Pathologic Complete Response and Oncologic Outcomes in Locally Advanced Breast Cancers Treated With Neoadjuvant Radiation Therapy: An Australian Perspective.

PURPOSE: To assess the degree of pathologic complete response (pCR), postoperative surgical complication rates, and oncological outcomes in women with locally advanced breast cancer or high-risk breast cancers treated with neoadjuvant radiation therapy (NART). METHODS AND MATERIALS: This retrospective, multi-institutional review involved 138 clinically staged patients with 140 breast cancers treated with NART between January 2014 and February 2021. Treatments involved sequential neoadjuvant chemotherapy and NART, followed by mastectomy with or without axillary surgery and immediate autologous breast reconstruction. Descriptive statistics were used to assess patient and disease features, treatment regimens, pathologic response, and factors affecting postoperative complications. Kaplan-Meier curves were performed to assess locoregional recurrence-free, distant metastasis-free, and overall survival outcomes. RESULTS: Median age was 47 years (interquartile range, 42-52). The median follow-up was 35.2 months (interquartile range, 17.1-46.5). pCR was achieved in 36.4% (as defined by Chevallier classification) or 42.1% (as defined by Miller-Payne scores) of patients. Greater pCR rates were achieved for HER2+ (73.8%-85.7%) and triple-negative phenotypes (47.6%-57.1%). There were 21 grade 3 surgical complications including 10 grade 3B breast events and 8 grade 3B donor-site events, where surgical reintervention was required. At 3-years' follow-up, the locoregional recurrence-free survival was 98.1%, distant metastasis-free survival was 83.6%, and overall survival was 95.3%%. CONCLUSIONS: NART is feasible to facilitate a single-stage mastectomy and immediate autologous breast reconstruction. This study demonstrated comparable rates of postoperative complication to standard of care, and high rates of pCR, which translates to high rates of locoregional control, distant metastasis-free survival, and overall survival.

Volumetric arc therapy: A viable option for right-sided breast with comprehensive regional nodal irradiation in conjunction with deep inspiration breath hold.

