bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR-KRAS genotyping and EGFR-CDX2 expression in sinonasal intestinal type adenocarcinomas: Toward a new targeted therapy?
Authors: Choussy Olivier , Abramovici Olivia , Paviot Alexandre , Lamy Aude , Dehesdin Daniele , Sabourin Jean-Christophe 
Published: March 2020

5565 Background: Sinonasal carcinomas are very rare tumors which are sometimes not eligible for curative surgery. Alternative therapies (i.e. conventional chemotherapies/radiotherapy) are used but with poor results. Therefore, the need for a more efficient treatment is mandatory. Aims of our study: Comparing EGFR and KRAS genetic profiles, EGFR and CDX2 phenotypes of sinonasal intestinal type adenocarcinomas (ITAC) with colorectal adenocarcinomas (CRC). Methods: 41 patients were treated in our institution between 1983 and 2007. All pathological specimens were reclassified according to the 2005 WHO classification. An immunohistochemical (IHC) study was carried out for EGFR and CDX2 expression. We were able to analyze 38 of the 41 specimens for KRAS and EGFR mutations. SNaPshot multiplex system was used to determine the presence of the most common mutations which are located in exon 18, 20 and 21 for EGFR and in exon 2 (codon 12 and13) for KRAS. Fragment analysis method was used for EGFR exon 19 deletions. Results: Thirty five of the 38 patients were classified as ITAC (33 men and 2 women). The mean age was 64.5 years. Exposure to wood work was found in 29 cases (85%). CDX2 expression was present in 31 (89%) cases of ITAC and absent in all non intestinal adenocarcinomas (3 cases). EGFR was expressed in 29 ITACs (83%) with various degrees of IHC expression: 19 (56 %) 1+, 7 (21%) 2+, and 3 with 3+ immunopositivity. No EGFR mutation was found in the whole population; 5 ITAC patients (14%) disclosed KRAS mutations. Conclusions: Histological, phenotype and genetic profiles of ITAC are very similar to those of colorectal adenocarcinoma. These results suggest that ITACs with wt KRAS could respond to anti MoAb anti-EGFR therapy in the same way as metastatic CRC. We propose that all sinonasal tumors should undergo: firstly, CDX2 IHC in order to confirm the ITAC histological subtype and then KRAS genotyping to select the wt population which could benefit from such anti EGFR targeted therapy.
ECOG 1308: A phase II trial of induction chemotherapy followed by cetuximab with low dose versus standard dose IMRT in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx (OP).
Authors: Marur Shanthi , Lee Ju-Whei , Cmelak Anthony , Zhao Weiqiang , Westra William H. , Chung Christine H. , Gillison Maura L. , Gilbert Jill , Bauman Julie E. , Wagner Lynne I. , Ferris Robert L. , Trevarthen David R. , Colevas A. Dimitrios , Jahagirdar Balkrishna N. , Burtness Barbara ,   Eastern Cooperative Oncology Group
Published: March 2020

5566 Background: Human papillomavirus (HPV) infection is now recognized as a risk factor of oropharyngeal squamous cell carcinoma (OPSCC) and approximately 60% of OPSCC are HPV positive (+). ECOG 2399 using induction chemotherapy (IC) followed by chemoradiation demonstrated significantly improved 2-yr progression-free survival (PFS; 85% vs. 50%, p=0.05) and overall survival (OS; 94% vs. 58%p=0.004). These results have generated interest in development of less toxic regimens for HPV(+) patients with lower dose radiation. Methods: Design: This is a phase II clinical trial .The primary objective is the estimation of the 2-year PFS in the reduced dose RT arm. Secondary objectives include toxicity, OS, objective response, quality of life (QOL) and correlative studies of biomarkers. Eligibility Criteria: Patients with Stage III or IV resectable HPV(+) OPSCC. HPV(+) disease is defined as p16 IHC strongly (+) on at least 70% of cells, and/or HPV-16 ISH (+).Treatment : Patients received IC with a combination of paclitaxel 90mg/m2 on days 1,8, and 15, cisplatin 75mg/m2 on day 1, and cetuximab loading dose of 400 mg/m2 on day 1, cycle 1 followed by cetuximab 250 mg/m2 weekly, thereafter. Each cycle was 21 days for a total of 3 cycles. After completion of IC, patients were assessed clinically with a complete head and neck exam and imaging studies. Those with clinical CR at primary site received radiation to 54Gy plus cetuximab. Patients with clinical PR or SD at primary site received standard dose RT with cetuximab. Correlative Studies: The expression of biomarkers on tumor and blood samples and QOL parameters will be correlated with the clinical outcomes. Results: Current enrollment: Target accrual was 83 patients. The study accrued 90 patients from March 17, 2010 to accrual on October 19, 2011. Baseline characteristics reveal; median age 57 years, 94% male, 95% white, 47% never smokers, 10% <10 pack year (pyr) smoking, 38% >10 pyr smoking, 84% not current smokers, 39% node (N) stage N2b and 29% N2c, 22% tumor (T) stage T1, 52% T2, 16% T3, and 10% T4. Conclusions: Enrollment has just completed with no data analysis available.
