Consensus statement on tumour bed localization for radiation after oncoplastic breast surgery.

Background: Oncoplastic surgery (ops) is becoming the new standard of care for breast-conserving surgery, leading to some challenges with adjuvant radiation, particularly when accurate tumour bed (tbd) delineation is needed for focused radiation (that is, accelerated partial breast irradiation or boost radiation). Currently, no guidelines have been published concerning tbd localization for adjuvant targeted radiation after ops. Methods: A modified Delphi method was used to establish consensus by a panel of 20 experts in surgical and radiation oncology at the Canadian Locally Advanced Breast Cancer National Consensus Group and in a subsequent online member survey. Results: These are the main recommendations:■ Surgical clips are necessary and should, at a minimum, be placed along the 4 side walls of the cavity, plus 1-4 clips at the posterior margin if necessary.■ Operative reports should include pertinent information to help guide the radiation oncologists.■ Breast surgeons and radiation oncologists should have a basic understanding of ops techniques and work on "speaking a common language."■ Careful consideration is needed when determining the value of targeted radiation, such as boost, in higher-level ops procedures with extensive tissue rearrangement. Conclusions: The panel developed a total of 6 recommendations on tbd delineation for more focused radiation therapy after ops, with more than 80% agreement on each statement. All are summarized, together with the corresponding evidence or expert opinion.

Exploring reasons for overuse of contralateral prophylactic mastectomy in Canada.

Background: Contralateral prophylactic mastectomy (cpm) in women with known unilateral breast cancer (bca) has been increasing despite the lack of supportive evidence. The purpose of the present study was to identify the determinants of cpm in women with unilateral bca. Methods: This qualitative descriptive study used semi-structured interviews informed by the Theoretical Domains Framework. We interviewed 74 key informants (surgical oncologists, plastic surgeons, medical oncologists, radiation oncologists, nurses, women with bca) across Canada. Interviews were analyzed using thematic analysis and an analysis for shared and discipline-specific beliefs. Results: In total, 58 factors influencing the use of cpm were identified: 26 factors shared by various health care professional groups, 15 discipline-specific factors (identified by a single health care professional group), and 17 factors shared by women with unilateral bca. Health care professionals identified more factors discouraging the use of cpm (n = 26) than encouraging its use (n = 15); women with bca identified more factors encouraging use of cpm (n = 12) than discouraging its use (n = 5). The factor most commonly identified by health care professionals that encouraged cpm was lack of awareness of existing evidence or guidelines for the appropriate use of cpm (n = 44, 75%). For women with bca, the factor most likely influencing their decision for cpm was wanting a better esthetic outcome (n = 14, 93%). Conclusions: Multiple factors discouraging and encouraging the use of cpm in unilateral bca were identified. Those factors identify potential individual, team, organization, and system targets for behaviour change interventions to reduce cpm.

Patient decision aid for contralateral prophylactic mastectomy for use in the consultation: a feasibility study.

Background: Rates of contralateral prophylactic mastectomy (cpm) continue to rise internationally despite evidence-based guidance strongly discouraging its use in most women with unilateral breast cancer. The purpose of the present study was to develop and assess the feasibility of a knowledge translation tool [a patient decision aid (da)] designed to enhance evidence-informed shared decision-making about cpm. Methods: A consultation da was developed using the Ottawa Patient Decision Aid Development eTraining in consultation with clinicians and knowledge translation experts. The final da was then assessed for feasibility with health care professionals and patients across Canada. The assessment involved a survey completed online (health care professionals) or by telephone (patients). Survey data were analyzed using descriptive statistics for closed-ended questions and qualitative content analysis for open-ended questions. Results: The 51 participants who completed the survey included 39 health care professionals and 12 patients. The da was acceptable; 88% of participants viewed it as having the right amount of information or slightly more or less information than they would like. Almost all participants (98%) felt that the da would prepare patients to make better decisions. The aid was perceived to be usable, with 73% of participants stating that they would be willing to use or share the da. Conclusions: The cpm patient da developed for the present study was viewed by health care professionals and patients across Canada to be acceptable and usable during the clinical consultation. It holds promise as a knowledge translation tool to be used by clinicians in consultation with women who have unilateral breast cancer to enhance evidence-informed and shared decision-making with respect to undergoing cpm.

