tbuckley/cabot-search huggingface dataset:
High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study.
Authors: Y Ravindranath, C P Steuber, J Krischer, C I Civin, J Ducore, R Vega, P Pitel, S Inoue, E Bleher, C Sexauer
Journal: Journal of Clinical Oncology (1991)

In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4) followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%] v 34% [SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/microL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children greater than or equal to 2 years and those with WBCs greater than or equal to 100,000/microL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.
A novel mode of antitumor activity for imatinib mesylate: Consequences for the design of surrogate markers of efficacy and combination therapies
Authors: L. Zitvogel, F. Ghiringhelli, M. Terme, C. Borg, N. Chaput, C. Ménard, A. Lecesne, J. Fletcher, M. C. Heinrich, T. Tursz, J. Taieb
Journal: Journal of Clinical Oncology (2005)

2516 We have recently reported that STI571 has not only a tumor cell autonomous effect but also acts on host dendritic cells (DC) to promote natural killer (NK) cell activation and NK cell-dependent antitumor effects in mice. Moreover, about 50% of gastrointestinal stromal tumor (GIST) bearing patients undergoing therapy with STI571 acquire NK cell activation correlating with clinical outcome. The study of the Time To Progression (TTP) for 43 patients that benefited from a median follow up of 13.2 months in both cohorts of GIST, those exhibited enhanced NK cell functions (22/43) at 2 months of Gleevec versus those who did not (21/43) revealed that TTP is significantly longer in patients with NK cell activation (Log Rank Test, p=0.03). The potential associated prognostic factors: type of c-kit mutation, extra-gastric primary tumor, haemoglobin level < 7 g/dL, performance status over 2 and pulmonary metastases at entry, were all comparable in these two cohorts. The lack of STI571-mediated NK cell induction found in the other 50% of cases could be assigned to the presence of high numbers of CD4+CD25highregulatory T cells (Treg) in blood at entry, which were shown, by us, to inhibit NK cell effector functions in human ex-vivo and in-vitro. The mean percentages of Treg among CD3+CD4+ T cells in GIST patients displaying NK cell induction were not elevated as compared with normal volunteers (1.1% ± 0.3% vs 1.2% ± 0.4%, respectively, p = 0.5) whereas these yields were increased by three fold in the group of patients with no NK cell induction (3.2% ± 0.8%, p = 0.02). We finally found that the combination of immunopotentiating dosages of cyclophosphamide, aimed at reducing Treg function, with STI571 was synergistic in a mouse (C57BL/6) model of lung melanoma (B16F10 cells) metastases. Altogether, NK cell activation is a novel surrogate marker of efficacy of STI571 which is critical for TTP and could be enhanced by pre-treatment of GIST patients with Treg inhibitors. No significant financial relationships to disclose.
Correlation of the intra-tumor phospholipid-related signatures determined noninvasively by phosphorus and hydrogen MR spectroscopy: An approach to increase the sensitivity and applicability of the technique to predict therapeutic outcome in non-Hodgkin's lymphoma.
Authors: F. Arias-Mendoza, F. Howe, J. R. Griffiths, J. D. Glickson, O. O'Connor, J. A. Koutcher, M. O. Leach, A. Heerschap, T. R. Brown
Journal: Journal of Clinical Oncology (2010)

8070 Background: We have previously reported that a lower pretreatment tumor value of the phospholipid-related intermediates phosphoethanolamine plus phosphocholine normalized to nucleoside triphosphates (PME/NTP ratio) determined by 31P MRS predicts complete long-term response to treatment in non-Hodgkin's lymphomas (NHL), especially in diffuse large B-cell lymphoma patients (DLBCL) undergoing anthracycline-based combination chemotherapy. However, our results have been hindered by the inherent lack of sensitivity of 31P MRS. The aim of the present work is to increase the sensitivity and applicability of the prediction of therapeutic outcome in NHL patients using MRS by including the measurement of the intratumoral total choline normalized to water determined by 1H MRS, which is more sensitive than 31P MRS and increases the acquisition time by only ten minutes. Methods: Localized 1H-decoupled, nuclear Overhauser enhanced, 31P MRS using the 3D chemical shift imaging algorithm and a water-suppressed/not-water-suppressed pair of PRESS single voxel 1H MR spectra using a TE of 135 ms were acquired in vivo from the tumors of eight NHL patients prior to start treatment, and the intratumoral PME/NTP and tCho/H2O ratios determined from the 31P and 1H spectra respectively. Results: The correlation of the PME/NTP vs. the tCho/H2O ratios determined on each of the NHL patients prior to receive treatment showed a statistically significant linear regression (y = 0.16x - 0.77, r2 = 0.7, p < 0.005). Conclusions: The correlation between the ratios PME/NTP and tCho/H2O suggests that prediction of treatment outcome may also be possible using the tCho/H2O ratio determined by 1H MRS. This will enable us to study NHL tumors with volumes as small as 1 milliliter, based on the increased sensitivity of the MR observations of 1H in comparison to those of 31P. In addition the simultaneous determination of in vivo 31P and 1H MRS could provide additional information to carry out a more adequate evaluation of the NHL patient undergoing treatment. No significant financial relationships to disclose.
A randomized, open-label, phase II study of afatinib versus cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Analysis of stage 2 (S2) following crossover.
Authors: Didier Cupissol, Tanguy Y. Seiwert, Jérôme Fayette, Eva Ehrnrooth, Alice Sarah Blackman, Xiuyu Julie Cong, Ezra E.W. Cohen
Journal: Journal of Clinical Oncology (2013)

