bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptomeningeal disease and breast cancer: Relationship of outcome and subtype.
Authors: Abouharb Sausan , Ensor Joe , Loghin Monica Elena , Katz Ruth , Gonzalez-Angulo Ana M. , Esteva Francisco J. , Moulder Stacy L. , Valero Vicente , Hortobagyi Gabriel N. , Melhem-Bertrandt Amal 
Published: March 2020

601 Background: Breast cancer (BC) is one of the most common tumors to involve the leptomeninges. Outcome of leptomeningeal disease (LMD) across BC subtypes is not well documented. We aimed to characterize clinical features and outcomes of LMD based on BC subtypes. Methods: We retrospectively reviewed medical records of patients diagnosed with LMD from BC (1997 to 2012). All patients had BC. Cases of LMD were based on the presence of neoplastic cells on cerebrospinal fluid examination and/or evidence of LMD by imaging studies. Survival was estimated by the Kaplan-Meier method and significant differences in survival were determined by Cox proportional hazards or log-rank tests. Results: 232 patients were included, 189 of them had available tumor subtype classified as: hormone receptor positive (HR+) BC N=67 (35.5%), human epidermal growth factor receptor 2 positive (HER2+) N=55 (29%), and 67 (35.5%) triple-negative BC (TNBC). Median age at diagnosis of LMD was 49.7 years. (Range 24-89). Median overall survival (OS) from LMD diagnosis across all subtypes was 3.1 months (95% CI, 2.5 to 3.7). Median OS correlated with BC subtype: 3.7 months (95% CI: 2.4, 6.0) in HR+, 4.0 months (95% CI: 2.6, 6.9) in HER2+, and 2.2 months (95% CI: 1.5, 3.0) in TNBC, (p=0.0002). There was an 11.4% chance a patient diagnosed with LMD would survive 1 year and the chance of surviving at least 3 years was 1.3%. When age was used as a continuous variable, older age was associated with worse outcome (p<0.0001). Patients with HER2+ BC and LMD were more likely to have received systemic therapy (ST) (70%), compared to HR+ (41%) and TNBC (41%) (p=0.002). 38% of patients with HER2+ BC received HER2 directed therapy. There was no difference in the use of intrathecal therapy (IT) (52%) across subtypes (p=0.3). Use of IT therapy (p<0.0001) and ST (p<0.0001) were both associated with improved age-adjusted OS. After adjusting for age, ST, there was no difference in OS between patients with HR+ and HER2+ BC (p =0.14), but a significant difference remained between TNBC and HER2+ BC (p < 0.0001). Conclusions: LMD carries a dismal prognosis. Our data shows that OS correlates with tumor subtype. Patients with TNBC had a significantly shorter OS compared to patients with HER2+ BC. New treatment strategies are needed.
Prognostication of survival from nasopharyngeal carcinoma by reduction of plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course: A new paradigm of prognostication.
Authors: Chan Anthony T. C. , Chan Allen K.C. , Ma Brigette , Hui Edwin Pun , Mo Frankie , Chow Katherine , Leung Linda , Chu Ka Wah , Zee Benny C.Y. , Lo Dennis YM , Leung Sing Fai 
Published: March 2020

6015 Background: To test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at mid-course of chemoradiotherapy (CRT)/ radiotherapy (RT), with respect to the plasma load of Epstein-Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC). Methods: 107 patients with stage IIB-IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The endpoints are post-DNA load, a recognized surrogate of survival, and clinical outcome. Results: 93% of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure (HR 12.02, 95% CI 2.78-51.93; P<0.0001), progression-free survival (HR 4.05, 95% CI 1.89-8.67, P<0.0001), and overall survival (HR 3.29, 95% CI 1.37-7.90, P=0.0077). About three-quarters of all failures were associated with detectable mid-DNA, whereas about one-third of all failures were associated with detectable post-DNA. Patients with detectable mid-DNA which disappeared after RT continued to sustain a less favourable prognosis than those with undetectable mid-DNA. Stratification by tumor stage (II, III, IV) has no significant prognostic effect. Conclusions: Unfavorable EBV DNA response at mid-course of radiotherapy/chemoradiotherapy is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of chemoradiotherapy, and adjuvant therapy.
Assessment of early tumor response to induction chemotherapy (IC) in locally advanced squamous-cell carcinoma of head and neck (LASCCHN) with 18FDG PET-CT: A prospective trial.
Authors: Nicolau Ulisses Ribaldo , Lima Eduardo Nobrega Pereira , Alves Marclesson S. , Oliveira Thiago Bueno , Jesus Victor Hugo Fonseca , Paiva Tadeu Ferreira , Cezana Loureno , Silva Virgilio Sousa , Pinto Paula Nicole , Porto Gislaine Machado , Pellizzon Antonio Cassio Assis , Carvalho Genival Barbosa , Kowalski Luiz Paulo 
Published: March 2020

