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Introduction Various techniques for whole breast radiation therapy (WBRT) have been reported to increase dose to contralateral tissues. Heart dose is of critical importance as there is no apparent dose threshold below which there is no risk. The aim of this study was to compare planning techniques for WBRT that achieves the best target dosimetry and lowest organ at risk (OAR) dose. Methods Thirty early‐stage whole breast patient datasets, 15 each left‐ and right‐sided cases, were retrospectively selected. Five techniques were generated for each data set: three‐dimensional conformal radiation therapy (3DCRT), hybrid intensity modulated radiation therapy (HYI), hybrid volumetric modulated arc therapy (VMAT) – (HYV), reduced arc VMAT – bowtie (BT), and BT flattening filter free (FFF) – (BTFFF). Plan goals and OARs were evaluated and compared between techniques. Results BT had the highest median conformity index (CI) values (0.82, IQR: 0.80–0.85 left and 0.83, IQR 0.80–0.86 right). BT recorded lower mean heart doses (median value 1.19Gy, IQR: 0.90–1.55), and BTFFF recorded lower heart V2.5 Gy , V5 Gy ; median 3.96% (IQR: 2.90–6.80) and 0.90% (IQR: 0.50–1.50) respectively for left‐sided patients. There was a statistically significant difference in all ipsilateral lung measures, (p < 0.001) with BTFFF producing significantly lower doses across all measures: mean, V5 Gy , V10 Gy and V20 Gy . Conclusion Overall BT and BTFFF techniques produced lower OAR doses and equivalent PTV coverage for WBRT. BT and BTFFF techniques increased contralateral lung and breast doses; however, these were within prescribed tolerances and comparable to results published in the literature.

This study produced a useful tool to measure patient experience during DIBH treatment. It demonstrated that the use of the technique was acceptable to patients and did not increase their distress. It provided a compelling case for the provision of tailored, well-communicated information, consistent routine and emotional support for patients throughout their entire treatment. The tool could be employed to assess the patient experience as new technologies are introduced into RT.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

Background: Programmed death-1 (PD-1) inhibitors have been approved and are currently widely used to treat lung cancer patients. However, comparative data on the adverse events (AEs) associated with different PD-1 inhibitors are very limited.Methods: Patients with histologically confirmed lung cancer who had been treated with at least 1 dose of PD-1 inhibitors between January 2017 and December 2019 at a tertiary cancer hospital were included in the study. Data on treatment-related AEs (tr-AEs) were collected from their electronic medical records.Results: A total of 227 lung cancer patients treated with nivolumab (n=83), pembrolizumab (n=65), camrelizumab (n=27), sintilimab (n=31), and toripalimab (n=21) were included. In relation to nivolumab, pembrolizumab, camrelizumab, sintilimab, and toripalimab, the incidence rates of all-grade tr-AEs were 37.34%, 24.62%, 62.96%, 29.03% and 9.52%, respectively (P=0.01), and the incidence rates of grade 3-4 tr-AEs were 2.41%, 3.08%, 22.22%, 3.23% and 0%, respectively (P=0.05). The most common allgrade tr-AEs were capillary hemangioma (22.22%) and abnormal liver function (22.22%) for camrelizumab, pneumonitis for nivolumab (12.05%), pembrolizumab (6.15%) and nausea/vomiting (12.9%) for sintilimab, and pneumonitis (4.76%), rash/pruritus (4.76%) and shingles (4.76%) for toripalimab. Sex, age, PD-1 inhibitors, histology type and PD-1 cycles were significantly associated with tr-AEs.Conclusions: There were significant differences in the incidence and most common tr-AEs among the different PD-1 inhibitors. Different monitoring priorities should be given to different PD-1 inhibitors during treatment cycles.

Introduction: Deep inspiration breath hold (DIBH) has been proven to reduce cardiac dose for women receiving left breast and chest wall radiation therapy. However, it utilises extra departmental resources and patient exertion. The aim of this exploratory study was to investigate if any factors existed that could identify breast cancer patients who may benefit most from DIBH, to facilitate appropriate utilisation of departmental resources. Methods: Left-sided breast cancer patients aged 18-70 years, and right-sided breast cancer patients with internal mammary nodes included, were recruited. DIBH and free breathing (FB) plans were created for all patients. Patient demographic and clinical history were recorded. Variables including lung threshold value, lung volume, patient separation, maximum heart in field, volume of planning target volume (PTV), heart dose, ipsilateral lung dose were compared between plans. Results: Plans for 31 patients were analysed. No correlations were found between lung threshold value or patient separation and cardiac dose. Moderate to strong correlations were found with BMI, PTV volume and lung volume change however no definitive thresholds were determined. A significant difference was found in the maximum heart in field between DIBH and FB (P < 0.001) with those patients with greater than 0.7 cm heart in the field on the FB scan demonstrating greater reductions in mean heart dose. Conclusion: Maximum heart in the field of greater than 0.7 cm in FB could be a potential factor to identify patients who may benefit most from DIBH. This factor warrants investigation in a larger patient cohort to test its validity.

