bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organ preservation with daily concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion for stage III, IV oral cancer: Analysis of therapeutic results in 112 cases.
Authors: Mitsudo Kenji , Koizumi Toshiyuki , Iwai Toshinori , Nakashima Hideyuki , Oguri Senri , Kioi Mitomu , Hirota Makoto , Tohnai Iwai 
Published: March 2020

6060 Background: Retrograde superselective intra-arterial chemotherapy for oral cancer has the advantage of delivering a high concentration of the chemotherapeutic agents to the tumor bed, it can be used to provide daily concurrent chemoradiotherapy for patients with advanced oral cancer. The purpose of this study was to evaluate the therapeutic results and rate of organ preservation in 112 patients of stage III or IV (M0) oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. Methods: Between August 2006 and July 2011, 112 patients with stage III or IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. And treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60 mg/m2, cisplatin, total 150 mg/m2) and daily concurrent radiotherapy (total 60 Gy) for 6 weeks. Results: The median follow-up for all patients was 46.2 months (range, 10–90 months). The median follow-up for living patients was 49.7 months (range, 36–90 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Thirty patients (26.8%) died. Using the Kaplan-Meier method, 3-year, and 5-year survival rates were 74.6% and 71.3%, respectively, while 3-year, and 5-year local control rates were both 79.3%. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1%. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure occurred in 0.9%, no patients died as a result of treatment toxicity. Conclusions: Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for Stage III, IV oral cancer provided good overall survival and local control rates, thus preserving organs and contributing to patients’ QOL.
Effect of early detection of recurrent disease by FDG PET/CT on management of patients with squamous cell cancer of the head and neck (HNSCC).
Authors: Kostakoglu Lale , Fardanesh Reza , Genden Eric , Rao Srikar , Doucette John , Som Peter M. , Gupta Vishal , Misiukiewicz Krzysztof , Posner Marshall R. 
Published: March 2020

6062 Background: Despite the increasing cure rates a substantial fraction of HNSCC patients (pts) will present with locoregional and/or distant relapse within 3 years of definitive therapy. The prognosis of HNSCC pts after failure of first-line therapy has been poor but recent changes in the biology of HNSCC, advances in surgical techniques and radiotherapy; and new drugs may lead to improved salvage therapy. Notably, the success of these developments are implicitly dependent on early diagnosis disease. Our objective was to compare the efficacy of surveillance FDG-PET/CT to that of high resolution CT (HRCT) and physical exam (PE/E) for detection of early relapse in HNSCC after completion of primary treatment. Methods: A retrospective analysis of FDG-PET/CT, neck HRCT and PE/E was performed in 99 curatively treated HNSCC pts during post-therapy surveillance (PTS) to compare the performance characteristics of the tests in the detection of early recurrence or metachronous cancer. Results: A total of 19/99 (20%) pts had recurrence during a median follow-up of 21mo (range:9-52). Median time to first PET/CT was 3.5mo. The median time to radiological recurrence was 6 mo (range:2.3-32). PET/CT detected more disease recurrences or second primaries and did so earlier than HRCT and PE/E. Sensitivity, specificity, PPVand NPV for detecting locoregional and distant recurrence or metachronous cancer : 100%, 87.3%, 56.5% and 100% for PET/CT vs. 61.5%, 94.9%, 66.7% and 93.8% for HRCT vs. 23.1%, 98.7%, 75% and 88.6% for PE/E. In all 19 pts with a true positive PET/CT there was a significant management change prompting either salvage or definitive surgery or initiation of systemic therapy. Of the 14 recurrent pts treated with curative intent, 11 were alive with no evidence of disease at a median follow up of 31.5 mo. Conclusions: FDG-PET/CT has a high sensitivity in the early detection of relapse or second primary cancer in HNSCC, associated with significant management implications. Given improvements in therapy and changes in HNSSC biology, appropriate modifications in the current recommended algorithms of the NCCN for PTS may be required to engage effective salvage or definitive therapies.
A blood-based epigenetic test for early detection of nasopharyngeal carcinoma (NPC).
Authors: Tan Yew-Oo , Alfanta Eduard M. , Lopa Ramon Antonio B. , Lim Elaine Hsuen , Whang Hwee Yong , Wong Karmen , Jordan Philip , Corfield Emily , Salter Matthew , Field Megan , Akoulitchev Alexandre , Loh Thomas Kwok Seng , Goh Boon C. , Hsieh Wen Son 
Published: March 2020

