Presenter: Kian Ang, MD, PhD Presenter's Affiliation: MD Anderson Cancer Center Type of Session: Scientific
The definitive treatment of locally advanced head and neck cancer with radiation has evolved greatly over the past 15 years.Various treatment regimens have been employed such as hyperfractionated radiation (EORTC 22791) and concurrent chemotherapy with radiation.The present study addresses the role of combined accelerated radiation with concurrent chemotherapy.
Data has shown that hyperfractionated radiation improves local control compared with daily fractionation in the definitive setting.
Concurrent chemoradiation has also been shown to provide improvement in local control and overall survival in various trails (GORTEC).
Hyperfractionated chemoradiation has been studied with promising results (Brizel DM et al. N Engl J Med. 1998 Jun 18;338(25):1798-804.).
The present study examines the compliance and complication rates of standard versus accelerated fractionation radiation used concurrently with cisplatin in definitive treatment of locally advanced head and neck cancer.
Materials and Methods
The present study is a Phase III randomized trial of 743 patients accrued from July 2002 to June 2005.
Patients with stage III of IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were accrued.Patients with T1, N+ disease and T2, N1 disease were excluded.
Patients were stratified by disease site, nodal status, and performance status.
All patients had a Zubrod performance status of 0-1 and adequate hematologic, renal, and hepatic function.
743 patients were randomized to radiation treatment with either 70 Gy in 35 fractions for seven weeks (single fraction arm (SFX)) versus 72 Gy in 42 fractions over six weeks (accelerated fraction arm (AFX-C).
SFX patients received cisplatin 100 mg/m2 for three cycles and the AFX-C arm received two cycles of cisplatin at the same dose.
Five patients withdrew from the study and 16 patients were found to be ineligible leaving 722 patients which were evenly divided between the two groups (n=361).
There was no significant difference between the two groups in the following categories:
age (SFX: 56 vs AFX-C: 55.5)
sex (SFX: 85% male versus AFX-C: 80%)
performance status (SFX Zubod 0: 57%, Zubod 1: 43% vs AFX-C: Zubod 0: 59%, Zubod 1: 41%)
Disease site (SFX: oropharynx: 60%, larynx: 25%, other:15% vs AFX-C: oropharynx: 60%, larynx: 27%, other: 13%)
primary site, T stage, and N stage (SFX: Stage IV:79% vs AFX-C: 78%)
Acute radiation toxicity was defined as those that occurred within 90 days of radiation and were scored using CTC version 2.
Late radiation toxicity was scored using the RTOG/EORTC scheme.
A total of 359 and 356 patients had their radiation plans reviewed.The majority of patients were able to tolerate radiation therapy with the patient either receiving treatment per protocol or with only minor deviations in 96% and 92% of the SFX and AFX-C arms, respectively.
Full dose cisplatin was delivered in 58% of patients in the SFX arm (3 cycles) and 83% of the AFX-C arm (2 cycles).
Acute toxicity was comparable between the two arms of the study.The maximal toxicity experienced by patients was evenly distributed between the two groups as well as the non-hematologic toxicity aside from mucositis where there was slightly higher in the AFX-C (40%) compared with the SFX arm (33%).
Median follow up for long term toxicity was 2.4 years.There was no difference seen between the two groups.
Approximately 25% of patients in both groups had feeding tubes prior to radiation.
During radiation 68% versus 67% required feeding tubes from the SFX and AFX-C arms, respectively.
After two years 14% and 16% required feeding tubes for the SFX and AFX-C arms, respectively.However, the majority of these patients had feeding tubes at baseline (~50% in the SFX arm and ~35% in the AFX-C arm).
Preliminary results of toxicity and compliance from this Phase III randomized trial comparing standard chemoradiation with accelerated chemoradiation in the treatment of locally advanced squamous cell carcinoma suggest that this treatment is safe.
The authors concluded:
That there was good compliance with both chemotherapy and radiation therapy in this trial.
There was no significant difference in toxicity between the two arms of the trial.
Presently there is not enough follow up data to comment on efficacy of treatment.
Improvement in local control with hyperfractionation and with concurrent chemotherapy and radiation has been demonstrated in previous trials.However, recurrent local disease remains a problem in patients with locally advanced head and neck cancer.Either of the above mentioned treatment modalities have severe side effects when used alone and the combined use of these treatment modalities may lead to unacceptable treatment related side effects.This trial is the first to demonstrate that concurrent chemotherapy with standard fractionation has a similar side effect profile compared with accelerated fractionation.
It is important to note that there was a difference in the number of cycles of chemotherapy between the two treatment arms. It appears that two cycles in the accelerated arm was well tolerated.In the standard arm three cycles were used, and fewer patients were able to complete all three cycles.Given that the two arms received different chemotherapy it may be difficult to determine if accelerated radiation has the potential to be superior to standard fractionation if the results of this trial show that the arms are equivocal (as addional chemotherapy may have improved results in the accelerated arm).However, we may also be reaching the limit of the tolerable toxicity with concurrent accelerated radiation with chemotherapy and the ideal dosing of chemotherapy with accelerated radiation remains to be seen.IMRT may further limit toxicity by allowing sparing of the larynx, when possible, further decreasing toxicity, such as feeding tube dependence.
Efficacy data are pending and presently the use of accelerated radiation with concurrent chemotherapy is best done on protocol.
Partially funded by an unrestricted educational grant from Bristol-Myers Squibb.
Apr 15, 2010 - Accelerated fractionation of radiotherapy is an effective alternative to conventional fractionation for squamous-cell carcinoma of the head and neck in developing countries, according to research published online April 9 in The Lancet Oncology.