The impact of dose heterogeneity on late normal tissue complication risk after hypofractionated whole breast radiotherapy

Tsang, Y.; Haviland, J.S.; Venables, Karen; Yarnold, John

doi:10.1016/j.radonc.2012.06.002

Cited by 20 publications

(14 citation statements)

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“…who demonstrated that larger volume receiving >53.9 Gy was a significant predictor of radiation induced skin toxicity [40]. The recent UK FAST trial reported that, after adjusting for breast size and surgical deficits, there was no evidence that the risk of late adverse effects of HF-WBI was associated with dose inhomogeneity [41]. Conversely, our results suggest that dose inhomogeneities (V > 104% and V > 107%) have a significant impact on the occurrence of severe subcutaneous late reaction (p = 0.00864 and p = 0.02045, respectively) but we did not find any correlation between dosimetric parameters and both acute and late skin toxicity.…”

Section: Discussionmentioning

confidence: 99%

Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors

Ciammella¹,

Podgornii²,

Galeandro³

et al. 2014

Radiat Oncol

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PurposeThe objective of this study is to evaluate toxicity and cosmetic outcome in breast cancer patients treated with adjuvant hypo fractionated radiotherapy to the whole breast, and to identify the risk factors for toxicity.Methods and materialsTwo hundred twelve women with early breast cancer underwent conserving surgery were enrolled in the study. The patients received 40.05 Gy in 15 daily fractions, 2.67 Gy per fraction. The boost to the tumor bed was administered with a total dose of 9 Gy in 3 consecutive fractions in 55 women. Physician-rated acute and late toxicity and cosmetic outcome (both subjective and objective) were prospectively assessed during and after radiotherapy.ResultsIn our population study the mean age was 63 with the 17% (36 pts) of the women younger than 50 years.The median follow-up was 34 months. By the end of RT, 35 patients out of 212 (16%) no acute toxicity, according to the RTOG criteria, while 145 (68%) and 31 patients (15%) developed grade 1 and grade 2 acute skin toxicity, respectively.Late skin toxicity evaluation was available for all 212 patients with a minimum follow up of 8 months. The distribution of toxicity was: 39 pts (18%) with grade 1 and 2 pts (1%) with grade 2. No worse late skin toxicity was observed.Late subcutaneous grade 0-1 toxicity was recorded in 208 patients (98%) and grade 2 toxicity in 3 patients (2%), while grade 3 was observed in 1 patient only. At last follow up, a subjective and objective good or excellent cosmetic outcome was reported in 93% and 92% of the women, respectively. At univariate and multivariate analysis, the late skin toxicity was correlated with the additional boost delivery (p=0.007 and p=0.023). Regarding the late subcutaneous tissue, a correlation with diabetes was found (p=0.0283).ConclusionThese results confirm the feasibility and safety of the hypofractionated radiotherapy in patients with early breast cancer. In our population the boost administration was resulted to be a significant adverse prognostic factor for acute and late toxicity. Long-term follow up is need to confirm this finding.

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Section: Discussionmentioning

confidence: 99%

Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors

Ciammella¹,

Podgornii²,

Galeandro³

et al. 2014

Radiat Oncol

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“…Deantonio et al 30 on a hypofractionated whole-breast study (45 Gy in 20 fractions, 2.25 Gy/fr and 9 Gy boost) reported that breast volume increased the hazard of late toxicity over time (hazard ratio =1.27, 95% CI =1.04–1.55, and P =0.016) when analyzed with Cox’s proportional hazards regression model. Despite these discrepancies, Tsang et al 31 in a report on hypofractionated UK FAST trials showed that the dose heterogeneity does not impact on the risk of 2-year change photographic breast appearance after hypofractionation so in the START A and B Trial large breast volume is not considered an exclusion criterion for hypofractionation because the lower limit of the α/β ratio for adverse effects regarding breast appearance was 2.0 Gy. 31 Anyway, a modern technique such as intensity-modulated radiation therapy seems to solve overdoses in large breasts as reported by Hannan et al 32 In our study, there was no significant correlation between BD (as surrogate of dose heterogeneity) with late toxicity and cosmesis although a PTVbr over 1,300 cc significantly correlated with greater toxicity as seen in the univariate and multivariate analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Despite these discrepancies, Tsang et al 31 in a report on hypofractionated UK FAST trials showed that the dose heterogeneity does not impact on the risk of 2-year change photographic breast appearance after hypofractionation so in the START A and B Trial large breast volume is not considered an exclusion criterion for hypofractionation because the lower limit of the α/β ratio for adverse effects regarding breast appearance was 2.0 Gy. 31 Anyway, a modern technique such as intensity-modulated radiation therapy seems to solve overdoses in large breasts as reported by Hannan et al 32 In our study, there was no significant correlation between BD (as surrogate of dose heterogeneity) with late toxicity and cosmesis although a PTVbr over 1,300 cc significantly correlated with greater toxicity as seen in the univariate and multivariate analyses. In regard to the role of adjuvant chemotherapy in breast cancer, the DBCG-82TM protocol 33 and a multivariate analysis by Recht 34 have reported a negative impact of chemotherapy on cosmetic outcome and late normal tissue reactions after standard whole-breast radiotherapy but no many data are available with hypofractionation trials.…”