6001 Background: This open-label trial assessed the efficacy of the irreversible ErbB Family Blocker afatinib (A) vs cetuximab (C) in R/M HNSCC pts following failure of platinum-containing therapy. In Stage 1 (S1), A and C had confirmed objective response rates (RECIST 1.0) of 16.1% vs 6.5% by investigator review (8.1% vs 9.7% independent central review [ICR]; Seiwert TY, et al. MHNCS 2012. Abs 235). S2 data after crossover are presented. Methods: In S1, pts were randomized 1:1 to oral A 50 mg/day or IV C 250 mg/m 2 /wk (400 mg/m 2 IV loading dose) until progressive disease (PD) or intolerable drug-related adverse events (DRAEs). Pts could then crossover to the other treatment arm (S2), with treatment given until further PD or intolerable DRAEs. Tumor response in S2 (RECIST 1.0) was evaluated at 4 wks after crossover and every 8 wks thereafter. Results: 56% of pts crossed over into S2: 32 from A to C and 36 from C to A. Of these, 88% crossed over after PD and 12% after intolerable DRAEs. Baseline characteristics of S2 pts were similar in the A and C groups and treatment duration in S1 prior to crossover was comparable (A: 3.7 [0.2–15.7] months; C: 3.5 [0.0–12.5] months). Median treatment duration in S2 was 2.1 (0.0–7.6) months for A and 1.2 (0.0–9.9) months for C. Tumor size decreases of ≥30% were observed in 1 pt in each treatment group (ICR). The disease control rate (DCR) for A was 33% vs 19% for C and the median progression-free survival time was 9.3 wks for A and 5.7 wks for C (ICR). The most frequently reported DRAEs (≥20%) for A were rash/acne (56%), diarrhea (53%) and stomatitis (22%), and for C was rash/acne (44%). DRAEs of ≥Grade 3 were seen in 47% of pts treated with A and 16% of pts treated with C. 12 A-treated patients had dose reductions to 40 mg and 1 pt had a further dose reduction to 30 mg; no C-treated pts had dose reductions. Conclusions: R/M HNSCC pts seem to benefit from sequential therapy with A/C or C/A, especially when using A treatment after C failure. Cross resistance is not universally present and further investigation of sequential treatment is warranted. Clinical trial information: NCT00514943.
Quality-of-life and LhRH agonist therapy among prostate cancer patients following PSA failure
Authors: N. Undevia-Yedavalli, N. Dandade, T. Luu, A. Samaras, O. Sartor, N. Nonzee, C. Bennett
Journal: Journal of Clinical Oncology (2009)

e16083 Background: Growing numbers of prostate cancer patients experience biochemical relapse (PSA failure) after initial treatment. LhRH agonist (hormonal) therapy can reduce PSA levels, but there is no clear evidence that it slows disease progression or reduces mortality. Quality of Life (QoL) issues are essential when deciding between observation (OBS) versus hormonal castration following biochemical relapse. We evaluated health related quality of life and treatment satisfaction among prostate cancer patients who experience PSA failure. Methods: Eligibility criteria were receipt of primary therapy for prostate cancer followed by a PSA nadir and subsequent PSA rise to at least 0.2 ng/ml. Data sources include medical records and interviewer administered surveys on health- related QoL at baseline, 3 and 12 months. Results: Castrated versus observed patients who are satisfied with their sexual activity report similar health-related QoL, with the exception of higher rates of maintaining an erection (73.3% vs. 32.0%) and not having prostate cancer affect sexual activity (66.7% vs. 28.6%). Castrated and expectant management patients with low levels of satisfaction and sexual activity report similar health-related QoL. Conclusions: Among patients with PSA Failure, the only health-related QOL difference is reflected in sexual activity related to erectile dysfunction, but not sexual satisfaction among patients who all have a high level of treatment decision satisfaction and sexual activity. [Table: see text] [Table: see text]
Adverse events affecting the mouth in two clinical trials of BEMA (BioErodible MucoAdhesive) Fentanyl
Authors: A. Finn, D. Blum, R. Kapoor, S. Hackett
Journal: Journal of Clinical Oncology (2008)

