Susan Lalondrelle

Quantitative and automatic plan-of-the-day assessment to facilitate adaptive radiotherapy in cervical cancer

Abstract Objective. To facilitate implementation of plan-of-the-day (POTD) selection for treating locally advanced cervical cancer (LACC), we developed a POTD assessment tool for CBCT-guided radiotherapy (RT). A female pelvis segmentation model (U-Seg3) is combined with a novel quantitative standard operating procedure (qSOP) to identify optimal and acceptable plans. Approach. The planning CT[i], corresponding structure set[ii], and manually contoured CBCTs[iii] (n = 226) from 39 LACC patients treated with POTD (n = 11) or non-adaptive RT (n = 28) were used to develop U-Seg3, an algorithm incorporating deep-learning and deformable image registration techniques to segment the low-risk clinical target volume (LR-CTV), high-risk CTV (HR-CTV), bladder, rectum, and bowel bag. A single-channel input model (iii only, U-Seg1) was also developed. Contoured CBCTs from the POTD patients were (a) reserved for U-Seg3 validation/testing, (b) audited to determine optimal and acceptable plans, and (c) used to empirically derive a qSOP that maximised classification accuracy. Main results. The median (interquartile range) dice similarity coefficient (DSC) between manual and U-Seg3 contours was 0.83 [0.80], 0.78 [0.13], 0.94 [0.05], 0.86 [0.09], and 0.90 [0.05] for the LR-CTV, HR-CTV, bladder, rectum, and bowel. These were significantly higher than U-Seg1 in all structures but bladder. The qSOP classified plans as acceptable if they met target coverage thresholds (LR-CTV ⩾ 99%, HR-CTV ⩾ 99.8%), with lower LR-CTV coverage ( ⩾ 95%) sometimes allowed. The acceptable plan minimizing bowel irradiation was considered optimal unless substantial bladder sparing could be achieved. With U-Seg3 embedded in the qSOP, optimal and acceptable plans were identified in 46/60 and 57/60 cases. Significance. U-Seg3 outperforms U-Seg1 and all known CBCT-based segmentation models of the female pelvis both in terms of scope and accuracy (median DSC improvement ranging from 0.03–0.06). The tool combining U-Seg3 and the qSOP identifies optimal plans with equivalent accuracy as two observers. In an implementation strategy whereby this tool serves as the second observer, plan selection confidence and decision-making time could be improved whilst simultaneously reducing the required number of POTD-trained radiographers by 50%.

Real World Multi-centre UK Review of Nivolumab Monotherapy in Metastatic Endometrial Cancer With Mismatch Repair Deficiency During COVID-19

Immunotherapy checkpoint inhibition has shown improvement in efficacy and survival in patients with mismatch repair deficient (MMRd) advanced endometrial cancer (mEC) compared to chemotherapy. This is combined with chemotherapy in the first-line setting or as monotherapy in later lines of therapy. To assess the efficacy, survival and toxicity of nivolumab monotherapy in metastatic endometrial cancer (mEC) in both first and later lines of therapy as used in the NICE COVID-19 systemic anti-cancer (SACT) guidelines. A multi-centre retrospective review of mEC patients with associated MMRd who received nivolumab as per NICE COVID NG161 at 10 NHS cancer centres. Patient demographics, molecular classification and previous treatments were recorded in addition to treatment responses, duration of response, overall survival, progression-free survival and toxicities. Kaplan-Meier curves analyse the survival data. 52 patients were identified. Median age was 67 (37-81) years. 87.5% of patients had endometrioid histology and 75% were oestrogen receptor (ER) positive. 10.4% patients were p53 mutated. 33.3% of mEC patients were stage IV at diagnosis. 30 (62.5%) patients received nivolumab as first-line mEC therapy. 33 (68.8%) patients received nivolumab 4-weekly. Treatment response was clinician-observed in 34 (70.8%) patients, with 7 (14.5%) more having stable disease. 52%, 45% and 36% of patients were progression-free at 12, 18 and 24months, respectively. 75%, 55% and 47% of patients were alive at 12, 18 and 24 months. There was no significant difference between survival or response whether nivolumab was given in the first line or subsequent lines. 29 (60.4%) patients have discontinued treatment with 23 (44.2%) being due to progressive disease or death. 18 (37.5%) patients developed G1-2 toxicity, and 3 (6.25%) patients discontinued due to G3 toxicity. This retrospective cohort shows that nivolumab monotherapy has good real-world disease control of mEC patients with MMR deficiency. Toxicity rates were low, and checkpoint monotherapy may be a viable option for selected first-line MMRd mEC patients.