6063 Background: NPC is highly curable in early stages but 70% of NPC patients are diagnosed with advanced disease due to lack of effective screening. Genetic and epigenetic alterations involved in the pathogenesis of NPC are known. The higher order chromosomal structures reflecting aberrant transcriptional states of these genes can be measured via techniques such as chromosome conformation capture. Detection of these changes in peripheral blood may provide an accurate test for the early cancer detection. Methods: Blood samples have been collected from 84 patients with histologically confirmed NPC and 100 matched controls. Samples from 45 NPC patients and 68 controls have been analyzed. Fourteen genes known to be dysregulated in NPC were investigated. Potential higher order juxtaposition sites in the candidate genes were predicted using pattern recognition software. PCR primer sets were designed around the chosen sites to screen potential markers. Twenty-two markers showing predictability between NPC and control samples were analysed for optimal reproducibility using alternative primer sets. The optimal sets of markers were then tested amongst the complete set of samples. The dataset was processed by re-sampling using the synthetic minority oversampling technique. The overall sample was split into two groups (66% training set and 34% test set) in the classification. Results: Sixteen markers from 7 candidate genes were found to be optimal in differentiating between NPC and control samples in the first 103 samples. Using the multilayer perceptron (MLP) classification, the following results were obtained: Sensitivity 88.9%, 95% CI (79.2% - 98.6%); Specificity 72.7%, 95% CI (58.9% - 86.5%); PPV 72.7%, 95% CI (58.9% - 86.5%); NPV 88.9%, 95% CI (79.2% - 98.6%). The accuracy of the test was similar in detection of stage I and II NPC versus that of stage III or IV NPC. Conclusions: Using a PCR-based method to detect alterations in the cancer epigenome, the feasibility of developing a blood test of potential utility in early diagnosis of NPC was demonstrated. Analysis of larger numbers of patient samples and optimization of markers are ongoing. The performance characteristics of the test in the total population of 184 samples will be presented.
Genetic profiling of advanced RAI-resistant differentiated thyroid cancer and correlation with axitinib response.
Authors: Schechter Rebecca B. , Nagilla Madhavi , Joseph Loren , Reddy Poluru L. , Khattri Arun , Watson Sydeaka , Locati Laura D. , Licitra Lisa F. , Greco Angela , Pelosi Giuseppe , Carcangiu Maria Luisa , Seiwert Tanguy Y. , Cohen Ezra E.W. 
Published: March 2020

6066 Background: The VEGFR inhibitor axitinib has demonstrated compelling antitumor activity in advanced RAI-resistant differentiated thyroid cancer (DTC). Biomarkers predicting which patients may benefit from axitinib are unavailable. We aimed to describe molecular markers in DTC that correlate with clinical outcome to axitinib. Methods: Pretreatment FFPE thyroid cancer blocks from patients treated with axitinib were collected and genomic DNA was isolated. The OncoCarta Mutation Panel was used to test for 238 mutations. Copy number of VEGFR1-3 and PIK3CA was determined using qPCR. Genomic DNA was analyzed for coding regions of VEGFR1-3 with custom primers. Clinical response to axitinib, including best response (BR) (RECIST) and progression free survival (PFS), was ascertained from corresponding patients. Fisher’s exact test and logistic regression models were used to correlate BR with molecular findings. Cox proportional hazards regression was used to correlate PFS with molecular defects. Results: A total of 22 pathology samples (11 primary, 11 metastatic) were identified. In patients with 2 samples (n = 4), results were concordant and only included once for analysis. Of 18 specimens, 4 tumors (22%) harbored BRAF V600E mutations, 2 (11%) had KRAS mutations (G12A, G13D) and 2 (11%) had HRAS mutations (Q61R, Q61K). One sample with mutated KRAS also had a PIK3CA (H1047R) mutation. qPCR showed increased copy numbers of PIK3CA in 6 (33%) tumors, VEGFR1 in 0 (0%) tumors, VEGFR2 in 4 (22%) tumors, and VEGFR3 in 6 (33%) tumors. VEGFR sequencing showed a possibly damaging non-synonymous SNP in VEGFR2 (G539GR) in 2 samples (11%), a possibly damaging SNP in VEGFR3 (E350VE) in 1 sample (6%), and a potentially novel mutation in VEGFR2 (T439IT) in 2 samples (11%). No significant relationship was seen between BR or PFS and the presence of molecular defects. Conclusions: While DTC is genetically heterogenous, primary and metastatic lesions showed identical alterations. Molecular evaluation of DTC specimens did not predict clinical response to axitinib but data were limited by small sample size. We did identify molecular changes in VEGFR that should be further explored. This study was supported by Pfizer, Inc.
Single nucleotide polymorphisms (SNPs) of hypoxia-related and DNA repair genes associated with toxicity and clinical outcome in head and neck squamous cell carcinoma patients treated with cetuximab plus radiotherapy.
Authors: Grau Juan J. , Munoz-Garcia Camen , Feliz Luis R , Caballero Miguel , Sosa Aaron R , Pereira Verónica 
Published: March 2020

