Biological Factors Influencing Optimum Fractionation in Radiation Therapy

Aim: To evaluate the results of hypofractionated conformal radiotherapy (RT) in limited disease small cell lung cancer (LD-SCLC) patients, with particular interest in the value of “early” RT, i.e., given before the 3rd chemotherapy (CHT) cycle. Material and Methods: Outcome of hypofractionated RT (42 Gy, 2.8 Gy/fraction, given over 19–21 days, using “concomitant boost” technique—elective volume [39 Gy, 2.6 Gy/fraction] and tumour volumes treated during the same fraction) combined with CHT in 100 consecutive LD-SCLC patients, was retrospectively assessed. The outcomes were compared with a previously published series of 117 LD-SCLC patients treated in the same institution with hyperfractionated or conventionally fractionated RT. Results: Forty-two patients (42%) received “early” RT. Grade 3 NCI CTC acute oesophageal toxicity appeared in 5% of patients. There were three treatment-related deaths. Three-year overall survival (OS) rate was 39.4%, median—24 months in the examined group vs. 26.0%, and 18 months in historical control, p = 0.02. Three-year OS for 78 patients with completed CHT was 42.2%, median—28 months vs. 30%, and 14 months for 22 patients who received ≤ 3 CHT cycles, (p = 0.03). The actuarial 3-year locoregional failure risk (LRFR) was 34.0% in the examined group vs. 51.0% in the historical control, p = 0.04. Multivariate analysis showed a marginally significant correlation between the “early” use of RT and LRFR: RR = 0.43 (95% CI: 0.17–1.04), p = 0.06, with no significant impact on OS. Conclusions: Shorter duration of RT using hypofractionation results in encouraging outcomes and acceptable toxicity. Completion of all planned CHT cycles is the most important factor for OS.

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“…To compare the effect of different fractionation schedules, the biologically effective dose (BED) formula, proposed by Fowler [23], was used:…”

Section: Methodsmentioning

confidence: 99%

Hypofractionated Conformal Radiotherapy in Combination with Chemotherapy in Limited Disease Small Cell Lung Cancer Patients

Socha

Guzowska²,

Tyc-Szczepaniak

et al. 2014

Advances in Respiratory Medicine

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“…Incidentally, the next longest Tpot in human tumors is for breast carcinoma, with a median Tpot of 14 days but a range extending to rapid growth (3 Á/70 days). Most carcinomas, however, have median Tpot values of 4 Á/9 days, and each type ranges from about 2 to 20 or 30 days [5].…”

Section: Introductionmentioning

confidence: 99%

The radiobiology of prostate cancer including new aspects of fractionated radiotherapy

2005

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Total radiation dose is not a reliable measure of biological effect when dose-per-fraction or dose-rate is changed. Large differences in biological effectiveness (per gray) are seen between the 2 Gy doses of external beam radiotherapy and the large boost doses given at high dose-rate from afterloading sources. The effects are profoundly different in rapidly or slowly proliferating tissues, that is for most tumors versus late complications. These differences work the opposite way round for prostate tumors versus late complications compared with most other types of tumor. Using the Linear-Quadratic formula it is aimed to explain these differences, especially for treatments of prostate cancer. The unusually slow growth rate of prostate cancers is associated with their high sensitivity to increased fraction size, so a large number of small fractions, such as 35 or 40 ''daily'' doses of 2 Gy, is not an optimum treatment. Theoretical modeling shows a stronger enhancement of tumor effect than of late complications for larger (and fewer) fractions, in prostate tumors uniquely. Biologically Effective Doses and Normalized Total Doses (in 2 Gy fraction equivalents) are given for prostate tumor, late rectal reactions, and */a new development */acute rectal mucosa. Tables showing the change of fraction-size sensitivity (the alpha/beta ratio) with proliferation rates of tissues lead to the association of slow cell doubling times in prostate tumors with small a/b ratios. Clinical evidence to confirm this biological expectation is reviewed. The a/b ratios of prostate tumors appear to be as low as 1.5 Gy (95% confidence interval 1.3 Á/1.8 Gy), in contrast with the value of about 10 Gy for most other types of tumor. The important point is that a/b0/1.5 Gy appears to be significantly less than the a/b0/3 Gy for late complications in rectal tissues. Such differences are also emerging from recent clinical results. From this important difference stems the superior schedules of, for example, 20 fractions of 3 Gy, or 10 fractions of 4.7 Gy, or 5 fractions of 7 Gy, which can all give tumor results equivalent to 80 Á/90 Gy in 2 Gy fractions, while keeping late complications equivalent to only 72 Gy in 2 Gy fractions. Combination treatments of external beam (EBRT) and brachytherapy boost doses (25F )/2 Gy plus 2)/10 Gy) can give higher biological tumor effects than any EBRT using daily 2 Gy doses, and with acceptable late complications. Monotherapy by brachytherapy for low-risk cancer prostate using two to four fractions in a few days can give even higher biological effects on the tumors.

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“…Initially, it was hypothesized that the restperiod would allow repair of normal tissue damage, decrease morbidity and increase oxygenation of tumour cells. However, later studies have suggested, in some tumour types, that tumour cell repopulation during the split period decreases local control (14). It has been suggested, though, that repopulation in bladder cancer starts late (5 Á/6 weeks) (15).…”

Section: Overview Of Studiesmentioning

confidence: 99%