bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant adenoviral human p53 gene combined radio- and chemotherapy after a tumorectomy in treatment of laryngeal carcinoma in advanced stage.
Authors: Chen Fei , Wang Feng 
Published: March 2020

6050 Background: To investigate the benefits of post-surgery using recombinant adenoviral human p53 gene (rAd-p53) combined with radio- and chemo-therapy in treatment of laryngeal carcinoma in advanced stage. Methods: A total of 61 patients with a stage III or IV laryngeal cancer, 51 males and 10 females with an average age of 63.2, were randomly divided into three groups: G1, G2 and G3. The 18 G1 patients received no treatment after surgery. The patients in G2 (21 patients) and G3 (22 patients) received rAd-p53 followed by radio-and chemo-therapy, and only radio- and chemo-therapy, respectively. The rAd-p53 was injected into the surgery wound bed at a dose of 2 x 1012 viral particles (VP) once per 3 days for 5 times. Radiotherapy was given at a total dose of 63-67 Gy in 7 weeks. The chemo-regimen included 5- Fu 500 mg/ m2 from day 1 to day 5 and DDP 30 mg / m2 from day 1 to day 3 in a treatment course of 21days for two courses. Results: All the study patients were followed up for at least 3 years. One patient in G2 lost to follow up. The local control rates (no recurrence) at 3 years were 38.9% (7/18), 75.0% (15/20), and 54.5% (12/22) for G1, G2, and G3, respectively. The 3-years progress free survivals (PSF) were 38.9%, 50.0%, and 45.0% for G1, G2, and G3, respectively. The 3-years overall survivals (OS) were 38.9%, 65.0%, and 45.0% for G1, G2, and G3, respectively. The three efficacy endpoints of G2 were significantly better than both G1 and G3. These efficacy measures of G3 were significantly higher than G1. Conclusions: Post-surgery chemo- and radiotherapy is necessary to increase the local control rate, prolong both PRF and OS. The rAd-p53 gene therapy can farther increase the efficacy measures.
Neoadjuvant erlotinib, erlotinib-sulindac, or placebo: A randomized, double-blind biomarker modulation study in operable head and neck squamous cell carcinoma (HNSCC).
Authors: Bauman Julie E. , Gross Neil D. , Gooding William E. , Denq William , Thomas Sufi M. , Wang Lin , Chiosea Simion I. , Hood Brian L , Flint Melanie S , Sun Mai , Conrads Thomas P. , Ferris Robert L. , Johnson Jonas Talmadge , Kim Seungwon , Argiris Athanassios , Wirth Lori J. , Siegfried Jill , Grandis Jennifer R. 
Published: March 2020

6051 Background: The epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) pathways are upregulated in HNSCC. Crosstalk potentiates growth, proliferation and invasion. Preclinical models show synergistic anti-tumor effects from dual blockade. We evaluated biomarker modulation in paired tumor specimens from a 3-arm phase 0 trial of erlotinib, a small molecule EGFR inhibitor; erlotinib + sulindac, a non-selective COX inhibitor; vs. placebo. Methods: Patients (pts) with untreated stage II-IVb HNSCC were randomized 5:5:3 to neoadjuvant erlotinib 150 mg daily (Arm 1, n = 19), erlotinib + sulindac 150 mg twice daily (Arm 2, n = 16), or placebo (n = 12). Pts were treated for 7-14 days. Tumor specimens were collected pre- and post-treatment. The primary endpoint was change in Ki-67 proliferative index. We hypothesized an ordering in Ki-67 down-modulation, with Arm 2 > Arm 1 > placebo. A Jonckheere-Terpstra test evaluated trend; a Wilcoxon test was applied to pairwise contrasts. We prepared tissue microarrays for IHC, to explore pharmacodynamic modulation of 21 EGFR and COX-2 pathway constituents including EGFR, Src, STAT3, Akt, EP2 and EP4. Results: From Dec 2005 – Dec 2008, 48 pts enrolled; 28 tumor pairs were evaluable for biomarker modulation. Class toxicities of EGFR inhibition, including acneiform rash and diarrhea, were observed on Arms 1 and 2. Compared to placebo, Ki-67 was reduced by erlotinib (p = 0.0005) or by erlotinib-sulindac (p = 0.0001). There was a trend in ordering of Ki-67 down-modulation, with greater effect from the addition of sulindac (exact Jonckeheere-Terpstra, Arm 1 vs. 2, p = 0.003). Among 21 protein candidates tested for association with Ki-67, only low baseline p-Src correlated with greater Ki-67 reduction in both erlotinib groups (R2 = 0.312, p = 0.024). Conclusions: Relative to placebo, brief neoadjuvant treatment with erlotinib or erlotinib-sulindac significantly decreased the proliferative index in operable HNSCC. Sulindac enhanced Ki-67 down-modulation. Efficacy studies of dual EGFR-COX inhibition are justified. Baseline p-Src warrants further study as a resistance biomarker for anti-EGFR therapy. Clinical trial information: NCT01515137.
