tbuckley/cabot-search huggingface dataset:
The effect of observation units in cancer care on hospital admissions.
Authors: Adam Klotz, Steven Martin, Coral L Atoria, Allison Nicole Lipitz Snyderman, Jeffrey S. Groeger
Journal: Journal of Clinical Oncology (2014)

e17633 Background: Reducing unnecessary hospital admissions has the potential to improve patient outcomes, reduce costs, and maximize limited resources. ‘Observation care’ provides an alternative to hospitalization for patients who do not meet admission criteria upon initial evaluation. It is intended to be used for additional monitoring to determine whether a hospital admission is required. For cancer patients, the impact of observation care on hospital utilization is not well understood but can have implications for patient care and payment policies. At Memorial Sloan Kettering Cancer Center (MSKCC), an urgent care observation unit (OU) was introduced in July 2013. Our objective was to assess the impact of observation care on hospital utilization for cancer patients. Methods: In this retrospective study, we assessed the proportion of hospital admissions for patients presenting to the Urgent Care Center (UCC) (MSK’s emergency room) for two six-month intervals: before OU implementation (7/9/12-12/31/12) and after (7/9/13-12/31/13). Clinical information about patients placed in this unit including oncologic history, presenting complaint, interventions performed, and hospital course were also noted. Results: During the interval prior to OU implementation, the proportion of hospital admissions from the UCC was 57% (5,822 admissions / 10,253 UCC visits). After OU implementation, 50% of visits to the UCC resulted in either direct admission to the hospital or admission from the OU (5,277 admissions / 10,592 UCC visits). The proportion of admissions with a length of stay less than 24 hours dropped after OU implementation (2.4% to 1.1%). There were 1,013 visits to the OU during this interval (10% of the total UCC visits). Of visits to the OU, 374 (37%) required admission to the hospital and 618 (61%) resulted in discharge to home. The most common reasons for OU placement include fluid and electrolyte disorders (14%), pain control (14%), and dyspnea (13%). Conclusions: Observation care was associated with an overall decrease in the proportion of hospital admissions from the UCC. Short-term care in an Observation Unit can provide a viable alternative to hospital admission for specific clinical syndromes in cancer patients.
Phase II study of rituximab and cladribine (2-CDA) in newly diagnosed mantle cell lymphoma (MCL) (N0189)
Authors: D. J. Inwards, D. W. Hillman, P. A. Fishkin, W. L. White, R. F. Morton, S. R. Dakhil, D. A. Nikcevich, D. B. Wender, T. R. Fitch, P. J. Kurtin
Journal: Journal of Clinical Oncology (2006)

17505 Background: A previous trial of 2-CDA as a single agent for therapy of mantle cell lymphoma demonstrated this agent to be efficacious with an overall response rate of 81% (31% complete responses) (Blood 1999 Nov 15; 94:660a). A phase II study of the addition of rituximab to 2-CDA was conducted by the North Central Cancer Treatment Group based on improved outcomes achieved by the addition of rituximab to other regimens active in MCL. Methods: This one-stage phase II study was designed to determine the complete response (CR) or complete response/unconfirmed (CRu) rate. Central pathology confirmation of cyclin D1 positive mantle cell lymphoma was required. No previous therapy for lymphoma was allowed, with the exception of splenectomy. The shedule was rituximab 375 mg/m 2 IV day 1; 2-CDA 5 mg/m 2 /d IV days 1–5 of a 4-week cycle. After 2 of the first 6 patients developed grade 4 neutropenia, subsequent patients received either pegfilgrastim or filgrastim support. Patients received 2–6 cycles of therapy, depending on response. Patients were required to achieve at least a PR after 2 cycles of therapy to continue on protocol therapy. Results: Patient characteristics of all 29 eligible pts: median age: 70 (range: 41–86); 21 male, 8 female; PS 0 (55.2%), PS 1 (41.4%), PS 2 (3.5%); stage II (6.9%), stage III (3.5%), stage IV (89.7%); prior splenectomy (20.7%). The only grade 4 adverse event occurring more than once was neutropenia (20.7%). One patient died of cerebral ischemia in the setting of pneumonia without neutropenia. Response has been determined in 26 pts with 50.0% (95% CI: 30.0–70.0%) achieving a CR, none of whom have relapsed to date. Three patients progressed early at 17, 45, and 46 days, two of whom have died, and a fourth relapsed day 222. 10 pts (34.0%) went on to receive further therapy off study, 5 in less than a PR after 2 cycles, 2 in PR after study therapy, and 1 who went off study for a rash. At last contact, 26 (89.7%) were alive (median follow-up 10.7 months; range: 1–28). Conclusions: Rituximab and cladribine were well tolerated for the treatment of MCL in a group including elderly patients. The response rate may have been underestimated due to the study design, which required at least a PR after 2 cycles to continue therapy. Despite this, 50% achieved a complete remission. [Table: see text]
CA19-9-low and Lewis(+) pancreatic cancer: A unique subtype.
