bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of interobserver variability in delineating clinical target volumes (CTV) for head and neck intensity modulated radiation therapy (IMRT): Potential for a geographical miss
Authors: Chilukuri S. , Surana S. , Mohanty P. P. , Kuppuswamy R. 
Published: August 2020

e17013 Background: Despite modern day imaging techniques and guidelines for delineation of the clinical target volume, there remains significant inter-observer variability in delineating the CTV. With the use of IMRT, the target volume receives a significant tumoricidal dose while the regions just outside the target receive unpredictable doses. In this report, the dose to the region just outside the planning target volume (PTV) (defined as volume of uncertainty [VOU]), presumed to represent the regions subject to maximum inter-observer variability, was studied. Methods: The IMRT plans of 12 patients with head and neck cancer were used to determine the dose just outside the high-risk CTV by growing volumes around CTV with 3 mm, 5 mm, and 7 mm margins. These volumes were edited at regions close to skin/air and bone. PTVs were subsequently grown using the same margins as used in the original plans. With the Boolean operations, each of these volumes was subtracted from the existing PTV to generate the volumes of uncertainty (VOU) in 3 dimensions. The dose to these VOUs was analyzed. D95, D90 and median dose which are the doses received by 95%, 90%, and 50% of the target volume respectively were studied. Results: The median prescribed dose was 68 Gy (60 Gy-72 Gy). The median percentage D95 for 3mm, 5mm and 7mm VOU was 82.5% ± 4.95, 77.25% ± 5.53, and 69% ± 6.93, respectively. The median percentage D90 for these VOU's was 87.7% ± 3.53, 83.2% ± 4.61, and 79% ± 4.5, respectively. The median dose to each of these VOU”s was 96% ± 1.6, 94.5% ± 1.95, and 92.5% ± 1.85 respectively. Conclusions: This study documents that the volumes of uncertainty surrounding the PTV, which could contain subclinical disease, in fact receive a significant amount of RT dose. Hence, despite a large amount of evidence for inter-observer variability in target delineation for head and neck cancer,the majority of locoregional recurrences are within the high dose region and not marginal failures. No significant financial relationships to disclose.
Correlation of global expresssion of ERCC1 in head and neck squamous cell carcinoma with prognosis
Authors: Saada E. , Thariat J. , Ettore F. , Sudaka A. , Chamorey E. , Italiano A. , Poissonet G. , Bensadoun R. , Dassonville O. , Peyrade F. 
Published: August 2020

e17016 Background: The overexpression of excision repair cross-complementation group 1 (ERCC1), element of the Nucleotid Excision Repair (NER) pathway has been associated with resistance to platinum-based chemotherapy. We studied the correlation of ERCC1 immunohistochemical expression with overall survival and cancer-specific survival in patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) treated with cisplatin-based chemotherapy. Methods: Using a monoclonal antibody against ERCC1 (clone 8F1, Neomarker), we analyzed its immunohistochemical expression in pretherapeutic samples of 142 HNSCC patients treated in our center from 2000 to 2006. Forty-three patients were treated with surgery followed by adjuvant radiochemotherapy, 86 with concomitant radiochemotherapy with or without neoadjuvant chemotherapy and 13 with cisplatin-based chemotherapy for metastatic disease. Two independent observers blinded to clinical data evaluated ERCC1 expression using the H-score protocol (ranging from 0 to 3). Survival rates were estimated using the Kaplan-Meier method. Survival univariate analysis was performed using log-Rank test. Results: ERCC1was expressed intensively and diffusely in the nuclei 89% of the tumor samples had an H-score at least equal to 2. Treatment type and metastatic status were predictive of overall survival (respectively, p = 0.003 and p = 0.005). Higher expression of ERCC1 tended to be correlated with longer overall survival (p = 0.08). Conclusions: Our observations are at variance with recently published data about the predictive role of ERCC1 (Handra Luca CCR 2008). Overexpression of ERCC1 has also been associated with better outcome of operated NSCLC. Such differences may be due to inherent biological differences between study populations and certainly attributable to different roles of ERCC1 through oncogenesis.These controversial correlative results among studies and the intense and diffuse patterns of ERCC1 expression might also indicate a central role of ERCC1 in HNSCC oncogenesis and then provide a potential target. Further investigations about the role and predictive value of ERCC1 protein in anticancer treatments including cisplatin are warranted. No significant financial relationships to disclose.
Concurrent chemoradiotherapy with weekly docetaxel and cisplatin for locally advanced head and neck cancer: Phase I study
Authors: Kim H. S. , Park K. , Ahn M. J. , Park Y. , Lee S. , Baek C. , Son Y. , Jeong H. , Ahn Y. , Park B. 
Published: August 2020