Paranasal sinus squamous cell carcinomas (PNSSCC) incidence and survival trends.
Authors: Ansa Benjamin , Goodman Michael , Ward Kevin , Kono Scott A. , Owonikoko Taofeek Kunle , Grist William , Wadsworth Trad , El-Deiry Mark , Chen Amy Y. , Ramalingam Suresh S , Beitler Jonathan Jay , Khuri Fadlo Raja , Shin Dong M , Saba Nabil F. 
Published: March 2020

5570 Background: PNSSCC are rare, accounting for 3 percent of all head and neck malignancies. They generally present with local invasion and have a high rate of local recurrence. There has been little information on the trends in incidence and survival of PNSSCC and no randomized trials to guide therapy. We analyzed the incidence rates and survival outcomes for patients diagnosed with PNSSCC in the SEER database. Methods: Data were obtained from the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Newly diagnosed PNSSCC reported to SEER from 1973 through 2008 were categorized according to the patient’s sex, age, year of diagnosis, and stage. The incidence and survival were then examined and compared across different demographic and disease-related categories. Results: A total of2,323 patients were identified. The mean age was 62 years, range: 14-85 yrs; males- accounted for 62.7%. Whites accounted for 75.8%, blacks for 12.2 % and 12.0% were of asian or pacific islanders and other groups. Maxillary sinus primary accounted for 76.3%, ethmoid (10.2%), sphenoid (4.3%). The disease was localized in 9.5%, had regional spread in 72.0% and distant disease in 12.2%, at diagnosis. A statistically significant decrease (Annual Percent Change of -1.6%, 95%CI= [-2.0, -1.1]) in the overall incidence was observed by Joinpoint analysis (p<0.01). The decrease in incidence was significant in patients with maxillary sinus (p<0.01) and was more pronounced in the white population compared to other groups. Both the observed and relative 5-year survival significantly increased over time and this was more notable in the white population compared to other groups. The observed 5-year survival rate increased from 24.9% (95% CI = [20.3-29.6]) during the 1975-1983 time-period to 40.8% (95% CI = [33.4-48.0]) during the most recent period of 2002-2008. Conclusions: There has been a decline in the overall incidence of PNSSCC more notably in the white population and for patients with maxillary sinus tumors. The 5-year observed and relative survival has significantly increased. Our findings should incite more efforts to understand the factors behind the change in incidence and survival.
Predictors for response to cetuximab in a prospective clinical trial (E2303) of patients with head and neck squamous cell carcinoma (HNSCC).
Authors: Psyrri Amanda , Lee Ju-Whei , Pectasides Eirini , Vassilakopoulou Maria , Burtness Barbara , Rimm David , Wanebo Harold J. , Forastiere Arlene A. 
