Axillary sentinel lymph node identification using superparamagnetic iron oxide versus radioisotope in early stage breast cancer: The UK SentiMag trial (SMART study).

BACKGROUND & OBJECTIVES: Sentinel lymph node biopsy (SLNB) is an accurate and reliable method for staging the axilla in early breast cancer. The gold standard technique for localizing the sentinel lymph node (SLN) is the use of radioisotope with or without blue dye. However, this technique has its limitations. Various alternatives have been explored to overcome the disadvantages of the standard SLNB technique and superparamagnetic iron oxide mapping agents have garnered significant attention. The SMART study aims to compare the magnetic technique using the superparamagnetic iron oxide particles (SPIO, Sienna+®) to the radioisotope technique (Tc99) +/- blue dye, for SLN identification in patients with early breast cancer. METHODS: A prospective, multicenter study was done that recruited 109 clinically node-negative early-stage breast cancer patients from five centres in the United Kingdom (UK). The patients received radioisotope ± blue dye injections, followed by intraoperative injection of magnetic tracer prior to SLNB. The sentinel node identification rate was compared between the magnetic and standard techniques to evaluate detection rate (per patient and per node), non-inferiority and concordance. RESULTS: Data was analysed for 107 patients. The per patient detection rate was 98.13% (105/107) when using the magnetic tracer and 92.26% (103/107) when using the standard technique. The nodal detection rate was 93.07% (188/202 nodes) when using the magnetic tracer and 96.53% (195/202) when using the standard technique. Of the 31 patients with positive sentinel lymph nodes (SLNs), all 31 (100%) were detected by both techniques. CONCLUSION: Our study demonstrates that the magnetic technique is a feasible method for SLNB, with an identification rate that is not inferior to the standard technique. The magnetic technique offers a suitable alternative to the standard technique thereby avoiding the need for the complexities of nuclear medicine, the hazards of radiation and the anaphylaxis risk of blue dye.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer.

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Impact of the menstrual cycle on commercial prognostic gene signatures in oestrogen receptor-positive primary breast cancer.

PURPOSE: Changes occur in the expression of oestrogen-regulated and proliferation-associated genes in oestrogen receptor (ER)-positive breast tumours during the menstrual cycle. We investigated if Oncotype® DX recurrence score (RS), Prosigna® (ROR) and EndoPredict® (EP/EPclin) prognostic tests, which include some of these genes, vary according to the time in the menstrual cycle when they are measured. METHODS: Pairs of test scores were derived from 30 ER-positive/human epidermal growth factor receptor-2-negative tumours sampled at two different points of the menstrual cycle. Menstrual cycle windows were prospectively defined as either W1 (days 1-6 and 27-35; low oestrogen and low progesterone) or W2 (days 7-26; high oestrogen and high or low progesterone). RESULTS: The invasion module score of RS was lower (- 10.9%; p = 0.098), whereas the ER (+ 16.6%; p = 0.046) and proliferation (+ 7.3%; p = 0.13) module scores were higher in W2. PGR expression was significantly increased in W2 (+ 81.4%; p = 0.0029). Despite this, mean scores were not significantly different between W1 and W2 for any of the tests and the two measurements showed high correlation (r = 0.72-0.93). However, variability between the two measurements led to tumours being assigned to different risk categories in the following proportion of cases: RS 22.7%, ROR 27.3%, EP 13.6% and EPclin 13.6%. CONCLUSION: There are significant changes during the menstrual cycle in the expression of some of the genes and gene module scores comprising the RS, ROR and EP/EPclin scores. These did not affect any of the prognostic scores in a systematic fashion, but there was substantial variability in paired measurements.

Qualitative exploration of patients' experiences with Intrabeam TARGeted Intraoperative radioTherapy (TARGIT-IORT) and External-Beam RadioTherapy Treatment (EBRT) for breast cancer.

