Christina Armpilia

Hypofractionated accelerated irradiation for stage I-II breast carcinoma: a phase II study.

To the Editor: There is no daily standard and total tumor dose for breast irradiation. The schedule that is commonly used in clinical practice is 50Gy in 25 daily fractions (Monday to Friday) with the optional addition of a boost to the primary site of 10-16Gy (1). Radiobiologic modeling can be used to compare different fractionation schedules by achieving the same biologically effective dose (2). The biological effective dose (BED) is regarded as a measure of the true biological dose delivered by a particular combination of dose per fraction and total dose to a given tissue characterized by a specific a ⁄b ratio value. The ratio a ⁄b is an inverse measure of the fractionation sensitivity of the tissue in question. The tumor control BED values were determined using a a ⁄b value of either 4 Gy, which has been suggested for breast carcinoma (3,4) or 10 Gy and is the approximate value used for most tumors (3). Biological effective dose calculations were also performed for normal tissue endpoints such as breast fibrosis, skin telangiectasia (late reacting tissues), and erythema (acute reacting tissue) using an a ⁄b value based on those reported in the previous studies (5). These values were 2.5, 4.0, and 8.0, respectively. Concerns that have been raised in the literature about rapid fractionation schedules related to two issues: the association of a large dose per fraction with the increased risk of late normal tissue toxicity and the reduction in total dose and potential for decreased effect on tumor control. The first concern arises from reports in older, retrospective case series (6). These studies were poorly controlled. They used older radiation therapy techniques. The radiation therapy was delivered with large dose per fractions (‡ 3 Gy) without reduction in the overall total dose. Radiobiologic models predict that normal tissue toxicity is not increased when the increase in fraction size is the modest and the total dose is reduced (7). Similar models also suggest that rapid schedules may be equally efficacious if the reduction in total dose is accompanied by a shorter overall treatment time or if the tumor is more sensitive to a larger daily dose. This approach is supported by data from randomized trials that compared hypofractionated radiation therapy with more conventional radiation therapy in women with early breast cancer (6). In these three trials, no difference was detected in late radiation morbidity or local recurrence. In this study, radiation therapy was delivered by a modern approach. All patients received radiotherapy at a total tumor dose of 53 Gy (EQD2 60 Gy), 265cGy per fraction, in 20 fractions, over 25 days. Acute and late effects as well as cosmetic results were assessed using the European Organisation for Research and Treatment of cancer (RTOG-EORTC) Cosmetic Rating System. For follow-up purposes, mammograms were performed before radiotherapy, six months after the end of treatment and yearly thereafter. The recovery from the acute radiation toxicity is shown in Table 1. A total of 90.7% of women presented grade 0 side effects in 6 months, and the 100% of women recovered completely 2 years after radiotherapy. The mammograms indicated that changes were more prominent in periareolar and the inferior portions of breast. We noticed increased density and thickening of trabecula and skin 6 months after RT. Changes usually resolved within 1–2 years. Approximately, 20% of women had a grade 1 residual skin thickening 2 years after radiotherapy. Skin thickening is a factor in the overall increased density of breast after radiotherapy. Address correspondence and reprint requests to: Anna G. Zygogianni, MD, Aretaieion Hospital, University of Athens – Radiology, Radiation Oncology Section, Vas. Sophias 76, Athens 11528, Greece, or e-mail: annaz1@otenet.gr.

A review on radiotherapy hypofractionation schedules for breast cancer treatment

Radiation therapy is an integral part of management in breast carcinoma treatment. Standard curative schedules of radiotherapy to the breast deliver 25 fractions of 2.0 Gy per day over 5–6 weeks. Considerable recent literature suggests that hypo-fractionation may be advisory in breast cancer. The use of fewer fractions of more than 2 Gy per day (hypo-fractionation) is based on data suggesting that breast carcinoma is more sensitive to fraction size than squamous carcinomas and therefore could have similar fractionation sensitivity to the dose-limiting healthy tissues, including skin, subcutaneous tissues, muscle and ribs. In this article, a review of published studies and currently ongoing trials, which may provide evidence for the use of hypo-fractionated radiotherapy in breast cancer patients, is presented. Also, for all these different hypo-fractionation regimens found in literature, biologically effective dose (BED) values are calculated and compared. Data from studies and randomised trials seem to support the concept that modest hypo-fractionation can be used to treat the whole breast after breast-conserving surgery with similar rates of local control and radiation morbidity as seen with conventional fractionation.