e17026 Background: This phase I study was performed to determine maximum tolerated dose of docetaxel when administered concomitantly with radiotherapy and cisplatin in patients with locally advanced head and neck cancer. Methods: Fifteen patients were treated at varying levels of docetaxel (level 1: 0 mg/m2, level 2: 10 mg/m2, level 3: 15 mg/m2, and level 4: 20 mg/m2, once per week for a total 6 weeks) with a fixed dose of 20 mg/m2 cisplatin weekly on an outpatient basis. Radiotherapy was delivered as a standard regimen (1.8–2.0 Gy/day, 5 fraction/week) to a total dose of 66–72 Gy. Results: One out of six patients presented with dose-limiting toxicity at the 10 mg/m2/week dose of docetaxel (grade 4 febrile neutropenia which results in treatment-related death). No DLTs was noticed at the 15 mg/m2, and 20 mg/m2 dose level. Thus, the weekly docetaxel dose of 20 mg/m2 was considered as the maximum tolerated dose. Radiotherapy was completed in all patients except one, and more than 95% of the scheduled cisplatin and docetaxel were given in 93% of patients. Acute grade 3–4 toxicities were dominated by anorexia (26.7%), xerostomia (13.3%), and febrile neutropenia (6.6%). Eight (57.1%) and six (42.9%) patients had complete response and partial response. The 2-year actuarial overall survival rate and local control rate were 93.3%, and 87.5%, respectively. With a median 17.5 months (1.25–23.6) of follow-up, 13 out of 14 patients are still alive without evidence of diseases, and only one is alive with evidence of diseases. Conclusions: We determined the MTD of docetaxel to be 20 mg/m2 administered once weekly concurrently with combined with conventionally fractionated RT and weekly 10 mg/m2 CDDP. This chemoradiotherapeutic regimen serves as a promising treatment modality, in which level 3 is the recommended dose for a phase II study. No significant financial relationships to disclose.
Assessment of phosphatidylinositol-3 kinase (PI3K) as a prognostic marker in head and neck squamous cell carcinoma (HNSCC)
Authors: Pectasides E. , Founztilas G. , Sasaki C. , Burtness B. , Psyrri A. 
Published: August 2020

e17028 Background: Deregulated signaling through phosphatidylinositol 3’-kinase (PI3K) pathway is common in several cancers, including HNSCC. In the present study we investigated the relationship between PI3K protein expression and outcome in patients with HNSCC. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for PI3K were analyzed using an immunofluorescence-based assay that provides an automated, quantitative analysis of expression within subcellular compartments (AQUA). Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance. Results: Mean follow-up time for the cohort was 40 months. Ninety-seven of 122 cases had sufficient tissue for analysis and continuous AQUA scores were divided into quartiles. Survival analysis showed that patients in the top and bottom quartile had a significantly shorter OS (p = 0.015). In multivariable analysis, adjusting for well-characterized prognostic variables, PI3K expression retained its prognostic significance. Conclusions: Our study suggests that in situ quantitative measurement of PI3K stratifies HNSCC into four expression levels where both low and high levels are associated with a worse outcome. We speculate that transmission of growth factor receptor signals that promote tumor aggression in these low expressers may occur via PI3K/Akt independent mechanisms. It is possible that activation of such alternate pathways in some tumors results in the down-regulation of PI3K expression via a feedback mechanism, producing aggressive tumors bearing a PI3K-low phenotype. No significant financial relationships to disclose.
Prognostic value of the expression of tumor necrosis factor-alpha (TNFa) and its receptors in head and neck cancer (HNC) patients: A pilot study
Authors: Clatot F. , Picquenot J. , Cornic M. , Hamidou H. , Tennevet I. , Choussy O. , François A. , Hong L. , Laberge-Le- Couteulx S. , Blot E. 
Published: August 2020

