Written by Margaret Spittle
The management of patients with head and neck cancer has always, to its credit, been a combined decision. Combined clinics with surgeons and oncologists and hopefully including pathologists, radiologists and other clinical staff have been in existence since the 1930’s. It is the cancer specialty with the longest history of formal combined management.
Surgery has always played the major part in management but for many years this was complimented by tumoricidal doses of radiotherapy to “sterilise” any persisting disease at the margins. Major surgery for head and neck cancer can cause serious and long standing side effects for the patient and the addition of high dose radiotherapy makes the situation worse, causing fibrosis and dryness.
The addition of chemotherapy to the surgery and radiotherapy regime resulted in a 4% increase in survival. The difficulty in management was that more toxicity was added and a particularly dangerous situation occurred when the chemotherapy caused the patient to develop neutropaenic sepsis. This can cause an interruption in the radiotherapy treatment. It is considered that there is a 1% reduction in control per day of radiotherapy interruption.
The testing ground of T3 larynx cancers showed a small advantage of adding chemotherapy to the surgery and radiotherapy regime. However when high dose chemotherapy was given pre-operatively some patients were shown to have such a good response that there was downsizing of the tumour and therefore surgery was thought possibly unnecessary. Tumoricidal doses of radiotherapy was given. It became clear that after three courses of high dose chemotherapy the response could mandate the subsequent treatment. Several trials were set up comparing chemotherapy, radiotherapy + or – nodal dissection with surgery subsequently if necessary versus routine surgery plus radiotherapy and chemotherapy. Although there was little difference in the absolute survival there were many less severe complications in the group that did not need surgery and those patients had a better quality of life.
The decision whether to have radiotherapy before or after surgery was the basis of further investigation, however when radiotherapy was to be given after the surgery fewer patients had the full intended treatment.
Independent predictors of successful organ preservation were the lower T stage, P53 over-expression and an elevated proliferating cell nuclear antigen index.
In nasopharyngeal cancer the place of chemotherapy became clear and synchronous chemoradiation became the new standard for nasopharyngeal cancer.
There were many attempts to improve radiotherapy treatment with accelerated fractionation. Funded by the MRC in the CHARTWELL trial, little improvement in survival for this enhanced treatment given in two and a half weeks was shown. The rationale was to prevent the repopulation of the tumour cells between treatment fractions and to exploit differences in cellular repair mechanisms.
The development of a fast neutron capability with its high dose Bragg peak was exploited. However, the dose fractionation regime was uncertain and the side effects of treatment considered to be extensive.
Some cells were hypoxic and these could regrow the tumour. The treatment of patients in hyperbaric oxygen was used hoping that it would increase the sensitivity of the anoxic cells within the tumour, but the hazard of putting patients into hyperbaric chambers regularly made this an extremely difficult programme to put into many centres.
The development of the proton beam in selected cases did have a place in the management of head and neck cancers due to its finite range in tissue and sharply defined lateral beam edges.
Surgical, radiotherapy and chemotherapy techniques are being improved and hopefully these will all give the patients not only a better survival but an improved quality of life.
Surgery will continue to be the main agent in the management of head and neck cancers and patients are reaping the advantage of the long standing close association among the many modalities that treat head and neck cancer.
It is an honour to be asked to give the Semon Trust Lecture and I thank my many head and neck expert colleagues for the benefit of working with them.