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295 Background: The optimum combination curative approach to locally advanced adenocarcinoma of the esophagus and esophago-gastric junction (AEG) remains controversial, specifically whether multimodal therapy or perioperative chemotherapy is superior. Neo-AEGIS was designed as the first randomized clinical trial (RCT) to directly compare the multimodal CROSS regimen (carboplatin/paclitaxel, 41.4Gy radiation therapy) with a modified MAGIC (epirubicin, cisplatin (oxaliplatin), 5-FU (capecitabine)) regimen (pre-2018) and more latterly the FLOT (docetaxel, 5-FU, leucovorin, oxaliplatin) regimen. Methods: 377 patients with cT2-3N0-3M0 AEG were randomly assigned to CROSS or peri-operative chemotherapy (ECF/ECX/EOF/EOX pre-2018, FLOT option 2019/20) at 24 sites (Ireland, UK, Denmark, France, Sweden). The primary outcome was overall survival. The initial power calculation was based on CROSS superiority of 10%. This was modified after the first futility analysis (70 events) to a non-inferiority margin of 5% for peri-operative chemotherapy. Secondary end points included toxicity, pathologic measures of response, and postoperative complications as per the Esophageal Complications Consensus Group (ECCG) definitions and Clavien-Dindo severity grade. Results: Of 362 evaluable patients, 178 CROSS, 184 MAGIC/FLOT (157/27), 90% were male, median (range) age 64 (35-83), 84% were cT3, and 58% cN1. At a median (range) follow up of 34.2 (0.43-111.8) months, there were 186 deaths, 91 CROSS and 95 MAGIC/FLOT arm, with 3-year estimated survival probability of 57% (95% CI 49,64) and 55% (95% CI 47,62), respectively [(HR 1.03 (95%CI. 0.77-1.38))]. Conclusions: This RCT reveals no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy in the primary outcome of overall survival, notwithstanding greater proxy markers of local tumor response in the CROSS arm. Oncologic and operative outcomes were consistent with optimum modern benchmarks. These data strongly suggest non-inferiority and support equipoise in clinical decision making in modern practice. Clinical trial information: NCT01726452 . [Table: see text]

Purpose To determine whether voluntary deep-inspiratory breath-hold (v-DIBH) and deep-inspiratory breath-hold with the active breathing coordinator™ (ABC-DIBH) in patients undergoing left breast radiotherapy are comparable in terms of normal-tissue sparing, positional reproducibility and feasibility of delivery. Methods Following surgery for early breast cancer, patients underwent planning-CT scans in v-DIBH and ABC-DIBH. Patients were randomised to receive one technique for fractions 1-7 and the second technique for fractions 8-15 (40 Gy/15 fractions total). Daily electronic portal imaging (EPI) was performed and matched to digitally-reconstructed radiographs. Cone-beam CT (CBCT) images were acquired for 6/15 fractions and matched to planning-CT data. Population systematic (Σ) and random errors (σ) were estimated. Heart, left-anterior-descending coronary artery, and lung doses were calculated. Patient comfort, radiographer satisfaction and scanning/treatment times were recorded. Within-patient comparisons between the two techniques used the paired t-test or Wilcoxon signed-rank test. Results Twenty-three patients were recruited. All completed treatment with both techniques. EPI-derived Σ were ≤1.8 mm (v-DIBH) and ≤2.0 mm (ABC-DIBH) and σ ≤2.5 mm (v-DIBH) and ≤2.2 mm (ABC-DIBH) (all p non-significant). CBCT-derived Σ were ≤3.9 mm (v-DIBH) and ≤4.9 mm (ABC-DIBH) and σ ≤ 4.1 mm (v-DIBH) and ≤ 3.8 mm (ABC-DIBH). There was no significant difference between techniques in terms of normal-tissue doses (all p non-significant). Patients and radiographers preferred v-DIBH (p = 0.007, p = 0.03, respectively). Scanning/treatment setup times were shorter for v-DIBH (p = 0.02, p = 0.04, respectively). Conclusions v-DIBH and ABC-DIBH are comparable in terms of positional reproducibility and normal tissue sparing. v-DIBH is preferred by patients and radiographers, takes less time to deliver, and is cheaper than ABC-DIBH. © 2013 Elsevier Ireland Ltd. All rights reserved.

