tbuckley/cabot-search huggingface dataset:
Correlation of survival with tumor antigen expression in patients with newly diagnosed glioblastoma receiving a multi-epitope pulsed dendritic cell vaccine.
Authors: Surasak Phuphanich, Christopher Jay Wheeler, Jeremy Rudnick, Mia Mazer, Hong Qiang Wang, Miriam Nuno, Jaime Richardson, Xuemo Fan, Jianfei Ji, Ray M Chu, James Bender, Elma S. Hawkins, Chirag Patil, Keith L. Black, John Yu
Journal: Journal of Clinical Oncology (2012)

2087 Background: This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107). These TAA epitodes AIM-2. TRP-2, HER2 and AIM-2, are also overexpressed on glioblastoma multiforme (GBM) cancer stem cells. Methods: TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1 and/or HLA-A2 positive glioblastoma (GBM) patients with gross total resection were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals in the axilla region after a standard treatment with concurrent temozolomide (TMZ) and radiation therapy for newly diagnosed (ND-GBM). Results: Twenty-one patients were enrolled with 17 ND-GBM and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33% responders. TAA expression by qRT-PCR showed all patient tumors expressed at least three TAA with 75% expressing all six. Correlations of increased PFS and quantitative expression of MAGE1, AIM-2, gp100 and HER2 were observed. A decrease or absence of CD133 expression was seen in five patients who underwent a second resection. As of February 1, 2012, six of 16 ND-GBM patients showed no evidence of tumor recurrence (44-63 months). Median progressive free survival (PFS) in newly diagnosed patients was 16.9 months with a two-year PFS rate was 43.8% (95%CI,19.8-66.0 ). The median overall survival rate (OS) was 38.4 months and a two-year OS was 80.3% (95%CI,58.6-96.7). Conclusions: Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumor.
Evaluating patterns of care in the treatment of bladder cancer with and without metastases.
Authors: Erin Zagadailov, Brian S. Seal, Kenneth Shermock, Carl V Asche, Jane Chang, Charles Kreilick, Jianying Yao, Jen Cameron, Kellie Morland, Michael Eaddy
Journal: Journal of Clinical Oncology (2015)

e15510 Background: This study evaluated patterns of care among patients diagnosed and treated for bladder cancer with and without metastases. Methods: Retrospective data from 2 large integrated claims databases (Pharmetrics, MarketScan) spanning July 2008 to December 2010 were used to identify adult patients with a diagnosis of malignant neoplasm of the bladder (ICD-9 188.0–188.9; ICD-10 C67.0–67.9). Patients were included if they had continuous eligibility for 6 months prior and at least 6 months following their index diagnosis, had no diagnosis of any other cancer in the pre-period, and received no chemotherapy in the pre-period. Patients were stratified into 3 cohorts based on the presence and timing of metastasis diagnosis: non-metastatic (NM), metastatic disease ≤ 180 days (M1), and metastatic disease > 180 days (M2). Treatment patterns were evaluated after cancer diagnosis. Results: There were 10,250 (9,268 NM; 427 M1; 555 M2) and 22,965 (20,786 NM; 830 M1; 1,349 M2) patients in each database meeting all inclusion criteria, respectively. Mean follow-up was 35.1 months and 38.6 months in the 2 datasets. Between 68.9–70.0% and 2.1–2.6% of NM patients received surgery or radiation compared to 88.7–93.7% and 29.0–31.3 of M1 and 93.2–93.3% and 30.1–32.4% of M2, respectively. Between 28.1–25.8% of NM patients received first-line (1L) chemotherapy compared to 60.1–63.0% of M1 and 58.0–62.3% of M2. Of those, NCCN-recommended therapy was given to 23.9–28.5% of NM patients compared to 22.2–38.7% of M1 and 21.3–27.3% of M2 patients. The most commonly prescribed 1L NCCN-recommended therapy was BCG immunotherapy in NM and M2 patients (19.7 and 12.6%, respectively), and gemcitabine and cisplatin in M1 patients (11.6%). Between 11.8–12.7% of NM patients received second-line (2L) chemotherapy compared to 34.8–38.4% of M1 and 35.1–38.6% of M2 patients. Of those, NCCN-recommended therapy was given to 50.7–54.5% of NM patients compared to 29.8–47.6% of M1 and 35.1–47.7% of M2 patients. Conclusions: Up to 76.1% of NM, 77.8% of M1, and 78.7% of M2 patients who received 1L chemotherapy did not received NCCN-recommended agents. Fewer patients did not receive NCCN-recommended agents in 2L therapy across the cohorts: 49.3% NM, 71.2% M1, and 64.9% M2.
Rates and risks of suicidality in young adults (YAs) with advanced cancer.
Authors: Kelly Marie Trevino, Karen Fasciano, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2012)