OBJECTIVE: To gather a deep qualitative understanding of the perceived benefits and impacts of External-Beam RadioTherapy (EBRT) and TARGeted Intraoperative radioTherapy (TARGIT-IORT) using Intrabeam to assess how the treatments affected patient/care partner experiences during their cancer treatment and beyond. DESIGN AND PARTICIPANTS: A patient-led working group was established to guide study design and to help validate findings. Patients with experience of receiving EBRT or TARGIT-IORT were purposively sampled by Hampshire Hospitals NHS Foundation Trust. These patients had been offered both regimens as per their clinical features and eligibility. Semistructured interviews were conducted with 29 patients and care partners with lived experience of either EBRT (n=12, 5-day FAST-Forward regimen and n=3, 3-week regimen) or TARGIT-IORT (n=14). Thematic analysis was then carried out by two coders generating 11 themes related to EBRT or TARGIT-IORT. SETTING: Semistructured interviews were conducted virtually via Zoom during February and March 2023. RESULTS: A number of procedural grievances were noted among EBRT patients. EBRT was perceived as being disruptive to normal routines (work, home and travel) and caused discomfort from side effects. TARGIT-IORT was perceived by patients and care partners as the safer option and efficient with minimal if any disruptions to quality of life. The need for timely accessible information to reduce anxieties was noted in both cohorts. CONCLUSIONS: This qualitative study found that patients perceived EBRT as being greatly disruptive to their lives. In contrast, the one-off feature of TARGIT-IORT given while they are asleep during surgery gives them the feeling of stamping out the cancer without conscious awareness. These insights can help healthcare staff and policy-makers further justify the incorporation of the treatment favoured by these patient perceptions (TARGIT-IORT) more widely in routine practice. Further research is planned to explore TARGIT-IORT in more diverse populations and in the 35 countries where it is an established treatment option.

Prophylactic Use of Negative Pressure Wound Therapy in High-risk Patients Undergoing Oncoplastic and Reconstructive Breast Surgery.

Background: Negative pressure wound therapy (NPWT) has emerged as an adjunct to reduce wound complication rates in many surgical domains. This study investigated the prophylactic use of PICO NPWT in high-risk patients undergoing oncoplastic and reconstructive breast surgery. Methods: This was a prospective multicenter national audit. The findings were compared against Association of Breast Surgery/British Association of Plastic, Reconstructive and Aesthetic Surgeons (ABS/BAPRAS) Oncoplastic Guidelines for best practice. Results: Data from 267 patients were included from seven centers. All patients had at least one high-risk factor for postoperative wound complications, whereas 78 patients (29.2%) had more than one. Thirty-six patients (13.5%) developed postoperative wound complications. An estimated 16 (6%) developed skin flap necrosis, wound dehiscence occurred in 13 patients (4.9%), and 15 patients (5.6%) developed postoperative wound infection. Eleven patients (4.1%) required further surgery due to wound complications. In total, 158 patients underwent mastectomy with immediate implant reconstruction. Postoperative wound complication rate was comparable in this subgroup (n = 22; 13.9%). Implant loss rate was 3.8%, which was within the 5% target mentioned in the ABS/BAPRAS guidelines. The estimated total cost saving was US $105,600 (£84,613) and US $395.50 (£316.90) per patient. Wound infection rate (5.6%) was much lower than the 25% reported by both iBRA study and National Mastectomy and Breast Reconstruction Audit. Conclusions: Our study suggests that prophylactic use of NPWT in oncoplastic and reconstructive breast surgery results in low rates of wound-related complications with associated healthcare cost benefits in patients with high-risk factors for wound-related complications. However, a prospective randomized control trial is required.

The impact of providing an oncoplastic service on the workload of a specialist breast unit.

Increasing breast specialization triggered a review of our surgical activity. All 10,000 elective inpatient and day case procedures between 1998 and 2008 were grouped into six categories: oncological, primary, secondary and revisional oncoplastic, and other breast and nonbreast procedures. Overall, surgical activity increased, with a rise in breast and a fall in nonbreast procedures, as a result of a changing caseload in each category (chi-squared for linear trend = 55.24: p < 0.00001). These included increases in oncological procedures, secondary oncoplastic, and revisional oncoplastic procedures. Increased oncoplastic activity was associated with a reduction in other breast procedures (chi-squared for linear trend = 04.94: p < 0.00001). The impact of breast specialization reported in the 1990's has accelerated with the introduction of oncoplastic surgery. This has major short-term and long-term implications when planning a modern breast service.

Extreme oncoplastic conservation is a safe new alternative to mastectomy.

OBJECTIVES: Extreme oncoplastic breast conserving surgery (eOPBCS) allows breast conservation for tumours ≥ 50 mm, but long-term outcomes are unclear. We investigated early complications and the longer-term clinical and oncological outcomes following eOPBCS to assess the clinical utility and safety of this technique. MATERIALS AND METHODS: A prospectively collected database of all eOPBCS procedures (1993-2016) using LD miniflaps (LDm) and therapeutic mammoplasties (TM) was interrogated and cross-checked with hospital records to establish length of follow up (FU), clinical outcomes (complications, revisions), local recurrence (LR) and survival. RESULTS: Ninety eOPBCS procedures (62 LDm, 28 TM) performed for large tumours (mean 67 [50-177] mm) were identified, overall FU 80 (10-308) months (LDm 91 [13-308], TM 54 [10-120] months). Forty two per cent were node positive, and 2 were benign (benign cases excluded from LR and FU analysis). Eleven patients required surgery for involved excision margins (LDm 3 re-excisions and 2 mastectomies, TM 6 mastectomies). Surgery for complications and subsequent revision was required in 6% and 37% of LDm and 18% and 7% of TM patients, respectively. Seven patients developed LR (LDm 5 versus TM 2) giving a predicted 5 and 10 year LR rate of 1.1% and 16%. CONCLUSION: Long-term FU of this unique series has confirmed that eOPBCS is a safe procedure for patients with bulky tumours normally treated by mastectomy, without risking local control. TM patients experienced more early complications but LDm patients required more revisions over a more prolonged period of FU.

Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer.

Importance: Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective: To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants: In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions: The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures: A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results: Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80). Conclusions and Relevance: These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration: ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.

Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. DESIGN: Prospective, open label, randomised controlled clinical trial. SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005). CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned. TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.

Menstrual cycle associated changes in hormone-related gene expression in oestrogen receptor positive breast cancer.

The major changes in hormone levels that occur through the menstrual cycle have been postulated to affect the expression of hormone-regulated and proliferation-associated genes (PAGs) in premenopausal ER+ breast cancer. Whilst previous studies have demonstrated differences in gene expression, here, we investigated if there are within patient changes in the expression of oestrogen- and progesterone-regulated genes (ERGs and PRGs) and PAGs in ER+ breast cancer during the menstrual cycle. Samples from 96 patients in two independent prospective studies of the effect of menstrual cycle on ER+ breast cancer were used. Plasma hormone measurements were used to assign tumours to one of three pre-defined menstrual cycle windows: W1 (days 27-35 and 1-6; low oestradiol and low progesterone), W2 (days 7-16; high oestradiol and low progesterone) and W3 (days 17-26; intermediate oestradiol and high progesterone). RNA expression of 50 genes, including 27 ERGs, 11 putative PRGs and seven PAGs was measured. The AvERG (geomean of PGR, GREB1, TFF1 and PDZK1) was used as a composite measure of ERG expression and showed significant changes between the three windows of the menstrual cycle increasing over 2.2-fold between W1 and W2 and decreasing between W2 and W3 and between W3 and W1. Proliferation gene expression also varied significantly, following the same pattern of changes as ERG expression, but the changes were of lower magnitude (1.4-fold increase between W1 and W2). Significant changes in the expression of eight individual ERGs, including GREB1, PGR and TFF1, and two PAGs were observed between W1 and either W2 or W3 with all genes showing higher levels in W2 or W3 (1.3-2.4-fold; FDR 0.016-0.05). The AvProg, a composite measure of PRG expression, increased significantly (1.5-fold) in W3 compared to W1 or W2 but no significant changes were observed for individual PRGs. In conclusion, we observed significant changes in ERG, PRG and PAG expression in ER+ breast tumours during the menstrual cycle that may affect the assessment and interpretation of prominent biomarkers (e.g. PgR) and commonly used multigene prognostic signatures in premenopausal ER+ breast cancer.

The Effect of the Timing of Radiotherapy on Clinical and Patient-Reported Outcomes After Latissimus Dorsi Breast Reconstruction: A 10-Year Study.

BACKGROUND: Breast reconstruction (BR) is considered to be adversely affected by radiotherapy (RT), particularly when an implant is used. The aim of this study was to compare clinical and patient-reported outcomes after expander-assisted latissimus dorsi breast reconstruction depending on the timing of RT. METHODS: Patients undergoing BR over a 10-year period (follow-up mean, 56 [14-134] months) were divided into 3 groups. Group 1, RT after mastectomy and BR, Group 2, RT before mastectomy and BR, and Group 3, RT after mastectomy but before BR. The primary endpoints were early and late surgical interventions. Validated questionnaires were circulated to all study patients and matched controls. RESULTS: Three hundred thirteen patients underwent 389 BRs. One hundred eighteen patients received RT, of which 65 had undergone expander-assisted latissimus dorsi breast reconstruction. Both use and timing of RT influenced clinical outcomes. Overall, use of RT resulted in a 3-fold increase in complications (P = 0.003). Postreconstruction RT resulted in more than double the number of complications compared with prereconstruction RT (P = 0.008) and delaying BR until after mastectomy and RT reduced complications to levels observed in control patients (P = nonsignificant). Complications were halved in patients undergoing autologous LD reconstruction (P = 0.0001). Patient-reported outcomes were similar for emotional well-being, satisfaction, and shoulder symptoms, although a nonsignificant increase in chronic breast symptoms was reported by the RT group. CONCLUSION: The timing and type of LD reconstruction chosen by patients receiving RT has a significant impact on the risk of subsequent complications and unplanned interventions but has little impact on longer term patient well-being or satisfaction.

Patient-Reported Outcomes Are Better after Oncoplastic Breast Conservation than after Mastectomy and Autologous Reconstruction.