20648 Background: The BEMA drug delivery system was designed for rapid oral transmucosal drug delivery with dose to dose reliability of plasma concentrations and ease of patient use. BEMA Fentanyl consists of a small, dissolvable, polymer disc formulated with the opioid narcotic fentanyl for application to the buccal (inner lining of cheek) membranes. The mucoadhesive polymers adhere and rapidly deliver fentanyl across the capillary-rich mucosa. Methods: Subjects with cancer-related breakthrough pain who were receiving concomitant chronic opioid therapy were enrolled in two studies: a double-blind, randomized, placebo-controlled, multiple crossover study (FEN-201) and an open-label study (FEN-202). In FEN-201, subjects entered a titration period followed by a double-blind period during which they received 6 doses of BEMA Fentanyl and 3 doses of placebo in random sequence. In FEN-202, subjects successfully completing FEN-201 and a second group of subjects meeting the same entry criteria as for FEN-201 were enrolled. Subjects in both studies were titrated to an effective dose (starting at 200 μg) and then continued with dosage adjustment as required. Results: In FEN-201, 5 of 151 subjects (3.3%) reported oral mucosa-associated adverse events (AEs), including 2 subjects with mucosal inflammation (mucositis) and 3 subjects with oral candidiasis (thrush). None of these events were considered to be related to BEMA Fentanyl, and none were severe in intensity. In FEN-202, adverse oral symptoms were seen in 11 of 220 subjects (5.0%). In 4 subjects, the symptoms were considered to be related to local cancer or infection. In the 7 remaining subjects, the oral events were considered to be potentially attributable to BEMA Fentanyl (3.2%). The events were mild in 6 subjects and moderate in 1 subject. None of the subjects discontinued use of BEMA Fentanyl in either FEN-201 or FEN-202 as a result of BEMA Fentanyl related adverse oral symptoms. Conclusions: In these studies, BEMA Fentanyl exhibited an excellent safety profile with respect to oral AEs, which is of particular importance in a population of cancer patients. Each of the events is typical of the background condition and treatments of the study population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration BioDelivery Sciences International BioDelivery Sciences International BioDelivery Sciences International BioDelivery Sciences International
Attempted suicide among young adults: progress toward a meaningful estimate of prevalence
Authors: P J Meehan, J A Lamb, L E Saltzman, P W O'Carroll
Journal: American Journal of Psychiatry (1992)

The results of epidemiologic surveys on attempted suicide are often difficult to interpret; they compare and provide varying estimates of the prevalence of attempted suicide. The authors sought to estimate the prevalence of attempted suicide in a young adult population and to define more precisely what respondents mean when they report a suicide attempt.Survey respondents were a representative sample of all 18-24-year-old freshman students at a major public university. The self-administered, anonymous survey included questions about suicidal thoughts and behaviors and about any injury and need for medical care resulting from reported attempts.Of the 694 respondents, 374 (54%) reported having ever considered suicide and 181 (26%) had considered suicide during the preceding 12 months. Thirteen (2%) students reported having attempted suicide during the preceding 12 months, and 72 (10%) reported ever having attempted suicide. The number of students answering affirmatively to questions about injuries sustained, medical care sought, and hospitalization as a result of attempted suicide decreased progressively: only 18 (3%) students reported having ever sought medical care due to a suicide attempt, and seven (1%) were ever hospitalized.The prevalence of self-reported attempted suicide is not representative of the prevalence of self-injury and provides little information concerning the seriousness of the attempt. The use of specific questions similar to those used in this study should be considered in future surveys.
Combination chemotherapy with bleomycin, etoposide, and cisplatin in metastatic non-small-cell lung cancer.
Authors: D Osoba, J J Rusthoven, K A Turnbull, W K Evans, F A Shepherd
Journal: Journal of Clinical Oncology (1985)

