DIBH reduces right coronary artery and lung radiation dose in right breast cancer loco-regional radiotherapy.

To determine whether deep inspiratory breath-hold (DIBH) reduces dose to organs-at-risk (OAR), in particular the right coronary artery (RCA), in women with breast cancer requiring right-sided post-mastectomy radiotherapy (PMRT) including internal mammary chain (+IMC) radiotherapy (RT). Fourteen consecutive women requiring right-sided PMRT + IMC were retrospectively identified. Nodal delineation was in accordance with European Society for Radiology and Oncology (ESTRO) guidelines and tangential chest wall fields marked. Patients were planned with Anisotropic Analytical Algorithm using free-breathing (FB) and DIBH datasets. Dose was calculated using Acuros External Beam algorithm. FB and DIBH dose comparisons were analyzed for heart, RCA and right lung, as were chest wall and IMC planning target volumes (PTVs). DIBH vs FB resulted in median decreases of: the RCA mean dose by 0.6Gray (Gy) (interquartile range (IQR) 0.1, 1.9) (p = 0.002), RCA max dose by 1.8Gy (IQR 0.8, 6.1) (p = 0.002), and V5Gy by 2.9% (IQR 0.0, 37.2) (p = 0.016). RCA data indicated no statistically significant dosimetric reduction ≥10Gy. A median reduction of 1.7Gy (c -0.0, 7.1) (p = 0.019) in maximum heart dose was recorded with DIBH vs FB; no significant difference was observed in other heart and left anterior descending coronary artery parameters. The median reduction in right lung mean dose was 2.8Gy for DIBH vs FB plans (IQR 1.6, 3.6) (p = 0.001); significant median reductions of V5Gy, V20Gy, and V30Gy were all achieved with DIBH. Chest wall PTV coverage did not significantly differ between DIBH and FB plans; IMC dosimetric coverage improved with use of DIBH (V47.5Gy, V45Gy, V42Gy). DIBH reduced OAR dose in right-sided PMRT + IMC patients. A novel finding was that DIBH decreased RCA dose. Heart and right lung dose were also decreased with DIBH, whilst optimally dosed PTVs were maintained.

Diagnosis and management of phyllodes tumours for the surgeon: An algorithm.

A Phyllodes Tumour (PT) is an uncommon fibroepithelial lesion, with three histological grades - benign, borderline and malignant. PTs cause significant challenges in diagnosis, management and prognostication. Recent publications have clarified the definitions and prognostication of PTs. Contemporary data currently challenge international guidelines on PT management. We performed an in-depth literature review to develop a best-practice management algorithm for PTs. Diagnostic recommendations are that neither current imaging techniques, nor fine-needle biopsies, can reliably diagnose a PT. Core needle biopsy is the optimal diagnostic technique. Indeterminate or suspicious lesions are recommended to undergo an excisional biopsy due to the inherently heterogeneous nature of PTs. Management guidelines are that benign PTs should be completely excised, although an involved margin is acceptable in select situations. Borderline PTs should have a clear margin on excision due to their higher risk of recurrence, as well as the potential for a recurrence to progress to a malignant PT. In malignant PTs, a margin of 3 mm is acceptable as there is no reduction in recurrence risk if margins are >3 mm. Routine axillary surgery is not indicated in PTs, with axillary surgery only indicated in a histologically-confirmed positive axilla. Adjuvant treatment recommendations are that borderline and malignant PTs should be discussed at MDT, with radiotherapy considered in both. Chemotherapy should be discussed in malignant PT patients. In summary, we have developed an up-to-date simple algorithm to guide the surgeon's management of patients diagnosed with PTs and reduce excessive surgery.

Impact of the EndoPredict genomic assay on treatment decisions for oestrogen receptor-positive early breast cancer patients: benefits of physician selective testing.