6072 Background: One of the standard therapy in inoperable head and neck squamous cell carcinoma (HNSCC) patients is cetuximab plus radiotherapy. However, the efficacy of this treatment varies greatly among individuals. In an attempt to identify predictive markers to determine the patients most likely to benefit from this treatment, we examined the potential effect on outcome and skin toxicity according to single SNPs in hypoxia-related genes and DNA repair genes. Methods: Sixty-one patients enrolled between May 2006 and August 2011 and diagnosed with HNSCC were included. Data on epithelitis, mucositis and folliculitis were collected in accordance with WHO criteria. SNPs were analyzed in HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1 and XRCC5 in DNA obtained from paraffin-embedded tumor tissues by allelic discrimination in an ABI PRISM 7500 Sequence detection system. Results were correlated with time to progression (TTP), overall survival (OS) and toxicity. Results: The median of TTPand OSwere better in patients with mucositis severe vs mild (17 vs 7 months, p=0.03, and 26 vs 12 months, p=0.016, respectively) and in those with folliculitis severe vs mild (10 versus 7 months, p=0.01, and 26 vs 10 months, p<0.001, respectively). Patients withHIF-1α CT/TT had better OS than those with HIF-1α CC or wild type (28 versus 13 months, p=0.035). Patients with XRCC5 GG/AA genotypes had longer TTP than patients with XRCC5 AG (11 versus 7 months, p=0.035). Conclusions: Our findings indicate that the presence of severe skin toxicities, as well as SNPs in HIF-1α and XRCC5, are associated with interindividual differences in outcome among HNSCC patients.
Outcomes for stage IVA squamous cell carcinoma of the oral cavity according to staging subtypes.
Authors: Marrone Kristen , Otremba Michael , Groisberg Roman , Deshpande Hari Anant , Crawford Forrest , Acevedo-Gadea Carlos Rodrigo , Gould Rothberg Bonnie , Judson Benjamin , Morgensztern Daniel 
Published: March 2020

