tbuckley/cabot-search huggingface dataset:
Results of a phase II trial of azacitidine (AZA) with or without epoetin beta (EPO) in lower-risk MDS.
Authors: Claude Gardin, Sylvain Thépot, Odile Beyne-Rauzy, Thomas Prébet, Sophie Park, Aspasia Stamatoulas, Agnes Guerci-Bresler, Stephane Cheze, Gerard Tertian, B Choufi, Laurence Legros, jean Noel Bastie, Jacques Delaunay, Eric Wattel, Francois Dreyfus, Norbert Vey, Simone Boehrer, Pierre Fenaux
Journal: Journal of Clinical Oncology (2012)

6523 Background: Although anemia of IPSS low and int-1 (LR) MDS initially responds to erythroid stimulating agents (ESA) in 40-50% of patients (pts), response is generally transient. Anemia recurrence with RBC cell transfusion dependency (RBC-TD) is an indicator of poor prognosis, even in absence of progression to higher risk MDS. AZA leads to RBC transfusion independence (RBC-TI) in 30–40% of LR-MDS (Lyons, JCO, 2009), but it has not been prospectively tested in LR-MDS patients resistant to ESA. It also remains unknown if the addition of ESA to AZA would be useful in such pts. Methods: In this randomized phase-II trial (GFMAzaEpo-2008-1 trial, NCT01015352), the Groupe Francophone des Myélodysplasies (GFM) compared AZA 75mg/m2/d for 5 days every 28 days for 6 cycles (AZA arm) to the same treatment plus EPO 60000U/week (AZA+EPO arm). Inclusion criteria were LR-MDS resistant to at least 12 weeks of ESA, with RBC-TD ≥ 4 RBC units in the previous 8 weeks. Responders in both arms were eligible for maintenance up to 12 monthly cycles, unless progression or loss of erythroid response occurred. The primary endpoint was RBC-TI (HI-E major using IWG 2000 criteria) after 6 courses. Results: Between 2009 and 2010, the 98 planned pts were included: M/F 65/28; median age 71y (41-84); 5 pts were excluded (one consent withdrawal, 2 early unrelated events and 2 with exclusion criteria). In the remaining 93 pts, IPSS risk was low in 69 and int-1 in 23 pts, with no imbalance between arms. Five pts received &lt; 4 cycles and 16 received only 4 or 5 cycles, mainly due to toxicity or progression. RBC-TI after 6 courses was observed in 16.7% (8/48) in the AZA arm and 18 % (8/45) in the AZA+EPO arm (P=1), and in 19.5% (8/41) and 26 % (8/31) respectively, in the 72 pts who received ≥ 6 cycles (P=.57). Overall best response rate (at least HI-E minor using IWG 2000 criteria) was 35 and 33% in the AZA and AZA+EPO arms, respectively (P=0.99). Of note, only 9 pts in the AZA+EPO arm required at least one hospitalization for a SAE, compared to 22 pts in the AZA arm (P=0.015). Conclusions: Erythroid response to AZA, in LR MDS with demonstrated ESA resistance, appears lower than expected, with no improved outcome when combined with an ESA. The latter may however improve tolerance of AZA in LR MDS.
Impact of African American (AA) race on outcomes with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).
Authors: Ravi Kumar Paluri, David James Mooney, Shi Wei, Gurudatta Naik, Okechukwu Nwakile Mgbemena, Charity Morgan, Jeffrey Nix, Guru Sonpavde
Journal: Journal of Clinical Oncology (2014)

