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Twice-daily radiation therapy cuts deaths from head and neck cancer

RadiationTherapyTreating head and neck cancer patients with a twice-daily radiation therapy combined with chemotherapy could save more lives, according to research presented at the European Cancer Congress 2017.

The study, led by Dr Claire Petit, a resident in radiation oncology from Gustave Roussy Cancer Centre in Paris and C van Marcke at the Centre Hospitalier Jolimont, medical oncology, La Louvière, Belgium, included patients with tumours in their mouths, throats or voice boxes, that had already begun to spread to neighbouring tissue. These patients tend to have lower rates of survival than those whose cancer was diagnosed at an earlier stage.

The twice-daily treatment is known as hyper-fractionated radiotherapy. By splitting the daily treatment in two portions, a higher and more effective dose can be given to patients. The researchers hope that this can be achieved without increasing side effects.

Around 600,000 people are diagnosed with head and neck cancer worldwide each year. It can be difficult to treat because the area of the body affected contains so many vital structures, including those responsible for breathing, swallowing and speech.

The researchers used a relatively new technique called a network meta-analysis to bring together data from 117 different trials, including 28,804 patients from around the world. This allowed them to compare 16 different treatments to find out which was best at reducing the spread of cancer and deaths from the disease.

They discovered that the twice-daily treatment, when combined with chemotherapy, cut deaths by 20% compared to the best standard treatment of once-daily radiotherapy with chemotherapy. It also reduced the risk of the cancer getting worse by 23%.

Petit told the congress: "There are a number of new treatments that have shown promise in head and neck cancer trials. This large study has enabled us to compare several of these treatments to see which is best overall in terms of reducing mortality."

Petit cautioned that she has not yet studied the side effects experienced by patients, either during treatment or in the longer term, and that more research is needed to examine this and to confirm the results. "Some of the studies we looked at did not include data on side effects; others did not follow patients long enough to pick up long-term side effects. This will be the focus of more research over the next year."

She added: "Moreover, the method we used, network meta-analysis, which combines direct and indirect treatment comparisons, is a new method that needs to be interpreted with prudence.

"However, this is an important finding for this group of patients who have a higher risk of their cancer recurring following treatment."

Professor Philip Poortmans, president-elect of ECCO and head of the radiation oncology department at Radboud University Medical Centre (Nijmegen, The Netherlands), said: "This research provides good evidence for the benefits of treating advanced stage head and neck cancer patients with a combination of twice-daily radiation therapy and chemotherapy, compared to one or even none of these separately. Before we can apply these very interesting results into daily clinical practice, we need to wait for the outcome of the next stage of this research – namely the evaluation of the short and long-term side effects. This is of utmost importance for the quality of life of the patients and their relatives.

"Moreover, it would be preferable to perform prospective trials to confirm these results. If that is not feasible, or if we cannot wait for their outcome for some subgroups of patients who have the worst survival currently, then we should at least register carefully all the outcome parameters in prospective multi-centre databases so that they are available later on for analysis."

Abstract
Background: Radical radiotherapy with concurrent high-dose cisplatin (100 mg/m2/3 weeks) (HDC) chemotherapy is standard of care in the non-surgical management of locally advanced head and neck squamous cell carcinoma (HNSCC). However, many patients are not eligible to receive this regimen due to poor performance status or medical co-morbidities. Low-dose cisplatin (40 mg/m2/week) (LDC) is an alternative, but as robust data is still lacking, it is not known if LDC is as effective as HDC. We aimed to add insight to this matter, by reviewing our experience in treating unresectable locally advanced HNSCC. We presented intermediate results at ESMO 2015 Congress in Vienna: the 1-year overall survival (OS) was improved with HDC compared to LDC. We present the final results with the 2-year disease-free survival (DFS) and OS of these patients.
Methods: Patients with locally advanced HNSCC who received radical radiotherapy associated with either HDC or LDC between December 2008 and December 2013 were retrospectively reviewed. Patients who did not complete their radiotherapy course and those who received chemoradiotherapy in adjuvant setting were excluded.
Results: 72 patients were analyzed (42 in HDC regimen and 30 in LDC regimen). Most patients had carcinoma of the hypo- and oro¬pharynx (75%). Median age was similar in the two regimens (57 years), as well as median performance status (Karnofsky index of 90%). The median number of administered cycle in the HDC and the LDC was 2 (range 1–3) and 5 (range 3–7), respectively. The estimated median DFS was 21.0±8.5 months in HDC compared to 15.0±11.6 months in LDC regimen (P = 0.159); the estimated 2-year DFS was 50.0% and 43.3%, respectively. The estimated median OS was 84.0±34.1 months in HDC compared to 24.0±6.1 months in LDC regimen (P = 0.042); the estimated 2-year OS was 64.3% and 50.0%, respectively. Grade 3 hematologic toxicities were observed at the same frequency (16%) in the two regimens, as well as grade 3 mucitis (34% in HDC versus 30% in LDC).
Conclusion: This limited retrospective monocentric analysis showed an improvement of median overall survival with HDC compared to LDC in patients with locally advanced HNSCC treated with definitive chemoradiotherapy. Toxicities appeared similar between the two groups.

Authors
C van Marcke, B Petit, C Confente, B Filleul, Y Neybuch, N Christian, JF Rosier, C Mitine, E Seront

[link url="https://www.sciencedaily.com/releases/2017/01/170126190553.htm"]ECCO Congress material[/link]
[link url="http://www.eccocongress.org/amsterdam2017/Scientific-Programme/Abstract-search?abstractid=30013"]ECCO Congress abstract[/link]

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