Definitive concurrent chemoradiotherapy is an accepted standard of management for unresectable tumours, in inoperable patients (medically or due to patient wishes), or resectable tumours for which the poor anticipated functional outcome/prognosis after an extensive surgery is not justifiable.rrr
Several retrospective studies have reported the treatment outcomes of definitive chemoradiation for locally advanced OCC which seem favourable in terms of locoregional control, these were single-armed, often with heterogenous treatment regimens over the study duration and had small sample sizes, with variable toxicity data.rrr Therefore the results of these studies must be interpreted with caution.
Resectable OCCs – definitive RT vs surgery + RT
In resectable OCC there is a paucity of randomised data comparing primary surgery and chemoradiation. A phase III RCT reported by Soo et al. 2005 and Iyer at al. 2015, found no statistically significant difference in the outcome between the two treatment approaches in stage III-IV head & neck cancers (including OCC); however, the proportion of patients with OCC was low at 27%.rr
Post-hoc subgroup analysis by Iyer et al. 2015 and a follow-up of another prematurely closed RCT by Robertson et al. 1998 reported significant survival benefit in those who had primary surgical treatment.rr
Figure 1. Kaplan-Meier plots
© Cancer 2015
Figure 1. Kaplan-Meier plots of patients with oral squamous cell carcinoma in the primary surgery and concurrent chemotherapy and radiotherapy (chemoRT) arms of a randomised controlled trial demonstrating limited but not statistically significant differences in (a) overall survival, (b) disease-specific survival, (c) locoregional recurrence-free survival (d) distant recurrence-free survival. r
Figure 2. Duration of local response
© Clinical Oncology 1998
Figure 2. Duration of local response - Kaplan-Meier plots demonstrating significant local control differences between patients treated on the surgery + PORT and RT alone arms of a randomised clinical trial. r
Figure 3. Time of death (all causes)
© Clinical Oncology 1998
Figure 3. Time of death (all causes) - Kaplan-Meier curve plots demonstrating significant overall survival differences between patients treated on the surgery + PORT and RT alone arms of a randomised clinical trial. r
The role of concurrent chemotherapy
Meta-analysis by Pignon et al. 2009 of locoregional therapy (LRT) + chemotherapy vs LRT in HN SCC (MACH-NC; 87 RCTs between 1965-2000) showed benefit of adding (induction/concomitant/adjuvant) chemotherapy to LRT across all HN tumour subsites.r In OCC, there was 5 year absolute OS benefit of 5.1% [95% CI 2.0-8.3]; HR 0.87 [95% CI 0.80-0.93] and PFS benefit of 6.9% [95% CI 2.8-11.0] in OCC. The interaction between chemotherapy timing and treatment effect was not significant for OCC (p=0.15), which was suggested secondary to lack of statistical power by authors. Subgroup analyses showed reduced benefit of adding chemotherapy in older age (p=0.003).
Figure 4. Overall survival
© Radiotherapy and Oncology 2011
Fig. 4. Overall survival in trials comparing locoregional treatment plus chemotherapy with locoregional treatment alone r
Peters et al. 2010 reported on the impact of radiotherapy quality on patient outcomes in a large international phase III trial (TROG 02.02). In patients with major deficiencies in their treatment compared to those whose treatment was initially protocol compliant a significanlt inferior outcome; 2 years overall survival of 50% vs 70%; hazard ratio (HR), 1.99; P< .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; <P .001, respectively.r These results show the critical importance of radiotherapy quality on outcome of chemoradiotherapy in locally advanced head and neck cancer.