6076 Background: Patients with locoregionally advanced squamous cell carcinoma of the oral cavity (SCCOC), defined as stages III to IVB without T4b, are treated similarly and combined for enrollment into most clinical trials. There are several combinations of tumor (T) and lymph node (N) categories for stage IVA. We evaluated the differences in outcomes according to subtypes of patients with stage IVA SCCOC. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with stage IVA SCCOC diagnosed between 1988 and 2007. Patients were subdivided according to tumor (T) and lymph node (N) status. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by using log-rank test. Cox proportional hazard regression models were used for multivariate analyses. Results: Among the 3,904 patients meeting inclusion criteria, most patients underwent surgery, either alone (24%) or with radiation (59%). There was a significant difference in outcomes according to AJCC subsets (T4aN0, T4aN1, T1N2, T2N2, T3N2 and T4N2), with 5-year OS ranging from 15.8% in T4aN2 to 41.3% in T4aN0 (HR 2.3; 95% CI 2.03-2.62, p < 0.001). Since the 5-year OS was similar for patients with T1N2-T2N2 and T3N2-T4aN2, these groups were further subdivided according to the T (T1-2 or T3-4a) and N2 subsets. The 5-year OS was significantly different according to the subgroups, ranging from 11.8% in T3-4aN2c to 37.5% in T1-2N2a (Table). The stage subgroups remained independent predictors for survival after adjusting for age, gender, race and treatment. Conclusions: Stage IVA SCCOC is a heterogeneous disease with significant differences in outcomes according to its subsets. If these findings are confirmed in additional studies, further subdivision of stage IVA may be warranted. [Table: see text]
Carboplatin (C), cetuximab (Cet), and everolimus (E) in recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Results of a phase Ib study.
Authors: Saba Nabil F. , Kono Scott A , Mendel Jennifer Robin , Hurwitz Selwyn J , Owonikoko Taofeek Kunle , Lewis Colleen Margaret , Harvey Donald , Rogerio Jaqueline Willemann , Chen Zhengjia , Wadsworth Trad , El-Deiry Mark , Chen Amy Y. , Higgins Kristin , Ramalingam Suresh S , Beitler Jonathan Jay , Shin Dong M , Khuri Fadlo Raja 
Published: March 2020

6083 Background: Platinum-based therapy in combination with Cet is the standard first line systemic therapy in RMSCCHN. Preclinical studies suggest that mTOR inhibitors may restore sensitivity to EGFR inhibitors in resistant cell lines, and that in combination with Cet may augment anti-tumor activity. We conducted a phase Ib trial of C, Cet and E for untreated RMSCCHN. Methods: Patients received C at AUC=2 on a 3 weeks on 1 off schedule with Cet weekly at a fixed dose and E at escalating dose levels of 2.5, 5.0, 7.5 and 10 mg daily using a 3+3 design. After 4 cycles of therapy patients without disease progression continued on maintenance Cet and E until disease progression or intolerable toxicity. Patients had previously untreated RMSCCHN not amenable to surgery or radiotherapy, age ≥ 18 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Results: After IRB approval, the study enrolled 18 patients with RMSCCHN between February 8, 2011 and Jan 25 2013. One patient was a screen failure. Four had an anaphylactic reaction to Cet and were excluded from the analysis. A total of 13 patients received E (M/F: 92%); median age 65 (44-75yrs). Two of six patients treated at dose level 1 (E-2.5 mg/day) experienced dose limiting toxicity (DLT) with grade 3 hyponatremia and nausea. Additional 7 patients were treated with de-escalated dose of E (2.5 mg QOD). No DLTs were observed at this dose level. Salient clinically relevant Grade >2 toxicities included: leukopenia (23%), neutropenia (15%) hyponatremia (18%), hyperglycemia, nausea, rash, hypokalemia, urinary infection, bacteremia, (each 8%). Dose reductions of C were necessary for a total of 18/61 delivered cycles of therapy. A response rate (RR) of 62.5% with all responders having partial responses (PR) was observed. The PFS was 7.8 months. Conclusions: The MTD of E in combination with Cet and C is estimated at 2.5 mg QOD. Though this is less than the commonly utilized dose of E, the regimen was associated with encouraging response rate and PFS Clinical trial information: NCT01283334.
Are three drugs better than two and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?
Authors: Noronha Vanita , Patil Vijay , Joshi Amit , Juvekar S , Bhosale Bharatsinha Baburao , Poladia Bhavesh , Rath Sushmita , Chaturvedi Pankaj , Chaukar D. , Pai P. S. , Dcruz A. K. , Prabhash Kumar 
Published: March 2020

