tbuckley/cabot-search huggingface dataset:
Biological effects of pegfilgrastim after myelosuppressive chemotherapy in breast cancer
Authors: M. Danova, K. Bencardino, D. Grasso, M. Manzoni, E. Collovà, S. Ferrari, E. Travaglino, B. Rovati, C. Porta, R. Invernizzi
Journal: Journal of Clinical Oncology (2006)

10521 Background: The dose and schedule of chemotherapy (CT), that play a crucial role in the outcome of pts with chemosensitive tumors, were made feasible with the primary use of colony stimulating factors. Few data are available on the in vivo biological effects of the “long-lasting” cytokine pegfilgrastim. We have focused on the cytokinetic effects on the CD34+/38+ peripheral blood (PB) progenitor cell subset and on its influence on neutrophils functional parameters. Methods: We studied PB samples from 14 breast cancer pts (median age 47 yrs; 35–61 yrs), treated with Docetaxel (80 mg/sqm, d 1) + Epirubicin (75 mg/sqm, d 1) + pegfilgrastim (6 mg s.c. on d +1). The % of CD34+/38+ circulating progenitor cells (CPCs) (sorted with immunomagnetic procedure) undergoing G0/G1, S and G2/M phases of the cell cycle or showing apoptotic features were evaluated using flow cytometry. Annexin V was quantitated at a single cell level and correlated with cell cycle phases. On PB buffy coat smears, alkaline phosphatase activity by cytochemistry, actin polymerization using FITC-labelled phalloidin and apoptosis by TUNEL technique, were evaluated on neutrophils. Results: Seven days following CT + pegfilgrastim the CD34+/38+ absolute numbers were: 46 (27–74) and 41 (25–66) on day 14+ from CT.On day 7+ the % of CD34+/38+ CPCs in S-phase was 13.0 ± 9 while 3.7% ± 6 of this cell subset showed apoptotic features. One week later, these values were 8.4% ± 7 and 7.7% ± 5, respectively. We also observed: stability of the absolute neutrophil count for all the duration of treatment; a significant increase of the leucocyte alkaline phosphatase; abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeleton organization, and a significant reduction of neutrophil apoptosis. Conclusions: 1) pegfilgrastim exerts stimulatory effects on cell cycle status of PB CD34+/38+ CPCs, protecting them from apoptosis; this is evident 7 days after its administration and tends to decrease one week later 2) pegfilgrastim improves the neutrophil function by inhibiting their accelerated apoptosis and prolonging survival. These data could be useful when dose-dense CT is planned with pegfilgrastim support. No significant financial relationships to disclose.
Percutaneous radiofrequency ablation of painful osseous metastases: A multicenter trial: American College of Radiology Imaging Network 6661
Authors: D. E. Dupuy, D. Liu, D. Hartfeil, L. Hanna, J. Blume, K. Ahrar, R. Lopez, H. Safran, T. DiPetrillo, W. Mayo-Smith
Journal: Journal of Clinical Oncology (2007)

9101 Background: Radiofrequency Ablation (RFA) can destroy tissue in a defined area. Single institutions have reported that RFA can reduce pain from bone metastases. To confirm this, the American College of Radiology Imaging Network (ACRIN) completed a multicenter study of RFA for bone metastases. Methods: Eligible patients had bone pain in one dominant site: tumor size &lt; 8 cm, and location &gt; 1 cm from the spinal cord or cauda equina. RFA was performed under CT guidance. The Memorial Pain Assessment Card was used prior to RFA and repeated daily for two weeks, and at 1 and 3 months after RFA. AEs were recorded in addition to four different pain assessment measures: pain relief, patient mood, pain intensity, and pain severity. Results: Fifty-six patients had RFA at 9 centers. Metastatic sites were pelvis (24), chest wall (19), thoracolumbar spine (8), and extremities (5). Six out of 56 patients experienced at least one adverse event of grade 3 or higher, yielding an AE rate of 10.7% (95%CI is 2.6% to18.8%). AEs attributed directly to RFA were nerve injury in 2 patients. Of the 56 participants, 43 completed the 1 month follow-up and 33 completed the 3 month follow-up. At the time of this analysis, assuming that missing data were missing at random and after adjusting for all covariates, RFA showed significant effect in reducing pain at 1 and 3 month follow-up for all 4 pain assessment measures. The average increase in pain relief from pre-RFA to 1 month follow-up is 26.4 (P&lt;0.0001) and the increase from pre-RFA to 3 month follow-up is 17.2 (P=0.003). The average increase in mood from pre-RFA to 1 month follow-up is 21.5 (P&lt;0.0001) and the increase from pre-RFA to 3 month follow-up is 16.3 (P=0.001). The average decrease in pain intensity from pre-RFA to 1 month follow-up is 25.9 (P&lt;0.0001) and the decrease from pre-RFA to 3 month follow-up is 13.0 (P=0.02). The odds of being in lower pain severity at 1 month follow-up is 12.6 (P&lt;.0001) times higher than that at pre-RFA, and the odds at 3 month follow-up is 7.1 (P&lt;0.0001) times higher than that at pre- RFA. Conclusions: This cooperative group trial confirms that RFA can safely palliate pain due to bone metastases. ACRIN receives funding from the National Cancer Institute through the grants U01 CA079778 and U01 CA080098. No significant financial relationships to disclose.
A phase III randomized trial of LV5FU2+CPT-11 vs. LV5FU2 alone in adjuvant high risk colon cancer (FNCLCC Accord02/FFCD9802)
Authors: M. Ychou, J.-L. Raoul, J.-Y. Douillard, R. Bugat, L. Mineur, F. Viret, Y. Becouarn, O. Bouche, J.-H. Jacob, S. Gourgou-Bourgade
Journal: Journal of Clinical Oncology (2005)