PURPOSE: Deep inspiration breath hold (DIBH) is an innovative technique routinely used for left-sided breast radiotherapy to significantly reduce harmful dose to the heart and ipsilateral lung. Currently, there is scant literature exploring DIBH for right-sided whole breast and regional nodal irradiation (WB & RNI). The purpose of this study is to examine if DIBH produces a clinically significant reduction in organ at risk (OAR) dose for right-sided WB + RNI, whilst comparatively analysing the use of volumetric arc therapy (VMAT) versus tangential inverse modulated radiotherapy (t-IMRT). METHODS AND MATERIALS: Ten patients, previously treated for left sided breast cancer (with a FB and DIBH CT scan), were selected from our database to be retrospectively replanned to the right breast and nodal regions. Planning target volumes (PTV) were marked to include the whole right breast and regional nodes, encompassing the supraclavicular fossa (SCF) and internal mammary nodes (IMN). PTVs and OARs were contoured on the Pinnacle workstation according to the Radiation Therapy Oncology Group (RTOG) guidelines. VMAT and t-IMRT plans were generated to a prescribed dose of 50 Gy in 25 fractions on both the DIBH and FB data sets for dosimetric analysis. RESULTS: Coverage of the right breast (mean, D95%) and SCF (D95%) were significantly improved with VMAT in comparison to t-IMRT, with no statistically significant variation on the IMN PTV (D95%). The use of DIBH did not impact PTV coverage compared with FB. VMAT reduced dose to the ipsilateral lung (mean, V20Gy), combined lungs (mean, V20Gy) and liver (D2cc); conversely dose to the heart (mean), left lung (mean, V5Gy) and contralateral breast (mean) were increased. For both techniques DIBH significantly improved dose to OARs including the ipsilateral lung (mean, V20Gy, V5Gy), total lung (mean, V20Gy), heart (mean, V25Gy) and liver (D2cc) when compared to FB. CONCLUSION: DIBH could be considered for patients treated with right-sided WB and RNI due to a significant decrease in heart, ipsilateral lung, total lung and liver doses. VMAT significantly improves PTV coverage over t-IMRT whilst reducing dose to the ipsilateral lung and liver, albeit to the detriment of the left lung, contralateral breast and heart. The increase in heart dose can be mitigated by the use of DIBH. We recommend if VMAT is utilised for superior target volume coverage, DIBH should also be implemented to reduce OAR toxicity. RÉSUMÉ:   BUT: La retenue respiratoire profonde (DIBH) est une technique innovante couramment utilisée pour la radiothérapie du cÔté gauche du sein afin de réduire de manière significative la dose nocive pour le cŒur et le poumon ipsilatéral (13-15). Actuellement, il existe peu d'ouvrages sur la DIBH pour l'irradiation du sein entier du cÔté droit et des nodules régionaux (WB+RNI). L'objectif de cette étude est d'examiner si la DIBH produit une réduction cliniquement significative de la dose d'organe à risque (OAR) pour la WB+RNI du cÔté droit, tout en analysant comparativement l'utilisation de l'arcthérapie volumétrique (VMAT) par rapport à la radiothérapie par modulation d'intensité tangentielle (t-IMRT). MéTHODOLOGIE ET MATéRIEL: Dix scans tomodensitométriques avec un ensemble de données DIBH et de respiration libre (FB) ont été sélectionnés de manière rétrospective. Les volumes cibles de planification (PTV) ont été marqués pour inclure le sein droit entier et les ganglions régionaux, englobant la fosse supraclaviculaire (SCF) et les ganglions mammaires internes (IMN). Les PTV et les OAR ont été définis sur la station de travail Pinnacle conformément aux directives du groupe de radiothérapie oncologique (RTOG) (17). Les plans t-IMRT et VMAT ont été générés pour une dose prescrite de 50Gy en 25 fractions sur les ensembles de données DIBH et FB pour l'analyse dosimétrique. RéSULTATS: La couverture du sein droit (moyenne, D95%) et du SCF (D95%) a été significativement améliorée avec la VMAT par rapport à la t-IMRT, sans variation statistiquement significative sur la PTV IMN (D95%). L'utilisation de la DIBH n'a pas eu d'impact sur la couverture du PTV par rapport à la FB. La VMAT a réduit la dose dans le poumon ipsilatéral (moyenne, V20Gy), les poumons combinés (moyenne, V20Gy) et le foie (D2cc) ; à l'inverse, la dose dans le cŒur (moyenne), le poumon gauche (moyenne, V5Gy) et le sein controlatéral (moyenne) a été augmentée. Pour les deux techniques, la DIBH a amélioré de manière significative la dose aux OAR, y compris le poumon ipsilatéral (moyenne, V20Gy, V5Gy), le poumon total (moyenne, V20Gy), le cŒur (moyenne, V25Gy) et le foie (D2cc), par rapport à la respiration libre. CONCLUSION: La DIBH pourrait être envisagé pour les patients traités par WB+RNI du cÔté droit en raison d'une diminution significative des doses dans le cŒur, le poumon ipsilatéral, le poumon total et le foie. La VMAT améliore considérablement la couverture de la PTV par rapport à la t-IMRT tout en réduisant la dose dans le poumon ipsilatéral et le foie, mais au détriment du poumon gauche, du sein controlatéral et du cŒur. L'augmentation de la dose au cŒur peut être atténuée par l'utilisation de la DIBH. Nous recommandons, si la VMAT est utilisée pour une couverture supérieure du volume cible, de mettre également en Œuvre la DIBH pour réduire la toxicité aux OAR.

Use of indocyanine green fluorescence compared to radioisotope for sentinel lymph node biopsy in early-stage breast cancer: systematic review and meta-analysis.

