bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of clinical outcomes between concurrent chemoradiotherapy followed by adjuvant chemotherapy and concurrent chemoradiotherapy alone for patients associated with locally advanced nasopharyngeal carcinoma: A retrospective analysis of single center experience.
Authors: Maeng Chi Hoon , Park Silvia , Jung Hyun Ae , Ahn Hee Kyung , Hwang Deok Won , Park Keunchil , Ahn Myung-Ju , Ji Jun Ho , Park Lee Chun , Cho Su-Hee , Lee Ji Yean 
Published: March 2020

e16003 Background: Up to date, the mainstay of treatment is concurrent chemoradiotherapy (CCRT) with or without adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma. However, the exact role of adjuvant chemotherapy has not been established yet. Methods: Medical record review and data collection were performed for 148 patients who were diagnosed of locally advanced nasopharyngeal carcinoma from October 1996 to September 2009. We analyzed clinical outcomes between the patients who received CCRT followed by adjuvant chemotherapy with cisplatin and 5-FU, and CCRT alone. Results: The estimated 5 year survival rates were 78.3% for the CCRT group and 69.1% for the CCRT followed by adjuvant chemotherapy, respectively (p=0.223). For patients of TNM stage IVA or IVB, the progression-free survival (PFS) and overall survival (OS) had no significant differences between the two groups (p=0.062 and 0.538, respectively). For the patients with stage I, II or III at diagnosis, the PFS and OS were not statistically significant either (p=0.112 and 0.266, respectively). Conclusions: For all stages of nasopharyngeal carcinoma, adjuvant chemotherapy after CCRT did not affect the survival or recurrent rate. A randomized prospective study with long-term follow-up is necessary.
Association of acute phase protein-haptoglobin, and epithelial-mesenchymal transition in buccal cancer.
Authors: Su Yu-Chieh , Lee Ching-Chih , Hung Shih-Kai , Yu Chih-Chia , Li Szu-Chin 
Published: March 2020

e16008 Background: The aim of this study was to determine the influence of inflammation on acute phase protein and epithelial-mesenchymal transition (EMT) in buccal cancer. Methods: Western blotting was carried out to investigate the expression of haptoglobin and epithelial-mesenchymal transition in oral cancer cell lines with or without IL-6 stimulation. We studies patients with buccal cancer patients without distant metastasis at diagnosis. Correlation between cellular haptoglobin, EMT, and clinical characteristics of buccal cancer was analyzed to assess the prognostic value of cellular haptoglobin level and EMT. The relationship of haptoglobin, and EMT expression with survival was assessed using Cox proportional hazard models. Results: Western blotting analysis showed that increased haptoglobin protein was associated with overexpression of vimentin. Under IL-6 stimulation, overexpression of haptoglobin, EMT-associated motile phenotype was noted in OC2 cell lines. Overexpression of haptoglobin was also associated with an increased risk for locoregional recurrence (hazard ratio [HR] 1.04; P=0.011) after adjusting for age, gender, disease site, stage, and treatment modality. Conclusions: Increased cellular expression of haptoglobin is associated with EMT in oral cancer cell lines and this phenomenon could be exaggerated with IL-6. Cellular expression of haptoglobin is related to locoregional recurrence rate in buccal cancer patients.
Induction chemotherapy for organ preservation versus surgery for advanced oral cavity squamous cell carcinoma (OCSCC).
Authors: Chinn Steven Bennett , Spector Mathew E , Light Emily , Lin Tasha Lotus , Teknos Theodoros Nicholas , Prince Mark E , Bradford Carol Rossier , Urba Susan , Carey Thomas E , Wolf Gregory T. , Eisbruch Avraham , Worden Francis P. , Chepeha Douglas Brian 
Published: March 2020