Authors: Guopei Luo, Xian Jun Yu
Journal: Journal of Clinical Oncology (2017)

339 Background: Pancreatic cancer is a lethal malignancy and patients often survive within one year. CA19-9 is the most important biomarker for pancreatic cancer and Lewis (-) individuals have no or scarce CA19-9 secretion. We have met several patients with low CA19-9 and metastatic disease survived over one year without major treatments, prompted us to examine the characteristics of CA19-9-Low subgroup (Lewis (+)&amp;CA19-9 ≤ 37 U/mL). Methods: Medical record of 1484 patients was retrieved from a prospectively maintained database. Lewis genotypes were determined by Sanger sequencing. Characteristics of CA19-9-Low pancreatic cancers were examined. Results: No significant difference was found between Lewis (-) (8.4%) and CA19-9-High (77.8%) patients in survival (HR = 1.16, P = 0.216). CA19-9-Low patients (13.8%) had strikingly better survival than CA19-9-High&amp;Lewis (-) patients (HR = 0.52, P &lt; 0.001). The 5-year survival rate of stage III, IV CA19-9-Low patients (28.2%) was even higher than that of stage I, II CA19-9-High&amp;Lewis (-) patients (21.5%). Compared with CA19-9-High&amp;Lewis (-) patients, CA19-9-Low patients had a lower proportion of nerve invasion (74.7% vs. 84.2%, P = 0.044), EGFR expression (37.5% vs. 51.2%, P = 0.047), a lower level of serum glucose (6.3 ± 1.9 vs. 7.4 ± 3.1, P = 0.001) and neutrophil-lymphocyte ratio (2.6 ± 2.4 vs.3.0 ± 3.1, P = 0.027), and poor response to Gemcitabine-based chemotherapy (stage I, II, HR = 0.73, P = 0.446; stage III, IV, HR = 0.70, P = 0.244). Conclusions: CA19-9-Low pancreatic cancer is a unique subtype with poor response to Gemcitabine-based chemotherapy.
Efficacy and safety of radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases who did or did not receive prior docetaxel (D) in the phase III ALSYMPCA trial.