Fifty-three patients with recurrent and advanced stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloroplatinum (BEP). Forty-eight patients were appraisable for response. The response rates were 44% for the entire group, 57% in 30 patients with combined squamous-cell and large-cell carcinoma, and 22% in 18 patients with adenocarcinoma (40%, 50%, and 19%, respectively, if patients not appraisable for response are included as nonresponders). The median survival time of patients with squamous-cell and large-cell carcinoma was slightly longer than that of patients with adenocarcinoma (23 weeks v 19 weeks). Patients with responsive disease survived significantly longer (median, 34 weeks) than did patients with unresponsive disease (median, 16 weeks) (P = .001). In the entire group, the median survival time of patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 was better (23 weeks) than of those with a status of 2 or 3 (15 weeks), but this difference was not seen in the subgroup with squamous-cell and large-cell carcinoma (24 weeks v 23 weeks, respectively). Thus, the performance status was not of prognostic value in the histologic subgroups experiencing the best response rate. There were two treatment-related deaths, but otherwise the toxicity of BEP was acceptable. Only four of the 119 treatment cycles were followed by fever even though there was significant neutropenia (0.5 X 10(9)/L) after 20 of 97 treatment cycles. The majority of patients receiving BEP experienced relief of cough, hemoptysis, pain, and fatigue associated with their disease. There was a good correlation between objective responses and palliation of symptoms. Thus, BEP offers good palliation, particularly for patients with squamous-cell and large-cell lung cancer.
Quality-of-Life Scores Predict Outcome in Metastatic but Not Early Breast Cancer
Authors: Alan S. Coates, Christoph Hürny, Harriet F. Peterson, Jürg Bernhard, Monica Castiglione-Gertsch, Richard D. Gelber, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2000)

PURPOSE: We compared the prognostic value of quality-of-life (QL) scores in the adjuvant setting and after relapse in two randomized trials of the International Breast Cancer Study Group. PATIENTS AND METHODS: More than 2,000 premenopausal and postmenopausal patients with node-positive breast cancer who were participating in randomized trials that compared adjuvant therapies completed QL assessments for physical well-being, mood, appetite, and coping at study entry and at months 3 and 18 if they remained relapse-free and, in case of relapse, at 1 month and at 6 months after relapse. Cox regression models were used to test the relationship between QL scores and disease-free survival (DFS), in the adjuvant setting, or overall survival, in the case of postrelapse QL measurement. All models were stratified by language/country group and included other factors related to QL and/or outcome. RESULTS: DFS was not significantly predicted by QL scores at baseline or month 18, or by changes in QL score between baseline and months 3 or 18. In contrast, after relapse, QL scores were predictive for subsequent overall survival. One month after relapse, better mood (P = .04) in premenopausal patients and better appetite (P = .005) in postmenopausal patients were associated with longer survival. Six months after relapse, better physical well-being (P = .03) and appetite (P = .03) in premenopausal patients and better physical well-being (P &lt; .0001), mood (P = .002), appetite (P = .0001), and coping (P = .0001) in postmenopausal patients predicted longer survival. CONCLUSION: Any prognostic significance of QL scores in the adjuvant setting is minimal or obscured by chemotherapy effects, but there is strong prognostic significance of QL scores after disease relapse. The contrast suggests that patient perception of the severity of underlying illness may determine reported QL scores.
A case-control study of desmoplastic melanoma
Authors: D. Livestro, A. Muzikansky, E. Kaine, T. Flotte, A. Sober, M. Mihm, J. Michaelson, B. Cosimi, K. Tanabe
Journal: Journal of Clinical Oncology (2005)

7529 Background: Previous studies have established that patients with desmoplastic melanoma have thicker primary tumors. Consequently, comparisons between desmoplastic melanoma and other forms of melanoma in these studies have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing desmoplastic melanoma with other forms of melanoma. Methods: From a database of 3202 melanoma patients treated at one institution, 89 patients with desmoplastic melanoma and 178 case-matched control patients (2:1) were identified by matching for thickness, age, gender, and year of diagnosis. Clinical, pathological, and outcome information were analyzed. Results: The median tumor thickness for all patients in the database is 0.96 mm, whereas the median thickness for desmoplastic melanoma patients is 2.60 mm. As per study design, the median tumor thickness for the 178 case-matched control patients is the same (2.60 mm) as for desmoplastic melanoma patients. Presentation with AJCC stage III or IV disease is less common in desmoplastic melanoma patients compared to case-matched control patients (5% versus 21%, p < 0.001). Re-excisions to obtain clear surgical margins are required more often in desmoplastic melanoma (21% versus 6%; p < 0.001). The risk of positive sentinel nodes is lower in desmoplastic melanoma patients compared to case-matched control patients (8% versus 34%, p = 0.013). Overall survival, cause-specific survival, and disease-free survival in desmoplastic melanoma patients are the same as those in case-matched control patients. Conclusions: Desmoplastic melanoma patients present with thicker primary melanomas than patients with other forms of melanoma. Use of case-matched control patients matched for tumor thickness avoids biases introduced by this observation. Desmoplastic melanomas are more locally aggressive, but have a lower risk of lymph node metastases compared to melanomas in case-matched control patients. The observed 8% rate of positive sentinel nodes in desmoplastic melanoma patients should be factored into decisions concerning sentinel lymph node biopsy. Importantly, desmoplastic melanoma patients have survival rates similar to patients with other melanomas of similar thickness. No significant financial relationships to disclose.