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Background Oesophageal and gastrooesophageal junction (GOJ) carcinoma frequently present with dysphagia and de novo metastatic disease. There is scope to improve treatment paradigms to both address symptoms and improve survival. One method is integrating immune checkpoint inhibition with novel treatment combinations. Methods PALEO is a single arm, phase II clinical trial in patients with previously untreated, oligometastatic or locoregionally advanced oesophageal or GOJ carcinoma and dysphagia. PALEO is sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG). Participants receive 2 weeks of therapy with concurrent hypofractionated radiotherapy of 30Gy in 10 fractions to the primary tumour, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m2 and durvalumab 1500 mg q4 weekly, followed by durvalumab monotherapy continuing at 1500 mg q4weekly until disease progression, unacceptable toxicity or 24 months of therapy. A single metastasis is treated with stereotactic radiotherapy of 24Gy in 3 fractions in week 7. The trial primary endpoint is the progression free survival rate at 6 months. Secondary endpoints include duration of dysphagia relief, nutritional status change, quality of life, response rate, toxicity, progression free survival and overall survival. The tertiary endpoint is prediction of outcome based on biomarkers identified from patient serial blood samples collected pre- and post-radiotherapy. Discussion This unique investigator-initiated clinical trial is designed to simultaneously address the clinically relevant problems of dysphagia and distant disease control. The overarching aims are to improve patient nutrition, quality of life and survival with low toxicity therapy. AGITG PALEO is a multidisciplinary collaboration and will add to the understanding of the relationship between radiotherapy and the anti-tumour immune response. Trial registration Australian and New Zealand Clinical Trials Registry: ACTRN12619001371189, registered 8 October 2019.

Purpose: The utilization of tissue-equivalent chest wall bolus in post-mastectomy radiotherapy (PMRT) varies significantly between institutions. There is a paucity of clinical evidence to support the need for bolus in this setting. This study reports on clinical outcomes for PMRT patients treated without the routine use of bolus. Methods and Materials: We included patients who received adjuvant chest wall +/- loco-regional nodal PMRT at a single institution for invasive breast cancer from 2004-2009. Patients received a median PMRT dose of 50Gy, typically delivered over 25 treatments and using an Intensity Modulated Radiotherapy technique. Patient, tumor and outcome data were collected from an established prospective database, with additional radiotherapy and acute toxicity details supplemented retrospectively. The use of chest wall bolus was decided by the treating radiation oncologist, based on features such as clinical or pathological dermal involvement. The bolus used was 5mm thickness and typically administered on alternate days of radiotherapy treatment. Outcomes measured included RTOG acute skin toxicity, loco-regional relapse, distant metastatic relapse, and overall survival (OS). Groups were compared using Gray's test, while hazard ratios were calculated using the Fine and Gray competing risk regression model. Results: A total of 314 patients were suitable for analysis: 52 received bolus and 262 did not. The median follow up was 4.2 years, with a mean age of 52.7 years. Patients who received bolus had a higher T stage than those without bolus, with T1 tumors 16% vs 26%, T2 tumors 24% vs 40%, T3 tumors 45% vs 27% and T4 tumors 10% vs 1% (p = 0.002). For the whole cohort, 35% had N1 disease and 38% had N2/N3 disease, with no significant differences in N stage between the two groups. There was a higher incidence of dermal invasion for the bolus group compared to non-bolus, 27% vs. 7% (p<0.001), as well as lympho-vascular invasion, 73% vs. 46% (p<0.001) and positive margins, 14% vs. 3% (p = 0.003). There were no significant differences between the 2 groups in terms of ER positivity (58 vs. 76% p = 0.07), HER 2 positivity (17 vs. 9% p = 0.09) or grade 3 disease (75 vs. 67%, p = 0.77). Four-year LRR was 14% in the bolus group and 3% in the non-bolus group. On uni-variate analysis, this resulted in a significant difference in LRR (HR 3.1; CI 1.2-8.3; p = 0.02). However, when adjusting for margin status (HR 5.0; CI 1.5-16.5; p = 0.008), this result was no longer significant (HR = 2.5; CI 0.8-7.5, p = 0.12). Four-year OS was 77% vs. 86% for bolus vs. non-bolus group (p = 0.07). The pattern of failure in this cohort was predominantly distant, with 50/314 patients (16%) developing distant metastases as the first site of failure, 17 patients (5%) in the chest wall and 4 (1%) in regional nodes. There was a significant difference in acute skin toxicity between the bolus vs. non-bolus groups (p = 0.01) with Grade 2 toxicity 37% vs. 21%, grade 3 toxicity 0 vs. 1% and grade 4 toxicity 2% vs. 0%. Conclusions: In this patient population, the LRR rates without the use of bolus were low and consistent with published reports. These results suggest that in the setting of PMRT, patients without higher risk features such as positive margins or dermal invasion may not require the use of bolus. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-01.