The incidence of oesophageal adenocarcinoma (OAC) is rising in Western countries, with a 5-year overall survival (OS) rate of 14%. Curative treatment based on oesophagectomy is only suitable for ~50% of patients due to late-stage diagnosis. While the addition of preoperative chemotherapy or chemoradiotherapy has improved OS in OAC patients, little is known about the molecular basis of treatment response and patient outcomes. We investigated multi-omics data including whole-genome sequencing, RNA sequencing, methylation profiles and immunohistochemistry from 115 OAC patients mostly from DOCTOR phase II clinical trial that utilized neoadjuvant therapy (ANZCTR-ACTRN12609000665235). We identified genomic features associated with poor OS, such as the APOBEC mutational signature. We also showed that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. RNA sequencing and methylation profiles suggested four immune clusters associated with OS and progression-free survival. The immune-suppressed cluster was associated with worse survival and epithelial-mesenchymal transition signature and enriched with myeloid-derived cells. The immune hot cluster was associated with better survival and enriched with T-cells, myeloid-derived cells, interferon-gamma and alpha responses, and immune markers such as CCL5, CD8A, and NKG7. We investigated multi-omic features of OAC tumours from patients who were part of phase II clinical trial. We discovered prognostic features such as mutational signatures and complex genomic events. We identified distinct immune clusters associated with patient outcomes and the potential of immunotherapy for select clusters. We characterized molecular features of OAC patients which has the potential to predict responses to neoadjuvant therapy and develop better-selected therapy, monotherapy, or combination therapy in the future.

Nivolumab, a human IgG4 anti-PD1 monoclonal antibody, has been shown to have promising results in patients with advanced non-small cell lung cancer (NSCLC) [1, 2]. Despite the improved outcomes compared to chemotherapy, only ∼20% of patients had a sustained favourable response, which highlights the need to identify measures that can augment the efficacy of immunotherapy in NSCLC [3]. Previous studies have demonstrated that radiation acts as an immune stimulus, facilitating immune mediators to enable antitumour responses within and outside the radiation field [4]. Multiple mechanisms have been shown to be involved in the systemic immune response from radiation therapy [5]. Preclinical studies also suggest that immune checkpoint inhibitors such as nivolumab can have a synergistic effect to radiation with enhancement of the antitumour T-cell activity [6], which should theoretically result in a greater clinical response in patients with NSCLC. There is also evidence to suggest an augmented abscopal effect from the combined treatment [7]. Despite the strong preclinical evidence, the impact of previous radiation therapy on the efficacy and safety of immunotherapy in real-world clinical practice in patients with NSCLC is less well defined. Here, we present the findings of a pilot case-controlled study investigating the impact of radiation therapy on outcomes with nivolumab in patients with advanced NSCLC in a large thoracic oncology unit in Brisbane, Australia. Consecutive patients with metastatic or progressive locally advanced NSCLC, who had previous radiation therapy to the chest and subsequently received nivolumab (RT group, n=23) were compared to a control group comprised of an age, sex, tumour histology and performance status matched cohort of patients who did not have previous radiation therapy prior to receiving nivolumab (non-RT group, n=23), between January 2015 and June 2017. Disease response was assessed with RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 [8]. The primary co-endpoints of the study were progression free survival (PFS) and overall survival (OS). The adverse effects of therapy were graded according to the CATCAE (Common Terminology Criteria for Adverse Event) classification. Ethical approval for this study was granted by the Queensland Metro South Human Research Ethics Committee (REC/17/QPAH/338). A total of 46 patients were included in the study with a median age of 62 years (IQR 55-67 years). All patients had metastatic or progressive locally advanced disease at baseline and the other clinical variables were equal between the two groups. The performance status at baseline was also very closely matched between the two groups. All patients had platinum-based chemotherapy before receiving nivolumab. The majority of patients had received one line of chemotherapy (84.8%, n/N=39/46). A total of 17.4% (n/N=4/ 23) of patients in the RT group and 13.0% (n/N=3/23) of patients in the non-RT group received more @ERSpublications This study investigated the effects of previous radiation...