Marianne C. Aznar

Deep inspiration breath hold to reduce irradiated heart volume in breast cancer patients.

Abstract Purpose: To evaluate the use of deep inspiration breath hold (DIBH) during tangential breast radiation therapy as a means of reducing irradiated cardiac volume. Methods and Materials: The Active Breathing Control (ABC) device designed at William Beaumont Hospital, Michigan was used to quantify the potential benefit of radiation delivery during DIBH for five left-sided breast cancer patients. This device initiates a breath hold at a predefined, reproducible lung volume. For each patient, two CT scans were acquired with and without breath hold, and virtual simulation was performed for regular tangent and wide-tangent techniques. The resulting dose–volume histograms were calculated, and the volume of heart irradiated to 25 Gy or more was assessed. Results: The influence of ABC on irradiated heart volumes varied considerably among the five patients. Three patients with substantial cardiac volume in the treatment field during normal respiration showed a significant dose–volume histogram reduction when deep inspiration was applied, with decreases in the heart volume receiving 25 Gy of more than 40 cc observed. For one patient, deep inspiration reduced irradiated cardiac volumes only with the wide-tangent technique, while one patient showed no substantial irradiated volume decrease. Conclusion: A DIBH technique during tangential breast irradiation has the potential to significantly decrease irradiated cardiac volume for suitably selected patients. The magnitude of the impact of the breath hold application depends on patient anatomy, lung capacity, and pulmonary function.

Real-time optical-fibre luminescence dosimetry for radiotherapy: physical characteristics and applications in photon beams

A new optical-fibre radiation dosimeter system, based on radioluminescence and optically stimulated luminescence from carbon-doped aluminium oxide, was developed and tested in clinical photon beams. This prototype offers several features, such as a small detector (1 x 1 x 2 mm3), high sensitivity, real-time read-out and the ability to measure both dose rate and absorbed dose. The measurements describing reproducibility and output dependence on dose rate, field size and energy all had standard deviations smaller than 1%. The signal variation with the angle of incidence was smaller than 2% (1 SD). Measurements performed in clinical situations suggest the potential of using this real-time system for in vivo dosimetry in radiotherapy.

ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer

BACKGROUND AND PURPOSE Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. MATERIAL AND METHODS During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. RESULTS Borders of the CTV encompassing a 5mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. CONCLUSION The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency.

Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma.

Abstract Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc® (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007–2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WRneutron). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.

Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.

Risk of Developing Cardiovascular Disease After Involved Node Radiotherapy Versus Mantle Field for Hodgkin Lymphoma

PURPOSE Hodgkin lymphoma (HL) survivors are known to have increased cardiac mortality and morbidity. The risk of developing cardiovascular disease after involved node radiotherapy (INRT) is currently unresolved, inasmuch as present clinical data are derived from patients treated with the outdated mantle field (MF) technique. METHODS AND MATERIALS We included all adolescents and young adults with supradiaphragmatic, clinical Stage I-II HL treated at our institution from 2006 to 2010 (29 patients). All patients were treated with chemotherapy and INRT to 30 to 36 Gy. We then simulated a MF plan for each patient with a prescribed dose of 36 Gy. A logistic dose-response curve for the 25-year absolute excess risk of cardiovascular disease was derived and applied to each patient using the individual dose-volume histograms. RESULTS The mean doses to the heart, four heart valves, and coronary arteries were significantly lower for INRT than for MF treatment. However, the range in doses with INRT treatment was substantial, and for a subgroup of patients, with lymphoma below the fourth thoracic vertebrae, we estimated a 25-year absolute excess risk of any cardiac event of as much as 5.1%. CONCLUSIONS Our study demonstrates a potential for individualizing treatment by selecting the patients for whom INRT provides sufficient cardiac protection for current technology; and a subgroup of patients, who still receive high cardiac doses, who would benefit from more advanced radiation technique.

Quality Indicators for Breast Cancer: Revisiting Historical Evidence in the Context of Technology Changes

Radiation therapy for breast cancer has considerably changed over the years, from simple simulator-based 2-dimensional techniques to sophisticated image-guided individualized treatments, with maximally protected normal structures. This has led to a substantial improvement in the outcome of breast cancer patients in terms of disease control, survival, and quality of life. This progress is based on clinical research and paralleled by progress in delivering sophisticated radiation treatment. Clinical trials resulted in identifying patients groups who will benefit from radiation treatment. They also stimulated the development of quality assurance tools and guidelines, which are now applied in daily clinical practice. The new technical opportunities to optimize dose distributions in patients require dedicated quality assurance measures because they may be more sensitive to variations throughout the treatment. Still, a large source of variation and uncertainty in radiation therapy remains in the definition of target volumes, which is clinically significant in terms of dosimetric target coverage as well as exposure of healthy tissues. This striving for continuous improvement of patient selection and treatment will lead to further improvement of local control while at the same time improving functional and cosmetic outcome and avoiding severe late complications, including cardiac toxicity.

Recurrences after intensity modulated radiotherapy for head and neck squamous cell carcinoma more likely to originate from regions with high baseline [18F]-FDG uptake.

BACKGROUND AND PURPOSE To analyze the recurrence pattern in relation to target volumes and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemoradiation. MATERIAL AND METHODS 520 patients received radiotherapy for HNSCC from 2005 to 2009. Among 100 patients achieving complete clinical response and a later recurrence, 39 patients with 48 loco-regional failures had a recurrence CT scan before any salvage therapy. The estimated point of origin of each recurrence was transferred to the planning CT by deformable image co-registration. The recurrence position was then related to the delineated target volumes and iso-SUV-contours relative to the maximum standard uptake value (SUV). We defined the recurrence density as the total number of recurrences in a sub-volume divided by the sum of that volume for all patients. RESULTS 54% (95% CI 37-69%) of recurrences originated inside the FDG-positive volume and 96% (95% CI 86-99%) in the high dose region. Recurrence density was significantly higher in the central target volumes (P<0.0001) and increased with increasing FDG avidity (P=0.036). CONCLUSIONS The detailed pattern-of-failure data analysis suggests that most recurrences occur in the FDG PET positive areas or the solid tumor.

Life years lost—comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale

The authors developed a framework for estimating and comparing the risks of various long‐term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma.

Evaluation of dose to cardiac structures during breast irradiation

OBJECTIVE Adjuvant radiotherapy for breast cancer can lead to late cardiac complications. The highest radiation doses are likely to be to the anterior portion of the heart, including the left anterior descending coronary artery (LAD). The purpose of this work was to assess the radiation doses delivered to the heart and the LAD in respiration-adapted radiotherapy of patients with left-sided breast cancer. METHODS 24 patients referred for adjuvant radiotherapy after breast-conserving surgery for left-sided lymph node positive breast cancer were evaluated. The whole heart, the arch of the LAD and the whole LAD were contoured. The radiation doses to all three cardiac structures were evaluated. RESULTS For 13 patients, the plans were acceptable based on the criteria set for all 3 contours. For seven patients, the volume of heart irradiated was well below the set clinical threshold whereas a high dose was still being delivered to the LAD. In 1 case, the dose to the LAD was low while 19% of the contoured heart volume received over 20 Gy. In five patients, the dose to the arch LAD was relatively low while the dose to the whole LAD was considerably higher. CONCLUSION This study indicates that it is necessary to assess the dose delivered to the whole heart as well as to the whole LAD when investigating the acceptability of a breast irradiation treatment. Assessing the dose to only one of these structures could lead to excessive heart irradiation and thereby increased risk of cardiac complications for breast cancer radiotherapy patients.