Background and purpose: In accelerated partial breast irradiation (APBI), accurate definition of the tumour bed is crucial to reduce the risk of local recurrence and the volume of healthy tissue... Show moreBackground and purpose: In accelerated partial breast irradiation (APBI), accurate definition of the tumour bed is crucial to reduce the risk of local recurrence and the volume of healthy tissue irradiated. Recently, hydrogels have been proposed to improve visibility of the lumpectomy cavity for APBI. The aim of this study was to alter two commercially available hyaluronic acid (HA) gels, with gadopentenate dimeglumine (GD), a magnetic resonance imaging (MRI) contrast agent. We hypothesize that after injection in the surgical cavity, the mixtures will be visible with computed tomography (CT) for improved treatment planning, cone-beam CT (CBCT) for improved patient setup and planar kilovoltage (kV) x-ray for real-time tracking during treatment. Materials and methods: In this ex vivo study, GD was mixed with the two HA gels, and 1 mL of each mixture was injected into fatty and muscular tissue of a pork phantom. Visibility with CT, CBCT and planar x-ray imaging was assessed. Contrast-to-noise ratios (CNR) were measured and compared to commercially available iodinated polyethylene glycol (PEG). Results: The gel mixtures showed increased visibility over HA gels without GD. When comparing CNR of the gel mixtures to that of iodinated PEG on CT, there was a 4-fold increase in muscle for both mixtures and a 1.6-fold to 3.6-fold increase in fat, depending on the HA gel. Gel mixtures showed better visibility with planar kV imaging over iodinated PEG. Conclusion: Addition of GD to HA gels increases visibility with CT, CBCT and planar x-ray imaging, indicating potential for improved delineation and positioning in APBI. Show less
Pignol, J.P.; Hoekstra, N.; Wilke, D.; Dahn, H.; Nolan, M.; Vicini, F. 2021
Purpose: Secondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT), and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue... Show morePurpose: Secondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT), and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue for early-stage breast cancer, and that lives could be saved using different RT techniques.Patients and Methods: The SEER database was used to extract breast patient age, stage survival, and radiotherapy utilization over time and per stage and to assess the factors associated with increased SLC risk with a multivariable competing risk Cox model. The number of SLC was calculated using the BEIR model modified with patient survival, age, and use of RT from the SEER database. Stage distribution and number of new breast cancer cases were obtained from the NAACCR. Mean lung dose for various irradiation techniques was obtained from measurement or literature.Results: Out of the 765,697 non-metastatic breast cancers in the SEER database from 1988 to 2012, 49.8% received RT. RT significantly increased the SLC risk for longer follow-up (HR=1.58), early stage including DCIS, stage I and IIA (HR = 1.11), and younger age (HR=1.061) (all p<0.001). More advanced stages did not have significantly increased risk. In 2019, 104,743 early-stage breast patients received radiotherapy, and an estimated 3,413 will develop SLC (3.25%) leading to an excess of 2,900 deaths (2.77%). VMAT would reduce this mortality by 9.9%, hypofractionation 26 Gy in five fractions by 38.8%, a prone technique by 70.3%, 3D-CRT APBI by 43.3%, HDR brachytherapy by 71.1%, LDR by 80.7%, and robotic 4 pi APBI by 85.2%.Conclusions: SLC after breast RT remains a clinically significant issue for early-stage breast cancers. This mortality could be significantly reduced using a prone technique or APBI. Show less
Introduction: With the introduction of accelerated partial breast irradiation (APBI) and the trend of reducing the number of fractions, the geometric accuracy of treatment delivery becomes critical... Show moreIntroduction: With the introduction of accelerated partial breast irradiation (APBI) and the trend of reducing the number of fractions, the geometric accuracy of treatment delivery becomes critical. APBI patient setup is often based on fiducials, as the seroma is frequently not visible on pretreatment imaging. We assessed the motion of fiducials relative to the tumor bed between planning CT and treatment, and calculated margins to compensate for this motion. Methods: A cohort of seventy patients treated with APBI on a Cyberknife was included. Planning and in room pretreatment CT scans were registered on the tumor bed. Residual motion of the centers of mass of surgical clips and interstitial gold markers was calculated. We calculated the margins required per desired percentage of patients with 100% CTV coverage, and the systematic and random errors for fiducial motion. Results: For a single fraction treatment, a margin of 1.8 mm would ensure 100% CTV coverage in 90% of patients when using surgical clips for patient set-up. When using interstitial markers, the margin should be 2.2 mm. The systematic and random errors were 0.46 mm for surgical clip motion and 0.60 mm for interstitial marker motion. No clinical factors were found predictive for fiducial motion. Conclusions: Fiducial motion relative to the tumor bed between planning CT and APBI treatment is non negligible and should be included in the PTV margin calculation to prevent geographical miss. Systematic and random errors of fiducial motion were combined with other