bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative morbidity after completion surgery in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma
Authors: Touboul C. , Uzan C. , Gouy S. , Rey A. , Maugen A. , Delpech Y. , Chanelles O. , Pautier P. , Lhomme C. , Duvillard P. , Haie-Meder C. , Morice P. 
Published: August 2020

5595 Background: The aim of this study was to evaluate the morbidity rate in patients undergoing completion surgery after homogeneous chemoradiation therapy (CRT) for locally advanced stage cervical cancer. Methods: Patients fulfilling following inclusion criteria were studied: 1. Stage IB2-IVA cervical carcinoma; 2. Tumor confined radiologically initially to the pelvic cavity; 3. Pelvic external radiation therapy with delivery of 45 Gy in pelvic cavity with concomitant chemotherapy (cisplatin 40 mg/m2/week) followed by utero-vaginal brachytherapy; 4. Completion surgery after the end of radiation therapy including at least a hysterectomy. Modalities of this completion surgery depended on the presence, location and size of residual disease. Results: One-hundred and fifty patients treated between 1998 and 2007 fulfilled inclusion criteria. Modalities of hysterectomy performed were: extrafascial hysterectomy in 106 (71%) patients and radical hysterectomy in 44 (29%). Para-aortic lymphadenectomy was performed in 131 (87%) patients and pelvic lymphadenectomy in 34 (23%) patients. Thirty-four (23%) patients had macroscopic (> 1 cm) residual disease on pathologic examination. Twenty-five (23%) patients had post-operative complications (in whom 17 severe morbidity requiring surgical or radiological treatment). Presence of residual disease was the only factor associated with overall morbidity rate in univariate and multivariate analysis. The use of radical hysterectomy and pelvic lymphadenectomy increased significantly the rate of severe morbidity (particularly bowel and urinary tract morbidity). Conclusions: In the present study involving a large number of patients undergoing completion surgery after homogeneous CRT in locally advanced cervical carcinoma the morbidity rate is important. Radical hysterectomy and pelvic lymphadenectomy increase the rate of severe morbidity. The interest on the survival of this completion surgery should be evaluated in prospective trial. No significant financial relationships to disclose.
Effect of BRAFV600E on response to sorafenib in advanced thyroid cancer patients
Authors: Brose M. S. , Troxel A. B. , Redlinger M. , Harlacker K. , Redlinger C. , Chalian A. A. , Flaherty K. T. , Loevner L. A. , Mandel S. J. , O'Dwyer P. J. 
Published: August 2020

6002 Background: We are conducting an open-label phase II study of sorafenib in patients with metastatic, iodine-refractory thyroid carcinoma. Methods: 55 Patients were administered sorafenib 400 mg orally BID. Responses were monitored by PET and CT. Primary endpoints were response rate (RR) and progression free survival (PFS) by RECIST criteria. BRAF and RAS mutation status is determined by DNA sequencing. Outcome data is evaluated using the Kaplan-Meier method and log-rank test. Biologic activity in tissue obtained during treatment at response and progression is being explored using immunohistochemistry (IHC) to pERK, pAKT and Ki-67 among others, in pretreatment blocks from virtually all patients, and a subset of 14 patients in whom on-treatment tissue is available. Results: We have completed accrual of the 55 patients planned for enrollment; median time on study is 34 weeks and 25 pts (45%) are male. Histological subtypes include papillary (PTC): 25 pts (47%); follicular/Hürthle Cell (FTC): 19 pts (36%); medullary: 4 pts (8%), and poorly differentiated/anaplastic: 5 pts (9%). 