9015 Background: Suicide rates in YA cancer patients are higher than in the general population. Although cancer is associated with a four-fold increase in the likelihood of a suicide attempt, little is known about suicidality in YAs with cancer. This study examined rates and clinical risk factors associated with suicidality in a sample of YAs with advanced cancer. Methods: Structured interviews were conducted between 4/2010 and 9/2011 with 70 YA advanced cancer patients (range 20-40 yrs, M=33.97, SD=5.61) receiving care at the Dana-Farber Cancer Institute. Validated measures assessed suicidality (i.e., Yale Evaluation of Suicidality), quality of life, major depressive disorder, grief over cancer-related losses, and social support. Scores on the suicidality measure were dichotomized into positive screen = 1 and negative screen = 0. Chi-square, t-test, and logistic regression analyses evaluated the relationship between suicidality and participant characteristics and psychosocial variables, controlling for confounding variables. Results: Over one-fifth (21.4%) of the sample screened positive for suicidality. Female gender χ 2 (1, N = 70) = 4.95, p = .026), breast compared with other cancer diagnosis χ 2 (1, N = 70) = 5.66, p = .017), and better performance status (t(68) = 3.13, p &lt; .01) were associated with lower rates of suicidality. Participants who met criteria for current (OR [95% CI] 8.67 [1.78, 42.22]) or lifetime major depressive disorder (5.38 [1.60, 18.12]) endorsed higher rates of suicidality. Better overall (.97 [.94, .99]), psychological (.93 [.87, .94]), and existential quality of life (.91 [.85, .98]) were associated with reduced suicidality risk. More severe grief was associated with greater risk (1.15 [1.04, 1.28]) whereas greater social support was associated with lower suicidality risk (.85 [.74, .97]). Conclusions: YAs with advanced cancer reported higher rates of suicidality than observed in other age groups. Developmentally targeted interventions that promote physical function, effectively treat depression, improve quality of life and reduce grief, and provide opportunities for social support may reduce rates of and risk for suicidality in this population.
The More Effective and the More (bio) Similar: Plerixafor and Filgrastim XM02 (tevagastrim) As First Line PBSC Mobilization Strategy in Patients with Multiple Myeloma and Lymphomas Candidate to ABMT
Authors: Daniele Laszlo, Giovanna Andreola, Aleksandra Babic, Mara Negri, Cristina Rabascio, Ambra Malerba, Monica Drera, Elezi Rufije, Giovanni Martinelli
Journal: Blood (2011)
Phase II open label randomized study of trabectedin (T) given as two different dosing schedules in women with platinum-sensitive, recurrent ovarian carcinoma: Preliminary results
Authors: J. Del Campo, A. Roszak, T. Ciuleanu, M. Bidzinski, T. Hogberg, M. Wojtukienicz, K. Boman, A. Poveda, A. Westermann, M. Izquierdo
Journal: Journal of Clinical Oncology (2006)

