tbuckley/cabot-search huggingface dataset:
Comparison of distress in patients with acute leukemia and advanced solid tumors.
Authors: G. Rodin, C. Lo, A. Rydall, A. Chan, J. Andrews, M. Minden, A. Schimmer, J. Brandwein, C. Zimmermann
Journal: Journal of Clinical Oncology (2010)

e19537 Background: Acute leukemia is a potentially fatal condition associated with considerable morbidity and mortality. However, the palliative care needs of leukemia patients are not well established. The present study was undertaken to compare physical and psychological distress in patients with acute leukemia to those with advanced solid tumors. Methods: In a longitudinal study of physical and psychological distress, 751 adults with metastatic gastrointestinal, lung, breast, ovarian and prostate cancer were recruited from outpatient oncology clinics at Princess Margaret Hospital (PMH), Toronto from Nov. 2002-Dec. 2008. In a subsequent similar study, 118 adults with acute myeloid, lymphocytic and promyelocytic leukemia, were recruited from hematology clinics and inpatient units at PMH. Common measures included: Beck Depression Inventory-II (BDI-II), Beck Hopelessness Scale (BHS), Memorial Symptom Assessment Scale, and Karnofsky Performance Status. The symptom profile in these two samples was compared controlling for age and gender. Results: Sample characteristics for Studies 1 and 2, respectively, were: mean age 61.6 vs. 51.0 years; 51% male vs. 61%; mean duration of illness 2.4 vs. 0.1 years; and % in active treatment at baseline 52% vs. 97.5%. Considerable physical distress was reported in both groups, with lack of energy (78% vs. 74%, p =.38) and nausea (30% vs. 42%, p =.06) common in both groups, respectively. Pain (53% vs. 44%, p<.005) was more common among solid tumor patients, while lack of appetite (55% vs. 29%, p<.0001) and weight loss (48% vs. 26%, p<.0001) were more common among leukemia patients. Clinically significant symptoms of depression (BDI-II≥15) and hopelessness (BHS≥8) were less common among leukemia patients (19.8% vs. 26.2%, p<.01, and 9.6% vs. 21.5%, p<.0001, respectively). Conclusions: Results suggest that acute leukemia patients report less psychological distress than solid tumor patients, despite a similar burden of physical distress. The shorter duration of illness and emphasis on curative treatment in the hematology setting may contribute to better psychological well-being in these patients, although longitudinal research is needed to determine whether such outcomes are sustained. No significant financial relationships to disclose.
Relative distribution of CD4+ naïve and memory T-cell subsets independently predicts course of disease in B-CLL
Authors: I. Tinhofer, R. Greil
Journal: Journal of Clinical Oncology (2005)

6587 Background: B-chronic lymphocytic leukemia (B-CLL) is characterized by clonal accumulation of B-cells. Since clonal B-cell expansion normally relies on T-cell help and this interaction might differ depending on the differentiation stage of T-cells, we hypothesized that the composition of the T-cell pool might interact with disease progression in B-CLL. Methods: Flow cytometric analysis of CD62L, a molecule involved in lymphocyte homing to secondary lymphoid organs and CD45RA was applied for determining relative distribution and absolute numbers of naive (Tnaive), central memory T-cells (TCM), effector memory T-cells (TEM) and effector T-cells (TEMRA) in peripheral blood of B-CLL patients (n=103) and healthy age- and sex-matched controls (n=67). The composition of the T-cell pool was correlated with clinical parameters such as stage, disease progression and time from diagnosis to first treatment. Furthermore, we evaluated potential interactions of the risk parameters CD38 and Zap-70 with the composition of the T-cell pool in patients. Results: A significant decrease in CD4+ Tnaive (p<.0001) and TCM cells (p<.0001) in favor of an increase in TEM (p<.0001) and TEMRA cells (p<.0015) was observed in the CD4+ T-cell pool whereas in the CD8+ T-cell pool, only a decrease of naive cells and a trend of increased relative numbers of TEM and TEMRA cells could be detected. The skewing of the CD4+ T-cell pool occured very early in clinical course since it was also observed when peripheral blood samples of patients at stage Rai 0–1 were compared with healthy controls (TEM: p=.0126; TEMRA: p=.0130) and importantly, it was significantly more pronounced in progressive as compared to stable patients. Univariate analysis identified the ratio of CD4+ Tnaive to TEM cells as risk parameter for a more aggressive disease (hazard ratio: 4.6, 95% CI 2.3–9.4, p<.0001), and it retained significance even when Rai stage, Zap-70 and CD38 expression profiles were included in multivariate analysis (hazard ratio: 3.2, 95% CI 1.1–9.8, p=.0413). Conclusions: As very recently demonstrated in follicular lymphoma for immune cells there is a also dominant influence of helper T-cells on the prognosis of B-CLL. No significant financial relationships to disclose.
Does the kinetic of tumor marker decline predict outcome in patients with relapsed disseminated germ-cell tumors treated by high-dose or conventional chemotherapy? An analysis of the IT94 randomized trial
Authors: C. Massard, A. Kramar, J. Pico, G. Rosti, R. Salvioni, H. Wandt, V. Koza, J. Droz, P. Biron, K. Fizazi
Journal: Journal of Clinical Oncology (2008)