3502 Background: LV5FU2+CPT-11 has shown more activity than LV5FU2 alone in first line metastatic colorectal cancer. This adjuvant trial evaluated the addition of CPT-11 to LV5FU2 in terms of Event-Free Survival (EFS) and safety in colorectal cancer patients (pts) at a high risk of relapse. Methods: Colon cancer pts with postoperative N2 or N1 detected by occlusion/perforation were randomized to either: A: LV5FU2 (leucovorin 200mg/m2 as a 2-h infusion, 5-FU 400mg/m2 bolus and 600mg/m2 22-h continuous infusion, d1–2) or B: LV5FU2+CPT-11 (irinotecan 180mg/m2 90-min infusion d1+LV5FU2) fortnightly for 12 cycles without any support of growth factors. Pts were stratified by center, type of detection, delay from surgery to chemotherapy (≤28d; >28d) and age (<65y;≥65y). A 0.64 hazard ratio was deduced from an expected change in 3-year EFS from 45% to 60% with 5% two-sided alpha and 85% power. ITT survival analysis used the Logrank test. Results: 400 pts were randomized 1:1 in 75 centers between 11/98 and 09/02. Median follow-up is 36 months. More T3/T4 (p<0.017), more 15+ positives nodes (p<0.014), more vascular invasion (p<0.031), and more perineural involvement (p<0.018) were observed in arm B. 5FU relative dose intensity (RDI) was >80% for 95% and 77% in arms A and B (p<0.001). CPT-11 RDI was >80% for 70% pts. More NCI G3–4 neutropenia in arm B (4% vs. 28%pts, p<0.001) is related to the absence of G-CSF support. In spite of only 97% necessary events observed, there was no significant difference in EFS rates between the 2 treatment arms. Conclusions: The two arms were unbalanced for important prognostic factors. Adjuvant LV5FU2+CPT-11 as compared to LV5FU2 alone is associated with more G3–4 neutropenia. These preliminary results show no improvement between the 2 arms in terms of EFS in the ITT analysis. Final analysis will be presented with more follow-up. No significant financial relationships to disclose.
Phase III, randomized study of trastuzumab emtansine (T-DM1) ± pertuzumab (P) vs trastuzumab + taxane (HT) for first-line treatment of HER2-positive MBC: Primary results from the MARIANNE study.
Authors: Paul Anthony Ellis, Carlos H. Barrios, Wolfgang Eiermann, Masakazu Toi, Young-Hyuck Im, Pier Franco Conte, Miguel Martin, Tadeusz Pienkowski, Xavier B. Pivot, Howard A. Burris, Alexander Strasak, Monika Patre, Edith A. Perez
Journal: Journal of Clinical Oncology (2015)