Clinical outcomes of transoral robot-assisted supraglottic laryngectomy: An experience of a French cooperative evaluation group of transoral robotic surgery.
Authors: Ceruse Philippe , Lallemant Benjamin , Aubry Karine , Morinieres Sylvain , Vergez Sebastien , Benlyazid Adil , De Mones del pujol Erwan , Malard Olivier 
Published: March 2020

6053 Background: Transoral, minimally invasive organ preservation surgeries are being increasingly used for laryngopharyngeal carcinomas to avoid the toxicities of combined chemotherapy and radiation therapy regimens. This study investigates the efficiency, safety, and functional outcomes of transoral robot assisted surgery (TORAS) for supraglottic laryngectomy. Methods: Experience of TORA supraglottic laryngectomy for patients with supraglottic carcinomas is presented in a multicentric study of a case series with planned data collection between 2009 and 2012. Results: Eighty-six of 262 patients underwent TORA supraglottic laryngectomy for supraglottic carcinomas. Thirty-three percent of patients were started an oral diet within 24 hours. For 77% of the other patients, the median use of a feeding tube was 8 days (0-10 months). Nine percent of them had a definitive percutaneous gastrostomy feeding. For 87% of patients no tracheotomy was performed, for 23% of the others patients, the median use of tracheotomy was 8 days, 3% of them had a definitive tracheotomy. Aspiration was observed in 22% of the patients in the postoperative course and was responsible for the death of one patient. Sixteen percent of the patients had a postoperative bleeding. Fifty percent of the patients received adjuvant radiation therapy based on pathology results. Conclusions: TORA supraglottic laryngectomy is a safe procedure with good functional outcomes and fast recovery but adverse events are possible. Consequently this technique needs a good selection of the patients to reduce the risk of postoperative complications.
Association of polymorphisms in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription factors (IKBKAP and ZNF415) with base of tongue squamous cell carcinoma risk.