Objective: The purpose of the work was to estimate the dose received by the heart throughout a course of breath-holding breast radiotherapy. Methods: 113 cone-beam CT (CBCT) scans were acquired for 20 patients treated within the HeartSpare 1A study, in which both an active breathing control (ABC) device and a voluntary breath-hold (VBH) method were used. Predicted mean heart doses were obtained from treatment plans. CBCT scans were imported into a treatment planning system, heart outlines defined, images registered to the CT planning scan and mean heart dose recorded. Two observers outlined two cases three times each to assess interobserver and intraobserver variation. Results: There were no statistically significant differences between ABC and VBH heart dose data from CT planning scans, or in the CBCT-based estimates of heart dose, and no effect from the order of the breath-hold method. Variation in mean heart dose per fraction over the three imaged fractions was

To evaluate breath-hold stability and constancy for a voluntary breath-hold (VBH) technique in a retrospective analysis.Movie loop sequences of electronic portal image data from multiple breath holds in a cohort of 19 patients were used to assess within and between breath-hold stability. In vivo dosimetry data based on electronic portal imaging (EPI) were analysed for 31 VBH patients plus a cohort of free-breathing (FB) patients to provide a reference. A phantom experiment simulated the impact on dose of FB, breath hold and unplanned release of breath hold.165/174 (93%) movie loop data sets had no detectable displacement. For the remaining 12, median displacement = 1.5 mm and maximum displacement = 3 mm (one patient on one fraction). In vivo dosimetry data analysis showed a median dose difference measured to planned of -0.2% (VBH) and -0.1% (FB). Dose distribution evaluation (γ) pass rates were 84% (VBH) and 91% (FB) including the lung region; 93% and 96% with a lung override. Unplanned release of phantom breath-hold position changed median dose by ≤1% and degraded γ pass rates to 79-62%. Failing regions were mostly in the periphery of the treated volume.The data confirmed that multiple VBHs using visual monitoring are stable; in vivo dose verification via EPI was within expected and acceptable levels.These data provide further reassurance that VBH is a safe technique for cardiac sparing breast radiotherapy and support its rapid, widespread implementation.

Purpose To compare mean heart and left anterior descending coronary artery (LAD) doses (NTDmean) and positional reproducibility in larger-breasted women receiving left breast radiotherapy using supine voluntary deep-inspiratory breath-hold (VBH) and free-breathing prone techniques. Materials and methods Following surgery for early breast cancer, patients with estimated breast volumes >750 cm3 underwent planning-CT scans in supine VBH and free-breathing prone positions. Radiotherapy treatment plans were prepared, and mean heart and LAD doses were calculated. Patients were randomised to receive one technique for fractions 1–7, before switching techniques for fractions 8–15 (40 Gy/15 fractions total). Daily electronic portal imaging and alternate-day cone-beam CT (CBCT) imaging were performed. The primary endpoint was the difference in mean LAD NTDmean between techniques. Population systematic (Σ) and random errors (σ) were estimated. Within-patient comparisons between techniques used Wilcoxon signed-rank tests. Results 34 patients were recruited, with complete dosimetric data available for 28. Mean heart and LAD NTDmean doses for VBH and prone treatments respectively were 0.4 and 0.7 (p < 0.001) and 2.9 and 7.8 (p < 0.001). Clip-based CBCT errors for VBH and prone respectively were ⩽3.0 mm and ⩽6.5 mm (Σ) and ⩽3.5 mm and ⩽5.4 mm (σ). Conclusions In larger-breasted women, supine VBH provided superior cardiac sparing and reproducibility than a free-breathing prone position.

