Time factor and treatment strategies in subclinical disease

Abstract

Rational biological development of treatment strategies for subclinical metastases has lagged behind such efforts with primary cancers: most adjuvant therapies for subclinical disease have been developed empirically, based on clinical observation. This paper reviews recent studies that point to rapid growth of subclinical disease. The effect of rapid growth of occult metastases and undetectable extensions of primary cancer is to increase the radiation dose necessary for their elimination if treatment duration is extended. This increase may be evident even when changes are made to short courses of treatment, consistent with no lag time between the start of treatment and rapid growth or regrowth of subclinical tumour deposits. This provides a strong rationale for avoiding gaps or delays in adjuvant treatments and suggest that accelerated regimens of radiation or chemoradiation may be advantageous in the treatment of subclinical disease provided that the total dose can be maintained or not greatly reduced from those used conventionally. Conversely, an escalation of total dose with a concomitant increase in overall treatment duration may not result in improved control rates because the rapid growth of small clonogen deposits might counterbalance the effect of the higher dose.

Comparison of the Effectiveness of “Late” and “Early” Prophylactic Cranial Irradiation in Patients with Limited-Stage Small Cell Lung Cancer

“…It has been shown that early application of PCI at a dose of about 30-35 Gy in 2-Gy fractions allows to obtain better results. This was confirmed by Auperin et al and Suwiński's group [3,27,28]. The latter presented a nearly linear dose-response relationship regarding reduction in brain metastases, demonstrated for "early" PCI in the dose range from 0 up to 35 Gy.…”

“…The latter presented a nearly linear dose-response relationship regarding reduction in brain metastases, demonstrated for "early" PCI in the dose range from 0 up to 35 Gy. Additionally, PCI applied at the beginning of chemoradiotherapy reduces the incidence of brain metastases by about 80% [27,28].…”

Comparison of Incidental Radiation Dose to Axilla and Internal Mammary Nodal Area by Conventional, 3DCRT, and IMRT Technique in Carcinoma of Breast

“…One possibility is that dose less that 95% of prescription dose is adequate to treat clinically negative axilla/microscopic disease. Wither et al have proposed a shallow dose response curve for microscopic disease though a dose of 45 Gy to 50 Gy seems more relevant for sterilization of subclinical disease [28]. It is possible that a dose in order of 30 Gy can bring about some regional control.…”

Incidental irradiation of mediastinal and hilar lymph node stations during 3D-conformal radiotherapy for non-small cell lung cancer

“…Following the radiobiological concepts of Withers et al [21] a dose of 50 Gy in 2 Gy per fraction is considered as necessary to achieve an overall 90% reduction in the incidence of metastases and it is a commonly prescribed dose-schedule for subclinical disease. On the other hand, there are also suggestions from the literature that worthwhile benefits can be achieved by doses as low as 14Á21 Gy under the condition of being delivered close to the treatment of the primary [22,23]. We did not make any attempt on the biological dose calculation though different dose per fraction and treatment times were used.…”