Authors: Nicholas J. Vogelzang, Svein Inge Helle, Dag Clement Johannessen, Joe M. O'Sullivan, Jose E. Garcia-Vargas, C. Gillies O'Bryan-Tear, Minghua Shan, Chris Parker
Journal: Journal of Clinical Oncology (2013)

5068 Background: Ra-223, a first-in-class α-emitter, significantly improved median overall survival (OS) by 3.6 mo vs placebo (Pbo) in CRPC patients (pts) with bone metastases (mets) receiving best standard of care (BSoC) in the ALSYMPCA study (HR = 0.695; 95% CI, 0.581-0.832; p = 0.00007), and had a highly favorable safety profile in the updated ALSYMPCA analysis (Parker et al. ASCO 2012). This predefined subgroup analysis assessed efficacy and safety of Ra-223 in pts who did or did not receive prior D (pD). Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets; had no known visceral mets; were receiving BSoC; and had received pD, or were unfit for or declined D (npD). Pts were randomized 2:1 to 6 injections of Ra-223 (50 kBq/kg IV) q4wk or matching Pbo and stratified by prior D use, baseline alkaline phosphatase level, and current bisphosphonate use. Survival data were compared using a log-rank test. Results: 395/921 (43%) randomized pts had npD (Ra-223, n = 262; Pbo, n = 133); 526/921 (57%) received pD (Ra-223, n = 352; Pbo, n = 174). Median ages were 74 y (npD) and 69 y (pD). In pts with npD, median OS was 16.1 mo in the Ra-223 group vs 11.5 mo in the Pbo group (HR = 0.745; 95% CI, 0.562-0.987; p = 0.039). In pts with pD, median OS was 14.4 mo vs 11.3 mo in the Ra-223 and Pbo groups, respectively (HR = 0.710; 95% CI, 0.565-0.891; p = 0.003). Overall, there was a low incidence of myelosuppression. Incidences of neutropenia and thrombocytopenia were higher in pts with pD vs pts with npD. Conclusions: Ra-223 significantly prolonged OS and had a highly favorable safety profile in CRPC pts with bone mets, regardless of whether they had pD or npD. pD pts had a slightly increased rate of grade 3 and 4 bone marrow suppression with Ra-223. Clinical trial information: NCT00699751. [Table: see text]
A multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma.
Authors: Daniel Peter Petrylak, Hendrik-Tobias Arkenau, Jose Luis Perez-Gracia, Matthew Krebs, Rafael Santana-Davila, Jing Yang, Jessicca Rege, Gu Mi, David Ferry, Roy S. Herbst
Journal: Journal of Clinical Oncology (2017)

349 Background: Hallmarks of tumor growth include immunosuppression and angiogenesis. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the urothelial tumor microenvironment. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02443324) enrolled patients (pts) with histologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with prior progression on platinum-based systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. Eligible pts received R at 10 mg/kg on Day 1 given with P 200 mg on Day 1 q3W. PD-L1 was classified as positive (≥1%) or negative using the DAKO PD-L1 22C3 IHC pharmDx assay. Tumor response was assessed every 6 wks (RECIST v1.1). The primary objective was to assess safety and tolerability of adding R to P and preliminary efficacy will be assessed as a secondary objective. Results: As of 23-June-2016, 24 pts have been treated. The median age was 63 years, 58% were male, 50% had ECOG PS 0, 50% were PD-L1 positive and 67% received study treatment as third or subsequent regimen. Median duration of treatment was 2.14 mo and 2.37 mo for R and P, respectively. All grades treatment-related AEs (TRAE) occurred in 13 (54%) pts; TRAEs occurring in ≥10% of pts were fatigue (21%), nausea (17%), pyrexia (13%), elevated alanine aminotransferase (13%) and elevated aspartate aminotransferase (13%). Three (13%) pts had grade 3 TRAEs (hypertension, colitis, pulmonary embolism; n=1 each). No treatment-related grade 4 or 5 events occurred. Preliminary efficacy data showed two (8%) PD-L1 positive pts had confirmed partial response, 10 (42%) pts had stable disease, and 10 (42%) had progressive disease as their best response. Two (8%) pts were not evaluable for response at the time of analysis. Median duration of response has not been reached (&gt;2.92 mo). Median PFS was 1.87 mo (95% CI, 1.28 to 3.38). Five (21%) pts remain on treatment. Conclusions: R plus P generated no new safety signals and demonstrated antitumor activity in pts with previously treated advanced urothelial carcinoma. Clinical trial information: NCT02443324.
