bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of cetuximab for the first-line treatment of squamous cell carcinoma of the head and neck (SCCHN) in Canada
Authors: Sambrook J. , Levy A. R. , Johnston K. M. , Ricard N. J. , Bourgault C. , Donato B. M. , Sheehan F. G. , Hotte S. J. , Chasen M. R. , Briggs A. H. 
Published: August 2020

e17000 Background: Squamous cell carcinoma of the head and neck (SCCHN) is a disfiguring and potentially fatal condition. Cetuximab is a new therapeutic option which has been shown to improve locoregional control (LRC) and reduce mortality in the treatment of locally and regionally advanced disease. Objectives: To estimate the incremental cost-utility of cetuximab plus radiotherapy (CxRT) versus cisplatin plus radiotherapy (CsRT) among platinum eligible patients and versus RT alone in platinum ineligible patients in Canada. Methods: A lifetime transition model was developed with four health states: 1) acute treatment phase; 2) LRC; 3) disease progression and 4) death. Adverse events were accounted for in the first two states. Efficacy of treatment (LRC and overall survival) was obtained from the literature. Based on network meta-analyses, CsRT and CxRT were assumed to have equal efficacy. Resource use was obtained from published literature and clinical expert opinion. The perspective adopted was that of a provincial ministry of health or cancer agency. Utilities were obtained from a previous study of United Kingdom oncology nurses. Costs (2008 CDN$) and outcomes were discounted at 5% annually. Incremental cost-effectiveness ratios (ICERs) were reported with one-way and probabilistic sensitivity analyses performed to assess robustness of results. A priori sub-group analyses were carried out by baseline Karnofsky Performance Scores (KPS). Results: Among all patients (KPS 60–100), the ICERs comparing CxRT to RT were $19,740/QALY (95% CI: $11,122 to $695,295) among platinum ineligible patients and for CxRT vs. CsRT, $99,147/QALY (95% CI: $75,998 to $148,951) among platinum eligible patients. ICERs decreased with increasing KPS scores. At a willingness to pay of $50,000 among platinum-ineligible patients and $100,000 among platinum-eligible patients, the likelihood that CxRT is cost-effective is 90% and 45% respectively. Sensitivity analyses indicated that time horizon and assumptions about CsRT effectiveness had the largest impact on results. Conclusion: Cetuximab is an economically attractive option for SCCHN patients. [Table: see text]
Efficacy of neoadjuvant therapy with cisplatin, fluorouracil, and cetuximab in locally advanced nonresectable epidermoid skin carcinoma
Authors: Mamelle G. , Fournier E. , Kolb F. , Janot F. , Duvillard P. , Robert C. , Mateus C. 
Published: August 2020

e17008 Background: No standard therapy is known for locally advanced unresectable cutaneous epidermoid carcinoma. Chemotherapy (platin ± fluorouracil) and radiotherapy are commonly used separately or in association (1) mostly as palliative treatments. We report six patients with locally advanced unresectable skin epidermoid carcinomas in whom the association of cisplatin, fluorouracil and cetuximab induced a tumor reduction allowing secondary complete surgical resection. Results: All 6 patients had voluminous tumours located on the face (nose, ear, cheek, forhead). For 5 patients, tumours were recurring after one or several surgical resections. One patient had a rapidly progressing non resectable inflammatory tumour on the nose when he was first diagnosed. All patients received 2 to 3 cycles of chemotherapy associating cisplatin 100 mg/m2 J1, fluorouracil 1,000 mg/m2 J1–5, cetuximab J1-J8-J15 (J1 = J21). Tolerance was manageable. A dramatic response with rapid tumour regression, allowing subsequent surgical resection was observed for all patients. Histology showed a complete sterilisation without any active tumoral residue in 2 patients and complete resection (R0) in the remaining patients. Conclusions: The association of cisplatin, fluorouracil and cetuximab is approved for treatment of metastatic head and neck carcinoma (2, 3) but has not been evaluated yet in cutaneous epidermoid carcinoma. The dramatic tumor responses observed in our 6 patients warrant evaluation of this association both in the neoadjuvant and in the metastatic settings for patients with non resectable skin squamous cell carcinomas. No significant financial relationships to disclose.
Phase I study of pemetrexed in recurrent/metastatic head and neck squamous cell cancer (HNSCC) and to assess the need for steroid premedication
Authors: Coscio A. , William W. N. , Feng L. , Glisson B. , Ayuste R. , Ginsberg L. , Lee J. J. , Obasaju C. , Lippman S. M. , Kim E. S. 
Published: August 2020