507 Background: In phase II and III studies, treatment with T-DM1 or with P + H + docetaxel has shown statistically significant increases in progression-free survival (PFS) and overall survival (OS) vs control regimens in patients with HER2-positive MBC. The combination of T-DM1 + P resulted in synergistic inhibition of tumor cell line proliferation in vitro. This and preliminary data from a phase II clinical trial provided the rationale for further study. Methods: In MARIANNE (NCT01120184), patients with centrally assessed HER2-positive (IHC3+ or ISH+) progressive/recurrent locally advanced BC or previously untreated MBC with a ≥ 6-month interval since treatment in the (neo)adjuvant setting with taxanes or vinca alkaloids were randomized 1:1:1 to HT (docetaxel or paclitaxel + H), T-DM1 (T-DM1 + placebo, hereafter T-DM1), or T-DM1 + P, at standard doses. The primary end point was PFS assessed by independent review. Comparisons between HT and T-DM1 or T-DM1 + P were considered separately. PFS was tested first for non-inferiority and for superiority only if non-inferiority was achieved. Results: At the clinical cutoff date, September 16, 2014, 365 patients had been randomized to HT, 367 to T-DM1, and 363 to T-DM1 + P. In each arm, approximately 31% of patients had prior (neo)adjuvant treatment with HER2-directed therapy. Approximately 37% overall had de novo disease. The study met the PFS non-inferiority end point, but not the superiority end point. OS was similar across treatment arms. Conclusions: These data demonstrate non-inferiority in PFS between T-DM1–containing arms and control. T-DM1–containing regimens were associated with a different toxicity profile than the control regimen. Clinical trial information: NCT01120184. Outcome HT T-DM1 T-DM1 + P Median follow-up, mo 34.8 34.9 34.7 Median PFS, mo 13.7 14.1 15.2 HR [97.5% CI] - 0.91 [0.73–1.13], p = 0.31 vs HT 0.87 [0.69–1.08], p = 0.14 vs HT 0.91 [0.73–1.13], p = 0.31 vs T-DM1 ORR, % 67.9 59.7 64.2 Median duration of response, mo 12.5 20.7 21.2 Grade 3−5 AEs, % 54.1 45.4 46.2 Most common grade 3−5 AEs, % Neutropenia 19.8 4.4 2.7 Febrile neutropenia 6.5 0 0 Anemia 2.8 4.7 6.0 AST increased 0.3 6.6 3.0 Thrombocytopenia 0 6.4 7.9
Angiogenic profile and pathological features in the prediction of clinical outcome of advanced renal cell carcinoma patients receiving sunitinib.
Authors: Maristella Bianconi, Mario Scartozzi, Luca Faloppi, Antonio Zizzi, Marco D'Anzeo, Riccardo Giampieri, Michela Del Prete, Alessandro Bittoni, Rodolfo Montironi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2015)

458 Background: Metastatic renal cell carcinoma (mRCC) ever represented a challenge in patients’ treatment, there is a wide variability in the amount and duration of response among patients. It has been previously reported how VEGF and VEGFRs SNPs could predict response to treatment with sunitinib. Tumour heterogeinity is a matter of debate in mRCC. The aim of our study is to assess if pathological features and the expression of VEGF and VEGFRs polymorphisms in tumour, metastatic, and normal renal tissues could have a role in patients’ treatment and prognosis. Methods: We enrolled 123 patients treated at our institution. We collected histologic samples of tumour, metastatic, and normal renal tissue of 92 patients with mRCC treated with first-line sunitinib. For 21 patients, all three tissues were available. A pathological revision was conducted evaluating: granular cells percentage, grading, necrosis, regressive and sarcomatoid areas, and vascularization pattern. Histologic samples were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Polymorphisms were correlated with pathological features and PFS and OS. We then analysed concordance in SPNs expression among tissues. Results: VEGF A rs833061, VEGF A rs699947, VEGF A rs2010963, and VEGR3 rs6877011 were confirmed as significant SNPs in PFS. 19 out of 21 patients presented concordance among tissues polymorphisms expression (97%). The presence of a G allele in the rs6877011 seems to correlate with a higher percentage of granular cells. The presence of C allele in rs2010963 correlates with an alterated vascularazation. Conclusions: A preliminary analysis of our data shows the predictive and prognostic value of angiogenic polymorphisms and their concordance in tumoral, metastatic, and normal tissue. Furthermore, they are correlated with the percentage of granular cells and the vascular architecture, with possible predictive and prognostic significance. Further data will be presented at the meeting.
A phase I study of oral belinostat (PXD101) in patients with advanced solid tumors
Authors: W. K. Kelly, T. Yap, J. Lee, U. Lassen, E. Crowley, A. Clarke, T. Hawthorne, P. Buhl-Jensen, J. de Bono
Journal: Journal of Clinical Oncology (2007)