52/55 patients are evaluable for response at this time. Median PFS was 84 wks. Genotyping of BRAF is complete in 16 patients. For patients with PTC/FTC, the PFS for those with BRAFwt was 54 wks compared to 84+ wks for patients with BRAFV600E (p = 0.028). On-treatment tissue at progression demonstrates heterogeneity, with p-ERK and p-AKT suppressed in some areas, but highly expressed in others. Data at 6 months post accrual of the last patient will be presented along with patient thyroglobulin levels, PET and CT scans. IHC and additional genotyping will also be presented. Conclusions: Sorafenib has activity in patients with advanced thyroid cancer with an overall PFS of 84 wks. While most patients with PTC or FTC achieve durable responses, patients whose tumors harbor BRAFV600E have significantly longer PFS than those that are BRAFwt. [Table: see text]
Randomized study of darbepoetin alfa as modifier of radiotherapy in patients with primary squamous cell carcinoma of the head and neck (HNSCC): Final outcome of the DAHANCA 10 trial
Authors: Overgaard J. , Hoff C. M. , Hansen H. S. , Specht L. , Overgaard M. , Grau C. , Andersen E. , Johansen J. , Andersen L. J. , Evensen J. F. ,   Danish Head and Neck Cancer Group (DAHANCA)
Published: August 2020

6007 Background: The study aimed to evaluate if correction of low hemoglobin (Hb) levels by means of the erythropoietin stimulating agent: darbepoetin alpha (Aranesp) during radiotherapy (RT) improves outcome in patients with HNSCC. Following a planned interim analysis which showed inferiority of the experimental treatment, the trial was stopped in November 2006. Methods: Pts with HNSCC eligible for primary RT alone and with Hb values below 14.0 g/dl were randomized to receive Aranesp together with accelerated fractionated RT. Pts. were stratified according to gender, T and N staging, tumor site, and institution. Aranesp was given subcutaneously in a dose of 150 micrograms weekly during RT, or stopped earlier if the Hb exceeded 15.5 g/dl. Results: In total, 522 patients (of a planned intake of 600) were included at the time of the interim analysis. Of these 514 pts were eligible for analysis (255 pts treated with Aranesp and 259 pts in the control group) with a median follow up of 49 months. Among these, 201 developed a loco-regional failure (primary endpoint). There have been 238 deaths of which 176 are due to HNSCC. The patients were evenly distributed according to the stratification parameters (gender, T and N staging, tumor site, institution).Aranesp resulted in the expected increase in Hb in more than 81% of the patients. The compliance to Aranesp was good with no significant difference in serious (cardiovascular) adverse events (3% vs. 1%). Overall, the results showed a poorer outcome in 5-year loco-regional control (59% vs. 68% (p = 0.04, RR: 1.47 [1.14–1.94]) for the Aranesp vs. control arm. This was also seen for the endpoint of disease-free survival (37% vs. 47%, p = 0.02, RR: 1.32 [1.04–1.68]), whereas there was no significant difference in overall survival (40% vs. 51%, p = 0.16, RR: 1.20 [0.93–1.55]). There were no differences in radiation related morbidity. All univariate analyses were confirmed in a multivariate setting. Conclusions: Correction of the Hb level with Aranesp in patients with HNSCC resulted in a significantly poorer tumor control after radiotherapy. The treatment principle was abandoned and the difference in outcome is being subjected to further examination. No significant financial relationships to disclose.
A randomized double-blind phase III study of efficacy of lactobacillus CD2 lozenges in preventing radiation- and chemotherapy-induced oral mucositis in head and neck cancer patients: Interim analysis
Authors: Sharma A. , Rath G. K. , Choudhary S. P. , Thakar A. , Mohanti B. K. , Bahadur S. , Sahu A. R. , Johar A. , Dwary A. 