BACKGROUND: In early-stage breast cancer, indocyanine green (ICG)-fluorescence based sentinel lymph node (SLN) detection is being considered. This is a meta-analysis of SLN detection rates and sensitivity of ICG-fluorescence compared to radioisotope (RI), to evaluate its clinical applicability. DATA SOURCES: Systematic review of full-text articles from PubMed and Scopus, of women with early breast cancer who underwent SLN mapping using ICG and RI concurrently was performed. The meta-analysis was performed using the Mantel-Haenszel method. RESULTS: 2301 patients from 19 studies were included. No significant difference was observed between ICG and RI for SLN detection (OR0.90,95%CI0.66-1.24) or sensitivity (OR1.23,95%CI0.73-2.05) with heterogeneity between studies (I2 = 58%,P = 0.003). Sensitivity of dual mapping (ICG + RI) was significantly better compared to single mapping with RI (OR3.69,95%CI1.79-7.62) or ICG (OR3.32,95%CI1.52-7.24) alone with no heterogeneity between studies (I2 = 0%,P = 0.004). CONCLUSION: ICG-fluorescence could complement RI method or provide alternative in centers with poor accessibility to RI lymphoscintigraphy.

Band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices.

BACKGROUND: The presence of oesophageal varices is associated with the risk of upper gastrointestinal bleeding. Endoscopic variceal ligation is used to prevent this occurrence but the ligation procedure may be associated with complications. OBJECTIVES: To assess the beneficial and harmful effects of band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices. SEARCH METHODS: We combined searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 9 February 2019. SELECTION CRITERIA: We included randomised clinical trials comparing band ligation verus no intervention regardless of publication status, blinding, or language in the analyses of benefits and harms, and observational studies in the assessment of harms. Included participants had cirrhosis and oesophageal varices with no previous history of variceal bleeding. DATA COLLECTION AND ANALYSIS: Three review authors extracted data independently. The primary outcome measures were all-cause mortality, upper gastrointestinal bleeding, and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RRs) with 95% confidence intervals (CIs) and I2 values as a marker of heterogeneity. In addition, we calculated the number needed to treat to benefit (NNTTB) for the primary outcomes . We assessed bias control using the Cochrane Hepato-Biliary domains; determined the certainty of the evidence using GRADE; and conducted sensitivity analyses including Trial Sequential Analysis. MAIN RESULTS: Six randomised clinical trials involving 637 participants fulfilled our inclusion criteria. One of the trials included an additional small number of participants (< 10% of the total) with non-cirrhotic portal hypertension/portal vein block. We classified one trial as at low risk of bias for the outcome, mortality and high risk of bias for the remaining outcomes; the five remaining trials were at high risk of bias for all outcomes. We downgraded the evidence to moderate certainty due to the bias risk. We gathered data on all primary outcomes from all trials. Seventy-one of 320 participants allocated to band ligation compared to 129 of 317 participants allocated to no intervention died (RR 0.55, 95% CI 0.43 to 0.70; I2 = 0%; NNTTB = 6 persons). In addition, band ligation was associated with reduced risks of upper gastrointestinal bleeding (RR 0.44, 95% CI 0.28 to 0.72; 6 trials, 637 participants; I2 = 61%; NNTTB = 5 persons), serious adverse events (RR 0.55, 95% CI 0.43 to 0.70; 6 trials, 637 participants; I2 = 44%; NNTTB = 4 persons), and variceal bleeding (RR 0.43, 95% CI 0.27 to 0.69; 6 trials, 637 participants; I² = 56%; NNTTB = 5 persons). The non-serious adverse events reported in association with band ligation included oesophageal ulceration, dysphagia, odynophagia, retrosternal and throat pain, heartburn, and fever, and in the one trial involving participants with either small or large varices, the incidence of non-serious side effects in the banding group was much higher in those with small varices, namely ulcers: small versus large varices 30.5% versus 8.7%; heartburn 39.2% versus 17.4%. No trials reported on health-related quality of life.Two trials did not receive support from pharmaceutical companies; the remaining four trials did not provide information on this issue. AUTHORS' CONCLUSIONS: This review found moderate-certainty evidence that, in patients with cirrhosis, band ligation of oesophageal varices reduces mortality, upper gastrointestinal bleeding, variceal bleeding, and serious adverse events compared to no intervention. It is unlikely that further trials of band ligation versus no intervention would be considered ethical.