e16014 Background: The objective of the study is to evaluate the outcomes of an induction selection (IS) concurrent chemotherapy protocol versus primary surgical extirpation in advanced OCSCC. Methods: Retrospective quasi-experimental comparison of patients treated by IS versus surgery. The cohorts were matched based on pretreatment characteristics and compared in an intent-to-treat model.19 patients were accrued with resectable stage III/IV OCSCC without bone involvement between 2000-2002 into a phase II IS trial using 1 cycle of IS to select patients for definitive chemoradiation (CRT). Tumor response was evaluated 3-weeks post-infusion. Patients with >50% response underwent concurrent CRT (70Gy; 35 fractions with concurrent cisplatin 100mg/m2 or carboplatin (AUC 6) every 3-weeks for 3 cycles). Those with <50% underwent surgical treatment and radiation therapy. A comparison cohort of patients with primary surgical extirpation was selected from an OCSCC database from 1998-2009. The surgical cohort of 53 patients was identified based on comparable pretreatment variables to the IS cohort. There was no difference in age, gender, pre-treatment AJCC stage, T-class, N-class, smoking status, alcohol status, or subsite between the two cohorts. Results: Kaplan-Meier estimates demonstrated overall survival (OS) at 5-years was 32% in the IS group and 64% in the surgical cohort. Disease-specific survival (DSS) at 5-years was 46% in the IS group and 76% in the surgical cohort. Local-regional control (LRC) at 5-years was 26% in the IS cohort and 72% in the surgical cohort. Multivariable analysis demonstrated significantly better OS, DSS and LRC (p=0.03, p=0.001 and p=0.0002 respectively) in the surgical cohort compared to the IS cohort. Conclusions: Primary surgical treatment showed significantly better OS, DSS and LRC compared to IS in this quasi-experimental designed comparison. These findings support surgery as the principal treatment for OCSCC.
The PARP inhibitor olaparib (AZD2281) as potent radiosensitizer of head and neck cancer cells.
Authors: Tinhofer Inge , Boyko-Fabian Mariya , Niehr Franziska , Keilholz Ulrich , Budach Volker 
Published: March 2020

e16018 Background: Current combined radiotherapy regimens for squamous cell carcinoma of the head and neck (SCCHN) are frequently not curative, necessitating novel therapeutic strategies. Inhibitors of poly(ADP-ribose) polymerases (PARPi), either alone or in combination with chemo- and radiotherapy have been shown to be highly active in tumor cells with intrinsic defects in DNA repair. Despite the frequent occurrence of genomic alterations in SCCHN cells also affecting their capacity of DNA repair the radiosensitizing potential of PARPi has not been addressed in detail so far. In this study, the efficacy of PARPi as radiosensitizer in SCCHN and possible mechanisms of cross-resistance between PARPi and cisplatin were evaluated. Methods: Usingthe clonogenic survival assay and a panel of 10 SCCHN cell lines the sensitivity of SCCHN cells to olaparib alone (0 to 500 nM) or in combination with irradiation (0 to 4 Gy) was determined. Survival fractions for given treatments were calculated on the basis of survival of untreated cells. In addition, the activity of cisplatin to inhibit clonogenic growth and its radiosensitizing potential was determined. From the dose-effect curves the IC50 values and the combinatory indices were calculated using the CalcuSyn Software. Results: In 9 of 10 cell lines, olaparib monotherapy showed significant inhibitory activity on clonogenic survival. Synergistic activity of olaparib in combination with irradiation was observed in all cell lines. No correlation between sensitivity of cells to olaparib and cisplatin (IC50 cisplatin vs IC50 olaparib: r2=0.042, p=.57; IC50 cisplatin vs CI [IR+olaparib]: r2=0.005, p=.95) was observed. Furthermore, the activity of olaparib was not dependent on the p53 genotype. Conclusions: The combination of PARPi with radiotherapy represents an active therapeutic regimen in SCCHN. The observed high activity of this combination even in cells with reduced sensitivity to cisplatin and p53 dysfunction suggests its clinical usefulness also in the group of patients with more aggressive disease and the second-line setting. Currently, detailed molecular characterization for identification of potential biomarker for tumor susceptibility to PARP inhibition is ongoing.
Methotrexate and cetuximab for metastatic advanced head and neck squamous cell carcinoma: A retrospective study.
Authors: Atassi Bassel , Alsibai Khaled , Yoo George H. , Lin Ho-Sheng , Dyson Gregory , Kim Harold , Jacobs John Robert , Kucuk Omer , Sukari Ammar 
Published: March 2020