5085 Background: Conventional dose chemotherapy is the standard salvage therapy for patients with progressive or relapsed germ-cell tumors (GCT). The IT94 phase III randomized trial compared conventional chemotherapy (4 cycles of cisplatin, ifosfamide, and vinblastine [VeIP]) with high-dose chemotherapy (3 cycles of VeIP followed by 1 cycle of high-dose carboplatin, etoposide, and cyclophosphamide [PEC]). Early serum tumor marker decline during chemotherapy was previously shown to predict survival in patients with poor prognosis disseminated non-seminomatous GCT in first line. The aim of this study was to assess whether serum tumor marker decline also correlates with outcome in the salvage setting. Methods: Serum tumor markers were obtained before chemotherapy and after two cycles of treatment from 235 patients accrued in the IT94 trial (114 and 121 in the 4VeIP and the 3 VeIP+PEC arms, respectively). The decline of serum alfa-fetoprotein (AFP) and human chorionic gonadotropin (hCG) was assessed and classified into the “favorable marker decline” and the “unfavorable marker decline” groups. Results: Serum AFP decline was significantly associated with PFS (HR=2.17; p=0.0003) while serum hCG decline did not affect the outcome. Among patients with a favorable AFP decline, those who were treated in the high-dose chemotherapy arm (95pts) had a better PFS (2-year PFS rate: 56% vs. 36%; HR=0.58; p=0.007), and a trend for a better OS (2-year OS rate: 70% vs. 56%; HR=0.69; p=0.11) compared with patients who were in the conventional chemotherapy arm (96pts). In contrast, among patients with an unfavorable AFP decline, those who received conventional chemotherapy (18 pts) had a better PFS (2-year PFS: 56% vs. 36%; HR=2.22; p=0.025) and a non-significant trend for a better OS (2-year OS: 54% vs. 21%; HR=2.43; p=0.34) compared with those who received high-dose chemotherapy (26 pts). Conclusions: AFP decline during the first 6 weeks of salvage chemotherapy predicts PFS in patients with disseminated GCT, and could identify two groups of patients. This prognostic factor could be used to better select salvage treatment in relapse germ cell tumor patients. No significant financial relationships to disclose.
Screening for Depression in Adults: U.S. Preventive Services Task Force Recommendation Statement
Journal: Annals of Internal Medicine (2009)

Description: Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for depression in adults. Methods: The USPSTF examined evidence on the benefits and harms of screening primary care patients for depression, including direct evidence that depression screening programs improve health outcomes. The USPSTF did not reexamine evidence for those key questions that had strong, consistent evidence in the 2002 review, including questions about the accuracy of screening instruments in identifying depressed adult patients in primary care settings, and the efficacy of treatment of depressed adults with antidepressants or psychotherapy. New areas of evidence considered for this review (and not reviewed in 2002) include efficacy of treatment of depression in older adult patients, harms of screening for depression in primary care settings, and adverse events from treatment of depression in adults. Recommendations: The USPSTF recommends screening adults for depression when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment, and follow-up. (Grade B recommendation) The USPSTF recommends against routinely screening adults for depression when staff-assisted depression care supports are not in place. There may be considerations that support screening for depression in an individual patient. (Grade C recommendation)
Early imaging and molecular response determinants in advanced pancreatic cancer.
Authors: H. R. Shah, D. Morgan, U. Manne, N. Jhala, A. Cantor, J. Posey
Journal: Journal of Clinical Oncology (2010)