e15503 Background: The impact of race on outcomes with RC is unclear. We examined the impact of race in patients (pts) with UCB undergoing RC at a single institution (UAB [University of Alabama, Birmingham]). Methods: Consecutive patients with UCB who underwent RC with curative intent between 2001 and 2012 with or without perioperative chemotherapy or chemoradiation were reviewed. Patient demographics, risk factors, clinical course, pathological characteristics and long term outcomes were collected. Descriptive statistics were performed. Results: A total of 215 patients (163 [76%] men and 52 (24%) women) with a mean age at RC 65.2y (range 35-85) were identified. 180 patients (84%) were Caucasian and 28 (13%) were AA. Median follow up after the surgery was 29.6 months (range 0.1 - 162.3). Histology consisted of transitional cell carcinoma (74%), squamous (13%), poorly differentiated (10%) and sarcomatoid subtypes (4%). AJCC stages were as follows: I (19%), II (24%), III (29%) and IV (28%). Lymphovascular invasion (LVI) was seen in 71 patients (33%), positive margins in 23 of 209 evaluable pts (11%), and 65 (30.2%) received peri-operative chemotherapy with or without radiation. Tumor recurrence was noted in 45 pts (21%). On multivariate analysis, AA race, positive margins and LVI were found to be significantly independently associated with tumor recurrence (Table). Conclusions: AA race conferred a significant negative impact on tumor recurrence following RC for UCB (HR =2.6, p=0.048; 95%CI 1.0-6.6). These data suggest a profound impact of host genomics on tumor biology and warrant further study and validation. Parameter Hazard ratio 95% Confidence interval P value Lower Upper Past smoker 0.86 0.30 2.4 0.78 Current smoker 0.65 0.25 1.69 0.38 African American 2.59 1.04 6.44 0.04 Female 0.45 0.16 1.23 0.12 Age at cystectomy 0.97 0.92 1.03 0.34 Margins 2.86 1.11 7.38 0.03 Lymphovascular invasion 5.11 1.45 18.05 0.01 Stage 2 3.39 0.36 31.57 0.28 Stage 3 3.38 0.38 30.32 0.27 Stage 4 1.32 0.15 11.55 0.80 Perioperative chemotherapy 1.79 0.67 4.84 0.25
Impact of PI3K aberrations on efficacy of perifosine (P), x-PECT: A phase III randomized study of P plus capecitabine (PC) versus placebo plus capecitabine (C) in refractory metastatic colorectal cancer (mCRC) patients.
Authors: Cathy Eng, Johanna C. Bendell, Scott Kopetz, Emily Tarco, Lianchun Xiao, Jun Ying, Xuemei Wang, Jonathan Phillips, Peter Sportelli, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2014)

3606 Background: P is an oral, synthetic alkylphospholipid that affects several signaling pathways, including PI3K/Akt. The X-PECT trial randomized 468 patients (pts) to PC (50 mg po QD) or C (1000 mg/m2BID, D1-14 q21D). We hypothesized pts having PI3K aberrations (PIK3CA and PTEN loss) would derive greater benefit from P for response rate, progression-free survival (PFS) and/or overall survival (OS). X-PECT did not meet its primary endpoint of OS (p = 0.32). Here we present the final tissue correlatives. Methods: Archival formalin-fixed paraffin-embedded (FFPE)tissues were requested on all pts. Sequenom MassARRAY (MALDI-TOF MS) was utilized for detection of PIK3CA, PI3KR1, Akt, Ras, and Raf mutations (MT). PTEN expression was assessed by IHC. Reverse phase protein array (RPPA) was evaluated in fresh frozen specimens, paired pre- and post-one cycle from pts at MD Anderson. Kaplan-Meier method was used to estimate median OS and PFS; Cox proportional hazard regression analysis and log rank test were applied to evaluate OS and PFS with patient demographics and markers. Wilcoxon rank sum test and Fisher’s exact test were performed for continuous or categorical variables. Results: 272 pts had FFPE tissue samples. 57% of pts were male. 45% of all pts had a KRAS MT; NRAS (1%); BRAF (3%); PIK3CA (9%); Akt (<1%), and loss of PTEN by IHC (16%). Loss of PTEN or PIK3CA MT were noted in 25% of pts. Ras WT was noted in 50% of all pts. Univariate analysis noted no difference for PFS for loss of PTEN/PIK3CA MT [p=0.32; HR= 0.81, (95% CI: 0.54-1.23)] or for RasMT (p=0.11; HR=1.34, (95% CI: .93-1.92)]. RPPA data of 9 pts was available; only 6 pts (5 placebo pts) with paired pre- and on-treatment samples were evaluable. C alone was associated with reduction in p-Akt T308 (p=0.05), downstream target p-PRAS40 T246 (p=0.03), as well as proliferation marker PCNA (p<0.01). Conclusions: The presence of a PIK3CA MT or loss of PTEN occurred in 25% of refractory mCRC pts but did not improve the efficacy of perifosine. Capecitabine alone appeared to inhibit Akt signaling and proliferation. Additional studies are needed for validation. Clinical trial information: NCT01097018.
Cost-effectiveness of surveillance after curative resection (CR) of metastatic colorectal cancer (CRC).
Authors: Richard M. Lee-Ying, Hagen F. Kennecke, Liem Nguyen, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2017)