6017 Background: Response to IC with triplet regimens adding taxanes to cisplatin and 5-fluorouracil (TPF), followed by chemoradiotherapy (CRT) for LASCCHN, is usually evaluated after 2 cycles of IC, based on bidimensional WHO or modified WHO criteria. Concerns regarding toxicity profile of TPF suggest a potential benefit of an early response evaluation approach that could select patients who would be spared from a toxic regimen and promptly started on an alternative treatment. The aim of this study is to assess the ability of evaluating early response after the first IC cycle based on a 40% decrease in standard-uptake value (SUV) measured by 18 FDG PET-CT on the 14th day. Methods: Patients with LASCCHN who underwent IC with TPF were prospectively evaluated. Staging procedure included locoregional and chest imaging, endoscopic examination and FDG PET-CT. At day 14 of first cycle, a second FDG PET-CT was performed and treating physicians were blinded for these findings. All cases were conducted according to the usual post-cycle 2 WHO or modified WHO criteria evaluation. Written informed consent was obtained from all recruited patients. Results: Between February 2010 and October 2012, 40 stage III/IV LASCCHN patients (34 oropharyngeal, 3 hypopharyngeal and 3 laryngeal) were recruited. With a median follow up of 11.4 months the actuarial 2 years overall (OS) and disease free survival (DFS) of all patients were 81.4% and 69.2%, respectively. Responders (any decrease of SUV) at day 14 PET CT had a better OS (90 vs. 27% - p<0,001) and DFS (76 vs. 0% - p<0,001) as compared to non-responders. Decrease of at least 40% in the SUV of primary tumor predicted a better DFS (100 vs. 51% - p=0,007). Conclusions: These results suggest a potential role of early response evaluation with 18 FDG PET-CT in patients with LASCCHN undergoing IC. A SUV decrease of at least 40% predicts better DFS. An increase in the SUV predicts a poor prognosis.
Positron emission tomography and stage migration for head and neck cancer.
Authors: VanderWalde Noam Avraham , Salloum Ramzi George , Liu Tsai-Ling , Hornbrook Mark Christopher , O'Keeffe-Rosetti Maureen Cecelia , Ritzwoller Debra Pearson , Fishman Paul Arthur , Lafata Jennifer Elston , Khandani Amir H , Chera Bhishamjit S. 
Published: March 2020

6018 Background: Positron emission tomography (PET) is often used for the staging of head and neck cancer (HNC). The purpose of this study is to explore the association between the increased utilization of PET and stage/survival in the managed care environment. Methods: Adult patients diagnosed with HNC (n=958) between 2000-2008, at 4 integrated health systems (Group Health Cooperative, Seattle; Health Alliance Plan/Henry Ford Health System, Detroit; Kaiser Permanente Colorado and Northwest, Portland) were identified via tumor registries linked to claims data. We compared AJCC stage distribution, patient/treatment characteristics, and survival between pre-PET era (2000-2004) vs. PET era (2005-2008), and those with PET vs. those without, during the PET era. AJCC stage was grouped into stage I/II (localized), stage III/IVa/IVb (locally advanced), and stage IVc (metastatic). Ordered logistic regression estimated the effects of PET utilization on upstaging. Kaplan-Meier estimates described overall survival (OS) differences between PET users and nonusers in the PET era. Cox proportional hazards regression evaluated the effect of PET use on survival. Results: There was a non-significant increase in stage III/IVa/IVb (40% to 44%) with a decrease in stage I/II (58% to 52%) between pre-PET era and PET era (p=0.11). During the PET era, patients with PET were more likely stage III/IVa/IVb and less likely stage I/II compared to patients without PET (III/IVa/IVb: 62% vs. 29%, I/II: 35% vs. 68%). On multivariate analysis those who were staged with PET were twice as likely to have locally advanced disease (OR 2.091; p=0.006). There was no difference in stage IVc. Patients with PET scans were more likely to receive chemotherapy with radiation and less likely to receive no treatment. 3-year actuarial OS for patients (all stages) with and without PET was 81% vs. 77% (p=0.261). 3-year actuarial OS for patients staged III/IVa/IVb with and without PET was 58% vs. 41% (p= 0.001). Conclusions: HNC patients were more likely to be upstaged with the use of PET. There was an improvement in survival in stage III/IVa/IVb patients, but no difference in survival across all stages. This likely reflects selection bias and stage migration rather than improved outcomes among individual patients.
A phase II study of dasatanib (BMS 354825) in recurrent or metastatic ckit-expressing adenoid cystic (ACC) and non-ACC malignant salivary glands tumors (MSGT).
Authors: Wong Stuart J. , Cohen Ezra E.W. , Karrison Theodore , Hayes David N. , Kies Merrill S. , Cullen Kevin J. , Tanvetyanon Tawee , Argiris Athanassios , Takebe Naoko , Lim Dean , Saba Nabil F. , Worden Francis P. , Gilbert Jill , Lenz Heinz-Josef , Razak Albiruni R.A. , Roberts John D. , Vokes Everett E. 
Published: March 2020