e17009 Background: Pemetrexed is a novel antimetabolite that inhibits both purine and pyrimidine biosynthesis. Because its mechanism of action is similar to that of both methotrexate and 5-FU, it may also have activity in recurrent/metastatic HNSCC, a disease with limited treatment options and very poor median survival. Pemetrexed is traditionally prescribed with steroids due to skin toxicities observed in early studies; however vitamin supplementation (B12 and folic acid) was not standard at the time of those studies. No study to date has evaluated the optimal use of steroids with pemetrexed in the era of vitamin supplementation. Methods: All patients had metastatic or recurrent HNSCC, were treated with at least one prior chemotherapy regimen, and had ECOG PS of 0–2. The first cohort of patients received pemetrexed 500 mg/m2 every 3 weeks and the next receiving 600 mg/m2 based on a predefined standard dose escalation design. Within each dose level, patients were randomized to one of 3 premedication regimens: no dexamethasone, 20 mg IV on day 1, or standard 4 mg orally bid for 3 days. All patients received vitamin supplementation. The primary endpoint of the study was to determine the maximum tolerated dose of pemetrexed based on steroid premedication. Results: From October 2005 to March 2008, 36 patients were enrolled and 31 were available for evaluation. Median age was 57 years (range 42–82). 51.5% of patients had more than one prior chemotherapy regimens, 81.8% of patients had prior radiation therapy, and 48.5% of patients had prior surgery. Incidence of rash and combined skin toxicities were: 1/11 (9%) and 3/11 (27%) of patients without steroids, 1/11 (9%) and 3/11 (27%) with single IV dose, and 4/9 (44%) and 5/9 (55%) with oral steroids. No treatment-related grade 3 toxicities were observed. One patient initially received no steroid and required dose reduction and addition of steroid due to grade 2 rash. A partial response was observed in one patient (3.2%), and stable disease in 8 patients (25.8%) for a disease control rate of 29%. Conclusions: This is the first study to report the role of steroids as a premedication for pemetrexed. Our data suggests that no steroid premedication is needed with pemetrexed and vitamin supplementation. [Table: see text]
Expression of angiogenic mediators in head and neck cancer
Authors: Usó M. , Sirera R. , Jantus Lewintre E. , Mosquera N. , Zapater E. , Cabrera A. , Sanmartín E. , Berrocal A. , Basterra J. , Camps C. 
Published: August 2020

e17032 Background: In cancer, systematic analysis of mRNA expression levels can contribute to define a molecular network of lung carcinogenesis and establish predictive and prognostic molecular markers. Altered mRNA expression in certain angiogenic and anti-angiogenic genes such as vascular endothelial growth factor family of ligands and their receptors together with other molecules implicated in angiogenesis could predict disease outcome and add prognostic information at diagnosis. Methods: We performed RT-qPCR in frozen head and neck cancer specimens from untreated patients who had undergone surgical resection (n = 23). Samples were processed for mRNA extraction following standard procedures and quantification of gene expression was expressed as relative concentration normalized by an endogenous gene. The following angiogenic genes were quantified: PDGF-A, PlGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D, COX-2, bFGF, HGF, IL-8; and anti-angiogenic genes: Angiomotin and endostatin. Results: Median age was 56.5 years, range (31–79), 17 patients presented squamous carcinoma of the larynx; 8 patients were stage III and the other 15 stage IV. None of the patients received pre-surgery chemo or radiotherapy and 10 patients reveived post-surgery treatment. Our results show that tumor samples had significant higher expression of PDGF, PlGF, COX-2, and IL-8 and a deep down-regulation of angiomotin. However, those data show no correlation between the levels of expression and stage of the disease. Conclusions: Our results reveal that there is an increase in the expression of the pro-angiogenic mediators PDGF, PlGF, COX-2, and IL-8 and a downregulation of angiomotin that may mediate the inhibitory effect of angiostatin on tube formation and the migration of endothelial cells toward growth factors during the formation of new blood vessels in the tumoral area. This data suggest that more research are needed in other angiogenic mediators that VEGF, that PlGF and angiomotin have some role in cancer progression and could be a promising new biomarker in head and neck cancer. No significant financial relationships to disclose.
Concurrent chemoradiotherapy of patients with locally advanced squamous cell carcinoma of the oral cavity (stage III, IV)
Authors: Adilbay D. G. , Adilbaev G. B. , Ahmetov D. N. 
Published: August 2020

