Sarah S. Kılıç

The relevance of molecular biomarkers in cervical cancer patients treated with radiotherapy

BACKGROUND Radiotherapy (RT) plays an integral role in the combined-modality management of cervical cancer. Various molecular mechanisms have been implicated in the adaptive cellular response to RT. Identification of these molecular processes may permit the prediction of treatment outcome and enhanced radiation-induced cancer cell killing through tailoring of the management approach, and/or the employment of selective inhibitors of these pathways. METHODS PubMed was searched for studies presenting biomarkers of cervical cancer radioresistance validated in patient studies or in laboratory experimentation. RESULTS Several biomarkers of cervical cancer radioresistance are validated by patient survival or recurrence data. These biomarkers fall into categories of biological function including hypoxia, cell proliferation, cell-cell adhesion, and evasion of apoptosis. Additional radioresistance biomarkers have been identified in exploratory experiments. CONCLUSIONS Biomarkers of radioresistance in cervical cancer may allow molecular profiling of individual tumors, leading to tailored therapies and better prognostication and prediction of outcomes.

Survival, Morbidity, and Quality-of-Life Outcomes for Sinonasal and Ventral Skull Base Malignancies

Sinonasal and ventral skull base malignancies are a rare, heterogeneous group of cancers. Although prognosis usually depends on many factors, long-term survival rates remain low despite recent advances. Population-based databases are powerful resources for studying survival outcomes. However, institutional retrospective chart-review studies have been able to provide more insight on recurrence patterns, morbidity, and quality-of-life metrics, as well as more details of the treatment information that may affect outcomes. This article discusses general considerations for understanding reported outcome data, summarizes the overall outcomes and their determinants, and provides histology-specific outcomes reported in the literature.

Significance of human papillomavirus positivity in sinonasal squamous cell carcinoma

The role of human papillomavirus (HPV) in sinonasal squamous cell carcinoma (SNSCC) is not well understood.

Comparison of endoscopic and open resection of sinonasal squamous cell carcinoma: a propensity score-matched analysis of 652 patients: Endoscopic vs open resection of sinonasal SCC

The use of endoscopic resection as an alternative to open surgery for sinonasal malignancies has increased in the past 20 years.

Predictors of Clinicopathologic Stage Discrepancy in Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study

Objective To determine the frequency, associated factors, and prognosis of clinicopathologic stage discrepancy in oropharyngeal squamous cell carcinoma (OPSCC). Study Design Retrospective study using a national database. Setting National Cancer Database. Subjects and Methods Cases of OPSCC diagnosed between January 1, 2004, and December 31, 2013, with full clinical and pathologic staging information available were identified. Demographic, clinicopathologic, and treatment variables associated with overall stage discrepancy were identified by multivariate logistic regression analysis. Results In total, 7731 cases of OPSCC were identified. Overall stage discrepancy was present in 30.2% of cases (21.9% upstaging, 8.2% downstaging). A total of 13.1% of cases were T-upstaged, and 10.5% of cases were T-downstaged; 22.9% of cases were N-upstaged, and 8.6% of cases were N-downstaged. Upstaging by overall stage was associated with a high Charlson-Deyo score, high tumor grade, number of lymph nodes examined, and increasing tumor size. No factors were positively associated with downstaging. High tumor grade was negatively associated with downstaging. For stage II, III, and IVA tumors, upstaging was associated with poorer OS. Conclusion Clinicopathologic stage discrepancy is common in OPSCC and is likely attributable to insensitive clinical staging techniques as well as to intrinsic tumor biologic properties. Upstaging is associated with poorer prognosis, which is likely due to advancement of disease.

Radiotherapy modality as a predictor of survival in hypopharyngeal cancer

The impact of radiotherapy (RT) modality and dose on survival in hypopharyngeal cancer managed with definitive RT is unclear.

Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell carcinoma: A National Cancer Database study

Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC).

Incidence and survival of sinonasal adenocarcinoma by site and histologic subtype

Abstract Objective: To determine the incidence and survival of sinonasal adenocarcinoma (SNAC) by subsite and histologic subtype. Study design: Retrospective database review. Methods: Using the SEER database, we performed a retrospective analysis, identified cases of SNAC diagnosed between 1973 and 2013 and analyzed demographic, histopathology, clinicopathology, and determinants of disease specific survival (DSS). Results: A total of 746 patients with SNAC were identified. Median age at diagnosis was 64 years. Overall incidence was 0.44 per million, and was higher among blacks (O.R.:1.10–2.07:1) and males (O.R.:1.38–2.06:1). Nasal cavity (41.5%) was the most common site, followed by maxillary (26.5%), and ethmoid (17.4%) sinuses. Intestinal-type adenocarcinoma was less likely than Adenocarcinoma not otherwise specified (ANOS) to be found in the maxillary sinus (8.8% vs. 30.6%, p < .05). Surgery alone (48.56%) was the most common treatment modality, followed by surgery and radiotherapy (RT) (32.5%), and RT alone (11.6%). DSS at 5, 10, and 20 years were 63.8%, 57.6%, and 47.0%, respectively. DSS was higher for nasal cavity SNAC, lower grade, lower stage, and those receiving surgery only. Conclusions: SNAC is more common among men and blacks. Incidence has not changed significantly in the past 40 years. Survival varies with grade, stage, histology, subsite, and treatment.

Geographic region: Does it matter in cutaneous melanoma of the head and neck?

The head and neck are two of the most common locations for cutaneous melanoma. We present the first population‐based analysis of geographic differences in anatomic subsite, clinicopathologic and demographical traits, histopathologic subtype, treatment modality, and disease‐specific survival (DSS) of cutaneous head and neck melanoma (CHNM).

The need for a dedicated Head and Neck Cancer Database in the United States

In the past 2 decades, due in large part to technological advances and the Internet, there has been a drastic increase in the amount of database-derived medical research, to the point where it is difficult to quantify the exact number of such studies. Dozens of clinical and administrative databases have been used for medical research, leading to thousands of published database studies. Perhaps no topic has been the focus of database studies more so than cancer. According to the Surveillance, Epidemiology, and End Results (SEER) program bibliography page, as of October 2015, there have been 9,857 publications published using SEER data alone. Currently, two major comprehensive cancer databases are available to researchers in the United States, the SEER database and the National Cancer Database (NCDB). SEER is a population-based database created by the National Cancer Institute in 1973. NCDB is a hospital-based database created by the American Cancer Society and the American College of Surgeons in 1989. Additionally, quality-improvement databases such as the National Surgical Quality Improvement Program, administrative databases such as the National Inpatient Sample and Kids’ Inpatient Database, and commercial claims databases such as QuintilesIMS’ LifeLink and Truven Health Analytics’ MarketScan have also been used in cancer research. The aforementioned databases vary widely in the variables they collect and the overall quality of the data. Each was developed to meet a specific need, and as a result has unique strengths and weaknesses. However, all of these databases have one feature in common: an enormous breadth of information that is limited in depth. Compared to conventional multi-institution chartreview–based studies, cancer database studies usually lack detailed information on patient history, comorbidities, laboratory testing, surgical approach, treatment side effects, quality-of-life outcomes, and recurrence. This can introduce substantial limitations to cancer database studies, ultimately limiting the conclusions that can be drawn from their findings. Many of these deficiencies stem from the fact that these are comprehensive cancer databases, which catalogue cancers of numerous primary sites. Because factors significant in one type of cancer may be irrelevant in another, it is difficult to design and maintain a comprehensive cancer database that captures data on every significant variable for every type of cancer. For example, ultraviolet radiation exposure, history of sunburns, mitotic count, BRAF V600E status, lactate dehydrogenase level, degree of pigmentation, the use of molecular targeted therapies (such as vemurafenib, ipilimumab), and tumor depth are just a few of the factors of interest in melanoma. In head and neck cancer (HNC), smoking status, human papillomavirus status, p16 status, the extent of neck node dissection, irradiation of the neck nodes, salvage surgery, and organ preservation are important factors. Including all of these variables in a single database is logistically challenging. Hence, most of these variables are not available in sufficient detail in US comprehensive cancer databases. Therefore, we need to move beyond the one-size-fits-all approach to cancer databases. Overall, HNC is rare, accounting for only 3% of all cancers. It is thus often difficult for any one institution to accumulate sufficient numbers of patients to conduct statistically rigorous HNC research, especially on rare subtypes. Therefore, a dedicated database could play a vital role in HNC research. The authors have extensive experience in conducting and/or reviewing cancer database studies and have dealt with their limitations firsthand. We believe that a multidisciplinary task force of national leaders in otolaryngology, radiation oncology, and medical oncology should be formed to lead the effort in creating a US HNC database. Two examples of such dedicated databases are the Danish Head and Neck Cancer Database and the Danish Melanoma Database. Compared to US cancer databases, these are quite elaborate. For example, the Danish HNC database collects information on recurrence and specific chemotherapy drugs, and the Danish Melanoma Database collects information on the presence of dysplastic nevi and family history of melanoma. Additionally, the Cancer Genome Atlas (TCGA), a genomic cancer database created by the National Institutes of Health, is an excellent example of a sophisticated US database. TCGA collects genomic data and allows researchers to link these data to a clinical dataset with site-specific variables. For the head and neck, these are smoking history (in pack-years), history of alcohol use, human papillomavirus status, and perineural invasion, variables which are usually not available in other databases. A dedicated HNC database would not be navigating uncharted territory. Such a database could improve the quality of database studies in HNC and improve patient care.