e16019 Background: After the failure of first line palliative chemotherapy in recurrent non-resectable or metastatic head and neck squamous-cell carcinoma (HNSCC), there is no standard of care treatment that improves survival or quality of life. Both, methotrexate and cetuximab have single agent activity in metastatic HNSCC. We are presenting our institutional experience in using unique combination chemotherapy with methotrexate plus cetuximab (MC). Methods: Retrospectively, single institution’s charts were reviewed from 2004-2010, all patients have documented recurrent non-resectable or metastatic HNSCC. Patients received weekly IV methotrexate 25 mg/m2 plus IV cetuximab 250 mg/m2. Each cycle is 4 weeks treatments. Patients who completed at least 2 cycles were included. Patients can receive MC as first line if they have poor performance status. Treatment was continued until progression. Results: Total of 39 patients were included, 27 male and 12 female. Median patients’ age was 57 years old. 35 patients received methotrexate plus cetuximab (MC) after failure of prior line of palliative chemotherapy. 17, 10 and 8 patients received MC as second, third and fourth line therapy, respectively. 4 patients received MC as 1st line because they were not candidate for more aggressive therapy. The average received number of weekly treatments was 31 (8-95) and average number of cycles was 7 (2-23). Prior chemotherapy regimens include taxanes, platinum, 5-flurouracil, and gemcitabin. 13 patients received prior cetuximab as single agent or in combination. Median progression free survival was 7.1 months and overall survival was 9.8 months. Considering the line of therapy, the median survival was 6.9, 10.1, 13.5 and 9.9 months for patients received MC as 1st, 2nd , 3rd and 4th line of therapy respectively (P= 0.356). Grade 1 and 2 skin rash and hypomagnesimia were observed in 47% and 36% of patients. Conclusions: Methotrexate plus cetuximab is a well tolerated regimen with a significant survival benefit. Prospective well designed studies are warranted in order to evaluate this regimen as a second line palliative therapy for patients with advanced non-curable head and neck squamous cell carcinoma.
Association of tissue factor expression in squamous cell head and neck carcinomas with well-differentiated tumors.
Authors: Jacobs Benjamin , Zhang Xinmin , Gaughan John P. , Bromberg Michael 
Published: March 2020

e16022 Background: Tissue factor (TF) is a glycoprotein that initiates coagulation when complexed with factor VIIa. High levels of TF expression have been found in many cancers and correlated with tumor aggressiveness. TF has been shown to be expressed in head and neck squamous cell carcinomas (HNSCC) but the role of TF on cell function and prognosis are not known. The epidermal growth factor receptor (EGFR) is overexpressed in many HNSCC and EGFR and TF expression are highly correlated in some tumor types. Our goal was to correlate the expression of TF and EGFR in HNSCC with tumor cell differentiation and prognosis. Methods: Twenty biopsy specimens of squamous cell head and neck carcinomas were studied. Immunohistochemistry for TF, EGFR, and p16 was performed. Cases were scored based upon the staining intensity of tumor cells using a semiquantitative scale as negative, weakly (+), moderately (++) or strongly (+++) positive. Results: The tumor stages ranged from T1N0 to T4N3. Of the 20 specimens, 5 were well differentiated, 12 were of moderate differentiation, and 3 were poorly differentiated. Median survival was 23 months, median follow-up 73 months. TF was expressed in 75% (15/20) of tumors at varying levels. Moderate TF expression was found in 6 specimens, and 9 showed weak expression. None of the poorly differentiated tumors expressed TF, and there was a definite negative correlation between TF expression and tumor differentiation (Pearson r=--0.747, p=0.0002). There was no association between TF expression and survival (Log-Rank 0.3115, p=0.8558). All of the tumors analyzed expressed EGFR and there was no correlation between TF expression and EGFR expression. Overall, 25% (5/20) of tumors expressed p16, suggesting human papilloma virus infection. Conclusions: Results from this retrospective study indicate that well differentiated HNSCC express higher levels of TF than poorly differentiated tumors and that TF and EGFR expression are not tightly linked. Moreover, unlike other cancer sites, HNSCC TF expression did not appear to worsen overall patient survival, and was actually associated with more well-differentiated tumors.
A phase I dose-escalation trial of SRS boost treatment of human papilloma virus (HPV)-unassociated oropharyngeal squamous cell carcinoma (OPSCC).
Authors: Schwartz David L. , Parise Sara , Denitz Jordan , Nguyen Vinh , Fantasia John , Mehrotra Bhoomi , Saltman Benjamin , Frank Douglas 
Published: March 2020