Optimal sequence of adjuvant endocrine and radiation therapy in early-stage breast cancer - A systematic review.

IMPORTANCE: Clinical equipoise exists around the optimal time to start adjuvant endocrine therapy in patients who will receive post-operative radiotherapy for breast cancer. Concerns continue to exist regarding potential reduced efficacy, or increased toxicity, when radiation, and endocrine therapy are administered concurrently. OBJECTIVE: To perform a systematic review of studies comparing outcomes between sequential and concurrent adjuvant radiation and endocrine therapy in early-stage breast cancer. All modalities of radiation therapy were considered, and endocrine therapy could be either tamoxifen or an aromatase inhibitor. Outcomes of interest included; local, regional or distant recurrence, overall survival and treatment-related toxicities. EVIDENCE REVIEWED: PubMed, Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1946 to December 2017. Two reviewers independently assessed each citation using the criteria outlined above. Study quality was assessed using the Cochrane Collaboration's tool for prospective studies, and the Newcastle-Ottawa scale for retrospective studies. FINDINGS: Of 2137 unique citations identified, 13 met eligibility criteria. Eleven were unique studies (7569 patients), while 2 of the studies were updated analyses of previous studies. Studies evaluated the timing of adjuvant radiation, and tamoxifen (5 studies, 1550 patients), or aromatase inhibitors (6 studies, 6019 patients). We identified 1 complete randomized clinical trial (150 patients), and 5 retrospective studies (1580 patients), in addition to conference abstracts (5 studies, 5839 patients). Overall, none of the studies showed a significant difference in efficacy, or toxicity, with concurrent versus sequential treatment. However, given the significant heterogeneity of the study populations, it was not possible to conduct a meta-analysis. CONCLUSIONS AND RELEVANCE: In the absence of high quality data, adequately powered randomized trials are required to answer this important clinical question.

Pre-operative versus post-operative radiosurgery for brain metastasis: Effects on treatment volume and inter-observer variability.

PURPOSE/OBJECTIVES: Compared to post-operative whole brain radiotherapy, resection cavity radiosurgery reduces impact on neuro-cognitive function and improves quality-of-life. However, coverage of the operative tract, in addition to tumour bed, may lead to large treatment volumes and inter-observer variability. We hypothesized that pre-operative radiosurgery reduces target volume size and inter-observer variability compared to post-operative radiosurgery. MATERIALS/METHODS: We identified 10 consecutive patients, with solitary brain metastasis, treated with post-operative cavity radiosurgery.Pre- and post-operative axial T1 contrast MRI were co-registered with the planning CT scans. Three radiation oncologists independently contoured the target volumes on the pre- and post-operative imaging. A 2mm-PTV margin was utilized for both strategies and radiosurgery treatment plans were generated. The following parameters were evaluated in the 2 plans: Mean target volume (cc), 50% isodose volume (cc), Inter-observer variability (Jaccard Index JI) and Conformity Index (CI). RESULTS: There was no significant difference in the mean target volume, nor 50% isodose volume, between pre- and post-operative strategies. (17.6 (95% CI 9.98 - 25.22) versus 19.4 (95% CI 10.11 - 28.69) cc, P=0.80; 61.7 (95% CI 38.4 - 85.0) vs 77.7 (95% CI 34.94 - 120.46) cc, P=0.65). There was significantly less inter-observer variability and improved conformity in the pre-operative group (Mean JI 0.84(95% CI 0.82 - 0.86) versus 0.70 (95% CI 0.62 - 0.78), P = 0.005; Mean CI 1.32 (95% CI 1.26 - 1.38) vs 1.45 (95% CI 1.36 - 1.54), P= 0.01). Planned subgroup analysis did not reveal any significant difference (between pre- vs post-op) in the mean volume of cystic versus non-cystic metastasis. Deep lesions (>2.5cm from dura) had a larger post-operative target volume (25.8 (95% CI 15.1 - 36.5) vs 12.3 (95% CI 6.54 - 18.06) cc, P=0.06) compared to superficial lesions. CONCLUSION: Pre-operative radiosurgery has less inter-observer variability and improved plan conformity. However, there was no difference in mean target volume between the pre- versus post-operative radiation. Contouring guidelines, and peer review, may help to reduce inter-observer variability for cavity radiosurgery.

