Chemoradiotherapy with concurrent durvalumab for the palliative treatment of oligometastatic oesophageal and gastrooesophageal carcinoma with dysphagia: a single arm phase II clinical trial (PALEO, sponsored by the Australasian Gastro-Intestinal Trials Group).

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.

Dosimetric evaluation of clinical target volume in the postimplant analysis of low-dose-rate brachytherapy for prostate cancer.

PURPOSE: Brachytherapy is an effective single treatment modality for low- and intermediate-risk prostate cancer. In this study, we defined a clinical target volume (CTV) and evaluated its dosimetry 1 month after the low-dose-rate brachytherapy procedure. METHODS AND MATERIALS: One hundred ninety-eight consecutive patients treated for prostate cancer by iodine-125 seed brachytherapy were assessed. Prostate dosimetry was stratified according to British Columbia Cancer Agency criteria, with good implants having both V100 (percentage of target volume that receives 100% of the prescribed dose) > 85% and D90 (percentage of the prescribed dose received by 90% of the target volume) > 90%, suboptimal implants with V100 of 75-85%, or D90 80-90%, whereas poor implants were defined as those with V100 < 75 or D90 < 80%. CTV dosimetry stratification was performed according to the same dose coverage criteria, albeit to the CTV. RESULTS: One hundred ninety-two patients (97%) had good prostate radiation coverage, whereas only 165 patients (83%) had good postimplant CTV dosimetry. Patients with suboptimal vs. good CTV dosimetry had prostate edema of 7.8 ± 0.2% vs. 0.2 ± 0.1%, respectively (p = 0.001). CONCLUSIONS: Prostate seed implants with optimal dosimetry to prostate may still have suboptimal D90 and V100 for the CTV, especially in the presence of postimplant edema. A consensus is needed for definition and evaluation of CTV in postimplant setting for low-dose-rate prostate brachytherapy.