5031 Background: Trabectedin (Yondelis, ET-743) is a marine derived compound which binds to the minor groove of DNA distorting the DNA structure and induces apoptosis and cell cycle arrest. It has shown clinical activity in soft tissue sarcoma, ovarian, prostate and breast cancer. Methods: Patients (pts) with recurrent platinum sensitive ovarian carcinoma were randomized in a multicenter, open label study to receive T as 1.5 mg/m 2 over 24 h infusion (schedule A) or 1.3 mg/m 2 over 3 h infusion (schedule B) both every 3 weeks. All pts received dexamethasone premedication. Primary objective is to evaluate the response rate (RECIST) and secondary objectives are response duration, CA-125 response, time to progression and safety. Results: 107 pts were enrolled in 23 centers. Demographic and disease characteristics were well balanced. Toxicity and response data on the first 99 pts are available: median age 57 (25–78) years; ECOG PS=0: 72% and =1: 28%; pts received a median of 4 cycles (range:1–19 in A, 1–13 in B). Relative dose intensity was 84% and 93% respectively. Objective responses due to investigator’s assessment were 29% (8% CR, 21% PR) with 52% SD in A and 28% (11% CR, 17% PR) with 45% SD in B, with 11 pts not yet evaluable for response. CA 125 responses ≥ 50% occurred in 23% in A and 26% in B. TTP data will be presented. Safety: 501cycles were delivered; the most common any grade drug-related AEs per patient were (A and B) fatigue (56% and 47%), nausea (63% and 70%), vomiting (56% and 45%) and constipation (25% and 30%). Consistent with previous experience, alopecia, stomatitis and neurotoxicity were uncommon and mild/moderate. Grade 3/4 fatigue occurred in 15% in A and 4% in B. Grade 3/4 lab abnormalities were non-cumulative neutropenia (50% and 32%) and reversible ALT increase (58% and 53%). G-CSF support was not routinely given. There were 4 deaths &lt;30 days last infusion date (3 in A unrelated to study drug, one in B due to related multiorgan failure). Conclusions: This analysis suggests that both T schedules appear active with manageable toxicity. There was a trend for less neutropenia and fatigue with schedule B. On the basis of these efficacy results, no additional phase III comparisons between these 2 schedules seem warranted [Table: see text]
The impact of interval cytoreduction and age in advanced-stage ovarian cancer: A GOG ancillary study.
Authors: Stuart M. Lichtman, James Java, John L. Lovecchio, Dennis Chi, William P. Tew, Michael A. Bookman, Andrew Menzin
Journal: Journal of Clinical Oncology (2012)

5056 Background: To determine if an age group exists for which interval cytoreductive surgery (ICS) in patients with suboptimal residual disease at primary surgery influences progression free survival (PFS) and overall survival (OS) among women with advanced ovarian cancer treated on GOG 182. Methods: GOG 182 was a prospective, randomized trial of first-line chemotherapy in patients with advanced ovarian cancer. Patients with both optimal and suboptimal residual disease were included, and those with suboptimal residual were considered for ICS, with intent registered and stratified prior to randomization. Patients were randomized to one of five chemotherapy arms, employing combinations of either two or three agents delivered intravenously, with a control arm of paclitaxel and carboplatin. A retrospective analysis was approved by the GOG Ancillary Study Committee to investigate the influence of age on treatment and outcomes. In that analysis, Cox regression was used to identify independent prognostic factors and estimate their covariate effects on the adjusted PFS and OS of patients with suboptimal residual disease. Statistical significance was set at p&lt;0.05. Results: Among the entire eligible study population, 28% (n=1,042) were registered with suboptimal residual disease (&gt; 1 cm) and 109 of these patients elected to undergo ICS. Hazard ratios (HR) were determined for patients undergoing ICS with reference to patients with suboptimal disease not undergoing ICS. Based on the most current follow-up data, the HR for progression or death was not statistically different between the groups, but the HR of death alone was significant at 0.72 (95% CI: 0.57–0.92, p=0.008). There was no significant association of age with ICS in either the PFS or the OS model. Conclusions: In this trial, a patient’s age did not influence the effect of ICS on PFS or OS. There is no demonstrable benefit in PFS associated with ICS, but there was a statistically significant improvement in OS. To elucidate this finding, further study is warranted, likely in the form of a meta-analysis incorporating data from other prospective trials.
Outcome of BC2001 patients (CRUK/01/004) who received neoadjuvant chemotherapy prior to randomization to chemo-radiotherapy (cRT) versus radiotherapy (RT).
Authors: Syed A. Hussain, Emma Hall, Nuria Porta, Malcolm Crundwell, Peter Jenkins, Christine Lisa Rawlings, Jean Tremlett, Carey Hendron, Rebecca Lewis, Robert Anthony Huddart, Nicholas D. James
Journal: Journal of Clinical Oncology (2017)