Patient-specific Monte Carlo dose calculations for (103)Pd breast brachytherapy.

This work retrospectively investigates patient-specific Monte Carlo (MC) dose calculations for (103)Pd permanent implant breast brachytherapy, exploring various necessary assumptions for deriving virtual patient models: post-implant CT image metallic artifact reduction (MAR), tissue assignment schemes (TAS), and elemental tissue compositions. Three MAR methods (thresholding, 3D median filter, virtual sinogram) are applied to CT images; resulting images are compared to each other and to uncorrected images. Virtual patient models are then derived by application of different TAS ranging from TG-186 basic recommendations (mixed adipose and gland tissue at uniform literature-derived density) to detailed schemes (segmented adipose and gland with CT-derived densities). For detailed schemes, alternate mass density segmentation thresholds between adipose and gland are considered. Several literature-derived elemental compositions for adipose, gland and skin are compared. MC models derived from uncorrected CT images can yield large errors in dose calculations especially when used with detailed TAS. Differences in MAR method result in large differences in local doses when variations in CT number cause differences in tissue assignment. Between different MAR models (same TAS), PTV [Formula: see text] and skin [Formula: see text] each vary by up to 6%. Basic TAS (mixed adipose/gland tissue) generally yield higher dose metrics than detailed segmented schemes: PTV [Formula: see text] and skin [Formula: see text] are higher by up to 13% and 9% respectively. Employing alternate adipose, gland and skin elemental compositions can cause variations in PTV [Formula: see text] of up to 11% and skin [Formula: see text] of up to 30%. Overall, AAPM TG-43 overestimates dose to the PTV ([Formula: see text] on average 10% and up to 27%) and underestimates dose to the skin ([Formula: see text] on average 29% and up to 48%) compared to the various MC models derived using the post-MAR CT images studied herein. The considerable differences between TG-43 and MC models underline the importance of patient-specific MC dose calculations for permanent implant breast brachytherapy. Further, the sensitivity of these MC dose calculations due to necessary assumptions illustrates the importance of developing a consensus modelling approach.

Role of hypofractionated radiotherapy in breast locoregional radiation.

Long-term results of randomised trials have confirmed the safety and efficacy of hypofractionated radiotherapy using approximately 2.6 Gy per fraction to lower total doses of 40-42.6 Gy delivered over 3 weeks, for postoperative treatment of early breast cancer. In these trials, hypofractionated radiotherapy was predominantly used for breast only treatment, while there are fewer trials that specifically examined hypofractionated radiotherapy to the breast plus regional nodes. Hypofractionated locoregional radiation is considered a standard of care in the United Kingdom and in some parts of Canada. We aim to review the radiobiology and normal tissue effects of hypofractionated locoregional radiation and to summarize available published clinical experiences using this treatment strategy as adjuvant therapy after breast conserving surgery or mastectomy for women with early breast cancer.