526 Background: Surveillance after CR of stage I-III CRC is recommended by most major oncology organizations to detect asymptomatic recurrences. Such recurrences are more likely to benefit from early interventions such as CR of metastases. Only the NCCN recommends a surveillance schedule after CR of metastases that includes CEA testing, imaging and clinical evaluation every 3-6 months for 2 years, and then every 6-12 months in years 3 to 5. Periodic endoscopy is also recommended. It is unclear if there is cost-effective surveillance strategy for metastatic CRC after CR. Methods: A Monte Carlo micro-simulation model was constructed using a 1-month cycle length and 10 year time horizon. Surveillance strategies were compared based on NCCN guidelines, with testing every 3 months (3M) or 6 months (6M), as well as two alternate strategies of testing every 12 months (12M) or no surveillance (None) for 5 years. Recurrence, repeat CR rates, and survival outcomes were modeled from population-based outcomes of 257 patients who had CR of mCRC in British Columbia, Canada. Asymptomatic recurrences were more likely to undergo CR, compared to symptomatic ones. Additional costs, utilities, and probabilities were derived from the literature. Costs are in 2015 CAD and utilities in Quality-adjusted life years (QALY), and both discounted at 3% and half-cycle corrected. Analyses were performed using TreeAge Pro with 1000 trials and 1000 distribution samplings. Results: The incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) are listed in the Table. Increasing the frequency of surveillance tests does lead to modest gains in QALY, however, the cost of surveillance and subsequent treatment is high. Using a willingness to pay threshold of 150 000 CAD, the 6M strategy would be favored. Conclusions: In the Canadian context, the optimal surveillance strategy after CR of mCRC matches with the 6M strategy recommended by the NCCN. An additional Canadian data set will be used to externally validate the model outcomes. [Table: see text]
Phase 2 studies of multiple peptides cocktail vaccine for treatment-resistant cervical and ovarian cancer.
Authors: Satoshi Takeuchi, Tadahiro Shoji, Masahiro Kagabu, Tatsuya Honda, Atsumi Kojima, Yukari Nitta, Toru Sugiyama, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2015)

5567 Background: We have conducted phase 2 studies of peptides vaccine (PV) immunotherapy for cervical (CC) and ovarian cancer (OC) using human leukocyte antigen (HLA)-restricted tumor specific epitope peptide and VEGF receptor1 (VEGFR1) and 2. Institutional review board had approved these studies. Methods: All patients (pts) with heavily treated and with HLA-A2402 or A0201 within PS2 were enrolled. Written-informed consent had obtained. Enrollment finished on October 20,2014. PV cocktail were as follows: FOXM1, MELK, HJURP,HIG2,VEGFR1 and VEGFR2 for OC, FOXM1, MELK, HJURP,URLC10 and HIG2 for CC. Each peptide (GMP grade) was mixed at a dose of 1mg with 1ml of adjuvant, MONTANIDE,ISA51. Vaccination schedule included 12 subcutaneous weekly injections. Thereafter, additional administrations (adms) were performed. CTL was analyzed by ELISpot assay. Clinical responses were evaluated every three months by RECIST v 1.1 and additional immune-responsive (ir-) RECIST Results: Twenty one pts of CC and 46 pts of OC were enrolled. PV was generally well tolerated with no major adverse events, and most of the patients developed specific CTL responses until 8 adms. Two patients showed complete response by RECIST. Median overall survival(mOS) of CC and OV was 15.4 months(m)and 8.8 m,respectively. No significant survival benefits were seen among HLA type and histology subtypes, but c-reactive protein levels (lower than 2.0 mg/dl) at base line in OC and dermatological hypersensitivity (DTH) during adms in CC and OC was strongly related their OS. Lower CRP group showed longer median OS (mOS = 19.0m vs. 3.0m, logrank p = 0.0016) in OC. As for DTH, negative versus positive patients, the mOS was 3.3 m vs. 21.2m, logrank p = 0.065, in CC, and it was 1.4 m vs. 17.7 m, logrank p < 0.0001, in OC. Conclusions: These findings suggest that this PV immunotherapy was safe and effective even for incurable patients and they would be applicable for maintenance therapy for cervical and ovarian cancer. Clinical trial information: UMIN000003860,3862,3902,3903.
Receptor-interacting protein kinase 3 controls keratinocyte activation in a necroptosis-independent manner and promotes psoriatic dermatitis in mice
Authors: Tetsuya Honda, Osamu Yamamoto, Yu Sawada, Gyohei Egawa, Akihiko Kitoh, Atsushi Otsuka, Teruki Dainichi, Saeko Nakajima, Yoshiki Miyachi, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2017)
Evaluation of nausea and vomiting in melanoma patients treated with consecutive days of cisplatin
Authors: T. Sato, M. Laudadio, E. Pequignot, I. Chervoneva, K. R. Chan, M. J. Mastrangelo
Journal: Journal of Clinical Oncology (2009)