Published: August 2020

6008 Background: Oral mucositis is major toxicity in patients receiving RT with or without chemotherapy (CTRT) for squamous cell carcinoma of head and neck (SCCHN). This compromises ones ability to tolerate and complete treatment. Interventions available till date to limit and restrict mucositis are unsatisfactory. This study was undertaken to test the efficacy of lactobacillus CD2 in rendering patients more tolerant to the anticancer therapy. Methods: Prospective randomized double blind phase III study. Inclusion criteria were: resectable SCCHN patients suitable for CTRT or radical RT, age group 18–70 years, KPS>70%, normal hematological and biochemical functions. Eligible patients were randomized to receive total of 6 lozenges (to be dissolved by itself in the mouth) of either study product or placebo daily from the day anticancer treatment was started until one week after completion of anticancer therapy. Randomization was done in block of 10 patients. Initially it was planned to enroll 150 evaluable patients but protocol was amended to have total of 200 patients, to have interim analysis after 150 evaluable patients. This would have α and β error of 0.05 and 0.20, respectively. RT was given as 70 Gy/ 35# over 7 weeks with cisplatin 40 mg/m2 weekly x 7. Study was started in January 2007. Primary end points are: percentage of patients able to complete anticancer treatment and incidence of grade 3 and 4 mucositis. Results: This analysis was carried out on first 150 evaluable patients (75 in each arm). 135 were stage III or IV. Forty one (54.7%) in study arm and 36 (48%) in placebo arm took lozenges as planned (p = 0.414). Sixty seven (89.3%) in study arm and 56 (74.7%) in placebo arm could complete anticancer treatment (two sided p = 0.023). Grade 3 and 4 mucositis was seen in 40 (55.6%) and 44 (58.9%) patients respectively in study product and placebo arms (two sided p = 0.062). Conclusions: Study met one of its primary endpoint. Significantly more patients could complete anticancer treatment in study product arm and there was reduction in incidence of grade III and IV mucositis. We expect final results to be available before meeting. [Table: see text]
Low pathologic complete response (pCR) rate to neoadjuvant chemotherapy in invasive lobular carcinoma of breast: Analysis of subgroup of four phase II trials
Authors: Khosravi-Shahi P. , Izarzugaza Peron Y. , Perez-Manga G. 
Published: August 2020

601 Background: Pathologic complete response (pCR) after preoperative chemotherapy (PCT) is associated with better outcome in locally advanced breast cancer (LABC). However, the pCR rate according to histology usually is not considered in trials. Methods: Patients (p) with histologically confirmed lobular carcinoma (LC), including in four phase II trials (AT, ATX, TXH, and BTX) conducted in our center, were eligible. Radiotherapy (RT) and hormone therapy (Ht) were allowed after surgery. Expression of markers was determined by IHC before CT. Primary objective of the study was to evaluate pCR rate in this subgroup of ps. Secondary endpoints were: clinical response rate (CRR), breast conservative surgery rate (BCSR), pathologic tumoral size (pTS), disease-free survival (DFS), and overall survival (OS). Results: A total of 185 ps including in the four trials were evaluated. Sixteen ps had LC (16/185 = 8.65%): median age = 50 y (38–66); premenopausal = 56.2%; left breast = 56.2%; median clinical (c) tumor size = 5 cm (3–6); stage:IIA = 6.7%; IIB = 26.7%; IIIA = 33.3%; IIIB = 33.3%; T:cT3 = 50%; cT4 = 28.6%; cN+ = 71.4% (median pN = 2 [0–32]); grade: G2 = 60%, G3 = 40%; ER+ = 78.6%; PgR+ = 64.3%; HER-2+ = 6.25%; phenotype by IHC: Luminal (HR+/HER-2-) = 75% (12/16); Luminal/HER-2+ (HR+/HER-2+) = 6.25%; triple negative (3/16) = 18.75%; p53+ = 25%; EGFR negative = 90%; median Ki-67 = 20% (5–70); adjuvant trastuzumab (H) = 6.25%; RT = 60%, median dose = 50Gy; Ht = 78.6% (tamoxifen = 55%; AI = 45%); type of PCT: docetaxel (T), capecitabine (X), and H (TXH) = 1p (6.2%); doxorubicin (A), T, and X (ATX) = 5 ps (31.2%); bevacizumab, T, and X (BTX) = 5 ps (31.2%); AT = 5 ps (31.2%); median of 5 cycles (2–6). Primary End-Point: Only 1 p (6.25%) had pCR in breast and nodes, and another p had a pCR only in breast, but not in nodes (pCR in breast = 2/16). Second End-Points: 1) CRR = 56.25% (complete = 12.5%; partial = 43.75%; no response = 37.5%; progression = 6.25%); 2) BCSR = 12.5%; 3) Median pTS = 2 cm(0 cm-6 cm); 4) Survival data are not mature. Only four events had occurred. With a median follow-up of 31 months, median DSF and OS has not been reached. Four-years DFS = 57%; and 3-y OS = 81%. Survival data will be updated in the meeting. Conclusions: PCT in LC is associated with very low pCR. No significant financial relationships to disclose.