Published: March 2020

5576 Background: Theidentification of resistance mechanisms to Epidermal Growth Factor Receptor (EGFR) inhibitors remains critical lack in the management of HNSCC. We sought to determine predictors for response to cetuximab in a phase II clinical trial. Methods: 63 patients (pts) with operable stage III/IV HNSCC participated in E2303, an Eastern Cooperative Oncology Group (ECOG) phase II trial of induction chemotherapy with weekly cetuximab, paclitaxel and carboplatin x 6 followed by chemoradiotherapy with the same regimen. A tissue microarray was constructed and EGFR, ERK1/2, Met, pAkt and STAT protein expression levels were assessed using AQUA. The objectives of analysis were to determine association of biomarkers with E2303 efficacy outcomes (best objective response (OR), overall survival (OS), progression-free survival (PFS), and event-free survival (EFS)). The logistic regression model was used to examine relationship between marker measurements (on a continuous scale) and OR. The univariate and multivariate Cox proportional hazards models were used to evaluate the relationship between markers and event-time distributions. Fisher’s exact test was used to evaluate differences in response rate between groups (high vs. low AQUA scores). Event-time distributions were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: Cytoplasmic ERK1/2 levels weresignificantly associated with PFS and OS (p=0.03 and 0.01, respectively). Nuclear ERK1/2 levels were significantly associated with OS (p=0.02) and tended towards significance for PFS (p=0.09). The multivariate Cox regression analysis shows that cytoplasmic and nuclear ERK1/2 are significantly associated with OS and PFS after controlling for primary site and disease stage, respectively There was no significant association between cytoplasmic or nuclear ERK1/2 status and OR (p-values 0.98 and 0.41, respectively).No association was found between expression of any of other biomarkers and outcome measures. Our data analysis was based on 35 pts with marker data available. Conclusions: Ras/MAPK/ERKpathway may be associated with resistance to cetuximab in HNSCC.
A combined evaluation strategy of FDG PET/CT and contrast-enhanced diagnostic CT (ceCT) for lymph nodes in the neck.
Authors: Gandikota Neetha , Ng Su Ann , Cotter Ryan , Akin Yildiz , Som Peter M. , Genden Eric , Heiba Sherif , Kostakoglu Lale 
Published: March 2020

5578 Background: Accurate assessment of cervical lymph nodes (LNs) for determination of metastatic involvement is of prime importance for management. Our objective was to determine the incremental value of combining metabolic and morphologic information in the differentiation between benign and malignant LNs. Methods: A total of101 pts with head and neck squamous cell (n=91) or thyroid cancer (n=6) or lymphoma (n=4) were included in the study. PET/CT and neck ceCT were acquired simultaneously or sequentially at staging (n=48) or restaging (n=53). In 131 LNs, variables evaluated includes SUVmax, size, shape (elliptical vs non-elliptical), presence of extracapsular extension (Ecext-irregular margins), necrosis, and fatty hilum. Histopathology (n=96) and 12 mo follow-up (n=35) were used for confirmation of the findings. ROC analyses determined the SUVmax cut-off. Results: Of131 LNs, malignancy wasconfirmed in 49 (37%).Results are shown in table. In the detection of malignancy, SUVmax of 4.5 yielded the best balance between the sensitivity and specificity, performing better than all CT variables alone. Combination analysis improved results only when SUVmax (4.5) was added to Ecext. However, best combination results were obtained at a SUV cut-off of 3.7. Higher SUV cut-off did not significantly improve overall performance of SUVmax alone (Table). Conclusions: In the differentiation of malignant from benign LNs, SUVmax (4.5) yields better results than CT variables alone. However combining a lower SUVmax (3.7) with Ecext produced the best results. Increasing SUVmax cut-off only produced a gain in specificity at a significant cost of sensitivity. [Table: see text]
A phase I/II study of concurrent nab-paclitaxel, carboplatin, and IMRT for locally advanced squamous cancer of the head and neck (LASCCHN).
Authors: Tishler Roy B. , Lorch Jochen H. , Sher David J , Clark John Ross , Chan Annie W , Suda Margaret , Balboni Tracy A. , Busse Paul M. , Haddad Robert I. , Wirth Lori J. 