e14636 Background: Pancreatic adenocarcinoma remains one of the most lethal human cancers. Standard chemotherapies have yielded sparse responses and corresponding median survival less than 12 months. Research focuses on novel therapies and more accurate predictors of response. After noting dramatic density changes in patients undergoing treatment with gemcitabine(GEM) and albumin-bound nanoparticle paclitaxel (NAB-PAC) for metastatic pancreatic cancer, we evaluated density measurement change on CT with three independent radiologists as an early predictor of response to therapy. Methods: 12 chemo-naive metastatic pancreas cancer patients at our center were treated on a clinical trial with GEM and NAB-PAC. Pts received NAB-PAC 125 mg/m2 along with GEM 1,000 mg/m2 IV weekly × 3 followed by a rest week (cycle) until disease progression or toxicity. Tumor response (RECIST) was evaluated every 4 weeks as part of the trial. Radiologists reread each patient's consecutive CT scans to account for density in Hounsfield units (HU) of the metastatic sites. The results were averaged to determine an overall change in enhancement at 4 and 8 weeks. Results: Patients received an average of 5.3 cycles (1-12). Five patients had a partial response by RECIST criteria. In metastases, the change in density (HU) at 1 month for responders was -4.42 versus 7.00 for nonresponders. At two months, the average change in metastatic site density in HU was -3.25 for responders versus 11.13 for nonresponders. The best response by RECIST criteria was noted at an average of 25 weeks (10-41). Responders had an average time to progression of 51 weeks as compared to 20 weeks for nonresponders. Arterial phase axial CT of the involved liver shows significant changes in tumor density for responders despite little change or slight increases in tumor area. Conclusions: GEM and NAB-PAC has anti-tumor activity via RECIST; however, we observed significantly earlier activity by change in metastatic tumor density which preceded best response by at least ten weeks. The alterations in metastatic site density were also an early predictor of clinical benefit i.e. improved time to progression. No significant financial relationships to disclose.
Panoramic Transesophageal Echocardiography in the Evaluation of Cardiac, Pericardial, Paracardiac, Aortic and Thoracic Abnormalities - Experience in 100 Patients
Authors: M. Kozàkovà, C Palombo, S. Schwartz, H Tsui-Lieh, A. Distante, N. Pandian
Journal: Journal of the American College of Cardiology (1993)
Tailor-made heart simulation predicts the effect of cardiac resynchronization therapy in a canine model of heart failure
Authors: Nirmal Panthee, Jun-ichi Okada, Takumi Washio, Youhei Mochizuki, Ryohei Suzuki, Hidekazu Koyama, Minoru Ono, Toshiaki Hisada, Seiryo Sugiura
Journal: Medical Image Analysis (2016)
Preoperative chemoradiation directed by primary site rebiopsy in stage III/IV squamous head and neck cancer is associated with high rate of local regional control, but is still plagued by long-term distant failure
Authors: H. J. Wanebo, P. Chougule, N. Ready, R. J. Koness, R. McRae, P. Nigri, K. Radie-Keane, R. Rathore, T. Kennedy
Journal: Journal of Clinical Oncology (2004)

5549 Background:Long term outcome was reviewed of two concurrent preoperative chemoradiation protocol studies for high staged (III/IV) head and neck (H&N) squamous cancer conducted by Brown University Oncology Group (BrUOG). Methods: Two consecutive chemo radiation protocols were done with Paclitaxel (P) (high dose 60mg/M2 in 38 H&N 53 pts or low dose P 40mg/M2 in 25 pts-H&N 67) combined with carboplatin 1 AUC and radiation with mandatory biopsy of primary site at 45Gy. If the biopsy was pathologically negative, completion chemoradiation 67–70 Gy was given to the primary site with subsequent neck dissection if indicated, otherwise surgical resection was done of the primary and neck. Results: In the total group of 67 patients from head and neck protocol H&N 53 (Stg III/ IV, 12/26) and H&N 67 ( Stg. III/IV, 9/15) complete pathologic response at the primary site was 66% and 77% respectively (75% overall). Residual disease in neck was 32%. The overall survival of 63 evaluable pts (>60 mo. follow-up) was 54%. There was no survival difference in pts requiring primary sitel resection vs. pts treated by chemoradiation alone. The long-term failure was 15% local, 5% regional and 22% at distant site. (shortest observation 6 yrs H&N 53 and 4.5 yr H&N 67). Of 22 recurrences, 14 (64%) were distant, 22% local and 15% were regional. New primarys developed in 4 pts (lung 2, esophagus 2). Results: See table. Conclusions: Preoperative chemoradiation with Stage III/IV H&N cancer directed by staged primary site biopsy is associated with high rate of tumor control of primary site by chemoradiation alone in >75% of patients and salvage surgery in the remaining pts with equivalent long term survival (>54%). Distant failure continues to be the major challenge. No significant financial relationships to disclose.
Modeling the growth dynamics of glioblastoma using magnetic resonance imaging
Authors: Chaitra Badve, Andrew E. Sloan
Journal: Neuro-Oncology (2015)