6085 Background: A variety of regimens have been used for induction chemotherapy in locally advanced head & neck cancers. Cisplatin & 5 FU drug combination is inferior to the combination of taxane & these 2 drugs. However, often in clinical practice at our center giving TPF is difficult in view of logistics & tolerance issues. In such scenarios we prefer to use 2 drug combination of platinum & taxane. However no study has addressed whether when the 2 drug combination includes taxane, is it still inferior to the 3 drug combination and which the taxane of choice is. Methods: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy in oral cavity cancers from 2010-2012. We chose for analysis those patients who had a baseline scan and a follow-up scan done within 2 weeks of completion of the second cycle of induction chemotherapy. Response was scored in accordance with RECIST 1.1. Data was analyzed using SPSS, version 16. Chi- square analysis was done to compare response rates between regimens. Results: Two hundred & forty five patients were indentified. The median age was 45 years (24-70 years), 208 (84.9%) were male patients & in 154 patients (62.9%) had primary in buccal mucosa. The regimen received were TPF 22 (9%), TP (Docetaxel + cisplatin) 97 (39.6%), PP (paclitaxel+cisplatin) 89 (36.3%), TC (Docetaxel+ carboplatin) 16 (6.5%) & PC (paclitaxel + carboplatin) 21 (8.6%).The overall response rates (RR) were CR, PR,SD & PD in 4 (1.6%), 56 (22.9%), 145 (59.2%) & 40 (16.3%). On comparison, 3 drug regimen (TPF) had 50% RR as against 22% RR with 2 drug regimen (p=0.004). On comparison for taxane, docetaxel containing regimens had 30.3% RR as against 17.2% RR with paclitaxel containing regimens (p=0.018). There was no statistically significant difference in RR between patients receiving carboplatin or cisplatin. Conclusions: TPF had better RR than a 2 drug taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for induction chemotherapy in locally advanced oral cavity cancers.
A comparative study of the response and toxicities in locally advanced head and neck cancer patients treated with paclitaxel, cisplatinum, 5-FU versus docetaxel, cisplatinum, 5-FU as neoadjuvant chemotherapy followed by concurrent chemoradiation.
Authors: Samanta Diptirani , Senapati Surendra nath , Mohanty Kirti Ranjan , Das Saroj 
Published: March 2020

6089 Background: To evaluate the response and toxicity of docetaxel, cisplatinum, 5-FU vs paclitaxel, cisplatinum, 5-FU as neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiation (CTRT) with weekly cisplatinum in locally advanced head and neck cancer. Methods: 40 locally advanced head and neck cancer patients who satisfied the eligibility criteria were randomized.21 patients received three cycles of NACT i.e paclitaxel (175 mg/m2) on d1, cisplatinum (30 mg/m2) and 5-FU (600 mg/m2) d2-d4 (TCF) and 19 patients received three cycles of NACT docetaxel (75 mg/m2) on d1, cisplatinum (30 mg/m2) and 5-FU (600 mg/m2) d2-d4 at three week intervals, followed by concurrent weekly cisplatinum 30 mg/m2 along with conventional external beam radiation of total tumor dose dose 66 Gy. Response was assessed after NACT and again after six weeks, three months and six months of completion of chemoradiation. Toxicities were assessed after each cycles of NACT and also weekly during CTRT and thereafter. Results: Two weeks after completion of NACT complete response (CR) in TCF was 4.76%, partial response (PR) 80.9% and no response 9.5%. However in DCF, CR was 15.78 % PR was 73.68%. 10.52% patientd died due to toxicity. With a median follow up of seven months, in TCF CR was 57.14%, PR 33.33% and no response was 4.76%, whereas in DCF CR was 78.94%, PR 10.52% and death 10.5%. On evaluation of toxicities during NACT, patients in DCF had more significant neutropenia and in TCF more incidence of neuropathy. During CTRT, in TCF grade II and III mucositis was 54%, grade II neutropenia 5.6%, and grade II anemia 5.3%. In DCF mucositis grade II and III was 49.0%, neutropenia grade II 18.7% and anemia grade II was 7.4%. Late toxicities included were comparable in both arms. Conclusions: With a median follow up of 7 months, the CR in DCF was 78.94%, superior than TCF i.e 57.14%. Neutropenia was significant in DCF and neuropathy was high in TCF. In CTRT mucositis was the commonest toxicity observed in both TCF and DCF which was not statistically significant.