6022 Background: ACC is a rare disease, accounting for 1/3rd of MSGT, in which 90% of cases express the protein product of the ckit proto-oncogene. Dasatinib is a potent and selective inhibitor of five oncogenic PTKs/kinase families including ckit. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. Methods: In a two-stage design, adult patients (pts) with recent radiographic progressive, recurrent or metastatic ACC, + cKIT, were treated with dasatinib 70 mg PO BID. Pts with non-ACC MSGT of other histologic types, were treated as a separate cohort. Response was assessed every 8 wks by imaging using RECIST criteria. The study design stipulated enrollment of n=40 ACC patients (20 in stage I and 20 in stage II) and 25 non-ACC patients (14 in stage I and 11 in stage II). Results: Fifty-four pts were enrolled, 40 ACC and 14 non-ACC. One additional pt was a screen failure. Baseline data on 54 pts are: M:F = 28:26, median age 56.6 yrs (range 20-82), PS 0:1:2 = 24:28:2, prior radiation:chemotherapy = 44:21. The most frequent adverse events experienced (as % of pts, worst grade 2 or higher and at least possibly related to study drug) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (11%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), and non-cardiac chest pain (6%). No grade 4 adverse events occurred and only 15 pts experienced a grade 3 adverse event (at least possibly attributed to study drug), primarily dyspnea (4 patients) and fatigue (3 patients). Significant cardiac toxicity was observed in one pt (grade 3 prolonged QT corrected interval). Among ACC pts, best response to dasatinib: 0 pts (0%) had PR, 21 pts (52%) had SD (range 2.8-13.8 months), 12 pts (30%) had PD, and 2 died prior to cycle 2. Median PFS was 4.8 mos. For 14 evaluable non-ACC pts, none had an objective response, triggering early stopping. 7 had SD (range 1.4-6.6 months), and 4 PD. Conclusions: Although there were no objective responses, dasatinib is well tolerated, with tumor stabilization achieved by 52% of ACC pts. Dasatinib demonstrated no activity in non-ACC MSGT. Clinical trial information: NCT00859937.
PARTNER: A randomized phase II study of docetaxel/cisplatin (doc/cis) chemotherapy with or without panitumumab (pmab) as first-line treatment (tx) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Authors: Wirth Lori J. , Dakhil Shaker R. , Kornek Gabriela , Axelrod Rita , Adkins Douglas , Pant Shubham , O'Brien Paul E. , Debruyne Philip R. , Oliner Kelly S. , Dong Jun , Bach Bruce A. 
Published: March 2020

