Interventions for the treatment of oral cavity and oropharyngeal cancer:chemotherapy

<b>Background:</b> Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.<p></p> <b>Objectives:</b> To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes.<p></p> <b>Search strategy:</b> Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 28th July 2010. Reference lists of recent reviews and included studies were also searched to identify further trials.<p></p> <b>Selection criteria:</b> Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included.<p></p> <b>Data collection and analysis:</b> Trials which met the inclusion criteria were assessed for risk of bias using six domains: sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting and other possible sources of bias. Data were extracted using a specially designed form and entered into the characteristics of included studies table and the analysis sections of the review. The proportion of participants in each trial with oral cavity and oropharyngeal cancers are recorded in Additional Table 1.<p></p> <b>Main results:</b> There was no statistically significant improvement in overall survival associated with induction chemotherapy compared to locoregional treatment alone in 25 trials (hazard ratio (HR) of mortality 0.92, 95% confidence interval (CI) 0.84 to 1.00). Post-surgery adjuvant chemotherapy was associated with improved overall survival compared to surgery +/- radiotherapy alone in 10 trials (HR of mortality 0.88, 95% CI 0.79 to 0.99), and there was an additional benefit of adjuvant concomitant chemoradiotherapy compared to radiotherapy in 4 of these trials (HR of mortality 0.84, 95% CI 0.72 to 0.98). Concomitant chemoradiotherapy resulted in improved survival compared to radiotherapy alone in patients whose tumours were considered unresectable in 25 trials (HR of mortality 0.79, 95% CI 0.74 to 0.84). However, the additional toxicity attributable to chemotherapy in the combined regimens remains unquantified.<p></p> <b>Authors' conclusions:</b> Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy is associated with a 9% increase in survival and adjuvant concomitant chemoradiotherapy is associated with a 16% increase in overall survival following surgery. In patients with unresectable tumours, concomitant chemoradiotherapy showed a 22% benefit in overall survival compared with radiotherapy alone.<p></p&gt

Recurrence dynamics does not depend on the recurrence site

Introduction: The dynamics of breast cancer recurrence and death, indicating a bimodal hazard rate pattern, has been confirmed in various databases. A few explanations have been suggested to help interpret this finding, assuming that each peak is generated by clustering of similar recurrences and different peaks result from distinct categories of recurrence. Methods: The recurrence dynamics was analysed in a series of 1526 patients undergoing conservative surgery at the National Cancer Institute of Milan, Italy, for whom the site of first recurrence was recorded. The study was focused on the first clinically relevant event occurring during the follow up (ie, local recurrence, distant metastasis, contralateral breast cancer, second primary tumour), the dynamics of which was studied by estimating the specific hazard rate.Results The hazard rate for any recurrence (including both local and distant disease relapses) displayed a bimodal pattern with a first surge peaking at about 24 months and a second peak at almost 60 months. The same pattern was observed when the whole recurrence risk was split into the risk of local recurrence and the risk of distant metastasis. However, the hazard rate curves for both contralateral breast tumours and second primary tumours revealed a uniform course at an almost constant level. When patients with distant metastases were grouped by site of recurrence (soft tissue, bone, lung or liver or central nervous system), the corresponding hazard rate curves displayed the typical bimodal pattern with a first peak at about 24 months and a later peak at about 60 months.Conclusions The bimodal dynamics for early stage breast cancer recurrence is again confirmed, providing support to the proposed tumour-dormancy-based model. The recurrence dynamics does not depend on the site of metastasis indicating that the timing of recurrences is generated by factors influencing the metastatic development regardless of the seeded organ. This finding supports the view that the disease course after surgical removal of the primary tumour follows a common pathway with well-defined steps and that the recurrence risk pattern results from inherent features of the metastasis development process, which are apparently attributable to tumour cells