298 Background: Neoadjuvant chemotherapy is considered standard of care for patients with muscle invasive bladder cancer (MIBC). Gemcitabine plus cisplatin or carboplatin (GC) has been adopted as a standard neoadjuvant regimen for MIBC. BC2001 showed that adding chemotherapy (5FU+MMC) to radiotherapy (55Gy/20f or 64Gy/32f) significantly improved rates of muscle invasive bladder cancer (MIBC) locoregional control (LRC) [James 2012]. We report outcome of patients (pts) receiving neoadjuvant chemotherapy prior to starting BC2001 trial treatment (cRT or RT alone). Methods: Between August 2001 and April 2008, 360 pts were randomised to RT (178) or cRT (182); 117 (32.5%) received neoadjuvant chemotherapy (61 RT, 56 cRT). Primary endpoint was LRC, secondary endpoints included toxicity, overall survival (OS) and metastasis free survival (MFS). Cox models adjusted by known prognostic factors were used to estimate randomised treatment effect in this subgroup of pts. Toxicities were compared by Chi squared tests. Results: Median age of the 117 pts was 66 (interquartile range: 60-73) years, 86% were male, 73% had baseline 0 WHO performance status. 81% had T2 and 87% G3 tumours. Neoadjuvant treatment received was GC (73.5%), MVAC (13.6%), CMV (11.1%) or other (&lt;2%). 92.3% cRT and 91.8% RT pts completed radiotherapy as planned. Grade 3 or above adverse events during treatment occurred in 27.4% pts (32.2% cRT vs 22.9 RT, p-value(p)=0.27), and in 9.5% during follow-up (13.4% cRT vs 5.3% RT, p=0.21). There was a trend for improved LRC in the cRT group (hazard ratio HR=0.64, 95CI% 0.33-1.23, p=0.18), while no differences in OS (HR=0.95, 95CI% 0.57-1.57, p=0.83) or MFS (HR=0.93, 95CI% 0.52-1.65, p=0.80) were observed. Median OS was 46.7 months ,cRT: 50.4 months vs RT: 46.7 months. MFS: Median: 68.5 months, cRT: 118.5 months vs RT: 54.2 months. Conclusions: The benefit in improved LRC of synchronous chemotherapy with 5FU/MMC was also found in the subgroup of BC2001 pts receiving neoadjuvant chemotherapy, with no significant increase in late toxicity. Neoadjuvant chemotherapy did not compromise the delivery of radical curative treatment with RT or cRT. Clinical trial information: ISRCTN68324339.
Reliability of prognostic and predictive factors evaluated by needle core biopsy for breast cancer in large tumors.
Authors: Camille Petrau, Florian Clatot, Anca Berghian, Liana Veresezan, Marie Cornic, Marc Baron, Francoise Callonnec, Corinne Veyret, Sophie Laberge, jean-Michel Picquenot
Journal: Journal of Clinical Oncology (2013)

1104 Background: Preoperative needle core biopsy (NCB) in breast cancer allows both invasive carcinoma diagnosis and the assessment of the main prognostic/predictive markers. However, large tumors, which may be candidates for preoperative chemotherapy, are potentially more heterogeneous than small ones, and the reliability of these factors measurements by NCB in these cases has been less documented than in whole surgical specimens (SS). The aim of this study was to evaluate the correlation for the main histological and immunohistochemical (IHC) features between NCB and SS in large tumors (&gt;2cm), and to assess major discordances that may impact the therapeutic decisions. Methods: All patients treated in our center for newly diagnosed early breast cancer between January 2008 and December 2011 were retrospectively screened. Large tumors for which both NCB and SS were available were included. Patients treated by preoperative chemotherapy were excluded. The assessed histological and IHC parameters were histological type, SBR grade, estrogen (ER) and progesterone receptors (PR) expression, HER2 status (completed by CISH if needed), intrinsic subtype, and proliferation markers (mitotic activity index (MAI), Ki67). All samples were independently read twice. Comparisons were performed using Kappa test. Results: 163 pairs of NCB-SS were analyzed. Average pathological tumor size was 3.2cm. Correlation was excellent for ER and HER2 (k=0.98 and 0.91 respectively), good for histological type (k=0.74), PR (k=0.79) and intrinsic subtype (k=0.73), but poor for Ki67 (k=0,60), SBR grade (k=0.29) and MAI (k=0.24). Among major discordances, 6 tumors were graded SBR I on NCB but SBR III on SS; 1 tumor was negative for ER on NCB but positive on SS. Importantly, 3 of the 21 HER2 positive cases (14%) were negative after CISH on NCB but positive on SS. Conclusions: Diagnostic NCB in large early breast tumors allows reliable determination of hormonal receptors expression, histological type and intrinsic subtype. SBR grade may however be deeply underestimated by this method, and false negative evaluation of the HER2 status in 14% of HER2 positive patients would have led to a detrimental lack of trastuzumab administration.
Postsurgical erlotinib and cisplatin concurrent chemoradiotherapy (CRT) promotes favorable outcomes in high-risk locally advanced head and neck squamous-cell cancer (LAHNSCC): A GICOR Working Group trial.
Authors: Fernando Arias, Ismael Herruzo, Jorge Contreras, Manuel de las Heras, Jose Angel Garcia Saenz, Alejandro de la Torre, Jesus Romero, Virginia Arrazubi, Isabel Prieto, Felipe A. Calvo
Journal: Journal of Clinical Oncology (2014)