e20702 Background: Chemotherapy-related nausea and vomiting (N/V) continue to be significant problems for cancer patients. In order to properly design a study leading to control of N/V in patients receiving consecutive days of cisplatin, stage IV melanoma patients who received three consecutive days of a cisplatin-containing chemotherapy were assessed. Methods: Patients were treated with cisplatin (25mg/m2, days 1–3), DTIC (220mg/m2, days 1–3), BCNU (150mg/m2, day 1) and tamoxifen (20mg twice a day, consecutively). The second cycle was given in 4 weeks without BCNU. Appropriate antiemetics were given during chemotherapy and then as needed for symptom control. N/V were assessed with the Functional Living Index-Emesis (FLIE) questionnaire for seven days (days 1–7). The median intensity of N/V during the early phase (days 1–3) and the late phase (days 4–7) was analyzed using the linear mixed effects model, adjusting for the subject random effects. The rates of intractable N/V (total FLIE score equal or less than 108) were analyzed in the random-effects logistic regression model. Results: A total of 14 patients answered the FLIE questionnaire. For nausea in cycle 1, the means of the median FLIE scores were similar in the early (52.7, 95%CI: 44.5, 60.8) and late (50.2, 95%CI: 42.0, 58.3) phases. In cycle 2, lower scores were observed in the late phase (45.2, 95%CI: 36.4, 54.0) than in the early phase (54.1, 95%CI: 45.6, 62.7) with a significant difference of 8.9 points (95%CI: 0.1, 17.7, p=0.049). For vomiting, the means of the median FLIE scores were similar in the early and late phases of either cycle. For the rates of intractable N/V, the differences between cycles and late vs. early phases were borderline significant. Higher odds of intractable N/V were estimated for cycle 2 vs. cycle 1 [OR=2.44 (95%CI: 0.945, 6.29; p=0.065)] and for late vs. early phases [odds ratio OR=2.39 (95%CI: 0.970, 5.870; p=0.058)]. Conclusions: The FLIE questionnaire is useful for objective assessment of N/V in patients who receive consecutive days of emetogenic chemotherapy. The data obtained from this study will form the basis for a future interventional study in which anti-emetics that are effective for late-phase N/V will be tested. No significant financial relationships to disclose.
Molecular profiles of screen-detected breast cancers from a Turkish breast cancer screening program.
Authors: Neslihan Cabioglu, Sibel Ozkan Gurdal, Arda Kayhan, Nilufer Ozaydin, Erkin Aribal, Vahit Ozmen
Journal: Journal of Clinical Oncology (2013)

e12545 Background: TurkishBahcesehir Breast Cancer Screening Project is a 10-year organized population based screening program carried out in one of the largest counties in Istanbul, Turkey. The aim of this study is to determine the biological features of screen detected breast cancers detected during the initial 4-year study period as an interim analysis. Methods: Between January 2009 and December 2012, a total of 5938 women with ages 40–69 years were recruited in this prospective study. Two-view mammographies were obtained by 2-year intervals, and classified according to Breast Imaging Reporting and Data System of the American College of Radiology (ACR). Patient and tumor characteristics were analysed for those diagnosed with breast cancer. Tumors were stained for estrogen (ER) and progesterone receptors (PR), HER2-neu and Ki-67 by immunohistochemistry. Results: A total of 49 breast cancers (% 0.83) were detected during the study period. The median age was 50 (40-70). The majority of patients (78%) were stage 0 or 1, whereas 23 patients (47%) were &lt;50 age. Of 49 tumors, 38 (78%) were invasive cancers and 11 (22%) were ductal carcinoma in situ. Forty-four patients (90%) underwent breast conservation, whereas 35 patients (75%) had sentinel lymph node biopsy. Of 38 invasive cancers, 24 (63%) were ductal carcinoma and 8 (21%) were lobular cacinoma. Among 31 invasive cancers stained for ER, PR, HER2-neu and Ki67, the majority of them (92%) were hormone receptor positive, whereas 13% were HER2-neu positive and 58% had low Ki67 levels (&lt;14). As molecular subtypes, the majority of them were found to be either luminal A (48%) or luminal B type (42%), whereas other nonluminal HER2 (7%) and triple negative cancers (3%) were less frequently detected. Conclusions: Our findings suggest that the majority of screen-detected breast cancers exhibit either luminal A or B subtype. However, more aggressive subtypes such as nonluminal HER2-neu or triple negative cancers are less likely to be detected by mammographic screening programs, requiring other preventive strategies.
Reporting quality of abstracts in cancer clinical trials.
Authors: Shanthi Sivendran, Kristina Braine Newport, Adam Albert, Matt D. Galsky
Journal: Journal of Clinical Oncology (2014)