A phase I/II trial of BAY 43–9006 and gemcitabine in advanced solid tumors and in advanced pancreatic cancer
Authors: L. L. Siu, C. H. Takimoto, A. Awada, M. J. Moore, M. Piccart, M. Poulin-Costello, C. Lathia, O. Petrenciuc
Journal: Journal of Clinical Oncology (2004)

3059 Background: With its potent inhibitory effects against Raf-1 kinase and VEGFR-2, BAY 43–9006 (BAY) is a novel oral anticancer agent targeting signal transduction and angiogenic pathways. This study is designed to combine BAY and gemcitabine (GEM) due to their compatibility in preclinical models and non-overlapping clinical toxicities. Methods: An initial dose-escalating phase enrolled patients (pts) with advanced solid tumors, followed by an extended phase at the recommended dose (RD) for pts with advanced unresectable or metastatic pancreatic cancer. BAY is administered continuously while GEM is given at 1000 mg/m2 weekly x 7 followed by 1 rest week, then weekly x 3 every 4 weeks. Results: Forty-two pts have been enrolled with the following demographics: M:F ratio = 26:16; median age = 61 (range 39–83); ECOG 0:1:2:missing ratio = 17:19:5:1. Nineteen of the 42 pts were enrolled in the dose-escalating phase, the majority had ovarian (6 pts) or colorectal (5 pts) primaries, and 16/19 pts have had prior chemotherapy. In the extended phase, 23 pts with pancreatic cancer were enrolled, and all but 1 pt were chemonaive. The RD of this combination is BAY 400 mg BID and GEM 1000 mg/m2. Preliminary analyses of Gr ≥ 3 toxicities are summarized below. Gr 1/2 rises in transaminases, hematological toxicity, fatigue, hand-foot skin reaction and rash were common, but were clinically tolerable. Antitumor activity has been observed: 2 confirmed PR (ovarian cancer), and 12 SD, among which 2 pts remained on study for >1 yr in the dose-escalating phase; 1 unconfirmed PR and 11 SD in the pancreatic cohort. Pharmacokinetic data showed a lack of interaction between BAY and GEM. Conclusions: BAY and GEM appear well tolerated in combination, and further evaluations of this combination in pancreatic and ovarian cancers are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Inc.
A Multicenter Phase II Study Using a Dose Intensified Pediatric Regimen in Adults with Untreated Acute Lymphoblastic Leukemia.
Authors: Daniel J. DeAngelo, Suzanne Dahlberg, Lewis B. Silverman, Stephen Couban, Philip C. Amrein, Matthew D. Seftel, A. Robert Turner, Brian Leber, Kang Howsan-Jan, Martha Wadleigh, L. Andres Sirulnik, Jeffrey Supko, Ilene Galinsky, Stephen E. Sallan, Richard M. Stone
Journal: Blood (2007)
Second autologous stem cell transplantation as a strategy for management of relapsed multiple myeloma.
Authors: Wilson I. Gonsalves, Shaji Kumar, Martha Lacy, Angela Dispenzieri, Suzanne R. Hayman, Francis Buadi, David Dingli, William J. Hogan, Morie A. Gertz
Journal: Journal of Clinical Oncology (2012)

8092 Background: High dose therapy and autologous stem cell transplant (SCT) remain an integral part of the treatment of multiple myeloma (MM). Despite the introduction of several new drugs, disease relapse remains inevitable and a second SCT often allows continued disease control. Methods: We examined the outcomes in 105 patients (pts) undergoing a second SCT (SCT2) for relapsed MM, from among 1033 pts receiving initial transplant between 1994 and 2009. Patients receiving an allogeneic SCT post SCT2 were not included in the survival analysis. Results: Median (range) age at SCT2 was 60 yrs (35-74) and the time between SCTs was 46 mos (10-130). The median follow-up was 5 yrs from SCT2. The median (range) number of regimens between the two SCTs and from diagnosis was 2 (0-7) and 3 (1-11), respectively. Conditioning regimen was Mel 200 in 85 (81%) pts. Median (range) CD34 cells infused was 4.6 (2.5-25 million/kg). Hospitalization was required for 53 pts (50%), median hospital stay was 7 days.. Median time to ANC of 500 and platelets of 50,000 were 13 and 16 days, respectively. Treatment related mortality was seen in 5 (5%) pts. A partial response or better was seen in 95 (90%) pts, including a stringent CR in 10%, CR in 19%, and VGPR in 21%. Stable disease or progression was seen in 7 pts and 3 pts died prior to disease assessment. The median (95% CI) PFS and OS after SCT2 were 10.4 (8, 14) and 33 (28, 51) mos, respectively. The median OS was not reached and 33 mos respectively, for those obtained a CR and those with &lt;CR, P=0.03. FISH pre-SCT2 was available for 73 pts; the PFS and OS were not affected by the presence of high-risk MM. In multivariate analyses, shorter duration of response to SCT1, higher plasma cell (PC) labeling index at SCT2, more regimens used prior to SCT2 all predicted shorter PFS and OS post SCT2. Lack of CR to SCT2 was also significantly associated with shorter PFS. Conclusions: Second SCT is an effective therapy for eligible pts relapsing after other treatments. It provides a meaningful duration of response and appears to be well tolerated. Pts with longer duration of response to first transplant and those achieving a CR appear to have maximum benefit.