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these techniques, patients hold their breath while radiotherapy is delivered, pushing the heart down and away from the radiotherapy field. Despite clear dosimetric benefits, these techniques are not yet in widespread use. One reason for this is that commercially available solutions require specialist equipment, necessitating not only significant capital investment, but often also incurring ongoing costs such as a need for daily disposable mouthpieces. The voluntary breath-hold technique described here does not require any additional specialist equipment. All breath-holding techniques require a surrogate to monitor breath-hold consistency and whether breath-hold is maintained. Voluntary breath-hold uses the distance moved by the anterior and lateral reference marks (tattoos) away from the treatment room lasers in breath-hold to monitor consistency at CT-planning and treatment setup. Light fields are then used to monitor breath-hold consistency prior to and during radiotherapy delivery. © JoVE 2006-2014. All Rights Reserved.

ObjectivesThis study was undertaken to assess the hematologic, clinical, and biochemical response to intravenous iron in patients with chronic heart failure (CHF) and anemia.BackgroundAnemia is common in patients with CHF and is associated with higher morbidity and mortality. The combination of erythropoietin (EPO) and iron increases hemoglobin (Hb) and improves symptoms and exercise capacity in anemic CHF patients. It is not known whether intravenous iron alone is an effective treatment for anemia associated with CHF.MethodsSixteen anemic patients (Hb ≤12 g/dl) with stable CHF (age 68.3 ± 11.5 years, 12 men, 9 participants New York Heart Association [NYHA] functional class II and the remainder class III, left ventricular ejection fraction 26 ± 13%) received a maximum of 1 g of iron sucrose by bolus intravenous injections over a 12-day treatment phase in an outpatient setting. Mean follow-up was 92 ± 6 days.ResultsHemoglobin rose from 11.2 ± 0.7 to 12.6 ± 1.2 g/dl (p = 0.0007), Minnesota Living with Heart Failure (MLHF) score fell (denoting improvement) from 33 ± 19 to 19 ± 14 (p = 0.02), 6-min walk distance increased from 242 ± 78 m to 286 ± 72 m (p = 0.01), and all patients recorded NYHA class II at study end (p < 0.02). Changes in MLHF score and 6-min walk distance related closely to changes in Hb (r = 0.76, p = 0.002; r = 0.56, p = 0.03, respectively). Of all baseline measurements, only iron and transferrin saturation correlated with increases in Hb (r = 0.60, p = 0.02; r = 0.60, p = 0.01, respectively). There were no adverse events relating to drug administration or during follow-up.ConclusionsIntravenous iron sucrose, when used without concomitant EPO, is a simple and safe therapy that increases Hb, reduces symptoms, and improves exercise capacity in anemic patients with CHF. Further assessment of its efficacy should be made in a multicenter, randomized, placebo-controlled trial.

Aims: To measure cardiac tissue doses in left-sided breast cancer patients receiving supine tangential field radiotherapy with multileaf collimation (MLC) cardiac shielding of the heart and to assess the effect on target volume coverage. Materials and methods: Sixty-seven consecutive patients who underwent adjuvant radiotherapy to the left breast (n=48) or chest wall (n=19) in 2009/2010 were analysed. The heart, left anterior descending coronary artery (LAD), whole breast and partial breast clinical target volumes (WBCTV and PBCTV) were outlined retrospectively (the latter only in patients who had undergone breast-conserving surgery [BCS]). The mean heart and LAD NTD and maximum LAD doses (LAD) were calculated for all patients (NTD is a biologically weighted mean dose normalised to 2Gy fractions using a standard linear quadratic model). Coverage of WBCTV and PBCTV by the 95% isodose was assessed (BCS patients only). Results: The mean heart NTD (standard deviation) was 0.8 (0.3) Gy, the mean LAD NTD 6.7 (4.3) Gy and the mean LAD 40.3 (10.1) Gy. Coverage of the WBCTV by 95% isodose was