Authors: Lima Carmen Silvia Passos , Carvalho Benilton , Pellegrino Renata , Khater Leticia , Chone Carlos Takahiro , Lourenco Gustavo Jacob 
Published: March 2020

6073 Background: Recently, we found 6.609 genetic single nucleotide polymorphisms (SNPs) with distinct frequencies between base of tongue squamous cell carcinoma (BTSCC) patients and controls. The study was performed using high-resolution DNA microarrays genotyping (Affymetrix). The SNPs identified never have been previously described with BTSCC risk. Some SNPs of interest were located in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription (IKBKAP and ZNF415) and they were selected to validation process. Objective: Validate the SNPs ERP29 c.*293A>G (rs7114); LEF1 c.*1213A>G (rs2107028) and g.127267A>G (rs4245926); MCC c.*5077A>G (rs7033); PTCH1 g.27369025G>A (rs16909856) and g.27369324G>A (rs16909859); IKBKAP c.3214T>A (rs3204145) and ZNF415 c.*443A>G (rs3814) associated to BTSCC risk. Methods: Genomic DNA from 49 BTSCC patients and 49 controls was genotyping by TaqMan assays (Applied Biosystems). The differences between groups were analyzed by logistic regression model. Power analysis (PA) was used to verify the effect of sample size on the results obtained. Results: Eight SNPs identified by Affymetrix were validated by TaqMan assays. The frequencies of ERP29 c.*293AG+GG (30 vs 11%, P=0.03; PA=65%), LEF1 c.*1213AA+AG (95 vs 80%, P=0.02; PA=61%) and g.127267AA+AG (93 vs 78%, P=0.02; PA=56%), MCC c.*5077AA+AG (85 vs 64%, P=0.008; PA=67%), PTCH1 g.27369025GG+GA (90 vs 73%, P=0.005; PA=58%) and g.27369324GG+GA (90 vs 73%, P=0.008; PA=58%), IKBKAP c.3214TT+TA (90 vs 72%, P=0.01; PA=62%) and ZNF415 c.*443AA+AG (59 vs 41%, P=0.02; PA=43%) were more common in patients than in controls. Individuals with these genotypes were at 2.9(CI95%: 1.1-8.4), 3.9 (CI95%: 1.4-11.2), 4.0 (CI95%: 1.2-14.7), 3.5 (CI95%: 1.2-11.9), 5.0 (CI95%: 1.7-16.9), 4.5 (CI95%: 1.5-15.2), 4.1 (CI95%: 1.4-12.9), and 3.9 (CI95%: 1.2-13.7)-fold increased risks for BTSCC than others, respectively. Conclusions: Our data present for the first time evidence that inherited abnormalities in ERP29, MCC, LEF1, PTCH1, IKBKAP, and ZNF415 genes may be important determinants of BTSCC. Financial support: FAPESP and FINEP.
Multicenter, open-end, randomized controlled study using P53 gene recombinant adenovirus injection (rAd-p53) combined with chemotherapy for orofacial carcinoma (OFC): Phase IV clinical trial—Progress report and conclusion.
Authors: Yang Maolin , Li Longjiang 
Published: March 2020

6080 Background: The gene therapy product (Gendicine, rAd-p53) had pre-market studies done around 1998 indicated its efficacy in the treatment of squamous cell nasopharyngeal carcinoma in multi-modality treatment regimen. Gendicine has been used successfully in treating over 40 cancer types since then. With the advancement in optimization of combined treatment methods over the years, there was a need for a medium term efficacy study. This report summarizes our phase IV study. Methods: Patient selection, intervention and allocation were done according to GCP and supported by statistical analysis. Orofacial cancer (OFC) patients of advanced stages (III/IV) from multiple hospitals (n=30) in China were recruited for this open-end, randomized, controlled study (2009.7--2012.06). The 2 groups were rAd-p53+chemotherapy (GT+CT) (n=743) and CT alone (n=232). Patient exclusion rate were 20.81% (n=128) and 13.9% (n=28) respectively. Virus particles were delivered intra-tumorally at a dose of 109 (tumor cell/cm2 tumor area) x area x100 (virus multiplicity of infection, MOI), every 3d totally 10 times on d 1-28 inclusive. In synchrony with GT, 5-fluorouracil (5-FU, 250 mg/m2/d), on d 7-11 and d 25-29 along with carbocisplatin (KP, 400 mg/m2/d, i.v.), and with methotrexate (MTX, 50mg/m2 /d) on d 7, 14, 25, 32 were administered. The control group received 5-FU, KP and MTX. Results: For advanced OFC treated with GT+CT, the efficacy and QoL were significantly (p<=0.001) improved, the result was in accordance with our phase II/ III studies. Conclusions: This study proved rAd-p53 when used as an adjunct is safe and efficacious. The side-effect was mostly self-limiting low-grade to mild fever. The combined treatment modality had complete remission (CR) improved by 21.38%, relief ratio (RR) by 11.53% and clinical benefit ratio by 20.82% over GT-CT. Long-term follow-up will be continued.
