hypofractionation in adjuvant breast radiotherapy
TRANSCRIPT
Letters to the Editor / The Breast 20 (2011) 99–100100
Hypofractionation in adjuvant breast radiotherapy
Khan and Haffty1 suggest that the natural consequence ofexcellent cure rates and lowmorbidity associated with hypofractio-nation trials is to consider economic impact and convenience insubsequent developments.
This is surely a step too far?Why are these trials such blunt instruments? Modern radiobio-
logical principles informed the START protocols and exceptionalquality control ensured conformity to them.2 The linear-quadraticequation imposes a choice of a/b ratio. Breast cancers havea wide range of tissue types and hence growth rates: the a/b ratiowill vary. The ratio 4–5 Gywas chosen becausemany breast cancersresemble normal tissues in their structure. Yet the growth ratesthat we adduced from measurement of shrinkage in response totreatment have a normal distribution with a 95% confidence limitof volume doubling times between 1 week and 4 months.3 Oneratio cannot fit all.
Histological grade was not included in randomization; the smallnumbers of tumours at the ends of the distribution need not beevenly distributed A skew distribution of rapidly growing tumoursand/or delays in starting radiotherapy could explain the ‘statisticaloddity’ of fewer metastases in the experimental arm of START B,since daily fractions of 2.67 Gy would be expected to be moreeffective in rapidly growing tumours.4,5,*
It is salutary to note that BED (Biologically Effective Dose)calculations predict greater long-term effects upon normal tissuesthan tumour in all the fractionation schemes, of which START Bexperimental arm has the lowest value. Indeed, for really rapidly
* In our 1991 paper we had used the cumulative radiation effect (CRE) asa measure of radiation accumulated. The data have been re-analysed using thelinear-quadratic model (as yet unpublished) and the original conclusionsconfirmed.
growing tumours hyperfractionation6 may be necessary toovercome the rapid proliferation rate while producing minimallong-term normal tissue damage.
References
1. Khan A, Haffty BG. Hypofractionation in adjuvant breast radiotherapy. The Breast2010;19:168–71.
2. Venables K, Winfield E, Deighton A, Aird E, Hoskin P. The START Trialdmeasure-ments in semi-anatomical breast and chest wall phantoms. Physics in Medicineand Biology 2001;46:1937–48.
3. Johnson AE, Bennett MH, Cheung CWD, Cox S, Sales JEL. The management ofindividual breast cancers. The Breast 1995;4:100–11.
4. Cheung CWD, Johnson AE. Carcinoma of the breast: measurement and themanagement of treatment. II. The regression of tumours. British Journal of Radi-ology 1991;64:121–32.
5. Johnson AE. The timing of treatment in breast cancer. Breast Cancer Research andTreatment 2000;60:201–9.
6. Fowler JF. How worthwhile are short schedules in radiotherapy?: a series ofexploratory calculations. Radiotherapy and Oncology 1990;18:165–81.
Ann Johnson*
Mount Vernon Hospital, Mount Vernon Postgraduate Medical Centre,Rickmansworth Road, Northwood HA6 2RN, United Kingdom
* Corresponding author. Swallows, 2 Kiln Farm Barns, Lower Road,Blackthorn, OX25 1TG, United Kingdom. Tel.: þ01 896 240058.
E-mail address: [email protected]. (A. Johnson)
29 October 2010
doi:10.1016/j.breast.2010.11.007