The significant intra- and intertumoral heterogeneity of gliomas, an improved appreciation for the biological differences among individual tumors, and the complexity of response assessment have led to increased interest in radiological modeling of glioma growth. The development of such models has been challenging due to the intra- and intertumoral heterogeneity of gliomas, as well as unique features of gliomas, including invasive growth, cellular migration, and differential tumor dispersion in gray and white matter.1,2 Tumor growth is determined by the complex interactions among proliferation, angiogenesis, and dispersion balanced by necrosis, apoptosis, and cell death. Three primary growth patterns have been proposed to explain tumor growth rates: the exponential pattern, radial linear pattern, and Gompertzian growth pattern (Fig. 1). The exponential growth model is based on the assumptions that tumors have a constant volume doubling time, and thus the size of the tumor increases exponentially with time. Conversely, the radial linear growth model assumes that the mean linear radius increases linearly with time. The Gompertzian model assumes initial exponential growth which then slows to linear growth as tumor volume increases before reaching a plateau. However, the clinical evidence to support one growth model over another in untreated tumors has been sparse.
Safety of front-line bevacizumab (BEV) combined with weekly paclitaxel (wPAC) and q3w carboplatin (C) for ovarian cancer (OC): Results from OCTAVIA.
Authors: Antonio Gonzalez-Martin, Laurence Gladieff, Bengt Tholander, Daniel Stroyakovsky, Martin Eric Gore, J.G.M. Segalla, An K.L Reyners, Nadezhda Kovalenko, Ana Oaknin, Frédéric Selle, David T. Bollag, Sandro Pignata
Journal: Journal of Clinical Oncology (2012)

5017^ Background: In two randomized phase III trials in OC (GOG218 and ICON7), front-line BEV + q3w PAC + q3w C followed by BEV alone significantly improved progression-free survival (PFS) vs chemotherapy (CT) alone. In the Japanese NOVEL trial, wPAC + q3w C was more effective than q3w PAC + C, but toxicity limited CT delivery. The single-arm OCTAVIA study evaluated front-line BEV + wPAC + q3w C. Methods: Patients (pts) received 6–8 cycles of BEV (7.5 mg/kg, d1) + wPAC (80 mg/m 2 d1, 8, 15) + C (AUC6, d1) iv q3w, with BEV q3w continued alone for a total of up to 17 cycles (1 y) as front-line therapy for newly diagnosed OC (FIGO stage I–IIa [grade 3/clear cell] or stage IIb–IV [any grade]). The trial was designed to recruit a pt population similar to that enrolled in ICON7. The primary endpoint was PFS. Secondary endpoints included response rate, duration of response, overall survival, biological progression-free interval, and safety. Previously we reported safety findings from the concurrent CT phase. Here we present final safety results from the entire treatment period. Results: Between Jun 2009 and Jun 2010, 189 eligible pts were enrolled. Baseline characteristics: median age 55 y (range 24–79 y); ECOG 0 74%; FIGO stage I/II/III/IV 10%/10%/63%/17%; serous/clear cell/mixed 65%/6%/6%; 71% optimally debulked. Pts received a median of 6 CT cycles (range 1–8) and 17 BEV cycles (range 0–18). Of the 168 pts who received single-agent BEV, 135 completed 1 y of therapy. In the entire treatment period, BEV was discontinued for adverse events (AEs) in 12% and disease progression (PD) in 10%. The most common grade ≥3 hematologic AEs were neutropenia (60%), anemia (8%), and thrombocytopenia (7%). The incidences of grade ≥3 AEs of special interest for BEV were: hypertension 4.2% (grade 2/3/4: 9.0%/3.2%/1.1%); thromboembolic events 6.3% (grade 3/4: 3.7%/2.6%); bleeding 0.5% (grade 3), wound-healing complications 0.5% (grade 3), and GI perforation 0.5% (grade 4). There was no grade ≥3 proteinuria or fistula/abscess. At the time of data cut-off, 9 pts had died, all from PD. Conclusions: BEV combined with wPAC is feasible and well tolerated. BEV AEs were no more frequent with wPAC in OCTAVIA than with q3w PAC in ICON7.
A randomized phase II study of two different schedules of RAD001C in patients with recurrent/metastatic breast cancer
Authors: S. Ellard, K. A. Gelmon, S. Chia, M. Clemons, H. Kennecke, B. Norris, L. McIntosh, L. Seymour
Journal: Journal of Clinical Oncology (2007)

