Selective boosting of tumor subvolumes Tomé, Wolfgang A.; Fowler, Jack F.
International journal of radiation oncology, biology, physics,
09/2000, Letnik:
48, Številka:
2
Journal Article, Conference Proceeding
Recenzirano
Purpose and background: It is no longer considered mandatory to deliver a uniform dose to the tumor volume in radiotherapy. Non-uniform doses are unavoidable in brachytherapy and in stereotactic ...radiosurgery, with often good results. Deliberately non-uniform doses may increase tumor control probability (TCP) and enable steeper dose gradients outside the treated volume to be achieved. New methods of tumor imaging might show regions of specific activity or hypoxia which could be selectively targeted. This paper investigates by modeling the effect of boosting, by dose ratios up to 2, for a range of tumor subvolumes.
Methods and Materials: A standard linear–quadratic algorithm was used to define the dose–response curve for tumors of various volumes (numbers of clonogenic cells), radiosensitivity (SF
2), assumed slope (γ
50) and dose for 50% tumor control (TCD
50). Curves of tumor control probability (TCP) were constructed to show the increase of TCP, as a function of the ratio of boost dose to the TCD
50, above the baseline 50% TCP, for a set of different proportions of tumor volume boosted.
Results: Calculated values of TCP increased rapidly with both boost dose ratio and with proportion of volume boosted. The increase in TCP reached a plateau after boost dose ratios of 1.2–1.3, as has been noted before, except where very large proportions of tumor volume exceeding 90% were boosted. Quite large increases of TCP, to about 75%, could be achieved if the γ
50 slope was steep, and especially in small tumors (having fewer cells). Radiosensitivity was not an independent factor because radiosensitive tumors had a low TCD
50 and this was the baseline dose considered as unity.
Conclusion: There were few situations where a boost dose ratio exceeding 1.3 appeared to be worthwhile or necessary. Significant increases of TCP, up from 50% to 75%, might therefore be achieved for a small increase in risk of necrosis, where a substantial proportion of tumor volume (60–80%) could be boosted.
Dr. Felix Leborgne, 1935-2009 Urtasun, Raul C; Fowler, Jack
International journal of radiation oncology, biology, physics,
12/2009, Letnik:
75, Številka:
5
Journal Article
Purpose/Objective
: Our goal was to analyze the repopulation of surviving tumor cells during a treatment gap in radiotherapy for head-and-neck cancer.
Methods and Materials
: Clinical material is ...based on the records of 1502 patients treated by radiotherapy alone in Maria Sklodowska-Curie Memorial Institute in Gliwice during the period between1980 and 1989. All patients had histologically confirmed squamous cell carcinoma of the larynx or pharynx. The mean gap duration was 9 days. Only 10% of patients were treated without gaps. The dose per fraction was in the range of 1.5 to 2.5 Gy. Patient data were fitted directly to the mixed linear-quadratic model using maximum-likelihood estimation. Tumor stage or tumor localization was introduced into the equation as a categorical variable. Tumor proliferation was estimated by dividing the treatment gaps into three groups: the first 2 weeks, second 2 weeks, and the period after 4 weeks of irradiation.
Results
: Tumor control probability was significantly correlated with radiation dose, tumor progression (according to TNM), overall treatment time, and gap duration. Laryngeal cancers had a better prognosis than cancers of the oro- and nasopharynx. Significant tumor repopulation was found after the first 2 weeks of radiotherapy. During the treatment gap, the proliferation rate was equal to 0.75 Gy/day. During the days with irradiation, repopulation was slower and equal to 0.2 Gy/day.
Conclusion
: The repopulation of tumor cells is faster during a gap than during the normal days of irradiation. Accelerated repopulation probably starts soon after 2 weeks of irradiation.