PURPOSE: Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application. METHODS: Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team. RESULTS: 233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p < 0.0001) in the selective cohort (43/110, 39.1%) compared to the consecutive group (11/123, 8.9%). The strongest driver of selective recruitment was intermediate grade histology, whilst logistic regression modelling demonstrated that nodal status (p < 0.001), proliferative rate (p = 0.001), and progesterone receptor positivity (p < 0.001) were the strongest discriminators of risk. CONCLUSION: Whilst molecular risk can be predicted by traditional variables in a high proportion of cases, EndoPredict® had a greater impact on treatment decisions in those cases selected for testing at team discretion. This is indicative of the robust ability of the clinical team to identify cases most likely to benefit from testing, underscoring the value of genomic tests in the oncologists' tool kit.

Verification using in vivo optically stimulated luminescent dosimetry of the predicted skin surface dose in patients receiving postmastectomy radiotherapy.

The purpose of this study was to evaluate whether dose to the skin surface underneath bolus, was accurately predicted by a 3D treatment planning system (TPS) in patients receiving 50 Gy/25# postmastectomy radiotherapy (PMRT) using optically stimulated luminescent dosimetry (OSLD) for verification. In vivo dosimetry using OSLDs was performed in 20 consecutive patients receiving PMRT. An array of 9 OSLDs were applied to the chest wall or neobreast in a grid arrangement. Dosimetry data were recorded on 3 separate treatment fractions, averaged, and extrapolated to 25 fractions. On the 3D TPS, the predicted dose was calculated using the departmental planning algorithm at points corresponding to the OSLDs. The mean within patient difference between the planned and measured dose at each of the 9 points was calculated and Bland-Altman limits of agreement used to quantify the extent of agreement. Paired t-tests were used to test for evidence of systematic bias at each point. The coefficient of variation of the 3 OSLD readings per patient at each of the 9 points was low for 8 points (≤4.4%) demonstrating comparable dose received per fraction at these points. The mean ratio between the in vivo measured extrapolated OSLD (IVME OSLD) dose and the planned TPS dose ranged between 0.97 and 0.99 across all points (standard deviation range 0.05 to 0.08). The mean within patient difference between the IVME OSLD and planned TPS was <1 Gy at 7 of the 9 points and the t-test for evidence of systematic bias was significant (p = 0.03) at only 1 of the 9 points. Our commercially available 3D TPS closely predicted PMRT skin surface dose underneath bolus as verified by OSLDs. At all sites, the average ratio of delivered to predicted dose was >0.97 but <1. This practical and feasible OSLD assessment of only 3 of 25 fractions facilitates quality assurance of a TPS in predicting skin surface dose under bolus.

Radiation-induced oesophagitis in breast cancer: Factors influencing onset and severity for patients receiving supraclavicular nodal irradiation.

AIM: The aim of this study was to determine dosimetric factors, such as mean dose and oesophageal length, which may influence the incidence and severity of oesophagitis in breast cancer patients receiving radiotherapy to the supraclavicular nodes. METHODS: This was a single-arm prospective observational study. Toxicity grading was undertaken twice weekly to determine the onset of grade 2 oesophagitis in consecutive patients prescribed IMRT to the breast or chest wall and supraclavicular fossa (SCF) nodes. Recorded variables included mean and maximum doses to the oesophagus, oesophageal length and pharynx length within the treatment area. Multivariate logistic regression and Fishers' exact test were used with a 0.05 significance level to compare the onset of grade 2 oesophagitis with these variables. RESULTS: A total of 77 patients were included in the study. Twenty-four (31%) patients reported grade 2 oesophagitis. There was a higher incidence of grade 2 oesophagitis in patients receiving a mean oesophageal dose of ≥31 Gy compared to those receiving < 31 Gy (18/24 versus 6/24, respectively, P = 0.025). There was a significant difference in the onset of grade 2 toxicity in patients who had ≥ 1 cm of pharynx included in SCF fields compared with those with <1 cm (15/24 versus 9/24, respectively, P = 0.0116). The odds ratios for developing grade 2 oesophagitis were 3.2 (95% CI = 1.05-9.62, P = 0.04) for a mean dose of ≥31 Gy and 3.4 (95% CI = 1.19-9.5, P = 0.022) for ≥1 cm of pharynx in the SCF field. CONCLUSION: By limiting the mean dose to the irradiated oesophagus to <31 Gy during the planning process and ensuring that <1 cm of pharynx is included in the radiation field, oesophageal toxicity may be minimised.

