks followed by a 2 week non-treatment period. Pts could receive addtional two-month cycles if PSAs and scans remained stable. MMP-9 levels, PSA, pharmacokinetics and imaging assessments were done at screening, and at weeks 2, 4 and 6. Results: Ten pts have been enrolled at each dose level. No adverse events were observed, however, declines in MMP-9 levels occurred in most pts by week #3 posttreatment. MMP-9 levels rose when drug was discontinued. Six pts were taken off study due to disease progression whereas 5 pts were discontinued due to rising PSAs. One pt at the 7.5 mg/m 2 biweekly dosing schedule received 4 additional cycles with stable PSAs and scans with a PSA doubling time which increased from 4 months pretreatment to 8 months posttreatment. Conclusions: PCK3145 was well-tolerated without toxicity. While early, the weekly dosing schedule appears to result in greater declines in MMP-9 levels and will likely be used in a forthcoming phase II trial in chemotherapy naive pts. [Table: see text]
Consultant who acted as loan shark must repay £525 000 or face jail term
Authors: Clare Dyer
Journal: BMJ (2017)

A hospital consultant who became a loan shark to nursing staff and other colleagues has been ordered to repay £525 000 (€600 000; $650 000) to his victims or face five years in jail.

Arjan Savani, 50, who worked in the emergency department at Central Middlesex and Northwick Park Hospitals in Harrow, northwest London, was sentenced last October to 10 months’ imprisonment, suspended for two years, and ordered to do 120 hours of unpaid work.

Prosecutors said that Savani, who had pleaded guilty at Harrow Crown Court to two counts of …
Neoadjuvant chemotherapy in “technically” inoperable locally advanced oesophageal (O) and gastro-oesophageal junction (GOJ) cancer
Authors: K. A. Cheong, K. Chrystal, M. Forshaw, J. Gossage, E. Galani, A. Botha, R. Mason, P. G. Harper
Journal: Journal of Clinical Oncology (2004)

4138 Background: Primary surgery results in a poor outcome for patients with locally advanced O and GOJ tumours who at staging have no distant metastases. For this group we routinely use 3 cycles of neoadjuvant ECF-based chemotherapy (Epirubicin:60mg/m2, Cisplatin:60mg/m2, 5FU 200mg/m2 CIVI q21). Following full restaging, surgical resection is offered if adequate clinical and radiological response. Methods We retrospectively reviewed the outcome of 236pts referred for consideration of surgery between Aug 1999- Jan 2003. Of these, 71 were considered initially inoperable, locally advanced with no distant metastasis. All patients commencing chemotherapy were included. Chemotherapy variations depended on comorbidities and renal function. Results: Median age: 62yrs, 86% males. Histology: adenocarcinoma 80%, squamous cell 20%. Tumour Location: GO junction 76%, oesophageal 24%. Stage at presentation: T3/T4N0 17%, T3/T4N1 58%, and T3/T4N1M1a 25%. Chemotherapy regimen: ECF 73%, ECSF 10%, ECarboF 10%, CF 7%. 85% of patients completed a minimum of 3 cycles of neoadjuvant chemotherapy. Grade 3/4 toxicities: neutropenia 34%, febrile neutropenia 8%, nausea/vomiting 8%, diarrhoea 5%, cardiovascular 5%, neuropathy 2%. The overall radiological response rate was 49% (7%CR and 42%PR) 36% SD and 15% PD. 42 pts (59%) proceeded to surgery. 5 were unresectable. 45% were pathologically downstaged with 4pts (9.5%) achieving a pCR. 18 pts had further adjuvant therapy (34% chemo, 7% chemoradiation, 2% radiation). Median F/U was 18mths (1–49) Median overall survival (mOS) for the whole group was 12.1 mth with 1yr and 2yr OS of 52% and 28% respectively. For the pts undergoing surgery the mOS was 23.8 mths and 1 and 2yr OS 69% and 45%. 8 pts are currently alive without disease at 3 years. Patients not proceeding to surgery had a mOS of 9.9 mths. Conclusions: Surgery following successful neoadjuvant chemotherapy for initially inoperable locally advanced O and GOJ cancer can produce encouraging survival rates. Prospective studies, including identification of prognostic and predictive factors for response to chemotherapy are required. No significant financial relationships to disclose.
Medical treatment consensus in unresectable midgut gastrointestinal neuroendocrine tumors.
Authors: Jonathan R. Strosberg, George A. Fisher, Al B. Benson, Jennifer L. Malin, Lowell Brian Anthony, Bulent Arslan, John F. Gibbs, Edward Greeno, Renuka V. Iyer, M. K. Kim, W. Maples, Philip Agop Philip, Edward M. Wolin, Dasha Cherepanov, Michael S. Broder
Journal: Journal of Clinical Oncology (2012)

e14610 Background: Neuroendocrine tumors (NETs) comprise mostly carcinoid or pancreatic NETs and are rare with symptoms that may be difficult to control. Current treatment guidelines lack some specificity. We summarize an expert panel consensus on medical treatment of well-differentiated unresectable midgut NETs. Methods: Consensus statements were developed via RAND/UCLA Delphi process, which involved a diverse group of physician experts (e.g., by specialty, geography, practice) developing comprehensive clinical patient scenarios and rating the scenarios on the appropriateness of various medical therapies before and after a face-to-face meeting. Experts and moderator were blinded to funding source. Scenarios were rated on a 1-9 scale and were labeled as appropriate, inappropriate, or uncertain. Scenarios with &gt;2 ratings in 1-3 and &gt;2 in 7-9 range were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists (age: 38-63 years) were from the northeast, midwest, south, and west regions. Specialties represented were medical and surgical oncology, interventional radiology, and gastroenterology. Panelists had practiced for a mean 15.5 years (range: 6-33). Panelists rated 202 scenarios. The proportion for which there was disagreement decreased from 11.7% (23 scenarios) before the meeting to 4.5% (9) after. Post-meeting, 49% (99 scenarios) were rated inappropriate, 29.7% (60) were uncertain, and 16.8% (34) were appropriate. Consensus statements from the scenarios included: 1) it is appropriate to use somatostatin analogs (SA) as 1 st -line therapy in all patients, 2) it is appropriate to increase the dose/frequency of octreotide-LAR as 2 nd -line therapy in patients with uncontrolled symptoms up to 60 mg every 4 weeks or up to 40 mg every 3 or 4 weeks for refractory carcinoid syndrome. Other treatment options may also be appropriate in 2 nd -line. Conclusions: Treatment consensus obtained in this study is concordant with NCCN recommendations. The Delphi process allowed quantification of ratings in a systematic and reliable way while improving consensus in a group of physicians on the appropriateness of medical therapies in midgut NETs.