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Delays in starting radiotherapy can increase risk of cancer recurrence

In both breast and head and neck cancers the risk of local recurrence increases with longer radiotherapy waiting times, finds a Canadian meta-analysis. The study, published in Radiotherapy and Oncology, concludes that delays in radiotherapy treatment should be kept to the minimum time possible.

Waiting times for radiotherapy were first identified as cause for concern around 20 years ago. Treatment delays can be attributed to increasing demands for radiotherapy caused by the growing incidence of cancer due to an ageing population and the discovery and adoption of new indications for radiotherapy. “When the increasing demand is not matched by a commensurate increase in treatment capacity, waiting lists for RT become inevitable,” write the authors Zheng Chen and colleagues, from Queen’s Cancer Research Institute ( Kingston, Ontario, Canada) and Cross Cancer Institute ( Edmonton, Alta, Canada).

Experimental evidence has suggested that the probability of eradicating a tumour by radiotherapy can be inversely related to the number of clonogenic cells it contains, and there is also clinical evidence that the probability of local control in many different types of human cancer can be inversely related to the volume of the cancer. Two recent studies have demonstrated clear evidence of tumour progression in a high proportion of patients waiting to start radiotherapy for head and neck cancer.

In the current study, Chen and colleagues set about trying to provide direct evidence that waiting times for radiotherapy influence patient’s clinical outcomes. The study was initiated in response to a request from the Canadian government for assistance to provide “evidence-based benchmarks” for waiting times for cancer treatment. Since it would be clearly unethical to perform a randomized trial exploring treatment delays, the investigators undertook a systematic literature to identify clinical studies published between 1975 and 2005 describing a relationship between waiting times and outcomes of radiotherapy. Altogether they identified 44 retrospective observational cohort studies, of which 20 met the high quality criteria for inclusion in the meta-analysis.

For each cancer considered by the meta-analysis, the mean of the local recurrence rates reported in the groups with the shortest waiting time was used to estimate a baseline for local recurrence. For head and neck cancer, the mean baseline rate of local recurrence following post operative radiotherapy was 22.7 % (range 9.9 to 25.5%), with each month of delay found to produce an absolute increase in the risk of recurrence of 6.3 %. For head and neck cancer radiotherapy, taking place without an operation, the mean baseline rate of local recurrence was 24.7 % (range (9.0-27 %), with each month of delay found to translate into an absolute increase in the risk of recurrence of 3.7 % per month of delay.

In contrast, the study found little evidence of an association between delays in radiotherapy and the risk of distant metastasis.

“Although the average increase in risk per month of delay in the individual patient is not large, it may have a very important detrimental effect on the overall value of a radiotherapy program because it potentially affects every patient who needs radiotherapy,” write the authors, adding that the negative effects of the prevailing delays in radiotherapy may be sufficient to cancel out the positive effects of many of the advances in radiotherapy over the last 20 years.

In head and neck cancer, tackling chronic waiting lists could deliver an absolute increase in local control of between 5 and 10 % simply by reducing radiotherapy waiting times by six weeks, calculate the authors.

“Given that there is no theoretical reason to believe that there is a threshold below which delay is safe, we believe that it is prudent to apply the principle that delays in RT should be as short as reasonably achievable,” conclude the authors.

Reference:
Chen Z, King W, Pearcey R, Kerba M, Mackillop W. The relationship between waiting time for radiotherapy and clinical outcomes: A systematic review of the literature. Radiotherapy and Oncology 2008, 87, 3-16

• 7 or 70% started their radiotherapy within 8 weeks after diagnosis.
• 3 or 30% waited more than 8 weeks

• Only 1 or 10% had radiotherapy within 4 weeks after surgery (understandable as time is needed for healing)
• 4 or 40% had radiotherapy between 4 - 8 weeks after surgery
• 2 or 20% had radiotherapy after 9 weeks after surgery