Sequential chemoradiotherapy (SCRT) for larynx preservation (LP): Preliminary results of the randomized phase II TREMPLIN study
Authors: Lefebvre J. , Pointreau Y. , Rolland F. , Alfonsi M. , Baudoux A. , Sire C. , de Raucourt D. , Bardet E. , Tuchais C. , Calais G. ,   Groupe Oncologie Radiotherapie Tete Et Cou (GORTEC)
Published: August 2020

6010 Background: Induction chemotherapy (ICT) followed by irradiation (RT) and concurrent chemoradiotherapy (CRT) are validated options for LP. Docetaxel-based ICT, concurrent cetuximab and RT are new options and SCRT (ICT followed by CRT) has been reported as a potential new approach. However, to date there are no data assessing SCRT specifically for LP. Methods: Previously untreated patients (pts) with larynx or hypopharynx squamous cell carcinoma and candidates for a total laryngectomy were eligible for this randomized phase II study. Eligible pts received 3 cycles of ICT (docetaxel and cisplatin both 75 mg/m2 on day 1 and 5-FU 750 mg/m2/day on days 1–5). In case of response ≥ 50 % pts were randomized to receive either in arm A: RT (70 Gy) with cisplatin (100 mg/m2 on days 1, 22 and 43 of RT) or in arm B: Cetuximab (400 mg/m2 loading dose before RT and 250 mg/m2 on the first day of the 7 weeks of RT. Pts with response < 50% had salvage surgery. Primary endpoint was LP 3 months after treatment, secondary endpoints were larynx function preservation at 18 months, quality of function and tolerance to treatment. Results: From March 2006 to April 2008 (end of accrual), 153 pts with stage III-IV larynx/hypopharynx cancer were enrolled in the study and could start ICT. Of them 74 % could receive the planned ICT while the others had either reduced dosages or less than 3 cycles. Toxic deaths occurred in 3 pts (2%). Of the 147 evaluable pts after ICT, 22 were non-responders (15%), 4 pts were withdrawn from the study, 6 responding pts with ICT-related toxicity precluding any further cisplatin could not be randomized and finally 115 pts could be randomized (59 in arm A and 56 in arm B). 3 months after treatment there was no significant difference in LP (93% in arm A and 96% in arm B). In arm A, 45 % of pts could receive the full CRT protocol vs 71 % in arm B. In arm A 50% of pts had cisplatin-related toxicity (definitive in 52% the cases) while in arm B 26 % of patients had cetuximab-related toxicity (definitive in only 1 case). There was no CRT treatment-related death. Conclusions: SCRT is considered for LP. ICT followed by RT with concurrent cetuximab appeared better tolerated than with concurrent cisplatin with the same LP rate 3 months after treatment. [Table: see text]
A phase II randomized study of oral seliciclib in patients with previously treated nasopharyngeal carcinoma
Authors: Yeo W. , Goh B. , Le Tourneau C. , Green S. R. , Chiao J. H. , Siu L. L. 
