Impact of Response to Neo-Adjuvant Therapy to Primary Rectal Cancer on Lung Metastases Treated With SABR

Abstract

We assessed outcomes in patients undergoing stereotactic ablative radiotherapy (SABR) to lung oligometastatic disease (OMD) of rectal origin in terms of overall survival (OS), progression free survival (PFS) and local control (LC). We assessed if LC and local failure (LF) of lung metastases (LM) is related to primary rectal cancer (PRC) histological response to neo-adjuvant therapy (NAT) to determine if this can act as a biomarker for local response.We undertook a retrospective review of patients with LM from rectal adenocarcinoma treated with SABR at two institutions, with at least 6 months follow up (FU). Data were collected from paper and electronic patient records. Statistical methods used were descriptive analysis, Kaplan Meier, log-rank test and Cox regression.A total of 33 patients with 55 LM were treated with SABR between 2013 and 2020. Median age was 69 (40.8-83.1). Median number of lesions per patient was 1 (1-4). 55% had a single LM. The median dose was 50 Gray in a median of 4 fractions. 21 patients with 35 LM had NA therapy to PRC with available histology. 30 patients (91%) were treated for OMD and 3 were treated for oligoprogression of polymetastatic disease. 33% had synchronous metastases at diagnosis. All patients had a controlled primary rectal cancer having undergone definitive surgery. The median FU was 30.6 months (8.3-94). At the last known FU, 23 patients (69.7%) were alive and 10 (30.3%) had died. The median, 1, 2 and 4-yr OS from SABR were 73 months (95% CI 30.9-115), 100%, 91.8% and 67%, respectively. The LC rate was 89%. There was a LF in 6 of 55 LM, with median time to LF of 11.3 months (2.8-36.1). The only variable associated with LC was response [complete (CR) or partial (PR)] of the PRC to NA therapy. The 2 patients who had no response to NAT both suffered LF of a LM (2 of 3 treated LM). In those with CR or PR (21 patients) there was no LF (0 of 32 treated LM). 2 of 10 patients with no NAT also experienced LF (4 of 18 treated LM). There was 1 patient with no rectal histology available, and 1 patient in whom no details of NAT were available. Neither experienced a LF (2 treated LM). The PFS was 5.97 months (1.6-38.5). None of the analyzed variables were associated with PFS, including PET staging prior to SABR or multiple vs single treated metastasis. 22 (67%) patients progressed post SABR. Pattern of 1st progression: 13 out of field lung (OOF) only; 1 local only; 5 distant only; 1 local and distant; 1 local and OOF; 1 OOF and distant; 11 patients (33%) did not develop further OMD or PMD. No patient experienced > G3 acute toxicity, most common being cough and fatigue.This is the largest reported cohort of rectal cancer patients undergoing lung SABR and the only to review LC in terms of response to NAT to PRC. This offers an insight into response and natural history post SABR for LM that can help inform treatment decisions. We have shown that LC is related to PRC response to NAT, which may act as a biomarker for success of lung SABR. This will need to be confirmed by larger studies.