14092 Background: Belinostat (PXD101) is a hydroxamate HDAC inhibitor which demonstrates broad anti-neoplastic activity in vitro and in vivo. In Phase I studies in patients (pts) with advanced cancer, IV belinostat is well-tolerated up to 1000 mg/m 2 daily x5. Preliminary results of an oral formulation of belinostat showed that the oral bioavailability was 20 - 50%. This Phase I trial of oral belinostat will determine the maximal tolerated dose (MTD) of once and twice daily dosing, tolerability and pharmacokinetics (PK) in pts with advanced solid tumors. Methods: Sequential cohorts of 3–6 pts with advanced solid tumors refractory to standard therapy or for which no standard therapy exists were administered belinostat 250–500mg once or twice daily in 4 week cycles. Fasting (day 1) and non-fasting (day 7) pharmacokinetic studies were performed on all patients along with serial ECGs to evaluate any potential effects on QTc prolongation. Patients were evaluated with routine blood work weekly and tumor imaging at the end of cycle 1 then every other cycle. Results: Sixteen pts have been treated in 3 dose levels at 250mg QD (6 pts), 500mg QD (6 pts) and 250mg BID (4 pts). The median number of cycles of therapy is 1 (range 1–5), nine pts continue to be treated. The most common reasons for discontinuation were adverse event (3 pts) and PD (3 pts). No DLTs were identified at 250mg QD or 250mg BID. DLTs of grade 3 dehydration and grade 3 fatigue were reported at 500mg QD. In pts from the first 3 dose cohorts, there were no grade 4/5 events reported. Other Grade 3 toxicities were fatigue (2 pts), abdominal pain (1 pt), ataxia (1 pt), prolonged INR (1 pt), prolonged PTT (1 pt) and confusion (1 pt). Symptoms were transient and usually resolved after drug was held. In &gt; 500 ECG’s collected, there were no QTcF &gt; 500 ms, and no QTcF increase &gt; 60 ms above baseline. To date, the best clinical response observed has been SD in 7 patients. Conclusions: Oral belinostat at doses of 250mg QD and 250mg BID given on a continuous schedule appears to be well tolerated. Alternative dosing schedules are being explored to further dose escalate the belinostat. Updated safety, activity and pharmacokinetic data will be presented on these and alternate dose schedules. [Table: see text]
The Complex Relationship Between Lung Tumor Volume and Survival in Patients with Non-Small Cell Lung Cancer Treated by Definitive Radiotherapy: a Prospective, Observational Prognostic Factor Study of the Trans-Tasman Radiation Oncology Group (Trog 99.05)
Authors: D. Ball, R. Fisher, B. Burmeister, M. Poulsen, P. Graham, M. Penniment, S. Vinod, H. Krawitz, D. Joseph, G. Wheeler, B. McClure
Journal: Journal of Thoracic Oncology (2012)
Breast radiation dose estimates compared to measured doses from involved field radiotherapy (IFRT) or mantle fields for early stage Hodgkin lymphoma (ESHL)
Authors: A. Wirth, H. Wittwer, T. Kron, K. Sullivan
Journal: Journal of Clinical Oncology (2007)

18503 Background Breast cancer risk after mantle irradiation has prompted concern regarding the use of IFRT for ESHL. As breast cancer risk is radiation dose related, reliable estimates of breast radiation dose from IFRT might aid individual patient risk assessment. However, estimates of breast dose from radiation scatter/leakage beyond the involved field, using standard computer algorithms, are of uncertain accuracy. The aims of this study were to compare computer estimates with measured breast dose, and to compare breast dose from mantle and neck IFRT. Methods A phantom with breast tissue equivalent was used to determine breast dose using computerized treatment planning (CMS XiO), and to perform measurements within the phantom breast tissue using thermoluminescent dosimetry (TLD). These measurements were made for mantle fields and (neck) IFRT. Results Computer estimates and TLD measurements of breast dose in centigray (cGY) are shown for IFRT and mantle treatment, for a prescribed dose of 3000cGy, using 6MV X-rays from a Varian 21eX linear accelerator. Conclusions Breast dose from neck IFRT was lower than from mantle treatment by an order of magnitude, but being well outside the treatment field, was not accurately estimated by our computer algorithm. Work in progress will examine breast dose from mediastinal IFRT and involved node irradiation. Modifications to the planning algorithm may improve accuracy of dose estimates at a distance from the primary field, allowing routine breast dose estimates for patients. Ultimately, utilisation of dose-risk data may allow risk modelling and risk-benefit analysis of IFRT for ESHL in individual patients. [Table: see text] No significant financial relationships to disclose.
Patient-reported burden of mucosal injury (MUI): Comparison of clinician-rated MUI and patient-reported outcomes
Authors: L. S. Elting, G. Calais, N. Selva, D. Brachman, M. Kudrimoti, F. Spijkervet, M. Vera-Llonch, G. Oster, D. Keefe, S. T. Sonis
Journal: Journal of Clinical Oncology (2007)