e17034 Background: Randomized trials have showed a good result of concurrent chemoradiotherapy in advanced SCC of the head and neck. But there are only few trials which evaluates separately the different sites of the head and neck. The aim was to evaluate the toxicity and efficacy of concurrent intra-arterial chemotherapy plus radiotherapy with altered fractionation in SCC of the oral cavity. Methods: 43 patients with previously untreated oral cavity SCC (T3–4N0–2M0) received concurrent chemoradiotherapy by followed scheme: first day intra-arterial chemotherapy: docetaxel - 80 mg/m2, cysplatin - 100 mg/m2, from second to 21st day RT (28 Gy by 4 Gy - 3 times week), 22nd day second course of intra-arterial chemotherapy and after RT (total dose- 60 Gy by 2 Gy 5 times week, total equivalent to 70Gy by conventional fractionation), depending on the results salvage surgery if necessary. Results: The clinical effects were pCR in 34 (79.1%) patients, pPR in 9 (20.9%) patients. The following main toxicities of chemoradiotherapy were observed: only 2 cases of grade 3 neutropenia, Non-hemathologic toxicity: 74.4% (32 patients) grade 3 mucosal events. All patients have totally completed the treatment. The 3-year overall survival rate were 83.7%, and 3-year disease free survival were 76.7%. Conclusions: This regimen of concurrent chemoradiotherapy where radiotherapy is used by altered fractionation is feasible, safe and well tolerated. No significant financial relationships to disclose.
Robotic radiosurgery for severe recurrent and primary head and neck cancer
Authors: Kawaguchi K. 
Published: August 2020

e17038 Background: We considered the functional reconstruction following head and neck tumor ablation, however, it was impossible to recover completely the function against the severe postoperative status. Here we describe our aim to improve local control and to obtain organ preservation by using the non-surgical outpatient procedure the CyberKnife frameless radiosurgery (CK). Methods: Between March 2006 and January 2008, 22 patients with severe recurrent, previously treated with conventional methods, and 14 patients with primary lesions were treated with CK in the management of head and neck cancer. All the patients had biopsy confirmation of disease prior to radiation therapy; rT2 (3 patients), rT3 (8), rT4 (9), T2 (5), T3 (3), T4 (6), N1 (4), N2b (3), M1 (1), tongue (11), mandibule (11), maxilla (6), maxillary sinus (4), soft palate (2), with sq. cell ca.(34), adenoid cystic ca.(1), fibrosarcoma (1). The treatment plan was set up based on CT, MRI and PET-CT in Yokohama CyberKnife Center. CK's lightweight linear accelerator always irradiates toward the target from 120 directions with image-guided computer based on CT. Marginal Doses were 2000–4200cGy in 3–5 fractions. Curative effects were evaluated assessed by RECIST included PET. Results: 11/22 (50.0%) of the severe recurrent cases were controlled from 6 to 25 months at follow-up range. The local recurrent cases with non-lymph node metastases were excellently controlled as 10/12 (83.3%). For the primary cases, significant tumor reduction were noted at the third-month follow-up, all the 14 patients went into remission with 5 cases in CR, and 9 cases in PR. Between the 4–6 month follow-up, 4 cases were performed additional CK treatment for the recurrent lesions, however, 3 patients with T4 tongue cancer were not cured. Finally, the total control rate of the primary cases was 10/14 (71.4%), however, 8/9 (88.9%) primary cases except tongue cancer has been controlled treated by CK with chemotherapy. The cases of non-lymph node metastases were cured 8/8 (100.0%) by CK. There have been no seriously complications of treatment caused by CK except severe osteoradionecrosis of the 4 patients irradiated with maximum dose. Conclusions: It is now possible with the development of CyberKnife Radiosurgery to improve our treatments of the local control in head and neck cancer. No significant financial relationships to disclose.
PET/CT fusion in radiotherapy treatment planning for head and neck cancer
Authors: Xiang Z. 
Published: August 2020