Preoperative prognostic value of dynamic contrast-enhanced MRI-derived contrast transfer coefficient and plasma volume in patients with cerebral gliomas.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging-derived plasma volume obtained in tumor and the contrast transfer coefficient has not been well-established in patients with gliomas. We determined whether plasma volume and contrast transfer coefficient in tumor correlated with survival in patients with gliomas in addition to other factors such as age, type of surgery, preoperative Karnofsky score, contrast enhancement, and histopathologic grade. MATERIALS AND METHODS: This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. The contrast transfer coefficient and plasma volume obtained in tumor maps were calculated directly from the signal-intensity curve without T1 measurements, and values were obtained from multiple small ROIs placed within tumors. Survival curve analysis was performed by dichotomizing patients into groups of high and low contrast transfer coefficient and plasma volume. Univariate analysis was performed by using dynamic contrast-enhanced parameters and clinical factors. Factors that were significant on univariate analysis were entered into multivariate analysis. RESULTS: For all patients with gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). In subgroups of high- and low-grade gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). Univariate analysis showed that factors associated with lower survival were age older than 50 years, low Karnofsky score, biopsy-only versus resection, marked contrast enhancement versus no/mild enhancement, high contrast transfer coefficient, and high plasma volume obtained in tumor (P < .05). In multivariate analysis, a low Karnofsky score, biopsy versus resection in combination with marked contrast enhancement, and a high contrast transfer coefficient were associated with lower survival rates (P < .05). CONCLUSIONS: In patients with glioma, those with a high contrast transfer coefficient have lower survival than those with low parameters.

Excision of the primary tumour in patients with metastatic breast cancer: a clinical dilemma.

BACKGROUND: Approximately 10% of new breast cancer patients will present with overt synchronous metastatic disease. The optimal local management of those patients is controversial. Several series suggest that removal of the primary tumour is associated with a survival benefit, but the retrospective nature of those studies raises considerable methodologic challenges. We evaluated our clinical experience with the management of such patients and, more specifically, the impact of surgery in patients with synchronous metastasis. METHODS: We reviewed patients with primary breast cancer and concurrent distant metastases seen at our centre between 2005 and 2007. Demographic and treatment data were collected. Study endpoints included overall survival and symptomatic local progression rates. RESULTS: The 111 patients identified had a median follow-up of 40 months (range: 0.6-71 months). We allocated the patients to one ot two groups: a nonsurgical group (those who did not have breast surgery, n = 63) and a surgical group (those who did have surgery, n = 48, 29 of whom had surgery before the metastatic diagnosis). When compared with patients in the nonsurgical group, patients in the surgical group were less likely to present with T4 tumours (23% vs. 35%), N3 nodal disease (8% vs. 19%), and visceral metastasis (67% vs. 73%). Patients in the surgical group experienced longer overall survival (49 months vs. 33 months, p = 0.01) and lower rates of symptomatic local progression (14% vs. 44%, p < 0.001). CONCLUSIONS: In our study, improved overall survival and symptomatic local control were demonstrated in the surgically treated patients; however, this group had less aggressive disease at presentation. The optimal local management of patients with metastatic breast cancer remains unknown. An ongoing phase iii trial, E2108, has been designed to assess the effect of breast surgery in metastatic patients responding to first-line systemic therapy. If excision of the primary tumour is associated with a survival benefit, then the preselected subgroup of patients who have responded to initial systemic therapy is the desired population in which to put this hypothesis to the test.

Diagnostic accuracy of dynamic contrast-enhanced MR imaging using a phase-derived vascular input function in the preoperative grading of gliomas.