Expression of mEGFR, pEGFR<sup>Thr654</sup>, and pPKN1<sup>Thr774</sup> to predict response to chemoradiation and prognosis in patients with cervical cancer.
Authors: Jin Yi Lang, Jianming Huang, Xin Lai
Journal: Journal of Clinical Oncology (2013)

e16531 Background: The aim of this study was to determine the relation between proteins involved in phosphorylation of EGFR Thr654 and response to chemoradiation and survival in a well-documented series of cervical cancer patients. Methods: Pre-treatment tissue samples of 90 consecutive FIGO stage IIA-IIIB cervical cancer patients treated with concurrent chemoradiotherapy between January 2007 and December 2009 were collected. Clinicopathologic and follow-up data were collected by a retrospective chart review. Protein expression of membranous EGFR (mEGFR), pEGFR Thr654 and pPKN1 Thr774 were examined by immunohistochemistry on FFPE tumor specimens. The correlations between protein expression and clinicopathological factors and outcomes were analyzed. Results: mEGFR staining was present in 67.78%, pEGFR Thr654 in 91.11%, pPKN1Thr774 in 56.67% of tumors. pEGFR Thr654 staining was positively correlated to pPKN1 Thr774 (p = 0.04) and to mEGFR staining (p = 0.015). In multivariate analysis, nuclear staining of pEGFR Thr654 [hazard ratio(HR)= 4.833; 95%CI=1.959-11.922, P=0.001)] and cytoplasmic staining of pPKN1 Thr774 (HR=3.095; 95%CI=1.019-9.406; P=0.046) were prognostic factors for poor overall survival (OS) and also were independent predictors of poor response to (chemo)radiation for progress-free survival (PFS) (HR=2.921, 95%CI=1.360-6.274, P=0.006; HR=2.963, 95% CI=1.187-7.394, P=0.020), and mEGFR staining was an independent prognostic factor for poor PFS (HR=5.934, 95% CI=1.378-25.555, p=0.017). The high expression of pEGFR thr654 is related to poor local control rate (p = 0.000) and to poor short-term efficacy (p = 0.009). Conclusions: mEGFR and pEGFR Thr654 immunostaining are frequently observed and independently associated with poor response to therapy and poor PFS and OS in cervical cancer patients primarily treated by concurrent chemoradiotherapy. Our data presents the pEGFR Thr654 nuclear translocation as a promising target in Integrated therapies of chemoradiotherapy combined with targeting inhibition of pEGFR Thr654 and its nuclear import for cervical cancer.
SWOG S0421: Phase III study of docetaxel (D) and atrasentan (A) versus docetaxel and placebo (P) for men with advanced castrate resistant prostate cancer (CRPC).