Introduction. Altered fractionation has demonstrated clinical benefits compared to the conventional 2 Gy/day standard of 70 Gy. When using synchronous chemotherapy, there is uncertainty about optimum ...fractionation. IMRT with its potential for Simultaneous Integrated Boost (SIB) adds further to this uncertainty. This survey will examine international practice of IMRT fractionation and suggest possible reasons for diversity in approach. Material and methods. Fourteen international cancer centres were surveyed for IMRT dose/fractionation practised in each centre. Results. Twelve different types of dose fractionation were reported. Conventional 70-72 Gy (daily 2 Gy/fraction) was used in 3/14 centres with concurrent chemotherapy while 11/14 centres used altered fractionation. Two centres used >1 schedule. Reported schedules and number of centres included 6 fractions/week DAHANCA regime (3), modest hypofractionation (≤2.2 Gy/fraction) (3), dose-escalated hypofractionation (≥2.3 Gy/fraction) (4), hyperfractionation (1), continuous acceleration (1) and concomitant boost (1). Reasons for dose fractionation variability include (i) dose escalation; (ii) total irradiated volume; (iii) number of target volumes; (iv) synchronous systemic treatment; (v) shorter overall treatment time; (vi) resources availability; (vii) longer time on treatment couch; (viii) variable GTV margins; (ix) confidence in treatment setup; (x) late tissue toxicity and (xi) use of lower neck anterior fields. Conclusions. This variability in IMRT fractionation makes any meaningful comparison of treatment results difficult. Some standardization is needed particularly for design of multi-centre randomized clinical trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
CONTEXT Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current ...management. OBJECTIVE To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer. DESIGN, SETTING, AND PATIENTS Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non–small cell tumors (measuring <5 cm in diameter) and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction × 3 fractions (54 Gy total) with entire treatment lasting between 1½ and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through August 31, 2009. MAIN OUTCOME MEASURES The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (ie, primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival. RESULTS A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 34.4 months (range, 4.8-49.9 months). Only 1 patient had a primary tumor failure; the estimated 3-year primary tumor control rate was 97.6% (95% confidence interval CI, 84.3%-99.7%). Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6% (95% CI, 76.0%-96.5%). Two patients experienced regional failure; the local-regional control rate was 87.2% (95% CI, 71.0%-94.7%). Eleven patients experienced disseminated recurrence; the 3-year rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). The rates for disease-free survival and overall survival at 3 years were 48.3% (95% CI, 34.4%-60.8%) and 55.8% (95% CI, 41.6%-67.9%), respectively. The median overall survival was 48.1 months (95% CI, 29.6 months to not reached). Protocol-specified treatment-related grade 3 adverse events were reported in 7 patients (12.7%; 95% CI, 9.6%-15.8%); grade 4 adverse events were reported in 2 patients (3.6%; 95% CI, 2.7%-4.5%). No grade 5 adverse events were reported. CONCLUSION Patients with inoperable non–small cell lung cancer who received stereotactic body radiation therapy had a survival rate of 55.8% at 3 years, high rates of local tumor control, and moderate treatment-related morbidity.
The prospects for new treatments for prostate cancer Fowler, Jack F; Chappell, Rick J; Ritter, Mark A
International journal of radiation oncology, biology, physics,
2002, 2002-Jan-01, 2002-1-00, Letnik:
52, Številka:
1
Journal Article
The aim of the study was to examine the influence of overall treatment time (OTT) on the value of calculated biological effective doses (BEDs) for different biological variables. These variables ...were: tumour proliferation rate, different cell radiosensitivity (α=0.2, 0.3, and 0.4 /Gy), and different start time for repopulation (Tk=21, 28, and 35 days). Also the influence of age (≤50 years >), Hb level (≤116 g/l>), tumor proliferation rate (bromodeoxyuridine labelling index; BrdUrdLI), and DNA ploidy on survival after shorter (≤60 days) or longer (>60 days) OTT was investigated. The study included 229 patients with cervix carcinoma treated entirely by standard radiotherapy (RT) (external beam RT plus low-medium dose-rate (LDR/MDR) brachytherapy (BT) at the Center of Oncology in Krakow. The linear quadratic equation was used to calculate BED, which is proportional to log cell kill. BEDs 10 (for tumours) were calculated with consideration of OTT for each patient and tumour proliferation rate (standardized potential doubling time; standardized Tpot) based on BrdUrdLI assessed on biopsy material before RT. Median OTT was 90 days (range 30-210). The mean calculated total BED for point A for tumour and 'early reactions' was equal to 103.0 Gy10. The longest median survival time-52 months-was seen for patients treated with OTT ≤60 days. If OTT exceeded 90 days to more than 120 days, loss in BED10 for relatively radiosensitive tumours (α=0.3-0.4/Gy and Tk=28 days) was equal to 0.37-0.26 Gy/day. However, for radioresistant tumours (α=0.2/Gy) it was 0.6 Gy/day. For fast proliferating tumours (BrdUrdLI >8.8%) BED loss was 1.4 Gy/day and for slowly proliferating tumours (BrdUrdLI ≤8.8%) it was 0.2 Gy/day. Assuming shorter (21 days) or longer (35 days) periods for Tk and relatively radiosensitive tumours similar BED loss of 0.38 Gy/day was observed. Kaplan-Meier analysis revealed that OTT ≤60 days was a significant prognostic factor for overall survival (OS) (p=0.019), disease-free survival (DFS) (p=0.0173), and local control (LC) (p=0.011). BED10 had significant influence on survival (p=0.047). Cox multivariate analysis revealed that for OTT shorter than 60 days the only favourable significant parameters were: age >50 years (p=0.003) and high Hb level (>116 g/l) (p=0.041). For longer treatments (OTT >60 days) the unfavourable parameters were: age ≤50 years (p=0.037), BrdUrdLI ≤8.8% (p=0.003), tumour aneuploidy (p=0.043), and BED10 ≤103 Gy (p=0.017). The examined tumour biological parameters should be taken into account for RT and provide a basis for adjuvant RT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models.
Methods and Materials: ...Consecutive patients (1008) treated radically with four different fractionation schedules during 1976–1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18–84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5–4.2 Gy, total dose 45.6–60 Gy, and overall time 38–75 days.
Results: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%,
p
< 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor:
p
= 0.0022, hazard ratio (HR) = 1.044 per Gy
2. Overall time and age were both insignificant. The α/β ratio calculated from our data was 2.9 Gy (95% CI: −1.8, 7.6 Gy). Biological effective dose (BED
Gy3), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (
p
< 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy
3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates.
Conclusion: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an α/β ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.
PDF