BACKGROUND AND PURPOSE: The accuracy of tumor plasma volume and K(trans) estimates obtained with DCE MR imaging may have inaccuracies introduced by a poor estimation of the VIF. In this study, we evaluated the diagnostic accuracy of a novel technique by using a phase-derived VIF and "bookend" T1 measurements in the preoperative grading of patients with suspected gliomas. MATERIALS AND METHODS: This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. Both magnitude and phase images were acquired during DCE MR imaging for estimates of K(trans)_φ and V(p_)φ (calculated from a phase-derived VIF and bookend T1 measurements) as well as K(trans)_SI and V(p_)SI (calculated from a magnitude-derived VIF without T1 measurements). RESULTS: Median K(trans)_φ values were 0.0041 minutes(-1) (95 CI, 0.00062-0.033), 0.031 minutes(-1) (0.011-0.150), and 0.088 minutes(-1) (0.069-0.110) for grade II, III, and IV gliomas, respectively (P ≤ .05 for each). Median V(p_)φ values were 0.64 mL/100 g (0.06-1.40), 0.98 mL/100 g (0.34-2.20), and 2.16 mL/100 g (1.8-3.1) with P = .15 between grade II and III gliomas and P = .015 between grade III and IV gliomas. In differentiating low-grade from high-grade gliomas, AUCs for K(trans)_φ, V(p_φ), K(trans)_SI, and V(p_)SI were 0.87 (0.73-1), 0.84 (0.69-0.98), 0.81 (0.59-1), and 0.84 (0.66-0.91). The differences between the AUCs were not statistically significant. CONCLUSIONS: K(trans)_φ and V(p_)φ are parameters that can help in differentiating low-grade from high-grade gliomas.

Towards an accurate and robust method based on fuzzy logic principles for the reconstruction and quantification of large volumes from MR and CT images.

The authors have previously evaluated a new method of volume reconstruction and quantification from MR images, based on fuzzy logic (FL) principles. The technique is evaluated here for larger and more complex structures by investigating its accuracy and robustness using MR and CT images. Four large (50-71 cm(3)) and complex (e.g. mimicking a prostate) structures were created and imaged on MR and CT scanners, both with increasing slice thickness. Contours were delineated to generate 112 volumes. MR and CT images were processed using the FL method and a "classical" method of reconstruction on research software. In addition, the CT images were also processed on commercial virtual simulation software. Calculated volumes were compared with actual volumes. The mean +/- standard deviation of the relative variations in calculated target volume using the FL method was found to be 4.4%+/-2.8%, whereas with the "classical" method it was 23.7%+/-6% from axial MR images and 23.3%+/-9.8% from CT images. With the "classical" method, the relative variations in calculated volumes rise with increasing slice thickness, and the displayed volumes show deformations in the longitudinal direction. With the FL method, the volume calculation is not sensitive to the slice thickness and so the deformations are minimal. When used with MR images, our FL method of volume reconstruction is accurate and robust with respect to changes in slice thickness. For CT images, the results are encouraging but some work is still needed to improve the accuracy of the FL method.

Poster - Thurs Eve-30: Investigation of a patient immobilization system for breast tomotherapy.

Using tomotherapy to deliver adjuvant radiation therapy for breast cancer treatment requires more precise immobilization than can be achieved using gravity alone. We evaluated the use of a thermoplastic shell to immobilize the patient's torso during breast cancer treatment. To measure intrafraction breathing motion, 4DCT scans were performed for eight post-lumpectomy or post-mastectomy breast cancer patients with the thermoplastic shell in place. The 4DCT scans were then analyzed to determine the magnitude of motion of the breast surface, chest wall, and heart over the breathing cycle. Maximum surface motion was typically less than 2mm, with a maximum of 4mm. Maximum displacement of the chest wall was less than 3mm with a maximum of 5mm in a single patient. Comparison with the setup errors recorded prior to repositioning the patients suggests that, with the thermoplastic shell in place, patient setup error will be a more significant source of uncertainty in patient position than breathing motion.

Clinical use of a commercial Monte Carlo treatment planning system for electron beams.

In 2002 we fully implemented clinically a commercial Monte Carlo based treatment planning system for electron beams. The software, developed by MDS Nordion (presently Nucletron), is based on Kawrakow's VMC++ algorithm. The Monte Carlo module is integrated with our Theraplan Plustrade mark treatment planning system. An extensive commissioning process preceded clinical implementation of this software. Using a single virtual 'machine' for each electron beam energy, we can now calculate very accurately the dose distributions and the number of MU for any arbitrary field shape and SSD. This new treatment planning capability has significantly impacted our clinical practice. Since we are more confident of the actual dose delivered to a patient, we now calculate accurate three-dimensional (3D) dose distributions for a greater variety of techniques and anatomical sites than we have in the past. We use the Monte Carlo module to calculate dose for head and neck, breast, chest wall and abdominal treatments with electron beams applied either solo or in conjunction with photons. In some cases patient treatment decisions have been changed, as compared to how such patients would have been treated in the past. In this paper, we present the planning procedure and some clinical examples.