The Impact of Intermediate Time between Chemotherapy and Hypofractionated Radiotherapy to the Radiation Induced Skin Toxicity for Breast Adjuvant Treatment

To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty‐four patients with stage I–II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose‐EQD2‐ 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow‐up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late‐toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy.

Comparison of Two Radiotherapeutic Hypofractionated Schedules in the Application of Tumor Bed Boost

AIM Evaluation of related radiation toxicity and efficacy in terms of local control of 2 radiotherapeutic hypofractionated schedules in the application of tumor bed boost by using 2 different planning techniques. METHOD Eighty-one patients with stage I-II disease were retrospectively selected with either concomitant (group A) or sequential (group B) boost for the tumor bed. In group A, 27 patients were treated with a total dose of 46 Gy to the whole breast and 54 Gy to the tumor bed in 20 concomitant fractions. In group B, 54 patients were treated with a total dose of 42.4 Gy in 16 fractions to the whole breast and 53 Gy to the tumor bed by 4 sequential fractions. The boost was administered with multiple photon-beam fields. The median follow-up time was 24 months. RESULTS The statistical analysis for the 2 groups of the study showed that skin toxicity was significantly worse in group A (P < .05, Kruskal-Wallis H test). For groups A and B at the completion of radiation therapy, grade 1 skin toxicity was observed in 18/27 patients (66.6%) and 13/54 patients (24.1%), respectively, whereas grade 2/3 was observed in 9/27 patients (33.3%) vs. 5/54 patients (9.3%), respectively (P < .001). One year after irradiation, in group A and in group B, the skin toxicity was of grade 1 in 6/27 patients (22.2%) vs. 2/54 patients (3.7%), respectively (P = .008). Within 2 years, the breast returned to its original form in all patients. No patient showed local disease recurrence. CONCLUSIONS The accelerated hypofractionated schedules in the application of the tumor bed boost by using the 2 different planning techniques appears to be effective and well tolerated.

Clinical implications of in silico mathematical modeling for glioblastoma: a critical review

Glioblastoma remains a clinical challenge in spite of years of extensive research. Novel approaches are needed in order to integrate the existing knowledge. This is the potential role of mathematical oncology. This paper reviews mathematical models on glioblastoma from the clinical doctor’s point of view, with focus on 3D modeling approaches of radiation response of in vivo glioblastomas based on contemporary imaging techniques. As these models aim to provide a clinically useful tool in the era of personalized medicine, the integration of the latest advances in molecular and imaging science and in clinical practice by the in silico models is crucial for their clinical relevance. Our aim is to indicate areas of GBM research that have not yet been addressed by in silico models and to point out evidence that has come up from in silico experiments, which may be worth considering in the clinic. This review examines how close these models have come in predicting the outcome of treatment protocols and in shaping the future of radiotherapy treatments.

MLC positional accuracy evaluation through the Picket Fence test on EBT2 films and a 3D volumetric phantom

The accuracy of MLC positions during radiotherapy is important as even small positional deviations can translate into considerable dose delivery errors. This becomes crucial when radiosensitive organs are located near the treated volume and especially during IMRT, where dose gradients are steep. A test commonly conducted to measure the positional accuracy of the MLCs is the Picket Fence test. In this study two alterations of the Picket Fence test were performed and evaluated, the first one using radiochromic EBT2 films and the second one the Delta4PT diode array phantom and its software. Our results showed that EBT2 films provide a relatively fast, qualitative visual inspection of the significant leaf dispositions. When slight inaccuracies need to be revealed or precise numerical results for each leaf position are needed, Delta4PT provides the desired accuracy of 1 mm. In treatment modalities where a higher accuracy is required in the delivered dose distribution, such as in IMRT, precise numerical values of the measurements for the MLC positional inspection are required. PACS number: 87.55.Qr, 87.56.bd, 87.56.Fc, 87.56.nk

Bilateral primary breast Burkitt's lymphoma.

VP shunt and placing a new one, if still indicated, in an alternative subcutaneous tunnel. Due to the patient’s age, dementia, and her presentation, an aggressive course with surgery, chemotherapy and radiation was deemed not appropriate at this time. She will be treated with an aromatase inhibitor and follow up for any additional symptoms. Breast cancer involving VP shunt is a rare finding, and this is the first reported case in the literature. It is uncertain whether the superficial nature of this particular VP shunt attracted a deposit site for synchronous metastasis. This case also demonstrates the importance of investigational imaging required in a patient with limited history with dementia.