geometric uncertainties to calculate comprehensive PTV margins for different treatment techniques. (c) 2021 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 163 (2021) 1-6 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Introduction: As the prognosis of early-stage breast cancer patients is excellent, prevention of radiation induced toxicity has become crucial. Reduction of margins compensating for intrafraction... Show moreIntroduction: As the prognosis of early-stage breast cancer patients is excellent, prevention of radiation induced toxicity has become crucial. Reduction of margins compensating for intrafraction motion reduces non-target dose. We assessed motion of the tumor bed throughout APBI treatment fractions and calculated CTV-PTV margins for breathing and drift.Methods: This prospective clinical trial included patients treated with APBI on a Cyberknife with fiducial tracking. Paired orthogonal kV images made throughout the entire fraction were used to extract the tumor bed position. The images used for breathing modelling were used to calculate breathing amplitudes. The margins needed to compensate for breathing and drift were calculated according to Engelsman and Van Herk respectively.Results: Twenty-two patients, 110 fractions and 5087 image pairs were analyzed. The margins needed for breathing were 0.3-0.6 mm. The margin for drift increased with time after the first imaging for positioning. For a total fraction duration up to 8 min, a margin of 1.0 mm is sufficient. For a fraction of 32 min, 2.5 mm is needed. Techniques that account for breathing motion can reduce the margin by 0.1 mm. There was a systematic trend in the drift in the caudal, medial and posterior direction. To compensate for this, 0.7 mm could be added to the margins.Conclusions: The margin needed to compensate for intrafraction motion increased with longer fraction duration due to drifting of the target. It doubled for a fraction of 24 min compared to 8 min. Breathing motion has a limited effect.(c) 2021 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 159 (2021) 176-182 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Purpose:Adjuvant accelerated partial breast irradiation (APBI) results in low local recurrence risks. However, the survival benefit of adjuvant radiotherapy APBI for low-risk breast cancer might... Show morePurpose:Adjuvant accelerated partial breast irradiation (APBI) results in low local recurrence risks. However, the survival benefit of adjuvant radiotherapy APBI for low-risk breast cancer might partially be offset by the risk of radiation-induced lung cancer. Reducing the lung dose mitigates this risk, but this could result in higher doses to the ipsilateral breast. Different external beam APBI techniques are equally conformal and homogenous, but the intermediate to low dose distribution differs. Thus, the risk of toxicity is different. The purpose of this study is to quantify the trade-off between secondary lung cancer risk and breast dose in treatment planning and to compare an optimal coplanar and non-coplanar technique. Methods:A total of 440 APBI treatment plans were generated using automated treatment planning for a coplanar VMAT beam-setup and a non-coplanar robotic stereotactic radiotherapy beam-setup. This enabled an unbiased comparison of two times 11 Pareto-optimal plans for 20 patients, gradually shifting priority from maximum lung sparing to maximum ipsilateral breast sparing. The excess absolute risks of developing lung cancer and breast fibrosis were calculated using the Schneider model for lung cancer and the Avanzo model for breast fibrosis. Results:Prioritizing lung sparing reduced the mean lung dose from 2.2 Gy to as low as 0.3 Gy for the non-coplanar technique and from 1.9 Gy to 0.4 Gy for the coplanar technique, corresponding to a 7- and 4-fold median reduction of secondary lung cancer risk, respectively, compared to prioritizing breast sparing. The increase in breast dose resulted in a negligible 0.4% increase in fibrosis risk. The use of non-coplanar beams resulted in lower secondary cancer and fibrosis risks (p< 0.001). Lung sparing also reduced the mean heart dose for both techniques. Conclusions:The risk of secondary lung cancer of external beam APBI can be dramatically reduced by prioritizing lung sparing during treatment planning. The associated increase in breast dose did not lead to a relevant increase in fibrosis risk. The use of non-coplanar beams systematically resulted in the lowest risks of secondary lung cancer and fibrosis. Prioritizing lung sparing during treatment planning could increase the overall survival of early-stage breast cancer patients by reducing mortality due to secondary lung cancer and cardiovascular toxicity. Show less