Published: March 2020

5579 Background: We studied escalating doses of weekly nab-paclitaxel (Abraxane, AB) combined with weekly carboplatin (CP) and daily IMRT in patients with LASCCHN to determine the safety and optimal dosing of AB. The favorable biodistribution of AB, an albumin bound formulation of paclitaxel, may allow for intensified locoregional treatment without increasing normal tissue toxicity. Methods: An AB dose escalation was performed, initially using concurrent weekly CP (AUC = 1.5), Erbitux (ER) and daily IMRT to 70 Gy. After ER was dropped, dose escalation of AB from 20 mg/m2 to 50 mg/m2 was performed in 10 mg/m2 increments using a 3 + 3 study design. Results: A total of 28 patients have enrolled and all have completed treatment. Patients ranged in age from 42 to 72 years old (median = 59), with follow up from 3 to 48 months (median = 25). Most patient had oropharyngeal primaries (n=22) and stage III (n=8) or IV (n=20) disease; 18 were HPV+, 6 HPV- and 4 unknown. Initially 6 patients received weekly AB (20 mg/m2), ER and CP, but ER was dropped due to greater than anticipated mucositis and dysphagia. Subsequently, 3 patients each received CP with AB at 20, 30 and 40 mg/m2 weekly and a total of 13 received CP with AB at 50 mg/m2. The median radiation dose is 70 Gy and the median number of weekly chemotherapy cycles is 7. The primary toxicities were Grade 3 dysphagia, mucositis and dermatitis in 24 of 28 patients. Only 3 (of 28) PEG tubes remain at 4, 6 and 14 months. No DLTs were observed at any dose level. There have been 5 recurrences, with 4 being local-regional. Two patients have died of disease and 26 are alive. Conclusions: Concurrent AB, CP, and IMRT is a safe chemoradiotherapy combination in LASCCHN with early data demonstrating feasibility and efficacy.
HPV and survival in patients with oropharyngeal squamous cell cancer of the head and neck (OPC) treated with induction chemotherapy followed by chemoradiotherapy (ST) versus chemoradiotherapy alone (CRT): The Dana-Farber experience.
Authors: Lorch Jochen H. , Hanna Glenn , Dai Wei , Thotakura Vijaya , Nair Vidya , Jaffa Zachary , Posner Marshall R. , Limaye Sewanti Atul , Rabinowits Guilherme , Tishler Roy B. , Sher David J , Haddad Robert I. 
Published: March 2020

5582 Background: HPV status is a major prognostic marker for survival in patients with OPC. We examined overall survival (OS) and progression free survival (PFS) in patients with OPC and known HPV status treated at Dana-Farber Cancer Institute with ST and CRT between 2002 and 2011. Methods: 280 patients with OPC and known HPV status were identified retrospectively and clinical information was recorded. Results: 174 patients were treated with CRT (124 HPV positive, 50 HPV negative) and 106 patients were treated with ST (77 HPV positive, 29 HPV negative). For all 280 patients, OS and PFS were significantly better for patients who were HPV positive compared to those who were HPV negative. 3 year OS was 89.1% for HPV positive (95% CI, 83.8-94.7) and 70.5% for HPV negative patients (95%CI, 59.9-83%, HR 0.37, p=0.0007). Among HPV positive patients treated with CRT, 13/124 had died at 3 years (OS 88.5%, 95%CI 81.7-95.9) while 13 deaths were recorded among 50 HPV negative patients (OS 72.2%, 95% CI 59.1-88.2, HR 0.38, p=0.011). PFS at 3 years was also significantly better for HPV positive versus HPV negative patients(81.7% vs 58.8%, HR 0.42, p=0.006). In the group treated with ST, outcomes were similar despite a higher rate of stage IV versus stage III disease compared to the group treated with CRT (100% stage IV in ST versus 77% stage IV and 23% stage III disease in CRT group). Three year OS was 89.7% for HPV positive and 68.2% in the HPV negative group (8/77 HPV pos vs 10/29 HPV neg, HR 0.33, p=0.015). PFS was borderline better for HPV positive patients (81% vs 61.7%, HR 0.48, p= 0.058). Conclusions: We present the DFCI experience treating OPC with ST and CRT for patients with known HPV status over one decade.OS and PFS were superior for HPV positive versus HPV negative patients. Outcomes were virtually identical for patients treated with CRT versus ST despite a higher rate of stage IV disease in the ST group. Outcomes for the HPV negative patients in particular were superior compared to the published literature.
Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation (XRT) in recurrent squamous cell carcinoma of the head and neck (SCCHN): Long-term follow-up of Radiation Therapy Oncology Group (RTOG) protocol 9911.
Authors: Langer Corey J. , Harris Jonathan , Horwitz Eric M. , Kies Merrill S. , Curran Walter J. , Wong Stuart J. , Zhang Qiang , Ang K. Kian ,   Radiation Therapy Oncology Group
Published: March 2020

5583 Background: Loco-regionally recurrent SCCHN or new second primary tumor (SPT) in a previous radiation field, if not curable by surgery, is virtually always fatal. Chemotherapy alone yields a median survival time (MST) of no more than 10 to 11 months, 1- and 2- year overall survival (OS) rates of 35% and 10-15% at best. Concurrent re-irradiation and chemotherapy is an alternative strategy. Methods: Eligibility for RTOG protocol 9911 stipulated measurable, recurrent SCCHN or SPT in a previous radiation field, PS 0-1, and adequate end-organ indices. Patients (pts) received twice-daily XRT (1.5 Gy per fraction BID x 5 d every 2 weeks x4), plus cisplatin 15 mg/m2 IV QD x 5 and paclitaxel 20 mg/m2 IV QD x 5 every 2 weeks x 4. G-CSF was administered days 6 - 13 of each 2-week cycle. Primary endpoints were OS and progression-free survival PFS at 1 and 2 yrs. Secondary endpoints included acute/late toxicities and patterns of failure. Results: 105 patients were enrolled from March 2000 through June 2003. 100 patients were analyzable (76% male, med age 60 yrs). Oropharynx (41%) and oral cavity (27%) were the predominant primary sites. 23% had SPT. Median prior XRT dose was 65.7 Gy. 73% of pts completed all chemotherapy. Grade > 4 acute toxicity occurred in 28%, grade > 4 acute hematologic toxicity in 21%. 9 treatment-related deaths (9%) occurred: five in the acute setting, four late (including three carotid hemorrhages at 116, 427 and 2772 days). 1-, 2-, and 5-year OS rates were 50%, 27%, and 15% respectively. PFS at 1, 2, and 5 yrs were 35%, 18%, and 7%. 64.9% died from the incident cancer, 3.2% from SPT, and 21.2% from other, non-cancer causes. Estimated 10 yr survival is 5% with 6 pts still alive, including 2 free from relapse. Conclusions: Despite a high incidence of grade 5 toxicity, 1-, 2-, and 5- yr OS rates for split-course bid XRT and concurrent cisplatin/paclitaxel exceed results usually seen with chemotherapy alone. At 5-10 yrs, we have observed longterm survivors free of recurrence.
Second primary tumors in head and neck squamous cell carcinoma patients: A cross-sectional study.