Long-term outcomes of ductal carcinoma in situ of the breast: a systematic review, meta-analysis and meta-regression analysis.

BACKGROUND: To summarize data on long-term ipsilateral local recurrence (LR) and breast cancer death rate (BCDR) for patients with ductal carcinoma in situ (DCIS) who received different treatments. METHODS: Systematic review and study-level meta-analysis of prospective (n = 5) and retrospective (n = 21) studies of patients with pure DCIS and with median or mean follow-up time of ≥10 years. Meta-regression was performed to assess and adjust for effects of potential confounders - the average age of women, period of initial treatment, and of bias - follow-up duration on recurrence- and death-rates in each treatment group. LR and BCDR rates by local treatment used were reported. Outside of randomized trials, remaining studies were likely to have tailored patient treatment according to the clinical situation. RESULTS: Nine thousand four hundred and four DCIS cases in 9391 patients with 10-year follow-up were included. The adjusted meta-regression LR rate for mastectomy was 2.6 % (95 % CI, 0.8-4.5); breast-conserving surgery with radiotherapy (RT), 13.6 % (95 % CI, 9.8-17.4); breast-conserving surgery without RT, 25.5 % (95 % CI, 18.1-32.9); and biopsy-only (residual predominately low-grade DCIS following inadequate excision), 27.8 % (95 % CI, 8.4-47.1). RT + tamoxifen (TAM) in conservation surgery (CS) patients resulted in lower LR compared to one or no adjuvant treatments: LR rate for CS + RT + TAM, 9.7 %; CS + RT(no TAM), 14.1 %; CS + TAM(no RT), 24.7 %; CS(alone), 25.1 % (linear trend for treatment P < 0.0001). Compared to CS + RT + TAM, a significantly higher invasive LR was observed for CS(alone), odds ratio (OR) 2.61 (P < 0.0001); CS + TAM(no RT), OR 2.52 (P = 0.001); CS + RT(no TAM), OR 1.59 (P = 0.022). BCDR was similar for mastectomy, breast-conserving surgery with or without RT (1.3-2.0 %) and non-significantly higher for biopsy-only (2.7 %). Additionally, the 15-year follow-up was reported where all like-studies had ≥ 15-year data sets; the biopsy-only patients had a meta-analysed total LR rate of 40.2 % and the invasive LR rate was 28.1 %. The biopsy-only patients had a ≥ 15-year BCDR (that included women with metastatic disease) of 17.9 %; the ≥ 15-year BCDR was 55.2 % for those with invasive LR. CONCLUSIONS: More local intervention was associated with greater local control for patients with DCIS at long-term follow-up. For patients undergoing breast-conservation, invasive LR was significantly lower when two rather than one adjuvant treatment modalities were given.

Review of deep inspiration breath-hold techniques for the treatment of breast cancer.

Radiation treatment to the left breast is associated with increased cardiac morbidity and mortality. The deep inspiration breath-hold technique (DIBH) can decrease radiation dose delivered to the heart and this may facilitate the treatment of the internal mammary chain nodes. The aim of this review is to critically analyse the literature available in relation to breath-hold methods, implementation, utilisation, patient compliance, planning methods and treatment verification of the DIBH technique. Despite variation in the literature regarding the DIBH delivery method, patient coaching, visual feedback mechanisms and treatment verification, all methods of DIBH delivery reduce radiation dose to the heart. Further research is required to determine optimum protocols for patient training and treatment verification to ensure the technique is delivered successfully.