6584 Background: Detailed and transparent abstracts are critical for assessing clinical trials. For some practitioners, access to full text manuscripts may be limited due to financial, language, and information technology considerations. In 2007, the Consolidated Standards of Reporting Trials (CONSORT) group generated an extension statement with recommendations regarding the minimum elements that should be included in an abstract. The degree to which these recommendations are adhered to in oncology publications has not been previously evaluated. Methods: A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified randomized, controlled, phase III trials in metastatic solid malignancies. Abstracts were assessed for the 18 elements recommended in the CONSORT extension statement for abstracts; a completeness score (range, 0 to 18) was calculated by adding the number of elements reported. Results: 175 eligible publications with data for 96,125 patients were included in this analysis. The median completeness score was nine (range, three to 17). 67% of the abstracts also had a full text available for review through open access. The median completeness score of abstracts with available full text on open access (nine; range, four to 14) was similar to those full texts that were not available (10; range, three to 17). Of the 18 abstract elements, the items that were least frequently reported included - description of the trial design (18%), the method by which participants were allocated to interventions (14%), use of blinding (22%), whether the trial is ongoing (23%), registration and name of trial (25%) and the funding source (19%). Although 46% of publications included the number of participants randomized to each group only 26% of publications included the number of patients analyzed. Conclusions: Cancer clinical trial abstracts typically report only half of the reporting elements recommended by the CONSORT group. Further, there is significant heterogeneity in the quality of reporting. Inclusion of the CONSORT elements may allow for better interpretation and application of clinical information.
Comparison of the effectiveness and complications of half and full doses of pegfilgrastim in breast cancer patients
Authors: E. E. Lower, M. E. Bartelt, S. Harman
Journal: Journal of Clinical Oncology (2007)

11058 Background: Pegfilgrastim (G-CSF) is a longer half-life synthetic growth factor used to reduce the incidence of infection following myelosuppressive chemotherapy but is associated with bone pain and hypergranulocytosis. Little data exists regarding efficacy and possible reduced toxicity with lower doses. Methods: A retrospective review identified early stage breast cancer pts who received reduced doses of G-CSF. Data collected prior to and after each dose of G-CSF included total white blood cell count (WBC), absolute granulocyte count (AGC),patient age, type and dose of chemotherapy, and stage of breast cancer. The occurrence of fever and infection was compared between the full and reduced dose groups. Pts completed a Likert scale (1–5) rating bone pain after each dose of G-CSF. Results: Thirty four pts received adjuvant treatment including adriamycin-cyclophosphamide (AC) followed by taxane (T) in 12, dose dense AC-T in 13, other regimens in 9. The median age was 53 years (range of 36 to 82). Thirty-two pts initially received 6 mcg but were reduced to 3mcg due to drug toxicity. Two pts received only 3mcg doses. There was a significant difference in the WBC post chemotherapy for the 98 treatments with 6 mcg (8400 (3000–49,600) cells/cu mm (Median (Range)) versus 116 treatments with 3 mcg (7600 (3000–18,900) cells/cu mm (p&lt;0.02). There was no significant difference between the post chemotherapy AGC for the 6 mcg (6000 (2200–38,000) cells/cu mm versus the 3 mcg (5800 (1000–16,600) cells/cu mm. Six pts receiving 6 mcg had a post G-CSF WBC &gt; 20,000 cells/cu mm vs none receiving 3 mcg (Fisher exact test, p&lt;0.01). No WBC &lt; 2,000 cells/cu mm or neutropenia of &lt;1000 cells/cu mm was noted with either regimen. Reported fever and infection was not significantly different between the 6 and 3 mcg doses (Fever: 6 mcg 3/98 (3.1%) vs 3 mcg 5/116 (4.3%); Infections: 6 mcg 5/98 (5.1%) vs 3 mcg 7/116 (6.0%)). Bone pain was more severe after 6 mcg dose than the 3 mcg dose (P &lt; 0.02). Conclusions: Although 6 mcg G-CSF was associated with a significantly higher total WBC, pts receiving 3 mcg G-CSF did not experience a difference in incidence of fever, infections, or neutropenia. However, lower doses were associated with significantly less bone pain and hypergranulocytosis. No significant financial relationships to disclose.