e17046 Background: Positron emission tomography/computerized emission tomography (PET/CT) creates fusion images which are a combination of tissue function (PET) and anatomy (CT). It is playing an increasingly important role in radiotherapy of cancer. Aim of this report is to investigate the value of PET/CT fusion in radiotherapy treatment planning for head and neck cancer. Methods: 17 patients with head and neck cancer underwent 18F-FDG PET/CT imaging. The primary lesions were all proved by pathology. PET/CT fusion images, PET images and CT images of the same patient were analyzed frame by frame. TNM stage was analyzed based on PET/CT and CT. PET/CT-GTV and CT-GTV volume were analyzed. Results: 59 malignant lesions were detected by PET/CT in the 17 patients. Among 59 lesions, 31 lesions were detected and displayed definitely by both PET and the plain scan of CT; 23 lesions were detected definitely by PET but not by the plain scan of CT; while 5 lesions were negative by PET but definitely by the plain scan of CT. The sensitivity of PET/CT was higher than PET and the plain scan of CT alone. Changes in TNM stage occurred in 7 patients (41%), based on PET/CT. The median PET/CT-GTV and CT-GTV volume was 84.3 cm3 (range, 46∼364 cm3) and 116.2 cm3 (range, 58∼472 cm3), respectively, showed significant differences (p = 0.0005). Conclusions: PET/CT can increase the accuracy of the staging and defining target volumes for radiation therapy fields for head and neck cancer. No significant financial relationships to disclose.
Capecitabine-based chemotherapy versus primary treatment for patients with advanced stages of undifferentiated nasopharyngeal carcinoma (UCNT): Preliminary results of a phase II study
Authors: Djedi H. , Bouzid K. 
Published: August 2020

e17049 Background: The combination of cisplatin and 5-fluorouracil (5-FU) is considered to be the standard treatment in induction chemotherapy for patients with undifferentiated nasopharyngeal carcinoma (UCNT). Capecitabine is an oral fluoropyrimidine. The aim of our study is to evaluate overall response and toxicity of this drug as a primary chemotherapy based-regimen for patients with advanced stages of UCNT. Methods: From January 2008 through December 2008, 34 chemo-naives patients with UCNT were included, mean age: 45.2 years (range 14–61 years), 12F/22M. One patient was stage IIB, nine patients stage III, 17 patients stage IVA, five patients stage IVB, and two patients stage IVC. All patients received at least 3 to 4 courses of neoadjuvant chemotherapy. The treatment plan included cisplatin at dose of 75 mg/m2 on D1 every 21 days, followed by capecitabine at a dose of 1,000 mg/m2 twice daily from D2 to D 15, with a 1-week rest period. Five patients received this scheme plus docetaxel at a dose of 75 mg/m2 on D1 with prophylactic granulocyte colony stimulating factors: lenograstim or filgrastim. All patients had a clinical evaluation of objective response and toxicity before at each cure . A CT scan was done at the end of treatment before radiotherapy. Results: After a total of 114 courses, all patients (34 pts) were evaluable for toxicity and 26 patients were evaluable for response (8 pts have not yet achieved their treatment). A clinical benefit was obtained for all patients since the first cure of chemotherapy. The overall objective response (CR+PR) was achieved in 96% of cases (25/26pts ), one patient had a stable disease. One of the two patients with stage IVC had a complete response on hepatic metastasis after 3 cures. Grade 3/4 toxicity included: diarrhea 5.2%, nausea/vomiting: 9.6%, hand-foot syndrome 3.5%, febrile neutropenia 4.3%, cardiac toxicity: 0.8%, thrombocytopenia 1.75%. Chemotherapy was interrupted for one patient after only one cure because of the cardiac toxicity. Conclusions: Capecitabine based chemotherapy is a safety and an effective regimen in patients with UCNT. However a longer follow-up is needed to confirm the benefit on disease-free survive (DFS) and overall survivor. No significant financial relationships to disclose.
Neoadjuvant versus concurrent chemotherapy in the management of carcinoma nasopharynx
Authors: Sharma R. , Kumar D. , Kaur S. , Kalsotra P. , Gupta A. 
Published: August 2020