Predictive biomarkers in a phase II trial of weekly carboplatin (CBDCA), paclitaxel (P), and cetuximab (C) induction and chemoradiation (CRT) in patients (pts) with resectable stage III/IVa,b head and neck squamous cell carcinoma (HNSCC): Eastern Cooperative Oncology Group E2303.
Authors: Psyrri Amanda , Lee Ju-Whei , Vasilakopoulou Maria , Pectasides Eirini , Burtness Barbara , Rimm David , Wanebo Harold J. , Forastiere Arlene A. 
Published: March 2020

6081 Background: We studied the addition of C to a sequential regimen of weekly CBDCA and P followed by CBDCA-P-radiation in pts with locally advanced resectable HNSCC. Tissue-based biomarkers may aid in pt selection for such approaches. Methods: Sixty-three eligible pts withoperablestage III/IV HNSCC participated in E2303, an Eastern Cooperative Oncology Group (ECOG) phase II trial of induction chemotherapy with weekly C, P and CBDCA x 6 followed by CRT with concurrent weekly C, paclitaxel, carboplatin. A tissue microarray was constructed and b-catenin, E-cadherin, Epidermal Growth Factor Receptor Variant III (EGFRVIII), insulin-like growth factor-1 receptor (IGF1R), NF-kappa b, p53, PI3Kp85, PI3Kp110a, PTEN, ΝRAS, and pRb protein expression levels were assessed using automated quantitative protein analysis (AQUA). For each marker, time-to-event distributions (OS, PFS, and EFS) were estimated by Kaplan-Meier estimates and compared using log-rank tests. Multivariable Cox proportional hazards models were used to estimate hazard ratios and test for significance, with primary site (oropharynx vs. non-oropharynx), disease stage (III vs. IV), and other important markers adjusted in the model. All p-values are two-sided. A level of p < 0.05 is considered statistically significant. Results: Based on the continuous scale, pRb tended to association with EFS (p=0.05). On multivariable analysis, low pRb level was a significant predictor for improved EFS (p=0.048). Our pRb data analysis was based on 32 pts with marker data available. Conclusions: pRb level is a potential predictive biomarker for response to cetuximab. HPV E7 oncoprotein binds and degrades pRb; therefore, low pRb protein level might be a surrogate marker for HPV association.Large prospective studies will be required to determine the association between pRb, HPV status and response to cetuximab in HNSCC.
Combination lapatinib and capecitabine in advanced, incurable squamous cell carcinoma of the head and neck (SCCHN).
Authors: Weiss Jared , Hayes David N. , Algazy Kenneth M. , Desai Arati Suvas , Horn Brenda , Gulino Sara , Flowers Dale , Frazee Diane , Feldman Arthur M. , Staddon Arthur P. , Grilley-Olson Juneko E. , Cohen Roger B. , Langer Corey J. 
Published: March 2020

6094 Background: In an era of increasing use of platinum-based induction chemotherapy and chemoradiotherapy, most metastatic/recurrent SCCHN patients (pts) have received multiple chemotherapeutic agents prior to being diagnosed with incurable disease, at which point PS is often poor, pts are often refractory to multiple agents, and standard therapies (Tx) are unacceptably toxic and inconvenient. Methods: We conducted a phase II study of 44 pts with metastatic/recurrent SCCHN with a primary endpoint of median OS. Pts received capecitabine 1,000 mg/m2 BID for 14/21 day cycles, with lapatinib at 1,250 mg daily for a total of four cycles. In the absence of disease progression or unacceptable toxicity, pts received maintenance Tx with lapatinib. Prior exposure to any chemotherapy other than capecitabine and lapatinib was allowed, as long as it was as part of therapy delivered with curative intent. Results: 36 of 44 planned patients are assessable at this time. 69% had prior resection, 75% prior radiation and 61% prior chemotherapy, of whom 18 (50%) had received prior platinum. Median age was 62, 11 pts (31%) had PS 0, 22 pts (61%) pts had PS1 and 3 pts (8%) had PS2. Median number of cycles given was 4; 14 pts have gone on to maintenance Tx. The most common grade 3-4 adverse events have included dehydration, diarrhea, and hand-foot syndrome, each occurring in 11% of pts. 2 patients did not have RECIST evaluable disease. Of the remaining 34 patients, 6 pts had PR and 1CR, for an ORR of 21% (24% in assessable pts). As of 1-31-13, 20 pts are alive, 2 are lost to followup, and 14 are deceased. Conclusions: The combination of capecitabine and lapatinib is tolerable and active in metastatic/recurrent head neck cancer, including pretreated patients. OS data, not yet mature, will be required to determine if this regimen is worthy of further testing. Clinical trial information: NCT01044433.