9117 Background: Patient (pt) reported outcome (PROs) tools identify MUI and its impact on functional and subjective outcomes. Among outpts, PRO tools are attractive because opportunities for direct assessment are limited, but agreement between PRO tools and objective MUI measures has not been uniform. We prospectively compared an objective MUI score and 3 previously validated PRO tools. Method: The Triad Burden of Illness study is an international, 41-center, prospective study of the risk and outcomes of radiation and chemotherapy-induced MUI. At baseline and during chemoradiation therapy (CRT), pts with larynx (L), hypopharynx (H), or non-small cell lung cancers (NSCLC) completed a daily MUI symptom tool (OMDQ) and 2 weekly PRO tools (FACT-E quality of life, FACIT- Fatigue). Clinicians examined pts twice weekly and scored MUI (WHO scale). In this interim analysis, we used random effects linear regression to compare clinician and pt ratings and t-tests to compare PRO scores in pts with and without severe MUI. Result: To date, 29 pts have completed =2 paired assessments; 23 (79%) had L or H cancers. Ulcerative MUI (WHO = 2) was more common among L/H than NSCLC pts (39% vs 17%). Pt-rated MUI predicted clinician-rated MUI (p = 0.001). FACT-E and FACIT-F scores were significantly lower (worse) among pts with clinician-rated ulcerative MUI than pts without and among pts with pt-rated severe MUI symptoms (OMDQ= 2) than pts without. Differences were largest in the subscales for physical and functional wellbeing and esophageal symptom special concerns. Conclusion: PRO tools estimate the burden of CRT-induced MUI in outpts with L/H or NCSL cancers. MUI appears to be associated with significantly poorer quality of life, functional status, and symptom scores. 1- 9 p &lt;0.01; 10 p = 0.06. [Table: see text] [Table: see text]
Outcome of patients relapsing early after autologous stem cell transplantation for multiple myeloma
Authors: S. T. Mahmood, S. Kumar, M. Q. Lacy, A. Dispenzieri, S. R. Hayman, S. V. Rajkumar, M. R. Litzow, M. A. Gertz
Journal: Journal of Clinical Oncology (2007)

8022 Background: Autologous stem cell transplant (ASCT) is the standard approach for eligible patients (pts) with multiple myeloma (MM). The median time to relapse after early ASCT is 2–3 yrs and overall survival (OS) is 4–5 yrs. Though various risk factors have been identified for early relapse, the outcome of this group of pts is not clearly described. With the advent of newer therapies, it is important to understand the natural history of MM in these pts to design treatment strategies. Methods: A total of 432 pts with MM, undergoing ASCT within 12 months (mos) of diagnosis, with a minimum follow up of 12 mos were studied. Clinical and laboratory data were obtained from a prospectively maintained database and clinical records. Pts were divided into 2 groups: early relapse (relapse &lt;12 mos from ASCT) and late relapse (either relapsed &gt;12 mos after ASCT or disease free at last follow up). Results: There were 94 pts (22%) in the early relapse group and among the late relapse group (N=338), 171 had relapsed beyond 12 mos and 167 were disease free at last follow up. The median time to ASCT was similar in all groups. The early relapse group had a significantly shorter median OS from diagnosis (23.9 vs. 82.2 months; P &lt; 0.001) and from transplant (17.6 mos vs. not reached; P &lt; 0.001). The median OS from relapse was 7.9 mos in this group compared to 39.6 months for the rest. In univariate analysis, elevated CRP, high BM plasma cell%, labeling index (PCLI) &gt;1%, abnormal cytogenetics, presence of circulating PCs at harvest and lack of CR from ASCT predicted for early relapse. In multivariate analysis, an elevated PCLI (RR=2.9; P=0.002) and failure to achieve CR (RR 2.7; P=0.002) was associated with early relapse. Conclusions: Pts who relapse within 12 mos of an ASCT have a very short survival and should be offered trials evaluating novel therapies and combinations. Survival figures from this study represent the benchmark for the comparison of novel approaches in this population. Pts with poor prognostic factors have a short PFS after ASCT and should be considered for alternative approaches. Inability to achieve CR appears to predict shorter PFS and clinical trials evaluating maintenance therapy should be offered in these pts. No significant financial relationships to disclose.