Background: In non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC. Methods: This single-arm, phase-II trial enrolled operable T3-4N0–2 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1 mg/kg intravenous and NIVO 360 mg intravenous on day-1, followed by chemotherapy plus NIVO 360 mg 3 weeks later. Thoracic radiotherapy was 50 or 60 Gy, in once-daily doses of 2 Gy. Resections were 6 weeks post-radiotherapy. Results: In a total of 30 patients in the intention-to-treat (ITT) population, grades 3–4 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1/30, 3.3%). pCR and MPR were achieved in 50% (15/30) and 63% (19/30) of the ITT; and in 58% (15/26) and 73% (19/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8⁺ T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8⁺CD39⁺ T cells and lower HLA-DR⁺ Tregs. Conclusions: Neoadjuvant IPI-NIVO-CRT in T3-4N0–2 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs. Trial registration number: NCT04245514.

Background: Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal pulmonary metastases. However, there is limited evidence comparing these local treatment modalities in similar patient groups. Methods: We retrospectively reviewed records of consecutive patients treated for colorectal pulmonary metastases with surgical metastasectomy or SABR from 2012 to 2019 at two Dutch referral hospitals that had different approaches toward the local treatment of colorectal pulmonary metastases, one preferring surgery, the other preferring SABR. Two comparable patient groups were identified based on tumor and treatment characteristics. Results: The metastasectomy group comprised 40 patients treated for 69 metastases, and the SABR group had 60 patients who were treated for 90 metastases. Median follow-up was 38 months (IQR: 26–67) in the surgery group and 46 months (IQR: 30–79) in the SABR group. Median OS was 58 months (CI: 20–94) in the metastasectomy group and 70 months (CI: 29–111) in the SABR group (p = 0.23). Five-year local recurrence-free survival (LRFS) was 44% after metastasectomy and 30% after SABR (p = 0.16). Median progression-free survival (PFS) was 15 months (CI: 3–26) in the metastasectomy group and 10 months (CI: 6–13) in the SABR group (p = 0.049). Local recurrence rate was 12.5/7.2% of patients/metastases respectively after metastasectomy and 38.3/31.1% after SABR (p < 0.001). Lower BED Gy₁₀ was correlated with an increased likelihood of recurrence (p = 0.025). Clavien Dindo grade III-V complication rates were 2.5% after metastasectomy and 0% after SABR (p = 0.22). Conclusion: In this retrospective cohort study, pulmonary metastasectomy and SABR had comparable overall survival, local recurrence-free survival, and complication rates, despite patients in the SABR group having a significantly lower progression-free survival and local control rate. These data would support a randomized controlled trial comparing surgery and SABR in operable patients with radically resectable colorectal pulmonary metastases.

To avoid delay in oncological treatment, a 6-weeks norm for time to treatment has been agreed on in The Netherlands. However, the impact of the COVID-19 pandemic on health systems resulted in reduced capacity for regular surgical care. In this study, we investigated the impact of the COVID-19 pandemic on time to treatment in surgical oncology in The Netherlands. Methods: A population-based analysis of data derived from five surgical audits, including patients who underwent surgery for lung cancer, colorectal cancer, upper gastro-intestinal, and hepato-pancreato-biliary (HPB) malignancies, was performed. The COVID-19 cohort of 2020 was compared to the historic cohorts of 2018 and 2019. Primary endpoints were time to treatment initiation and the proportion of patients whose treatment started within 6 weeks. The secondary objective was to evaluate the differences in characteristics and tumour stage distribution between patients treated before and during the COVID-19 pandemic. Results: A total of 14,567 surgical cancer patients were included in this study, of these 3292 treatments were started during the COVID-19 pandemic. The median time to treatment decreased during the pandemic (26 vs. 27 days, p < 0.001) and the proportion of patients whose treatment started within 6 weeks increased (76% vs. 73%, p < 0.001). In a multivariate logistic regression analysis, adjusting for patient characteristics, no significant difference in post-operative outcomes between patients who started treatment before or after 6 weeks was found. Overall, the number of procedures performed per week decreased by 8.1% during the pandemic. This reduction was most profound for patients with stage I lung carcinoma and colorectal carcinoma. There were fewer patients with pulmonary comorbidities in the pandemic cohort (11% vs. 13%, p = 0.003). Conclusions: Despite pressure on the capacity of the healthcare system during the COVID-19 pandemic, a larger proportion of surgical oncological patients started treatment within six weeks, possibly due to prioritisation of cancer care and reductions in elective procedures. However, during the pandemic, a decrease in the number of surgical oncological procedures performed in The Netherlands was observed, especially for patients with stage I disease.