e16026 Background: HPV-negative status and/or significant smoking history predict for poor radiation response in patients with OPSCC. To improve disease control outcomes in this population, we are conducting a phase I dose-escalation trial of stereotactic radiotherapy boost delivery to primary disease. Methods: Thirteen consecutive patients with newly diagnosed HPV-unassociated OPSCC were enrolled onto this IRB-approved clinical trial between 5/2010 and 10/2011. Eligible patients had HPV-negative disease and/or tobacco exposure history of >10 pack-years. The cohort consisted of 12 males/1 female with a median age of 58.5 yrs (range: 46-64). There were 9 tonsil/2 tongue base/1 soft palate/1 GP sulcus cases, with 5 T2/5 T3/3 T4 primaries and 2 AJCC stage III/11 stage IV disease. Primary disease received 60 Gy, gross nodal disease 66 Gy, and prophylactic nodal target volumes 54-60 Gy with routine IMRT technique in 30 daily fractions. All patients received concurrent chemotherapy (12 cisplatinum-based, 1 cetuximab). Within one week of IMRT completion, SRS boost treatment was delivered to the primary disease target volume. Initial SRS dose level was set at 8 Gy, and has been delivered to 11 enrolled patients, with 1 patient pending and 1 patient self-removed from protocol. Median follow up for completed patients is 11 (range: 5-17) months. Results: Twelve cases are evaluable. Post-SRS boost adverse events have remained limited mostly to Gr 2-3 xerostomia, pain, and dysphagia. Five patients have required PEG placement. No acute or chronic Gr 4-5 toxicity has been observed. One patient with bulky T4 disease died of persistent disease. One patient with residual adenopathy had consolidative neck dissection and remains free of disease, as do the remaining 10 patients who responded completely. Conclusions: 8 Gy SRS boost treatment to high-risk primary OPSCC disease is feasible and safe, and step-wise dose escalation is ongoing.
The impact of medical comorbidities on the quality of care for patients with head and neck cancer.
Authors: Ernst Brenda , Busowski Mary T , Weber Randal S. , Shellenberger Thomas D. 
Published: March 2020

e16030 Background: Objectively assessing the treatment of patients with cancer offers a basis for raising the standard of care. Quality indicators provide criteria by which the safety of care can be measured and compared to defined benchmarks. However, variables influencing the metrics in quality can limit generalizability and applicability. Medical comorbidities pose significant threats to the care of patients with head and neck cancer. We sought to investigate the impact of medical comorbidities on quality indicators for patients undergoing management by the multidisciplinary team. Methods: Comorbidities were assessed in relation to quality indicators in 49 patients treated for squamous cell carcinoma of the head and neck over a 16-month period. Treatment with surgery, radiation, and chemotherapy was classified by the number and type of modalities delivered. Surgical procedures were stratified by high and low acuity as defined by extent. By univariate and multivariate analysis, medical comorbidities were correlated with length of hospital stay, readmission within 30 days, return to the operating room within 7 days, 30-day mortality, use of blood products, and surgical site infection. Results: Cardiovascular disease was present in 49% of patients, diabetes mellitus in 12%, liver disease in 8%, previous congestive heart failure in 4%, and chronic obstructive pulmonary disease in 17%. The presence of any single comorbidity was correlated with each of the negative indicators (p<0.05), and with multiple negative indicators (p<0.05). Comorbidities occurred more frequently in patients undergoing high acuity surgery (p<0.05) and combined modality therapy (p<0.05). Decreasing performance status and major clinical predictors were the factors most strongly associated with negative quality indicators. Conclusions: Approaches to adjust for comorbid status are critical to accurate assessment of quality indicators. Risk stratification of patients at initial evaluation can offer valuable criteria for selecting treatment. Evaluation and management of comorbidities by evidence-based guidelines may improve care.
Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.
Authors: Fayette Jerome , Polivka Valentine , Chabaud Sylvie , Favier Bertrand , Racadot Severine , Pommier Pascal , Montbarbon Xavier , Neidhardt Eve Marie , Girodet Didier , Zrounba Philippe 
Published: March 2020

