**4. Conclusion**

The management of early glottic cancer is controversial, with no head to head randomized controlled trials comparing oncologic/survival or functional/QOL outcomes between modalities. The majority of studies in the literature consist of single arm retrospective series, with few head to head retrospective series. A meta-analysis by our group (Higgins et al., 2009) showed a significant increase in overall survival with TOL surgery, and similar local control and laryngectomy-free survival between modalities. Voice outcomes were similar between modalities, but with an overall tendency for improved voice outcomes with radiotherapy. Three recent head-to-head studies have been published since our analysis, with two of these studies (Mahler et al., 2010; Schrijvers et al., 2009) showing a significant increase in LFS with TOL surgery. A recent systematic review (Spielmann et al., 2010) was unable to find clear differences in voice outcomes and QOL measures between modalities. The review demonstrated improved electroacoustic scores in some patients treated with radiotherapy, but did not demonstrate improvement in voice QOL. The most striking difference between treatment modalities is financial, with four of five recent studies (Higgins, 2011; Philips et al., 2009; Goor et al., 2007;, Brandenburg et al., 2001) showing TOL surgery to be more cost-effective. It is also worthwhile to note that TOL surgery is less time consuming for patients. Patients undergoing TOL surgery convalesce over a matter of days while patients undergoing radiotherapy are treated over four or more weeks. In summary, it is our view that although TOL surgery and radiotherapy may share similar oncologic, voice, and QOL outcomes, TOL surgery offers the distinct advantages of reduced health care costs and shorter duration of treatment.

#### **5. References**

174 Otolaryngology

(Performance Status Scale for Head and Neck Cancer Patients), and were more likely to have a Voice Handicap Index (VHI-10) score of 10 or more. However, another Canadian study by Osborn et al demonstrated a non-significant trend for increased voice-related quality of life (V-

Our meta-analysis (Higgins et al., 2009) demonstrated a trend for improved voice quality with radiotherapy, yet this was a non-significant finding. Currently, the major argument in favour of radiotherapy is improved voice quality, but this has yet to be born out in largescale systematic studies. It is also difficult to link electroacoustic analytic outcomes with

Our group (Higgins, 2011) recently published a cost-utility analysis comparing TOL surgery to radiotherapy and demonstrated an almost two-fold increase in cost with radiotherapy. The TOL surgery cost \$2475.65 CAD/case, generating 1.663 QALYs, whereas radiation cost \$4965.85 CAD/case, generating 1.506 QALYs. Another Canadian cost analysis was reported by Philips et al (Philips et al., 2009) and concluded that radiotherapy was four times as costly as TOL surgery. A recent Dutch study (Goor et al., 2007) also demonstrated the increased cost of radiotherapy. The total cost of radiotherapy and TOL surgery was 8322 euros and 4434 euros, respectively. In addition, an American study by Brandenburg et al (Brandenburg et al., 2001) demonstrated increased costs associated with radiotherapy compared to TOL surgery. In contrast, a single Belgian study (Gregoire et al., 1999) documented an increased cost of TOL surgery compared to radiotherapy. However, this study reported a 30% positive margin rate in the TOL surgery group, and positive margins

Overall, the majority of studies point to an increased cost with radiotherapy compared to TOL surgery. However, it is worthwhile to note that each of these five studies did not include patients undergoing robotic TOL surgery, which may impact significantly on cost

The management of early glottic cancer is controversial, with no head to head randomized controlled trials comparing oncologic/survival or functional/QOL outcomes between modalities. The majority of studies in the literature consist of single arm retrospective series, with few head to head retrospective series. A meta-analysis by our group (Higgins et al., 2009) showed a significant increase in overall survival with TOL surgery, and similar local control and laryngectomy-free survival between modalities. Voice outcomes were similar between modalities, but with an overall tendency for improved voice outcomes with radiotherapy. Three recent head-to-head studies have been published since our analysis, with two of these studies (Mahler et al., 2010; Schrijvers et al., 2009) showing a significant increase in LFS with TOL surgery. A recent systematic review (Spielmann et al., 2010) was unable to find clear differences in voice outcomes and QOL measures between modalities. The review demonstrated improved electroacoustic scores in some patients treated with radiotherapy, but did not demonstrate improvement in voice QOL. The most striking difference between treatment modalities is financial, with four of five recent studies

RQOL) among patients who underwent radiotherapy as opposed to TOL surgery.

subjective vocal function and QOL outcomes.

were managed with adjuvant radiotherapy instead of re-excision.

**3.3 Cost effectiveness** 

effectiveness.

**4. Conclusion** 


**12** 

*Romania* 

**Epigenetics in Head and** 

Magdalena Chirilă

**Neck Squamous Cell Carcinoma** 

*"Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca,* 

In addition to the genetic information required to establish an organism, recent decades have unveiled a previously unknown type of chromatin modification, known as epigenetic, which is defined as heritable DNA changes that are not encoded in the sequence itself. Unlike genetic modifications, the epigenetic ones are reversible, and increasingly appear to

It is increasingly evident that genetics alone cannot explain the complexity of phenotypes in the living world. Heritable phenotypic characteristics that are not caused by DNA sequence alterations represent the object of epigenetics and include potentially reversible changes such as histone modifications, DNA methylation, and imprinting. At the interface between epigenetics and genomics, a new discipline that is emerging, epigenomics, promises to profoundly change the way we envision phenomena in the biological and medical sciences. Epigenetic modifications can provide an astronomic number of distinct signatures, with huge diagnostic and prognostic value, but it is essential to consider all the different sources

Epigenomics-based diagnostic tools for early cancer detection represent an exciting development. Tumors shed their DNA into the blood, and epigenetic changes that occur early during tumorigenesis, sometimes even in premalignant lesions, can provide valuable biomarkers. Previous research at Epigenomics identified Septin 9 as a single gene in which DNA methylation changes occur very early in colorectal cancer development and are present in the vast majority of tumors of all stages. In most tissues, CpG (cytosine 5 phosphorylated guanine) islands around transcription start sites are largely unmethylated, but their methylation has been described in many tumors and can serve as potential biomarkers. One of the advantages of using epigenomic biomarkers is that, in most cases,

Stephen B. Baylin, M.D., professor of cancer research and deputy director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and colleagues recently presented a molecular model to explain how DNA methylation causes gene silencing in mammalian cells. They used the GATA-4 gene as a model to investigate how polycomb protein complexes and DNA methylation maintain the chromatin in its silent state. They found that polycomb protein occupancy at genomic regions enriched in trimethylated

serve fundamental roles in cell differentiation and development.

DNA methylation changes precede clinical symptoms.

**1. Introduction** 

of information.

