Adding Chemotherapy to Radiation Questioned For High-Risk Salivary Gland Carcinoma

Findings cast doubt on the benefit of adding chemotherapy to radiotherapy after resection of high-risk salivary gland carcinoma

medwireNews: Survival outcomes do not support the addition of chemotherapy to postoperative radiation in patients with salivary gland carcinoma (SGC) with at least one high-risk feature, suggests a study of patients entered into the US National Cancer Database.

After a median follow-up of 39 months, unadjusted 2-year overall survival (OS) was poorer in patients who began chemotherapy within 2 weeks of radiation initiation compared with those given radiotherapy alone, at 71.3% versus 80.2%.

Five-year OS was also significantly poorer with chemoradiotherapy than radiation alone, at 38.5% versus 54.2% and a hazard ratio (HR) of 1.51, say Sana Karam, from the University of Colorado School of Medicine in Aurora, USA, and co-workers.

And this association was confirmed in both multivariate analysis (HR=1.22) and a propensity score-matched analysis of 350 pairs of patients at 2 and 5 years (71.6 vs 78.9% and 39.6 vs 46.0%, HR=1.20), the authors report in JAMA Otolaryngology–Head & Neck Surgery.

Subgroup analysis comparing adjuvant radiotherapy versus chemoradiotherapy was significantly in favour of radiotherapy for patients aged less than 65 years (HR=1.39) and had no significant impact in older patients.

Similarly, radiotherapy was supported for patients with positive tumour margins (HR=1.30) and parotid site tumours (HR=1.23) but treatment choice had no significant impact for those with submandibular disease. Radiotherapy was also superior for patients with T3 or T4 disease (HR=1.37) and patients with mucoepidermoid carcinoma (HR=1.47) but did not alter survival for those with other histological types.

Finally, among patients who were treated with chemoradiotherapy, those who received more than one chemotherapy drug had significantly poorer survival compared with radiation alone (HR=1.34), whereas those given one agent had comparable outcomes. This result may be “representative of increased toxicity that affects OS”, the authors suggest.

The current study included National Cancer Database records for 2210 patients, aged a median of 63 years, who had major SGC resected between 1998 and 2011. All patients had at least one high-risk characteristic – T3–T4 or N1–N3 stage disease or a positive margin.

Acknowledging a lack of definitive data on the benefit of chemotherapy in this population, the researchers write that they look forward to the results of the ongoing RTOG 1008 trial, comparing adjuvant chemoradiotherapy and radiotherapy in patients with similar characteristics to the present analysis.

The primary endpoint of OS, with additional focus on quality of life and patient-reported outcomes will “provide further insight on this controversial topic”, Sana Karam and co-workers hope.

For now, the authors conclude: “Outside clinical trials, clinicians must critically consider each patient based on disease risk factors and comorbidities when deciding whether to administer concurrent chemotherapy in patients who have undergone resection of high-risk SGC.”

References

Amini A, Waxweiler TV, Brower JV, et al. Association of adjuvant chemoradiotherapy vs radiotherapy alone with survival in patients with resected major salivary gland carcinoma. Data from the National Cancer Data Base. JAMA Otolaryngol Head Neck Surg; Advance online publication 18 August 2016

doi:10.1001/jamaoto.2016.2168

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