Superselective intra-arterial chemotherapy for oral cancer by subcutaneous implantation of an intra-arterial catheter and an infusion reservoir: A new chemotherapy method to improve the quality of life and curative effect.
Authors: Ohmae Masatoshi , Tohnai Iwai , Kato Itsuro , Nakazawa Mitsuhiro 
Published: March 2020

6096 Background: We have developed a superselective intra-arterial chemotherapy (iaCT) approach for oral cancer, in which intra-arterial catheter is retrogradely inserted via the superficial temporal artery (STA) and/or occipital artery (OA). This approach increases chemotherapy efficiency but remarkably decreases activities of daily living (ADL) because the catheter penetrates the skin over the approaching artery (STA/OA). Methods: This study assessed our new outpatient iaCT approach involving implantation of an intra-arterial catheter connected to a subcutaneous infusion reservoir. We included 10 patients who had oral cancer treated using outpatient iaCT: tongue carcinoma, 7; cheek mucosal carcinoma, 1; upper gingival carcinoma, 1; palatal carcinoma, 1. In this approach, the STA or OA or both were percutaneously dissected out, a catheter was inserted, and the catheter tip was superselectively placed in the tumor-feeding artery. The extra-arterial catheter portion was implanted through a subcutaneous tunnel and was connected to a subcutaneous infusion reservoir implanted around the mastoid process. The patients were discharged after catheterization, and the chemotherapeutic agent was intra-arterially administered at the Outpatient Chemotherapy Center of Rinku General Medical Center once or twice a week. Intra-arterial infusion was repeated 6 times per course. Results: The response rate was 100%, i.e., 8 cases of CR and 2 of PR; patients with PR underwent surgery.Their ADLs were scarecely disturbed exept for ambulatory visits. Conclusions: In this approach, the catheter is completely implanted subcutaneously; therefore, usual catheter-related issues (e.g., infection, catheter fall out) rarely occur. Because this leads to very good ADLs, outpatient chemotherapy can be safely performed. Consequently, the quality of life (QOL) improves and medical expenses decrease.Our new outpatient iaCT approach improves QOL of and curative effects for oral cancer patients if the ambulatory convenience and the performance status are good.
Multicenter phase II trial of neoadjuvant carboplatin, weekly nab-paclitaxel, and trastuzumab in stage II-III HER2+ breast cancer: A BrUOG study.
Authors: Sinclair Natalie Faye , Sakr Bachir Joseph , Abu-Khalaf Maysa M. , Somlo George , Black Robert C , Chung Gina G. , Rizack Tina , Strenger Rochelle , Fenton Mary Anne , DiGiovanna Michael , Constantinou Maria , Lannin Donald R. , Legare Robert Duffy , Chagpar Anees B. , Sambandam Sundaresan T. , Bossuyt Veerle , Rosati Kayla , Harris Lyndsay , Sikov William M. 