e17029 Background: TNFa was initially described as an inductor of apoptosis in cancer cells. In vitro data showed that TNFa can also activate anti-apoptotic signaling in cancer cells. We analyzed the prognostic value of the expression of TNFa and its receptors TNFR1 and TNFR2 in HNC patients. Methods: Twenty-four patients treated for HNC were retrospectively analyzed for TNFa, TNFR1, and TNFR2 expression by real-time PCR (RT-PCR). Tissue samples were collected at the time of initial diagnosis. Total RNA was reverse-transcribed with TaqMan quantitative RT-PCR (Applied Biosystems). Results were recorded as average threshold cycle, and relative expression was determined using Normalized Expressions method. Expression of TNFa, TNFR1, and TNFR2 was related to survival after 3 years of follow-up. Results: In the 24 patients, expression of TNFa (mean value 7.8, median 2.4, range 0.02–62.3), TNFR1 (mean value 58, median 49, range 0.02–246.9) and TNFR2 (mean value 4.8, median 3.3, range 0.8–18.9) demonstrated a great variability between patients. After a 3-year follow-up, 14 patients were alive without evolution of cancer (group A) and 10 were dead because of cancer evolution (group D). In group D, median level of TNFa was 8.8 whereas it was 1.1 in group A (p = 0.02). Median level of TNFR1 was 71.8 in group D and 28.5 in group A (p = 0.01). In contrast, median level of TNFR2 was 3.3 for both groups. Patients with high level of TNFa or TNFR1 expression had a worse survival (p = 0.01 and p = 0.009, respectively). There was also a strong correlation between high expression of TNFa and of TNFR1 (p = 0.0007). Conclusions: In this small series, TNFa and TNFR1 expression seem to have significant prognostic value to predict survival of HNC patients. This result needs to be confirmed in larger series and compared with usual prognostic factor. It suggests that TNFa expression could have a dual effect in HNC and that TNFR1 expression may play a role in this process. No significant financial relationships to disclose.
Analysis and utility of pretreatment and posttreatment total body iodine-131 scans in patients with thyroid carcinoma
Authors: Billan S. , Nasrallah H. , Abdah-Bortnyak R. , Kuten A. 
Published: August 2020

e17031 Background: The purpose of this study was to evaluate the efficacy of post-I-131 treatment total body scans. Methods: The records of 108 consecutive patients with thyroid carcinoma treated by surgery and postoperative I-131 were reviewed. All patients underwent a postoperative diagnostic total body I-131 and post I-131 therapy scintigraphies .83% of patients were considered low risk according to AMES (age, metastasis, extracapsular extension, size) criteria. Results: The postoperative diagnostic total body I-131 scintigraphy revealed uptake in the neck in 95 out of 108 patients (88%). Three patients had lung and mediastinal uptake in known sites of metastatic disease. Additional foci of neck, mediastinal and lung uptake were revealed in the post-131 therapy total body scintigraphies in ten patients ( 9.3%). Variables found to correlate significantly with additional uptake on the post-I131 therapy total body scintigraphies were tumor size >4cm, lymph-node involvement and extracapsular extension. Conclusions: Post- I-131 therapy scans yielded additional information in 9.3% of the patients treated by postoperative I-131 for well differentiated thyroid carcinoma. The value of posttreatment scintigraphies is questionable in low risk patients. No significant financial relationships to disclose.
Treatment-related toxicities in patients with squamous cell carcinoma of the head and neck (SCCHN)
Authors: Ulcickas Yood M. , Feng Wang P. , Hensley Alford S. , Oliveria S. , Wells K. , Phillips S. , Ali H. , O’Malley C. D. 
Published: August 2020

e17041 Background: Although treatment effects and toxicities have been reported from randomized clinical trials of patients with squamous cell carcinoma of the head and neck (SCCHN), little information is available from real-world clinical practice where heterogeneous treatment patterns and patient populations may lead to different estimates than those observed in clinical trials. Methods: Using a population-based tumor registry at a large, Midwestern integrated health system, we identified all cases of stage III or IV SCCHN diagnosed 2000–2006. The incidence/severity of acute and late toxicities associated with SCCHN treatment was obtained from detailed medical record review of health system encounters, including physician notes. Grading of toxicities (using CTCAE3 criteria), distinction between acute and late toxicity, and analyses by treatment are ongoing. The incidence and severity of toxicities will be presented by treatment regimen, tumor location and tumor stage. We presented here an interim analysis. Results: Among the target population of 194 patients that will ultimately be included in this study, 137 medical record reviews have been completed to date. The percentages of patients with toxicities, including 95% confidence intervals are presented in the table , below. Conclusions: Toxicity in patients with advanced SCCHN is common. Data from clinical practice quantifying the incidence are lacking, these data from an observational real-world study provide important baseline information on the incidence of toxicities in patients with advanced SCCHN and also call for safer effective treatment for SCCHN. [Table: see text] [Table: see text]
Paclitaxel in relapsed squamous cell carcinoma of head and neck (SSCHN): Retrospective study of a single institution
Authors: Fayette J. , Montella A. , Bachelot T. , Pommier P. , Girodet D. , Racadot S. , Montbarbon X. , Favier B. , Zrounba P. 
Published: August 2020