Background and purpose: During oncoplastic breast-conserving surgery (BCS), the surgical cavity is closed to reduce seroma formation. This makes the radiotherapy target definition using clips... Show moreBackground and purpose: During oncoplastic breast-conserving surgery (BCS), the surgical cavity is closed to reduce seroma formation. This makes the radiotherapy target definition using clips challenging, leading to poor inter-observer agreement and potentially geographical misses. We hypothesize that injecting a radiopaque hydrogel in the lumpectomy cavity before closure improves radiotherapy target definition and agreement between observers.Materials and methods: Women undergoing BCS in a single university hospital were prospectively accrued in the study. Three to 9 ml of iodined PolyEthylene Glycol (PEG) hydrogel and clips were inserted in the lumpectomy cavity. A CT-scan was performed at 4 to 6 weeks. CT images of BCS patients with standard clips only were used as control group, matched on age, specimen weight, and distance between clips. Six radiation oncologists delineated the tumor bed volumes and rated the cavity visualization scores (CVS). The primary endpoint was the agreement between observers measured using a Conformity Index (Cx).Results: Forty-two patients were included, 21 hydrogel procedures and 21 controls, resulting in 315 observer pairs. The feasibility of the intervention was 100%. The median Cx was higher in the intervention group (Cx = 0.70, IQR [0.54-0.79]) than in the control group (Cx = 0.54, IQR [0.42-0.66]), p < 0.00, as were the CVS (3.5 [2.5-4.5] versus 2.5 [2-3.5], p < 0.001). The rate of surgical site infections was similar to literature.Conclusions: The use of radiopaque PEG enables to identify the lumpectomy cavity, resulting in a high inter-observer agreement for radiotherapy target definition. This intervention is easy to perform and blend well into current practice. (C) 2018 Elsevier B.V. All rights reserved. Show less
Linge, A. van; Os, R. van; Hoekstra, N.; Heijmen, B.; Stienstra, L.; Dallenga, A.; ... ; Romero, A.M. 2018
BackgroundAlthough stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore... Show moreBackgroundAlthough stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore wished to assess the change in hearing loss after SRT and to determine which patient, tumor and treatment-related factors influence deterioration.MethodsWe retrospectively analyzed progression of hearing loss in patients with vestibular schwannoma who had received stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) as a primary treatment between 2000 and 2014. SRS had been delivered as a single fraction of 12Gy, and patients treated with FSRT had received 30 fractions of 1.8Gy. To compare the effects of SRS and FSRT, we converted cochlear doses into EQD(2). Primary outcomes were loss of functional hearing, Gardner Robertson (GR) classes I and II, and loss of baseline hearing class. These events were used in Kaplan Meier plots and Cox regression. We also calculated the rate of change in Pure Tone Average (PTA) in dB per month elapsed after radiationa measure we use in linear regressionto assess the associations between the rate of change in PTA and age, pre-treatment hearing level, tumor size, dose scheme, cochlear dose, and time elapsed after treatment (time-to-first-audiogram).ResultsThe median follow-up was 36months for 67 SRS patients and 63months for 27 FSRT patients. Multivariate Cox regression and in linear regression both showed that the cochlear V90 was significantly associated with the progression of hearing loss. But although pre-treatment PTA correlated with rate of change in Cox regression, it did not correlate in linear regression. The time-to-first-audiogram was also significantly associated, indicating time dependency of the rate of change. None of the analysis showed a significant difference between dose schemes.ConclusionsWe found no significant difference between SRS and FSRT. As the deterioration in hearing after radiotherapy for vestibular schwannoma was associated with the cochlea V90, restricting the V90 may reduce progression of hearing loss. The association between loss of functional hearing and baseline PTA seems to be biased by the use of a categorized variable for hearing loss. Show less
Hoekstra, N.; Fleury, E.; Lara, T.R.M.; Baan, P. van der; Bahnerth, A.; Struik, G.; ... ; Pignol, J.P. 2018
Introduction: For early stage breast cancer patients, non-breast cancer mortality including secondary cancers and cardiac events can overshadow the benefit of adjuvant radiotherapy. This study... Show moreIntroduction: For early stage breast cancer patients, non-breast cancer mortality including secondary cancers and cardiac events can overshadow the benefit of adjuvant radiotherapy. This study evaluates the excess risk of secondary cancer for various breast radiotherapy techniques including accelerated partial breast irradiation (APBI).Methods: Secondary cancers Lifetime Attributable Risks (LAR) were calculated using a modified BEIR-VII formalism to account for the specific survival of breast cancer patients. Those survivals were extracted from the SEER database. Doses scattered to various organs were measured into a Rando phantom with custom-made breast phantoms. Treatments delivered typical doses of brachytherapy APBI (34 Gy in 10 fractions), external beam APBI (38.5 Gy in 10 fractions) using 3D-conformal, Cyberknife stereotactic (CK), or VMAT, as well as whole breast irradiation (WBI) delivering 42.5 Gy in 16 fractions.Results: WBI resulted in the highest total LAR, with 4.3% excess risk of secondary cancer for a patient treated at age 50 years. Lung cancers accounted for 75-97% of secondary malignancies. For a typical early stage patient irradiated at 50, the excess risks of secondary lung cancer were 1.1% for multicatheter HDR, between 2.2% and 2.5% for 3D-CRT or CK, 3.5% for VMAT APBI, and 3.8% for WBI.Conclusions: APBI reduces the risk of secondary cancer 2-4 fold compared to WBI. These techniques are well suited for long-living early stage breast cancer patients. HDR brachytherapy and 3D-conformal APBI achieve mean lung doses between 1 and 1.5 Gy, which could serve as reference. (C) 2018 Elsevier B.V. All rights reserved. Show less