e17053 Background: Chemotherapy is added to radiotherapy in the treatment of nasopharyngeal carcinoma with advanced locoregional disease to enhance therapeutic gain. Thirty percent patients with locally advanced nasopharyngeal carcinoma (LA-NPC) still die of distant metastases despite concurrent chemoradiation being the standard of care. In this retrospective study we performed the pooled analysis of these patients to assess the impact of neoadjuvant chemotherapy versus the concurrent chemoradiation approach. Methods: Between January 2000 and December 2007, 45 patients of stage IIB- IVB nasopharyngeal were treated with 3 cycles of induction chemotherapy with cisplatin and 5FU (n = 23) followed by conventional radical radiotherapy, or concurrent chemoradiation with weekly cisplatin (n = 22). Results: Total numbers of patients eligible for analyses were 45. Median age of the patients was 52 years (range 19–76 years). Median follow up was 17 months (range 6–60 months). At the time of last follow up, 13 patients (out of 23, i.e. 56.53%) were alive and disease free in the neoadjuvant group and 13 patients (out of 22, i.e. 59.1%) were alive and disease free in the concurrent chemoradiation group. The 2-year failure free survival in the concurrent chemoradiation arm was 63% versus 35% in the neoadjuvant arm (p = 0.197). Survival analyses adjusted for the gender male revealed 2-year failure free survival as 81% in the concurrent chemoradiation versus 44% in the neoadjuvant chemotherapy group among male patients (p = 0.0143). On multivariate analysis age and stage were the two significant predictive factors for failure free survival. Conclusions: The neoadjuvant chemotherapy seems to be at least as effective as concurrent chemoradiation in this small cohort of patients. No significant financial relationships to disclose.
Evaluation of p53 and BCL2 expression, mutation, and aneuploidy status on treatment response in an Indian cohort of primary Ca larynx
Authors: Sahoo R. , Babu V. , Patil G. , Kulkarni J. , Rao S. , Thakur S. , Dondhalay G. , Banerjee A. , Kumar BS A. , Korlimarla A. , Rao M R. 
Published: August 2020

e17057 Background: Organ-sparing therapy consisting of cisplatin and 5-fluorouracil, combined with radiation for advanced head and neck squamous cell carcinoma (HNSCC) have been advocated in Ca larynx patients. However, failure of some tumors to respond to treatment or tumor recurrence limits the overall success of these therapies. P53 mutations have been linked to cisplatin resistance in other solid tumors. In this study we evaluate the relationships between P53 overexpression/mutations, BCL2 expression and ploidy status on treatment response in retrospective cohort of Ca Larynx patients. Methods: Samples from 18 patients with histopathologically confirmed Ca Larynx were analysed from our biorepository after consent. Clinical, sociodemographic information and response to treatment were abstracted from case records. P53 and BCL2 over expression were checked by IHC and p53 mutation by PCR and direct sequencing. DNA ploidy and S-phase fractions were also analysed. Bivariate relationships were determined between these variables using Spearmans rank correlation. Independent samples t tests were used to determine changes in P53 over expression, BCL2 expression Ploidy status and S phase fractions in both responders and non responders. Results: There was a trend for increase in P53 over expression and BCL2 expression and decrease in S phase fractions in responders vs non responders. Neither p53 over expression (75% of cases) and BCL2 over expression (17% of cases) correlated significantly with treatment response. However, BCL2 expression correlated negatively with disease stage (r = - 0.57, p = 0.02). Aneuploidy was observed in node positive tumors (p = 0.04). Conclusions: The results suggest poor association of molecular markers with treatment response and should not be relied as a marker for treatment response. Though there is a trend for association a larger sample size is required to demonstrate the findings. No significant financial relationships to disclose.