e17047 Background: For relapse or metastatic SCCHN the standard treatment is the combination of cisplatin and 5FU that showed higher response rate than methotrexate but similar overall survival. Cetuximab demonstrated in a phase III (N Engl J Med. 2008;359:1116) its efficacy and paclitaxel showed efficacy in a phase II study (Cancer. 1998;82:2270). The objective of this study was to evaluate paclitaxel (P) in our institution in various situations. Methods: We retrospectively reviewed 56 pts with relapse or metastatic SSCHN treated with P in a single institution in Lyon (France) between June 2002 and February 2008. P was administered in first line for locally advanced disease, in first line for relapsed or metastatic disease, or in second or more line. P was administered q1w or q3w, alone or in combination with carboplatin or cetuximab. Results: Median age was 59 years (36–84) at the beginning of paclitaxel. Localizations of primitive tumor: oral cavity (14%), oropharynx (30%), hypopharynx (39%) larynx (7%), rhinopharynx (4%), or other (6%). All patients received adequate initial treatment with surgery and/or radiotherapy, 47% had have neoadjuvant chemotherapy (71% with cddp-5fu, but 5 pts received P). Five patients received P as neoadjuvant treatment. Among 52 evaluable patients, 33 received P in first line of treatment after relapse, 12 in second line. Monotherapy was administered to 20 patients and 22 received P combined with carboplatin, and 1 with cetuximab. For all patients, objective response rate (OR) was 30.8% (95% CI 18.7–45.1%). In first line of relapse, OR was 39.4% (95% CI 22.9–57.9%) and 16.7% (95% CI 2.1–18.4%) in second line. In monotherapy OR was 30.0% (95% CI 11.9–54.3%) and 36.4% (95% CI 17.2–59.3%) in combination with carboplatin. The overall survival (OS) of all patients was 6.3 months (95% CI 3.9–7.9 m), and 7.7 m (95% CI 3.9–11 m) and 5.2 m (95% CI 2.8–7.9 m) in first and second line, respectively. There is no difference in OS between monotherapy and combination: 6.1 m (95% CI 3.9–7.9 m) and 5.3 m (95% CI 3.9–7.9 m), respectively. Conclusions: P did not improve overall survival but showed interesting response rate in relapsed patients who are often symptomatic. Recent studies suggest high potentialities in combination with EGFR inhibitors. No significant financial relationships to disclose.
Pattern of head and neck cancers in a Nigerian tertiary health center: A 10-year review
Authors: Alabi S. , Rahman G. , Badmos K. 
Published: August 2020

e17054 Background: Cancer is a rising health problem worldwide, Nigeria inclusive. A variety of different tumour types may arise at a host of sites within the head and neck region. This 10-year review is to assess the various sites of primary lesion, gender and age distribution and histopathological types, so as to update data with an earlier study done in our centre between 1997–2001. Methods: This 10 year review of patients with head and neck cancers was carried out at the University of Ilorin teaching, Ilorin, North central Nigeria between January 1997 and December 2006.The hospital is one of 2 teaching hospitals in the zone of 6 constituent states out of 36 states in Nigeria, with an average population of 5 to 6 million (2003 Nigerian census). Information extracted from the case notes of patients with histological results included: Age, sex, clinical features, site of tumour, and the histological types of tumour. The International classification of disease oncology (ICDO) ninth version was used to categorize the sites of the tumour. Results: A total of 138 cases of head and cancers were seen over the 10 year period with an average occurrence of 14 cases/year, male/ female ratio of 1.1 to 1.0, age range of 1.5 years to 85 years with a mean age of 45.23 years, the peak age incidence of fifth to sixth decades of life being 47.2%.The commonest histological type was carcinoma (78.3%), then lymphomas (12.3%), blastomas (5.1%), sarcomas (4.3%). The commonest site were the nose, paranasal sinuses and ears (23.9%), eye (15.2%), nasopharynx (13%), neck (13% -metastatic unknown primary 4.3%), thyroid (12.3%), larynx (10.2%), oral cavity and oropharynx (6.5%), salivary glands (3.6%), mandible (1.4%), and skin (0.74%). Conclusions: This result shows that head and neck cancers occur among Nigerians with no sex differentiation in their prime of life, the histological types are similar to the previous series, however the site seems to have changed with the nose and paranasal sinuses, eye, and nasopharynx being the commonest sites. The metastatic unknown primaries in the neck are much lower. The devastating effects on the individual, family and the community are enormous in a setting with late presentations at the hospital and a strong belief in traditional medicine. Emphasis on prevention of these cancers is stressed. No significant financial relationships to disclose.
Actual proportion of patients (pts) receiving chemotherapy or cetuximab for head and neck squamous carcinoma (HNSC)
Authors: Grau J. J. , Caballero M. , Verger E. , Blanch J. L. 
Published: August 2020