6067 Background: The approach to LAHNSCC including surgery, radiotherapy(RT), and chemotherapy (CT) lacks of significant improvements in long-term survival. In an attempt to explore tolerance and potentially improve outcomes, the Spanish Clinical Research Group on Radiation Oncology (GICOR) designed a phase I/II study, with a dose-finding period to determine the maximum-tolerated dose (MTD) of daily erlotinib(E) administered in combination with cisplatin(C) and RT, followed by a phase II study to evaluate the therapeutic activity and safety of the selected dose combination. Methods: 13 patients(pts) were enrolled in phase I. The MTD was defined at C, 40 mg/m2 and E, 150 mg, based on G3 infection and mucositis in 2 out of 3 pts at dose level III. Phase II: 56 pts from 5 institutions were assigned to receive RT, 63 Gy (35 fractions over 7 weeks) combined with C, 30 mg/m2, on days 1, 7, 15, 22 and 29 of a 7-week radiation course, and E, 150 mg once daily on a continuous basis. The trial was designed to detect a 15% increase in disease free survival (45% to 60% at 2 years) with a 0.05 significance level, and a power of 0.8. Results: RT, C and E were completed on schedule in 87,5%, 64,3% and 80,4% of the cases, respectively. At a median follow-up (FU) of 40,6 months(mo), the 2-year DFI, locoregional DFI and OS was: 64,9%, 72,6% and 77,9%, respectively. High-risk criteria defined by involved surgical margins, extranodal extension and/or perineural infiltration were reported in 31 pts (55,4%). Treatment-related toxicity was generally mild to moderate: G-3/4 radiation skin changes included mucositis (n=33, 59%) and erithema (n=14, 25%). C-related G-3/4 toxicities were mucositis (n=15, 11%) and neutropenia (n=4, 7%). E-associated skin toxicity ≥G3 occurred in 14 (25%) pts. No toxic death occurred during the treatment. Conclusions: After surgery, CRT using conventional fractionated RT, with concurrent C and E promoted remarkable 2-year DFI, locoregional control rate and 2-year OS. The addition of erlotinib to cisplatin/RT is acceptably tolerated with a manageable side-effect profile. Clinical trial information: 2005-001506-29.
Use of tumor growth rate (TGR) to provide useful clinical information in phase I trials and reveal clear drug-specific profiles.
Authors: Charles Ferte, Marianna Fernandez, Antoine Hollebecque, Serge Koscielny, Antonin Levy, Rastislav Bahleda, Christophe Massard, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2013)

3010 Background: The evaluation of treatment response by RECIST does not take into account the tumor growth kinetics along the treatment sequence and may induce misleading information regarding the evaluation of the drug activity. TGR incorporates the time between the tumor evaluations and allows for a dynamic and quantitative evaluation of the tumor kinetics. How TGR is modified along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown. Methods: Medical records from all patients (n=304) prospectively treated at Institut Gustave Roussy in 19 phase I trials between 2009 and 2011 were analyzed. TGR was computed both during the pre-treatment period (REFERENCE) and between baseline and first evaluation (EXPERIMENTAL). TGR is defined as: log 10 (Vt/V0)/dt and is represented as a percentage increase of tumor volume per month for clinical relevance. The associations between TGR, RECIST, the most commonly used prognostic scores (ECOG, RMH score, PFS ratio) and the outcome (OS, PFS) were computed (multivariate analysis). The effect of treatment, prognostic scores, histology, and the number of previous treatment lines on TGR were assessed. Results: Overall, we observed a reduction of TGR between the REFERENCE vs. EXPERIMENTAL periods (11.5 vs. 1.5, P&lt;.0001). Although most of the patients were classified as stable disease (57%) or progressive disease (28%) by RECIST at the first evaluation, 88% and 69% of them exhibited a decrease in TGR, respectively. TGR reveals clear drug specific profiles along the 19 experimental regimens tested, allowing for an early evaluation of the drug activity. The TGR decrease was associated with both PFS (P=.004) and OS (P=.001) and remained significant even after adjustment to the other prognostic scores for phase I patients. Conclusions: Adding TGR assessment in phase I patients is simple and provides clinically relevant information: (i) It allows for an early and precise assessment of the tumor growth, (ii) It reveals drug-specific profiles, suggesting its potential use for the early assessment of drug activity, (iii) TGR is independently associated with prognosis in phase I patients.