[P148] Evaluation of delta4 phantom’s spatial sensitivity

Purpose The aim of this study is to evaluate the spatial sensitivity of the Delta4 diode array phantom (Scandidos, Uppsala, Sweden) investigating how set up errors affect the measurement’s results during head and neck treatment plan verification. Method The Delta4 phantom is used to verify ten IMRT head and neck plans, created on Oncentra v4.5.2 (Nucletron, Elekta) treatment planning system. Patient plans were transferred to the Delta4 geometry and were delivered on a 6MV photon beam SIEMENS Oncor Impression linac. Each reference (no-shift) plan was then delivered on the linac with a ± 3 mm shift of the phantom at lateral, longitudinal and vertical direction. The measurements’ results for all delivered plans were evaluated using the gamma index criteria (3%/3 mm). The application of the treatment plan is considered successful with an over 90% gamma index passing rate. Results The gamma index passing rate was measured at no-shift position (96.1  ±  0.7) %. Mean gamma index for each direction (lateral, longitudinal, vertical) was measured as 85.5% (SD = 2.6), 85.7% (SD = 4.5) and 85.2% (SD = 4.5) respectively. For all shifts, in all directions, the mean gamma index passing rate was found enough below the passing rate limit of 90% and more specifically 10.6% less than the no-shift measured gamma index. Conclusion Delta4 is an efficient QA tool for individual patient treatment plan verification exhibiting high reproducibility of results for γ -index. Shifts of 3 mm reveal significant deviation of measured 3%/3 mm gamma index passing rates, indicating high spatial sensitivity and efficiency of this QA tool. Future work with 3DVH software analysis is needed to report more statistics apart from γ -index values.

Evaluation of intensity modulated radiation therapy delivery system using a volumetric phantom on the basis of the task group 119 report of american association of physicists in medicine

The current work describes the implementation of the American Association of Physicists in Medicine (AAPM)s Task Group 119 report on a volumetric phantom (Delta4, Scandidos, Uppsala, Sweden) following the stated dose goals, to evaluate the step-and-shoot intensity modulated radiation therapy (IMRT) system. Delta4 consists of diode detectors, lying on two crossed planes, measuring the delivered dose, and providing two-dimensional dosimetric information. Seven plans of different goals and complexity were performed, with individual structure sets. TG199 structure sets and plans were transferred and implemented on the Delta4 phantom taking into account its cylindrical geometry. All plans were delivered with a 6 MV linear accelerator equipped with multileaf collimator of 1 cm thickness. Plan results for each test met the recommended dose goals. The evaluation was performed in terms of dose deviation, distance to agreement, and gamma index passing rate. In all test cases, the gamma index passing rate was measured >90%. Delta4 phantom has proven to be fast, applicable, and reliable for the step-and-shoot IMRT commissioning following TG119s recommended tests. Although AAPMs TG119 report is referring to the implementation of test plans that do not correspond to patient plans, it could be used as an evaluation tool of various IMRT systems, considering the local treatment planning system and the delivery system.

A Retrospective Analysis of Toxicity and Efficacy for 2 Hypofractionated Irradiation Schedules Versus a Conventional One for Post-Mastectomy Adjuvant Radiotherapy in Breast Cancer

Introduction: The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients. Methods: 3 irradiation schedules were analyzed: 48.30 Gy in 21 fractions (group A, n = 60), 42.56 Gy in 16 fractions (group B, n = 27) and 50 Gy in 25 fractions (group C, n = 30) of the front chest wall. All groups were also treated with a supraclavicular field, with 39.10 Gy in 17 fractions (group A), 37.24 Gy in 14 fractions (group B) or 45 Gy in 25 fractions (group C). Results: No local recurrences were noted in any group during 36 months of follow-up. Acute skin toxicity presented in all groups, with 58.3%, 70.4% and 60% of grade I; 35%, 25.9% and 40% of grade II; 6.7%, 3.7% and 0% of grade III being seen in groups A, B and C, respectively. Late skin toxicity was noted only as grade I in 16.7%, 25.9% and 26.7% of groups A, B and C, respectively. No significant difference was noted among all groups for either acute or late skin toxicity, or for radio-pneumonitis (chi2 test, p > 0.05). Conclusion: All schedules were equally effective with equivalent toxicity. A prospective randomized study is needed to confirm our results.