e17058 Background: With the new indications of chemotherapy or cetuximab in HNSC, the rate of pts receiving these therapies nowadays is unclear. Methods: This retrospective study identified all consecutive pts with HNSC from January 1, 2006, to December 31, 2007, presented in a multidisciplinary team to decide further treatment in a single institution. ASCO guidelines for larynx preservation were followed to select surgery or chemoradiotherapy (ChRt). We classified the intention-to-treat as palliative, adjuvant or induction therapy. In the last case, always with concomitant radiotherapy (Rt) or prior to concomitant ChRt. Cetuximab was indicated with Rt as induction therapy for pts with problems to receive platin-based chemotherapy. Results: : A total of 350 pts were identified, 320 were male (91%), and 30 female (9%), with mean age 60.4 (range 41–90). Primary tumor was located in glottis (41%), supraglottis (19%), hypopharynx (11%), oropharynx (20%), or mouth (9%). Staging was I (27%), II (22%), III (16%), or IV (35%). Surgery alone was performed in 136 pts (39%) and chemotherapy or cetuximab in 214 other pts (61%). The intention-to-treat was palliative in 69 (32%), adjuvant in 51 (24%), or induction 94(44%) of the pts respectively. Rt plus cetuximab was administered to 31/97 (33%) and Rt plus chemotherapy in 63/97 (67%) pts as induction therapy. During this 2-year period, some pts received both induction/adjuvant and palliative chemotherapy. Conclusions: Chemotherapy or cetuximab is indicated as part of treatment in more than a half of pts with HNSC. Induction therapy is the most frequent indication. No significant financial relationships to disclose.
Introduction of computerized provider order entry (CPOE) and time impact in an inpatient hematology/oncology service: Serial time and motion studies
Authors: Hanauer D. A. , Beasley R. W. , Schumacher J. , Duck M. G. , Blayney D. W. 
Published: August 2020

e17507 Background: The impact of CPOE on inpatient hematology/oncology care is not well studied. CPOE has many benefits, but concerns exist about increased time required to enter electronic orders compared to handwritten orders. We hypothesized that CPOE would require more order-related time from caregivers, and reduce the amount of time for direct patient care. Methods: Physician assistants (PAs) enter all patient orders (except those for chemotherapy) and are the dedicated and exclusive care providers on this non-house staff service at the main Hospital of the University of Michigan Health System. We chose the PA service for observation as we could eliminate potential biases introduced by rotating house staff we observed in earlier studies. PAs were directly observed at -1, +3 and +8 months post implementation of a CPOE system (Sunrise Clinical Manager, Eclypsis, Atlanta GA). Dedicated observers used a data entry tool with a modified database (available on the Health IT Tools section at healthit.ahrq.gov) on a tablet computer. For analysis, the 60 individual activities were grouped into 6 major categories, as well as an ordering category. We observed the same three PAs for 82.5 hours pre-CPOE, for 75.0 hours at 3 months post and for 70.5 hours 8 months post. Productive time was all non-personal and non-administrative time. The faculty entered chemotherapy orders and supervised the PAs, but were not studied. Results: Overall time for order-related activities was unchanged during the three observation periods, requiring 10.3, 10.6 and 11.4% of productive time, respectively. Time spent on direct patient care (as a percentage of productive time) was also unchanged once CPOE was implemented (50.7% pre vs. 49.8% and 47.8% post). Conclusions: We could not detect differences in order-entry time by well-trained PAs using standardized order sets before and after CPOE implementation on an inpatient hematology/oncology service. The decision to adopt CPOE should not be based on the hypothesis that there will be less (or more) time spent on order entry tasks. No significant financial relationships to disclose.