3513 Background: RAD001C exerts antiproliferative and antiangiogenic effects by mTOR (mammalian target of rapamycin) inhibition. mTOR is critical in the transduction of proliferative signals mediated via the PI3K/Akt pathway. This signal transduction pathway is relevant to HER2 and ER signaling, and in PTEN mutated tumors, thus mTOR may be a central and relevant factor in breast cancer. Methods: Multi-center randomized phase II study assessing two oral schedules of RAD001C: Arm A (A)_10 mg daily, or Arm B (B)_70 mg weekly, assessed clinically each 4 weeks, imaged each 8 weeks. Eligibility: Patients (pts) with measurable metastatic breast cancer (MBC) who may have received adjuvant chemotherapy (CT), with up to one prior CT for advanced/recurrent disease. Stratification factors: 0 or 1 prior CT for MBC; presence/absence of visceral metastases. Primary endpoint: clinical/radiologic response and early progression (&lt;8 wks). Two-stage accrual design with 15 evaluable pts in each arm in first phase. If =1 response and &lt;10 early PD, add 15 pts. Arm B was discontinued after stage 1 as no responses were seen. A higher than expected occurrence of pneumonitis (Pn) occurred in both arms, higher in arm A. Results: Median age was 60yrs, 32 pts had prior CT, 20 pts had liver metastases. The most common drug related toxicities were fatigue, rash, anorexia, diarrhea, stomatitis, cough and pneumonitis; pulmonary effects appeared schedule related. (See results table below) Conclusions: Daily oral RAD001C has activity in MBC. The final results of this randomized Phase II trial will provide data to plan future breast cancer trials of RAD001C. [Table: see text] [Table: see text]
Daily RAD001 plus mitomycin C, every three weeks in previously treated patients with advanced gastric cancer or cancer of the esophagogastric junction: Preliminary results of a phase I study.
Authors: C. Pauligk, S. Janowski, K. Steinmetz, A. Atmaca, A. Pustowka, E. Jaeger, S. Al-Batran
Journal: Journal of Clinical Oncology (2010)

e14531 Background: The mTOR pathway could be a potential target in the treatment of gastric cancer. This study was designed to determine the maximum-tolerated-dose and preliminary safety and efficacy of the mTOR inhibitor RAD001 in combination with mitomycin C in patients with previously treated advanced gastric cancer. Methods: In this dose-escalation phase I trial, patients received mitomycin C at 5 mg/m2 i.v. every 3 weeks combined with escalated doses of oral RAD001 (starting with 5 mg/day) once daily in 3-week cycles. Patients were investigated for safety every week and for efficacy every 6 weeks. Results: 15 patients (11 male, 4 female) have been included. All patients were pretreated with a platinum-based chemotherapy, and 11/15 had also received docetaxel. Treatment cohorts were: 5 mg/day, 3 patients; 7.5 mg/day, 3 patients; and 10 mg/day, 9 patients. Median treatment duration was 49 days (range, 11 to 320 days). There were no dose limiting toxicities, until dose escalation of RAD001 was stopped at the 10 mg/day dose. Grade 3-4 toxicity observed were leukopenia in 15,4% of patients, mucositis, neutropenia, lymphopenia and bilirubin (7,7% each). Frequent grade 1-2 toxicities with possible relationship were mucositis 61%, thrombocytopenia 54%, nausea 54%, leukopenia 46%, fatigue 31%, and diarrhea 23%. Only mucositis and leukopenia were associated with higher dose levels. Thrombopenia was not severe but caused frequent treatment interruptions in patients receiving more than two cycles. At the time of analysis, three (23.1%) of 13 evaluable patients experienced a major response (partial response). Three patients had stable disease, two patients were not evaluable for efficacy analysis, and the rest of the patients had disease progression. Responses were independently confirmed. Conclusions: Oral RAD001 up to 10 mg once daily can be safely combined with mitomycin C at 5 mg/m2 every 3 weeks in previously treated patients with advanced gastric cancer. The achievement of major responses with the combination in this heavily pretreated population is encouraging. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis