The prognostic role of comorbidity in salivary gland carcinoma

BACKGROUND.

Patients with head and neck cancer are prone to develop significant comorbidity mainly because of the high incidence of tobacco and alcohol abuse, both of which are etiologic and prognostic factors. However, to the authors' knowledge little is known regarding the prognostic relevance of comorbidity in patients with salivary gland cancer.

METHODS.

A retrospective cohort of 666 patients with salivary gland cancer was identified within the Dutch Head and Neck Oncology Cooperative Group database. For multivariate analysis, a Cox proportional hazards model was used to study the effect of comorbidity on overall survival and disease‐specific survival.

RESULTS.

According to the Adult Comorbidity Evaluation‐27 (ACE‐27) index, 394 patients (64%) had grade 0 comorbidity, 119 patients (19%) had grade 1 comorbidity, 71 patients (12%) had grade 2 comorbidity, and 29 patients (5%) had grade 3 comorbidity. In multivariate analysis for overall survival, the ACE‐27 comorbidity grade was a strong independent prognostic variable. The hazards ratio (HR) of death, including all causes, was 1.5 (95% confidence interval [CI], 1.1‐2.1) for patients with ACE‐27 grade 1 comorbidity versus grade 0 comorbidity (P < .007). The HR was 1.7 (95% CI, 1.2‐2.5) for grade 2 comorbidity (P = .003) and 2.7 (95% CI, 1.5‐4.7) for grade 3 comorbidity versus grade 0 comorbidity (P = .001). In the current analysis, ACE‐27 comorbidity grade was not an independent prognostic factor for disease‐free survival.

CONCLUSIONS.

To the authors' knowledge, this is the first study concerning the prevalence and relevance of the prognostic comorbidity variable ACE‐27 grade in patients with salivary gland cancer. Overall survival, but not disease‐free survival, was correlated strongly with ACE‐27 grade. Compared with other studies that investigated the effect of comorbidity on patients with head and neck cancer, patients with salivary gland cancer had less comorbidity. Their comorbid status appeared to be reasonably comparable to that of patients with other nonsmoking‐ and nonalcohol‐related cancers. Cancer 2008. © 2008 American Cancer Society.     

Interaction of EGFR with the tumour microenvironment: Implications for radiation treatment

Treatment failure through radioresistance of tumours is associated with activation of the epidermal growth factor receptor (EGFR). Tumour cell proliferation, DNA-repair, hypoxia and metastases-formation are four mechanisms in which EGFR signalling has an important role. In clinical trials, a correlation has been demonstrated between high EGFR expression in tumours and poor outcome after radiotherapy. Inhibition of EGFR signalling pathways improves the effectiveness of radiotherapy of head and neck cancers by overcoming these main mechanisms of radioresistance. The fact that only a minority of the patients respond to EGFR inhibitors reflects the complexity of interactions between EGFR-dependent signalling pathways and the tumour microenvironment. Furthermore, many components of the microenvironment are potential targets for therapeutic interventions. Characterisation of the interaction of EGFR signalling and the tumour microenvironment is therefore necessary to improve the effectiveness of combined modality treatment with radiotherapy and targeted agents. Here, the current status of knowledge is reviewed and directions for future research are discussed.     

Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts: effects of carbogen and nicotinamide.

BACKGROUND AND PURPOSE: A better understanding of the vascular architecture and the microenvironmental parameters (VAMP) will allow the identification of tumours that can be more effectively treated by intensified fractionated radiotherapy or modifiers of blood flow and oxygenation or combinations of these approaches. MATERIALS AND METHODS: Proliferation (BrdUrd), vascular architecture (endothelial marker), perfusion (Hoechst 33342) and oxygenation (NITP) were studied in two human laryngeal squamous cell carcinoma tumour lines grown as xenografts in nude mice. The effects of carbogen and nicotinamide on these parameters were evaluated. RESULTS: Carbogen treatment resulted in a decrease of the number of perfused blood vessels from 66% to 55% in one of the two tumour lines. In this tumour line nicotinamide prevented this reduction of tumour blood flow by carbogen. In both tumour lines the labelling index (LI) decreased after treatment with carbogen for 1 h, from 11-13% to 5-7%. Both tumour lines showed a drastic reduction of hypoxia by carbogen alone or by carbogen plus nicotinamide. CONCLUSIONS: In both laryngeal squamous cell carcinoma xenograft tumour lines carbogen was very effective in reducing diffusion limited hypoxia. Only in one of the two tested tumour lines carbogen also caused a reduction of tumour blood perfusion, which could be compensated for by nicotinamide. In addition, carbogen reduced tumour cell proliferation. The fact that differences in response to nicotinamide and carbogen were observed and that they can be studied in vivo provides a basis for further development of a 'predictive profile' which will guide the clinician to select the optimal treatment for individual patients or groups of patients.     

Effects of nicotinamide and carbogen on oxygenation in human tumor xenografts measured with luminescense based fiber-optic probes.

BACKGROUND AND PURPOSE: In head and neck cancer, addition of both carbogen breathing and nicotinamide to accelerated fractionated radiotherapy showed increased loco-regional control rates. An assay based on the measurement of changes in tumor pO(2) in response to oxygenation modification could be helpful for selecting patients for these new treatment approaches. MATERIALS AND METHODS: The fiber-optic oxygen-sensing device, OxyLite, was used to measure changes in pO(2), at a single position in tumors, after treatment with nicotinamide and carbogen in three human xenograft tumor lines with different vascular architecture and hypoxic patterns. Pimonidazole was used as a marker of hypoxia and was analyzed with a digital image processing system. RESULTS: At the position of pO(2) measurement, half of the tumors showed a local increase in pO(2) after nicotinamide administration. Steep increases in pO(2) were measured in most tumors during carbogen breathing although the increase was less pronounced in tumor areas with a low pre-treatment pO(2). A trend towards a faster local response to carbogen breathing for nicotinamide pre-treated tumors was found in all three lines. There were significant differences in hypoxic fractions, based on pimonidazole binding, between the three tumor lines. There was no correlation between hypoxic marker binding and the response to carbogen breathing. CONCLUSION: Temporal changes in local pO(2) can be measured with the OxyLite. This system was used to quantitate the effects of oxygen modifying treatments. Rapid increases in pO(2) during carbogen breathing were observed in most tumor areas. The locally measured response to nicotinamide was smaller and more variable. Bio-reductive hypoxic cell marker binding in combination with OxyLite pO(2) determination gives spatial information about the distribution patterns of tumor hypoxia at the microscopic level together with the possibility to continuously measure changes in pO(2) in specific tumor areas.     

Effect of postoperative radiotherapy on the functional result of implants placed during ablative surgery for oral cancer

The purpose of this retrospective study was to evaluate the survival of dental implants placed during ablative surgery in the interforaminal region of the original edentulous mandible in patients with squamous cell carcinoma of the oral cavity in relation to postoperative radiotherapy. Forty-eight patients treated in 1996–2003 with surgery alone or in combination with postoperative radiotherapy were analysed. In all patients, 2 to 4 Brånemark Mk II/III 2-phase implants were placed during tumour resection. A total of 139 implants were placed of which 61 (21 patients) received postoperative radiotherapy: 60–68 Gy as a boost dose on the primary tumour site and 10–68 Gy on the symphyseal area. No difference was found in percentage of functional dentures on implants between the radiated and non-radiated groups. The success rate of osseointegration was 97% in the postoperative irradiated group and 100% in the non-irradiated group. The prosthetic success rate (75%) was lower because in 12 of the 48 patients (34 implants) a functional denture could not be fitted due to tumour recurrence or metastasis (7 patients, 22 implants) or for psychological reasons (4 patients, 12 implants), independent of whether radiotherapy was administered. Postoperative radiotherapy does not affect the osseointegration of dental implants placed during tumour ablation and the ultimate number of functional dentures. Primary implant placement in edentulous mandibles may have advantages over secondary implant placement in patients with oral squamous cell carcinoma.