Published: August 2020

6026 Background: Seliciclib is a selective inhibitor of cyclin dependent kinases (CDKs) 2, 7 and 9. In a phase I study of 2 weeks of oral administration, clinical antitumor activity was observed in patients with treatment-naive nasopharyngeal carcinoma (NPC) and biological effects consistent with CDK inhibition were detected in tumor biopsy samples. We are conducting a multicenter, randomized phase 2 study to evaluate the safety and efficacy of prolonged administration of seliciclib in patients with previously treated NPC. The study has a lead-in phase where the safety and tolerability of 2 dosing schedules of seliciclib are to be confirmed in patients with advanced solid tumors (including NPC) before being used in the randomized phase of the study where only NPC patients are eligible to participate. The primary efficacy endpoint is 6-month progression free survival. Here we report interim findings from the lead-in phase. Methods: Eligible patients must be ≥18 years with previously treated NPC or other incurable solid tumors; must have measurable disease according to RECIST, ECOG 0–1, and adequate bone marrow, hepatic and renal function. The planned sample size is 6 to 12 patients per dosing schedule. A dosing schedule is considered tolerable for proceeding to the randomized phase if <33% patients experienced dose-limiting toxicities (DLT) during the first treatment cycle. Results: Twenty-three patients (age 38 - 74) were enrolled and treated. DLTs were observed in 4 patients: grade 3 increase in ALT or AST (n=3), and treatment delay > 2 weeks for grade 1 creatinine (n=1). Common adverse events (all grades, regardless of causality) included fatigue, nausea/vomiting, constipation, cough, fever, hypokalemia, hyponatremia, and elevation in ALT/AST, most of which were mild to moderate in intensity. Conclusions: These interim data confirm that both dosing schedules are tolerable for proceeding to the randomized phase. Majority of stable disease occurred in NPC patients. Updated data will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.
Screening of nasopharyngeal carcinoma by serology and nasopharyngoscopy and treatment outcome in endemic region
Authors: Chua D. T. , Ji M. , Zong Y. , Chan K. , Ng M. 
Published: August 2020

6029 Background: To study the incidence and treatment outcome of nasopharyngeal carcinoma (NPC) detected by serology and nasopharyngoscopy in endemic region. Methods: A prospective screening program for NPC using Epstein-Barr virus-specific viral capsid antigen IgA antibody level and nasopharyngoscopy was carried out in Southern China from 1996 to 2002. Subjects without NPC at the time of enrollment were followed-up annually by serology and clinical examination irrespective of their serology status. Subjects diagnosed to have NPC at the time of enrollment or during follow-up received conventional radiotherapy using megavoltage photon. Results: A total of 42,048 adults in Zhongshan city of China were enrolled into the screening program. About 7.4% had elevated IgA titre at the time of enrollment. NPC was diagnosed at first screening in 40 subjects and during follow-up in 131 subjects. Among the 171 NPC patients, 74 were asymptomatic and the disease was detected by the screening procedures, whereas the disease was detected in 97 following onset of symptoms. Stage distribution in those diagnosed by screening program was 59.5% stage I, 8.1% stage II, 21.6% stage III, and 10.8% stage IV. The corresponding stage distribution in subjects diagnosed after onset of symptoms was 7.2%, 12.4%, 39.2%, and 41.2%. In all NPC patients the IgA titre was found elevated and there was a serologic window in which the raised titre preceded the diagnosis of NPC for a period of up to 10 years. The median interval of this serologic window was 29 months in patients with stage I NPC and 39 months in those with stage II-IV disease. The 5-year disease-specific survival rate was 90% for stage I disease, 56% for stage II, 48% for stage III, and 52% for stage IV. Conclusions: Screening by serology and nasopharyngoscopy leads to the early diagnosis of NPC in endemic region with a high survival rate after treatment for stage I disease. In view of the rapid transition of disease from stage I to more advanced stage, a screening interval shorter than 10 months is recommended for subjects entering the serologic window. No significant financial relationships to disclose.
Outcome and molecular features of head and neck squamous cell carcinomas (HNSCC) bearing a p16 high phenotype
Authors: Psyrri D. , Pectasides E. , Weinberger P. , Sasaki C. , Burtness B. , Fountzilas G. 