[In vivo dosimetry and radiation therapy of breast cancer]. / Dosimétrie in vivo et radiothérapie des cancers du sein.

INTRODUCTION: Verification of absorbed dose in target volume is a key factor for quality assurance in radiotherapy. In vivo measurements allow evaluation of the variations in dose with time and variations between measured doses and calculated doses by TPS. The aim of this work were to evaluate reproducibility of patient positioning and to compare calculated doses by 2 different TPS. PATIENTS AND METHODS: Twenty patients were divided in 2 groups according to the thickness of their breast (mean SSD = 92.9 cm). In vivo measurement was performed within the first two sessions. RESULTS: Reproducibility of SSD evaluation was made on 12 beams between 2 fractions. With a tolerance margin of 0.5 cm, positioning errors were present in 33% (4/12). The 2 TPS were in agreement in 75% (30/40). CONCLUSION: In vivo dosimetry can be a very interesting tool to assess patients positioning variations and TPS dose calculation.

[Comparison of conventional and conformational dosimetry in radiotherapy of cerebral neoplasms]. / Comparaison entre dosimétries classique et conformationnelle dans l'irradiation de tumeurs cérébrales.

PURPOSE: We prospectively compared a conventional treatment planning (PT2D) and 3-dimensional conformal treatment planning (PT3D) for radiotherapy of cerebral tumours. PATIENTS AND METHODS: Patients treated between 1/10/98 and 1/4/99 by irradiation for cerebral tumours were analysed. For each case, we planned PT2D using conventional orthogonal x-ray films, and afterward, PT3D using CT scan. Gross tumor volume, planning target volume and normal tissue volumes were defined. Dose was prescribed according to report 50 of the International Commission on Radiation Units and Measurements (ICRU). We compared surfaces of sagittal view targets defined on PT2D and PT3D and called them S2D and S3D, respectively. Irradiated volumes by 90% isodoses (VE-90%) and normal tissue volumes irradiated by 20, 50, 90% isodoses were calculated and compared using Student's paired t-test. RESULTS: There was a concordance of 84% of target surfaces defined on PT2D and PT3D. Percentages of target surface under- or-over defined by PT2D were 16 and 13% respectively. VE-90% was decreased by 15% (p = 0.07) with PT3D. Normal brain volume irradiated by 90% isodose was decreased by 27% with PT3D (p = 0.04). CONCLUSION: For radiotherapy of cerebral tumors using only coplanar beams, PT3D leads to a reduction of normal brain tissue irradiated. We recommend PT3D for radiotherapy of cerebral tumors, particularly for low-grade or benign tumors (meningiomas, neuromas, etc.).

[Progress in dosage optimization for stereotactic radiosurgery]. / Progrès en optimisation dosimétrique pour la radiochirurgie stéréotaxique.

Stereotactic radiosurgery is a technique for treatment of intracranial lesions requiring high precision in all steps--from image acquisition to final irradiation. One of most difficult steps is the treatment planning phase, consisting of determination of irradiation parameters sufficient to cover the target volume by avoiding sensitive volumes. A manual and empirical definition can be very long and difficult, especially in the case of complex target volumes situated in sensitive zones. As in conventional radiotherapy, stereotactic radiosurgery has taken advantages from dosimetric optimization. The question is: "What is the configuration of irradiation parameters used in order to obtain the treatment plan by satisfying defined constraints?". The purpose of this article is to summarize optimization methods used in radiosurgery and to describe the technical alternatives proposed for this treatment as well as the possibilities of plan evaluation between different techniques. This purpose will be illustrated by the optimization methodology used in the Center Oscar Lambret of Lille, France for the radiosurgical treatment with linear accelerator.