6029 Background: PARTNER was a multicenter, randomized phase II estimation study evaluating 1stEline tx of R/M SCCHN with doc/cis ± pmab. Methods: Patients (pts) were randomized 1:1 to doc/cis with pmab (Arm 1) or doc/cis alone (Arm 2). Arm 1 received 9 mg/kg pmab on day 1 of each 21-day cycle, and all pts received 1stEline doc/cis both at 75 mg/m2 on day 1 for up to 6 cycles. In Arm 1, pts could receive pmab monotherapy upon completion of 6 cycles of doc/cis until disease progression (PD). In Arm 2, pts could receive pmab as 2ndEline monotherapy upon PD. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. HPV status was determined using p16 INK IHC. No formal hypothesis was tested. Results: Baseline characteristics were balanced between arms. Of 103 pts, HPV status was evaluable in 66 (64%); 29% were HPV positive. Efficacy results are shown (Table). Worst grade 3/4 adverse events (AEs) were 73% in Arm 1 vs 56% in Arm 2. Conclusions: Median PFS was increased in both arms over historical doublet cytotoxic chemotherapy. PFS and ORR were higher in the pmab arm in the overall population, in the HPV positive (n=19) group, and in the HPV negative (n=47) group. There was an increase in grade 3/4 AEs with this regimen. The crossover design, with 57% of Arm 2 pts receiving pmab as 2ndEline monotherapy, confounds interpretation of OS. Clinical trial information: NCT00454779. [Table: see text]
Trastuzumab-based adjuvant chemotherapy for breast cancer: Early myocardial dysfunction detected by “speckle tracking” echocardiography (STE).
Authors: Mantovani Giovanni , Dessi Mariele , Orgiano Laura , Piras Alessandra , Cadeddu Christian , Deidda Martino , Ghiani Massimo , Antoni Giorgia , Serpe Roberto , Mercuro Giuseppe 
Published: March 2020

603 Background: While anthracycline-induced type 1 cardiotoxicity is well established, type 2 trastuzumab (TZM)-induced cardiotoxicity, although less relevant and reversible, is nonetheless significant in combination with other drugs, such as taxanes (TAX). A paradigmatic clinical example of this regimen is the adjuvant setting of breast cancer patients overexpressing HER-2. In the present study we chose STE with longitudinal and circumferential Strain (S) and Strain Rate (SR), as a very sensitive tool to timely identifying left ventricular dysfunction. The biological markers of chronic inflammation/oxidative stress were also studied. Methods: A phase IV prospective non-randomized study was carried out to assess cardio-toxicity induced by the combination of epirubicin (EPI) + TAX followed by TZM administered with the conventional schedule in adjuvant setting of breast cancer patients (pts) overexpressing HER-2. Inclusion criteria: 18–70 y, histologically confirmed HER-2+ve breast cancer candidates for TZM-based 3 weekly regimen; LVEF ≥55%; ECOG PS score 0-1, no history of cardiac disease. STE parameters (longitudinal and circumferential S and SR) and chronic inflammation (IL-6 and TNF-a)/oxidative stress (reactive oxygen species) markers were assessed at baseline before TZM and after each of the subsequent 18 TZM administrations. Results: Forty pts (mean±SD age 53±10 y) were assessed up to the 8th TZM administration. A progressive reduction of longitudinal SR was observed, becoming significant from the 4th TZM dose (0.65±0.18 s-1 vs 0.81±0.16 s-1, p<0.005); a significant reduction of circumferential SR (0.60±0.15 s-1 vs 0.51 ±0.14 s-1, p< 0.01) and rotation index was also observed from the 2ndTZM dose. These changes are all indicative of myocardial systolic dysfunction. No changes of biological parameters were observed. Conclusions: The sequential administration of TZM after EPI/TAX induced an early left ventricular dysfunction detected by STE which persisted at least up to the 8th TZM administration. This study is in progress with close monitoring of pts and its ultimate goal is to select pts candidates for an effective cardio protective treatment.
Phase I study of weekly albumin-bound paclitaxel (ab-P) plus weekly cetuximab (Cet) plus intensity-modulated radiation therapy (IMRT) in patients with stage III/IVb head and neck squamous cell carcinoma (HNSCC).
Authors: Fury Matthew G. , Sherman Eric Jeffrey , Rao Shyam S. , Wolden Suzanne L. , Smith-Marrone Stephanie , Ng Kenneth K. , Mueller Boris , Gelblum Daphna Y. , Dutta Pinaki R. , Lee James , Shen Ronglai , Kurz Sarah , Katabi Nora , Haque Sofia , Lee Nancy Y. , Pfister David G. 
Published: March 2020