Authors: David I. Quinn, Catherine M. Tangen, Maha Hussain, Primo Lara, Amir Goldkorn, Mark Garzotto, Philip C. Mack, Michael Anthony Carducci, J. P. Monk, Przemyslaw Twardowski, Peter J. Van Veldhuizen, Neeraj Agarwal, Celestia S. Higano, Nicholas J. Vogelzang, Ian Murchie Thompson
Journal: Journal of Clinical Oncology (2012)

4511 Background: The endothelin pathway has a mechanistic role in bone metastases (mets). Atrasentan (A), an endothelin receptor antagonist, has reported activity in CRPC. This trial tested the survival impact of A + docetaxel (D) vs. D+ placebo (P) in CRPC pts with bone mets. Methods: Eligible CRPC pts, stratified for progression type, baseline pain index (BPI), extraskeletal mets and bisphosphonate (BisP) use, were randomized 1:1 to D+A vs. D+P for 12 3-wk cycles. Non-progressors could continue blinded drug alone for 16 more wks. Co-primary endpoints: overall (OS) and progression-free survival (PFS). 930 pts were needed to detect a 25% increase in med OS with D+A (1-sided log-rank, α=0.025, 87% power). Results: 991/1,038 pts were eligible: med age 69, 16% non-white, 61% on BisP, 31% prior prostatectomy, 42% worst pain by BPI ≥ 4, 20% PSA only progression and 56% extraskeletal mets. Multivariate analysis of baseline prognostic factors predicting worse OS were: measurable or evaluable disease progression, high BPI and extraskeletal mets (all p&lt;0.02). No differences in median OS, PFS, or response between arms. Toxicities were similar between arms. Most common toxicities were fatigue, dyspnea, neutropenia and anemia. Addition of A trended to worse OS in pts with visceral mets (HR=1.13 p=0.21) and better OS in those without: bone only (HR=0.86, p=0.20). 357 pts continued A or P up to 52 weeks, no OS difference was seen post-chemo for this subset (p=0.92). Conclusions: This phase III study found no benefit for the addition of A to D in CRPC. Unless specific biomarkers can stratify a population for benefit, endothelin modulators have limited future use in advanced CRPC. Further analyses will test putative surrogacy effects of PSA, serum bone markers and circulating tumor cell kinetics for OS. [Table: see text]
QTWIST analysis in the RECOURSE trial.
Authors: Josep Tabernero, Eric Van Cutsem, Atsushi Ohtsu, Nadia Amellal, Stéphanie Cadour, Ronan Fougeray, Benjamin Haffemeyer, Robert J. Mayer
Journal: Journal of Clinical Oncology (2017)

698 Background: RECOURSE showed that treatment with trifluridine/tipiracil in patients in patients (pts) with refractory metastatic colorectal cancer was associated with significantly improved survival vs placebo. As quality of life (QoL) was not captured in the trial, other methods were used to evaluate potential impact on QoL. Methods: We used the QTWIST method, i.e. quality-adjusted TWIST (time without symptoms of disease or toxicity), to explore survival adjusted for QoL with trifluridine/tipiracil vs placebo in the RECOURSE population. QTWIST incorporates a trade-off between time spent with treatment-related adverse events versus improvement in progression-free survival, and combines an estimate of the mean duration of each health state (TOX, TWIST, and RELAPSE [REL]), weighted by a utility coefficient, into a global QTWIST score. TOX represents time with grade 3/4 treatment-related adverse events that are expected to impact QoL (i.e. nausea, vomiting, diarrhea, fatigue/asthenia, anorexia, febrile neutropenia) before progression, TWIST represents time without symptoms or toxicity; and REL represents time from progression (as defined in the RECOURSE trial) until death. We applied a utility coefficient of 1 for TWIST and values of 0.5 for TOX and REL. A sensitivity analysis varied the utility coefficients for TOX and REL from 0 to 1. Results: 798 pts (533 trifluridine/tipiracil vs 265 placebo) were included with median follow-up time of 11.8 mo. The between-group difference in the global QTWIST score was 1.5 mo (95% CI, 1.49–1.52) in favor of trifluridine/tipiracil. Using varying utility coefficients for TOX and REL from 0 to 1 as a sensitivity analysis, the between-group difference in the global QTWIST score ranged from 1.3 to 1.7 mo, always in favor of trifluridine/tipiracil. Conclusions: The median overall survival benefit observed with trifluridine/tipiracil vs placebo in RECOURSE was 1.8 months. Consistently, patients' QoL as evaluated by QTWIST showed that quality-adjusted survival with Lonsurf is significantly improved by 1.5 months vs placebo. Clinical trial information: NCT01607957. [Table: see text]