Authors: Landeiro Luciana Garcia , Trufelli Damila , Matos Leandro Luongo , Cubero Daniel de Iracema Gomes , Kanda Jossi Ledo , Del Giglio Auro , Castro Gilberto 
Published: March 2020

5588 Background: Head and neck squamous cell carcinoma (HNSCC) patients (pts) are at elevated risk of developing a second primary tumor (SPT). Here we aimed to study the frequency of SPTs and those characteristics related to an increased probability of SPT occurrence. Methods: It is a cross-sectional study in pts diagnosed with SCC primary located in oral cavity, oropharynx, hypopharynx or larynx, treated in two Brazilian institutions, with an index tumor diagnosed from Jan/2000 to Jan/2009. All pts were followed according the current recommendations, including clinical visits, imaging and endoscopic procedures. A SPT was defined following the Warren and Gates criteria (Am J Cancer 51:1358,1932), and they were classified as synchronous or metachronous if detected less or more than six months after the diagnosis of the index tumor, respectively. Results: 38 out of 318 HNSCC pts (12%) were diagnosed with 41 SPTs in their follow-up, being 12 synchronous (29%) and 29 metachronous (71%), all classified as SCC. Regarding the index tumor, it was primary located in oral cavity (114 pts, 36%), oropharynx (87 pts, 27%), larynx (83 pts, 26%) and hypopharynx (34 pts, 11%), and staged as I-II (30%) or III-IV (67%). The SPTs were located more frequently in oral cavity (27%), lungs (27%), oropharynx (15%) and esophagus (12%) and staged as I-II (44%) or III-IV (42%). Among the 29 metachronous SPTs, 12 (41%) were diagnosed in the first two years of follow-up, 11 (38%) between two and five years, and 6 (21%) after five years. Considering all the studied HNSCC pts and index tumor characteristics, including primary site, persistence of tabacco and alcohol habits, and treatment, none was identified as related to an increased probability of developing a SPT. In the median follow-up of 40 mo., the median overall survival was not reached in all 318 HNSCC pts. No difference in overall survival was observed between those pts diagnosed or not with a SPT (HR 0.35, p=0.555). Conclusions: We found a 12% incidence of SPTs in these HNSCC pts. At diagnosis, SPTs were located more frequently in oral cavity and lungs, in advanced stages, and may occur even after five years after the index tumor. More efficient primary and secondary preventive strategies of SPTs must be developed.
Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial.
Authors: Piccart-Gebhart Martine J. , Noguchi Shinzaburo , Pritchard Kathleen I. , Burris Howard A. , Rugo Hope S. , Gnant Michael , Hortobagyi Gabriel N. , Melichar Bohuslav , Petrakova Katarina , Arena Francis P. , Xu Cindy , Cahana Ayelet , Taran Tanya , Sahmoud Tarek , Lebwohl David Edward , Campone Mario , Baselga José 
Published: March 2020

559 Background: Current treatment options for postmenopausal patients with estrogen-receptor–positive (ER+) breast cancer (BC) who relapse or progress on a nonsteroidal aromatase inhibitor (NSAI) are limited. The BOLERO-2 trial supports the activity of everolimus (EVE; an oral mammalian target of rapamycin [mTOR] inhibitor) added to the steroidal aromatase inhibitor exemestane (EXE) to prolong progression-free survival (PFS) in this patient population. Long-term PFS and survival data are awaited. Methods: BOLERO-2 is a phase III double-blind, randomized, international trial comparing EVE (10 mg once daily) plus EXE (25 mg once daily) versus placebo (PBO) plus EXE in postmenopausal women with advanced ER+ BC progressing or recurring after NSAIs (letrozole or anastrozole). Patients were randomized (2:1) to EVE + EXE or PBO + EXE. The primary endpoint was PFS by local investigator assessment. Main secondary endpoints included centrally assessed PFS, overall survival (OS), safety, bone turnover, and overall response rate (ORR). Results: Baseline disease characteristics including tumor burden and prior cancer therapy were well balanced between treatment arms (N = 724). Median PFS was doubled and response rates were consistently improved with EVE + EXE (n = 485) vs PBO + EXE (n = 239) in interim analyses. Median PFS by local assessment was ~3 mo with PBO + EXE vs 6.9 mo (hazard ratio [HR] = 0.43; P < .0001) and 7.4 mo (HR = 0.44; P < .0001) with EVE + EXE at 7.5 mo and 12.5 mo follow-up, respectively. Fewer deaths were reported with EVE + EXE (17.2%) vs PBO + EXE (22.7%) at 12.5 mo follow-up. Safety profiles were consistent with previous reports for mTOR inhibitors. PFS data including 528 events (protocol-specified final analysis), and updated OS and safety data will be presented. Conclusions: Adding EVE to EXE markedly prolonged PFS in patients with NSAI-refractory advanced ER+ BC. There were fewer deaths among patients receiving EVE, and further follow-up will evaluate the effect of EVE on OS.