Oncoplastic breast-conserving surgery (OBCS) avoids mastectomy for larger tumors, but patient-reported outcomes are unknown. METHODS: The BREAST-Q questionnaire was distributed to 333 women following therapeutic mammaplasty or latissimus dorsi (LD) miniflap since 1991 [tumor diameter, 32.5 (5-100) mm). QScore software generated scores/100 for breast appearance, physical, emotional, and sexual wellbeing. Outcomes following therapeutic mammaplasty and LD miniflap were compared and qualitative data analyzed to identify common themes relating to satisfaction. RESULTS: One hundred fifty (45%) women responded [mammaplasty versus LD miniflap, 52% versus 42%; age, 52 (30-83) years; follow-up, 84 (4-281) months). Eighty-nine percent rated OBCS better than mastectomy, > 80% recommending it to others. Mean outcome scores for breast appearance, physical, and emotional wellbeing were high and persisted beyond 15 years. Therapeutic mammaplasty patients were significantly more satisfied than those undergoing LD miniflap with the shape (P < 0.05), the size (P < 0.005), and the natural feel of the treated breast (P = 0.01). They demonstrated similar scores for physical and emotional wellbeing and a lower score for sexual wellbeing than LD miniflap patients. More LD miniflap patients reported back/shoulder symptoms and were more likely to report upper back pain (P < 0.05), but very few (< 5%) were concerned about donor-site appearance. Overall satisfaction with surgical outcomes was high in both OBCS groups (82% "excellent/very good") but greatest after therapeutic mammaplasty (P < 0.005). CONCLUSIONS: Patients report long-lasting satisfaction after OBCS and outcomes that compare very favorably with those reported following mastectomy and immediate autologous reconstruction.

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.

BACKGROUND: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). METHODS: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. RESULTS: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (<31%) or recommended (>31%). CONCLUSIONS: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

Is IORT ready for roll-out?

Two large randomised controlled trials of intraoperative radiotherapy (IORT) in breast-conserving surgery (TARGIT-A and ELIOT) have been published 14 years after their launch. Neither the TARGIT-A trial nor the ELIOT trial results have changed the current clinical practice for the use of IORT. The in-breast local recurrence rate (LRR) after IORT met the pre-specified non-inferiority margins in both trials and was 3.3% in TARGIT-A and 4.4% in the ELIOT trial. In both trials, the pre-specified estimates for local recurrence (LR) with external beam radiation therapy (EBRT) significantly overestimated actual LRR. In the TARGIT-A trial, LR with EBRT was estimated at the outset to be 6%, and in the ELIOT trial, it was estimated to be 3%. Surprisingly, LRR in the EBRT groups has been found to be significantly lower, 1.3% in the EBRT arm of the TARGIT-A and 0.4% in the EBRT arm of the ELIOT trial, respectively. Median follow-up was 2.4 years for the TARGIT-A trial and 5.8 years for the ELIOT trial. However, the initial cohort of patients in the TARGIT-A trial (reported in 2010) now have a median follow-up of 3.8 years and data on LR were available at 5 years follow-up on 35% of patients (18% who received IORT). Although further follow-up will increase confidence with the data, it will also further delay clinical implementation. By carefully weighing the risks and benefits of a single-fraction radiation treatment with patients, IORT should be offered within agreed and strict protocols. Patients deemed at low risk of LR or those deemed suitable for partial breast irradiation, according to the GEC-ESTRO and ASTRO recommendations, could be considered as candidates for IORT. These guidelines apply to all partial breast irradiation techniques, and more specific guidelines for IORT would assist clinicians.

Immediate latissimus dorsi miniflap volume replacement for partial mastectomy: use of intra-operative frozen sections to confirm negative margins.

BACKGROUND: Latissimus dorsi (LD) miniflap volume replacement is used for immediate reconstruction after partial mastectomy. This prospectively collected series was analyzed to evaluate the accuracy of intraoperative frozen sections. METHODS: After partial mastectomy, "bed biopsies" were submitted for intraoperative frozen-section analysis. If disease free, volume replacement was undertaken; if involved, targeted re-excisions were taken. Demographic, pathological, and outcome data were recorded. The proportion of breast excised was calculated. Local recurrences were recorded. RESULTS: One hundred ten partial mastectomies with LD miniflap volume replacement were completed. The median proportion of breast excised was 28% (maximum 72%); median weight 207 g. Frozen sections were positive in 33% of patients with a sensitivity of 83% and accuracy of 96% when compared with paraffin sections. Local recurrence occurred in one case. The median follow-up was 41.4 months. CONCLUSIONS: LD miniflap volume replacement extends the role of breast-conserving surgery. Frozen-section analysis of bed biopsies facilitates a single-stage procedure.