e16036 Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.
Overall survival (OS) and risk of distant failure among malignant salivary gland tumors (MSGTs) in a large single-institution registry cohort.
Authors: Rodriguez Cristina P. , Mason Teresa , Mongoue-Tchokote Solange , Stott Will , Andersen Peter , Holland John M , Gross Neil D. 
Published: March 2020

e16045 Background: MSGTs are rare, biologically diverse cancers. Registry data and large series suggest 5-year OS exceeding 50%, superior to historical data and attributed to postoperative radiation (pXRT). Hypothesizing OS has remained poor despite modern therapy, we reviewed our cancer registry (OHSUCR), which began collecting data on MSGTs in 1995. Methods: We interrogated the OHSUCR for pts with MSGTs (WHO classification) and obtained data on age, sex, race, AJCC stage, histology, primary site, surgery, pXRT. OS was estimated using the Kaplan Meier (KM) method. The log rank test was used to compare OS among pts treated with and without pXRT, and those diagnosed between 1995-2000, 2001-2005, and 2005-present. Results: 110 pts with MSGTs were entered into the OHSUCR from 5/1996 to 5/2011. The median age was 60 (range 10-90), 65 (59%) were male, and 106 (96%) were white. The primary site was: 101 (92%) parotid, 3 (3%) unspecified major salivary gland, 4 (3%) submandibular gland, and 2 (2%) minor salivary gland. MSGT histologies were: 41 (37%) mucoepidermoid carcinoma, 24 (22%) adenoid cystic carcinoma, 21 (19%) adenocarcinoma, 12 (11%) acinar cell carcinoma, 5 (4%) carcinoma ex pleomorphic adenoma, 3 (3%) epithelial-myoepithelial carcinoma, 1 (1%) undifferentiated carcinoma, 1 (1%) small cell carcinoma, 1(1%) salivary duct carcinoma, 1 (1%) carcinosarcoma. AJCC Stage was: I in 29, (26%) II in 20 (18%), III in 16 (15%), IV in 45 (41%). 102 (96%) underwent surgical resection, 73 (66%) pXRT. 89 (81%) pts were rendered disease free, although 23 (21%) eventually recurred, 20 in distant sites. At the time of analysis 57 (52%) pts were alive and disease free. With a median follow up of 30 months (range 1 to 165), the 5 year KM OS for the entire cohort is 46%. Median survival was not influenced by pXRT (p=0.93) or period of diagnosis (1995-2000, 2001-2005, or 2005-present; p=0.83). Conclusions: In this large single institution series, pts with MSGT remain at high risk for mortality despite routine administration of pXRT. Distant metastasis is the most common pattern of failure indicating a clear unmet need for improved systemic therapy for MSGTs.
Outcome after different treatments for patients with HPV+ tonsillar cancer.
Authors: Attner Per 
Published: March 2020

e16048 Background: In the last few years, oncological treatment for tonsillar cancer has intensified with accelerated radiotherapy and chemotherapy, which has resulted in more side effects. Patients with HPV-positive tonsillar cancer have better prognosis than those with HPV-negative tumors, and it is possible that patients with HPV-positive tonsillar cancer may benefit from a reduced, less-toxic treatment without compromising survival. Methods: To evaluate the possible difference in survival after different oncological treatments of patients with HPV-positive tonsillar cancer, we evaluated all 211 patients diagnosed with tonsillar cancer between 2000-2007, in Stockholm, Sweden. Included patients were those with available pretreatment biopsies, and treated with intent to cure. A total of 172 patients had HPV-positive tumors and of those, 98 were treated with conventional radiotherapy, 44 were treated with accelerated radiotherapy and 30 were treated with chemoradiotherapy. Results: No significant differences in overall and disease-free survival were seen between the three treatment groups, but there was a trend, where chemoradiotherapy was better than radiotherapy; and accelerated radiotherapy was better than conventional radiotherapy. This trend needs to be followed further. Conclusions: In this study, patients with HPV-positive tonsillar cancer treated with conventional radiotherapy, accelerated radiotherapy or chemoradiotherapy had similar survival rates. However, there is a trend for better survival and less metastasis after intensified treatment underlining the need for prospective studies, where less intense treatment is compared to more intense treatment.