Published: March 2020

619 Background: Patients (pts) with human epidermal growth factor receptor-2 amplified (HER2+) breast cancers (BrCa) who achieve a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) + trastuzumab (T) have an excellent prognosis (Cortazar, SABCS 2012). We tested a novel NAC + T regimen, designed to avoid potential cardiac and other toxicities associated with anthracyclines (A) and eliminate steroid premedication by replacing standard paclitaxel with nab-paclitaxel (nP). Methods: Clinical stage IIA-IIIC HER2+ BrCa pts received single agent either nP or T, with research biopsies and MRIs obtained before and after, then carboplatin (Cb) AUC 6 q3wks, nP 100 mg/m2and T 2 mg/kg weekly x 18 wks. If present, residual tumor was collected at surgery. Post-op pts complete a year of T; other adjuvant treatment is at MD discretion. Endpoints include clinical + pathologic response (pCR is defined as no invasive BrCa in breast + axillary nodes), residual cancer burden (RCB), treatment delivery and toxicities. Results: 53 pts (of 60 planned) are evaluable for response, median age 51 (34-72). Median delivered dose intensity for nP was 89 mg/m2/week; nP doses were omitted or reduced for neutropenia (ANC) (in 20% of pts) and neurotoxicity (Nt) (5%). Cb was reduced for thrombocytopenia (tcp) in 15%. Grade 3-4 toxicities: ANC 65%, tcp 22%, anemia 37%, Nt 7%. Serious adverse events: febrile neutropenia (5 pts), infections w/o neutropenia (4), vomiting, diarrhea or dehydration (7), thrombosis (2). LVEF fell by >10% in 3 pts with no clinical CHF. Response data are tabulated below: 28 pts (53%) achieved pCR or RCB class I; 15/21 who did not received A-based adjuvant chemotherapy. Of 38 clinically node-positive pts, 26 (68%) were node-negative at surgery. Conclusions: The Cb/nP/T regimen was well tolerated, with pCR rates comparable to those reported with A-containing regimens. Final treatment and response data will be presented; correlative studies will be reported separately. Clinical trial information: NCT00617942. [Table: see text]
Longer-term cardiac safety and outcomes of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC).
Authors: Morris Patrick Glyn , Iyengar Neil M. , Patil Sujata , Chen Carol , Abbruzzi Alyson , Lehman Robert James , Steingart Richard , Oeffinger Kevin C. , Lin Nancy , Moy Beverly , Come Steven E. , Winer Eric P. , Norton Larry , Hudis Clifford , Dang Chau T. 
Published: March 2020

630 Background: The addition of H to chemotherapy has improved outcomes in HER2-positive early BC. This approach is associated with (w/) an increased risk (<4%) of congestive heart failure (CHF). At a median f/u of 36 months, the addition of anti-HER2 Rx to dose-dense (every 2 weeks) anthracycline-taxane therapy (Rx) was not associated with excess cardiotoxicity. Here we report the incidence of NYHA Class III/IV CHF in 2 phase II studies with longer follow-up. Methods: We conducted a retrospective review of pts w/ HER2 + early stage BC treated at MSKCC and DF/HCC on two trials: In trial A - pts received dd AC (60/600 mg/m2) x 4 → T (175mg/m2) x 4 (w/ pegfilgrastim) w/ H x 1 year. Trial B differed w/ use of weekly T (80mg/m2) x 12 and the addition of L (1000mg orally daily) x 1 year. In both trials, H was begun after completion of AC and concurrent with T. Left ventricular ejection fraction (LVEF) was prospectively assessed by multi-gated acquisition scan serially throughout Rx. Results: Trial A enrolled 70 pts and Trial B enrolled 95 pts w/ the median age of 46 years (range 27-73 years). Overall, the 5-year distant disease-free survival (DDFS) for trials A and B is 92% (95%Cl; 83-97%) and 89% (95%CI; 81-94%), respectively. The baseline median LVEF was 68% (range 52-81%). In total, 28 of 165 (17%) pts had pre-existing hypertension. Now at a median follow-up of 84 and 57 months respectively, only one (1.4%, 95%CI; 1.36-7.7%) and 4 (4.2%, 95%CI; 4.2-10.4%) pts developed CHF. Since our earlier report, 1 additional CHF event occurred (Trial B) at month 44. Conclusions: Longer follow-up of these 2 studies demonstrate that dd AC → TH with or without L is associated w/ a low risk of CHF. This is consistent w/ the long-term cardiac toxicity reported from the randomized phase III studies of H w/ conventionally scheduled anthracycline-based regimens (with or without taxanes). DDFS outcomes are also encouraging. Clinical trial information: NCT00482391.