Section: Discussionmentioning

confidence: 99%

Predictive parameters in hypofractionated whole-breast 3D conformal radiotherapy according to the Ontario Canadian trial

Lazzari¹,

Terlizzi²,

Scarpati³

et al. 2017

OTT

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AimTo evaluate the possible role of dosimetric parameters according Normal Tissue Complication Probability (NTCP) model as predictive of late toxicity and cosmesis in hypofractionated whole-breast three-dimensional conformal radiotherapy.Patients and methodsA retrospective analysis on 215 consecutive early breast cancer patients treated with breast conserving surgery and adjuvant hypofractionated whole-breast radiotherapy (according the Ontario Canadian trial), with a 6 years median follow-up was conducted. To assess the impact of 10%–20% dose hotspots on different percent values of planning target volume (PTV) of the breast, we retrospectively employed the NTCP model of Lyman. PTV breast (PTVbr), V110 were identified. For statistical analysis the χ2 and paired t-test were used to find a correlation between late skin and subcutaneous toxicity and cosmetic outcome with dosimetrical parameters Multivariate analysis was performed with the aim to assess independently the impact of dosimetric and clinical parameters on late toxicity and cosmesis using Pearson’s covariance.ResultsLate skin toxicity was recorded in 47/215 (22%); and G3 toxicity occurred in 11 patients (5%). Cosmesis with excellent–good score was found in 172 patients (80%) while fair–poor score was found in 43 patients (20%). In univariate χ2 analysis the V110 >10% of the PTV breast significantly correlated with higher toxicity (P<0.005, OR 9.60 [CI 3.89–23.72]). Cosmesis related to V110 >10% and PTV breast volume over 1,300 cc was significant at multivariate analysis (P<0.005, OR 6.07 [CI 2.36–15.59]).ConclusionTo safely use one of the most important whole-breast hypofractionated radiotherapy schedules, we found some predictive paramaters on the basis of NTCP model by Lyman. These parameters may be useful in selection of elegible patients.

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“…• cosmesis in breast cancer (FAST trial) 111 • proctoscopy at 1 year for rectal toxicity post radiotherapy for prostate cancer 112 The individual risk of non-malignant tissue toxicity to radiotherapy treatment can be assessed using markers such as serum TGF-β1 levels as a surrogate of fibrosis in breast cancer 113 and pneumonitis in lung cancer 114 . F-FDG-PET • Low post-treatment SUV associated with better overall survival in a meta-analysis (using trial-specified cut-off values) 154 • Decrease in SUV max of ≥50% from baseline to week 1 or 2 (10 or 20 Gy) of CRT was associated with higher 2-year OS 155 Examples of some clinical parameters are provided, as they might represent useful primary or secondary end points for certain patient subgroups or for important areas of clinical need (for example, likelihood of accelerated approval by regulatory agencies).…”

Section: Box 6 | Non-malignant Tissue Toxicitymentioning

confidence: 99%

Clinical development of new drug–radiotherapy combinations

et al. 2016

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The impact of dose heterogeneity on late normal tissue complication risk after hypofractionated whole breast radiotherapy

Cited by 20 publications

References 20 publications

Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors

Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors

Predictive parameters in hypofractionated whole-breast 3D conformal radiotherapy according to the Ontario Canadian trial

Clinical development of new drug–radiotherapy combinations

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