Published: August 2020

6031 Background: We have previously demonstrated that p16 expression defines a biologically distinct subgroup of oropharyngeal squamous cell cancers (OSCC). Thus, OSCC can be Class I: human papillomavirus (HPV)-, Class II: HPV16+/p16-, or Class III: HPV16+/p16+. Tumors bearing a high p16 phenotype were associated with superior outcome. Using in situ automated quantitative protein expression analysis (AQUA) to explore the biomarker signatures of these 3 classes we found that beta-catenin, epidermal growth factor receptor (EGFR) and Met were upregulated in class III tumors. Our aim was to validate these findings using an independent cohort. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for a panel of 13 markers (EGFR, MET, STAT 3, ERK 1/2, pAkt, PI3Kp85, PI3Kp110, PTEN, p53, Bcl-2, E-cadherin, β-catenin, NFκB) were analyzed using AQUA. P16 protein levels were correlated with progression-free (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance.Comparison of expression between the p16 positive and p16 negative groups was done using unpaired t-tests. Results: Mean follow-up time for the cohort was 40 months. AQUA scores were divided into quartiles. Survival analysis showed that patients in the top quartile had a significantly better DFS (p = 0.01) and OS (p = 0.002). In multivariable analysis, adjusting for well-characterized prognostic variables, p16 expression retained its prognostic significance. Expression of E-cadherin and β-catenin was significantly higher in the p16 positive versus the p16 negative group (p = 0.014 and p = 0.006, respectively). p16 positive tumors also expressed higher levels of PTEN (p = 0.0009), PI3Kp110 (p = 0.03), NFκB (p = 0.007), and Bcl-2 (p = 0.005). Conclusions: These results validate p16 as a favorable prognostic marker in HNSCC. They also validate beta-catenin as a distinct biomarker in HNSCC bearing high p16 phenotype. Given that HPV+ tumors are p16+, beta-catenin is a candidate biomarker that distinguishes HPV+ versus HPV- HNSCC. No significant financial relationships to disclose.
Clinical significance of type 1 insulin-like growth factor receptor and insulin-like growth factor binding protein-3 expression in squamous cell carcinoma of head and neck
Authors: Jun H. , Chang M. , Ko Y. , Ahn Y. , Jeong H. , Son Y. , Baek J. , Park Y. , Park K. , Ahn M. 
Published: August 2020

6036 Background: Type 1 insulin-like growth factor receptor (IGF-1R) plays an important role in the growth and apoptosis of cancer cell. The activities of IGF-1R are modulated by a family of high-affinity insulin-like growth factor binding proteins (IGFBPs), of which IGFBP-3 is the major serum carrier protein. The expression and significance of IGF-1R and IGFBP-3 in squamous cell carcinoma of the head and neck (SCCHN) is unknown. Methods: This study explored immunohistochemical expression of IGF-1R and IGFBP-3 in tumor samples from 131 patients with surgically resected SCCHN. Results: The positive expression of IGF-1R and IGFBP-3 was observed in 96 (73.3%) and 117 (89.3%) patients. There were no significant differences in baseline characteristics between the positive and negative expressed groups of IGF-1R and IGFBP-3. With the median follow up of 53.5 months, 3 year progression free (PFS) and overall (OS) survival rate was 64.0% and 72.9%, neither IGF-1R nor IGFBP-3 expression had prognostic values in the whole cohort. Thirty-seven (67.3%) of 55 stage IV patients demonstrated IGF-1R positivity. The subgroup analysis of in stage IV patients showed the poor PFS ( = 0.029) and OS (pp = 0.025) in IGF-1R positive groups. In a multivariate analysis using IGF-1R expression and other clinicopathological parameters, the IGF-1R expression was remained as an independent factor for PFS (p = 0.037, HR = 2.816, 95% C.I. 1.065 - 7.446) and OS (p = 0.034, HR = 3.169, 95% C.I. 1.089 - 9.225). Conclusions: Our work exhibited that IGF-1R expression is frequent in SCCHN patients and related with poor survival in advanced stage, this could support the attempts using the IGF-1R inhibitor for treatment of SCCHN. No significant financial relationships to disclose.