6034 Background: There is a clinical need to improve the efficacy of standard Cet + concurrent RT for pts with stage III/IVB HNSCC. Taxanes have potent activity against HNSCC, and ab-P may offer therapeutic advantages in comparison with other drugs of this class. Methods: This was a single institution phase I study with a modified 3 + 3 design. 4 dose levels (DLs) of weekly ab-P were explored (30, 45, 60, and 80 mg/m2) during IMRT. Standard Cet (450 mg/m2 loading dose followed by 250 mg/m2 weekly) concurrent with IMRT (total dose, 70 Gy) was prescribed for all pts. The maximum-tolerated dose (MTD) would be exceeded if >2/6 pts experienced DLTs at a given dose level. NCI CTCAE v.3 was used, and DLT monitoring extended until 2 wks after IMRT. Results: 25 eligible pts (20M, 5F) enrolled, with median age 58 years (range, 46-84) and median KPS 90 (range 80-100). Primary tumor sites were oropharynx, 20 (10 HPV pos, 5 HPV neg, 5 not done); neck node with unknown primary, 2; and larynx, oral cavity, and maxillary sinus, 1 each. Two pts never received ab-P and were deemed inevaluable. At DL 1 (ab-P, 30 mg/m2), there was one DLT (g.4 pneumonia) among 6 pts. At DL2 (ab-P, 45 mg/m2), there were 2 DLTs (g.4 cerebrovascular accident; g.3 decrease in L. ventricle ejection fraction/CHF exacerbation) among 6 pts. At DL3 (ab-P, 60 mg/m2), there was 1 DLT (g.3 supraventricular tachycardia) among 6 pts. MTD was exceeded at DL4 (ab-P, 80 mg/m2) with 3 DLTS (g.3 neuropathy, g.3 dehydration, g.3 anemia) among 5 evaluable pts. For the entire study population, most common ≥ g3 AEs were: lymphopenia 100%, functional mucositis, 56%, and pain in throat/oral cavity, 52%. There were no treatment-related deaths. Among 23 evaluable pts at a median follow up of 29 months, 2y PFS rate is 64% (95% CI: 41-80%) and 2y OS rate is 90% (95% CI: 66-97). Conclusions: The recommended phase II dose is ab-P 60 mg/m2 weekly when given concurrently with IMRT and standard weekly Cet. This regimen merits further study as an alternative to IMRT + Cet alone for pts who require a non-platinum regimen. This study was approved and funded by the NCCN from general research support provided by Celgene, Inc. Clinical trial information: NCT00736619.
A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC).
Authors: Goncalves Priscila Hermont , Kummar Shivaani , Siu Lillian L. , Hansen Aaron Richard , Savvides Panayiotis , Sukari Ammar , Chao Joseph , Heilbrun Lance K. , Pilat Mary Jo , Smith Daryn W. , Casetta Lindsay , Boerner Scott Anthony , LoRusso Patricia 
Published: March 2020

6045 Background: SAHA is a small molecule inhibitor of histone deacetylases (HDAC). Based on confirmed responses noted in 2 ACC patients treated with SAHA at our institution; we initiated this phase II trial. Methods: Patients with LA, recurrent or metastatic ACC and adequate organ function were eligible. Any prior number of chemotherapy regimens was allowed. Tumor tissue and blood were collected for correlative studies. SAHA was administered orally 400 mg daily for 28 days. The primary objective was to evaluate response rate (RR). Secondary endpoints included: time to tumor response (TTR); response duration (RD); progression-free survival (PFS); overall survival (OS); and adverse events (AE). 29 evaluable patients were needed in a Simon 2-stage optimal design to distinguish RR of at most 5% vs. at least 20%, with alpha = 0.15 and power = 0.90. Results: 30 evaluable patients (overenrolled by 1) were accrued from at 5 different centers between August 2010 and June 2012. Median follow up among the censored patients is 3.8 months for PFS, and 7.2 months for OS. 19 patients were female, 24 were Caucasian, median age was 53 years (range 21-73); 21 patients had a performance status of 1; 20 patients were chemo-naïve. The median number of cycles completed was 5 (range 1-27+). Lymphopenia (n=5), hypertension (n=3), oral pain (n=2), thromboembolic events (n=2) and fatigue (n=2) were the only grade 3 AEs that occurred in more than 1 patient. 5 patients were dose reduced due to AEs. At the time of data cut-off, 9/30/2012, 1 patient with lung metastasis had a PR, with RD of 11.2+ months. TTR was 7.7 months. SD was the best response in 25 patients. Median PFS is 12.7 months (90% confidence interval lower limit: 3.7 months). Median OS has not been reached. There were 6 patients with PFS > 1 year. The correlative studies results will be presented. Conclusions: SAHA shows promise in the treatment of ACC. We are awaiting genomic analysis of the tumors to study the basis of clinical benefit (PR and SD) of SAHA in ACC. Future drug combination studies in ACC are being considered focusing on the epigenetic mechanism of SAHA. Supported by 5U01CA062487/19. Clinical trial information: NCT01175980.