Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or <10 evaluated lymph nodes (LNs). Adjuvant chemotherapy administration and its effect on survival was evaluated for each known risk factor. All patients with high-risk stage II colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to nonrecipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between receipt of adjuvant chemotherapy and survival was observed. In high-risk stage II colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated.

Purpose The main objective of this preliminary analysis of the IMaging PAtients for Cancer drug selecTion (IMPACT)-renal cell cancer (RCC) study is to evaluate the lesion detection of baseline contrast-enhanced CT, [ 89 Zr]Zr-DFO-girentuximab-PET/CT and [ 18 F]FDG-PET/CT in detecting ccRCC lesions in patients with a good or intermediate prognosis metastatic clear cell renal cell carcinoma (mccRCC) according to the International Metastatic Database Consortium (IMDC) risk model. Methods Between February 2015 and March 2018, 42 newly diagnosed mccRCC patients with good or intermediate prognosis, eligible for watchful waiting, were included. Patients underwent CT, [ 89 Zr]Zr-DFO-girentuximab-PET/CT and [ 18 F]FDG-PET/CT at baseline. Scans were independently reviewed and lesions of ≥10 mm and lymph nodes of ≥15 mm at CT were analyzed. For lesions with [ 89 Zr]Zr-DFO-girentuximab or [ 18 F]FDG-uptake visually exceeding background uptake, maximum standardized uptake values (SUV max ) were measured. Results A total of 449 lesions were detected by ≥1 modality (median per patient: 7; ICR 4.25–12.75) of which 42% were in lung, 22% in lymph nodes and 10% in bone. Combined [ 89 Zr]Zr-DFO-girentuximab-PET/CT and CT detected more lesions than CT alone: 91% (95%CI: 87–94) versus 56% (95%CI: 50–62 , p = 0.001), respectively, and more than CT and [ 18 F]FDG-PET/CT combined (84% (95%CI:79–88, p < 0.005). Both PET/CTs detected more bone and soft tissue lesions compared to CT alone. Conclusions The addition of [ 89 Zr]Zr-DFO-girentuximab-PET/CT and [ 18 F]FDG-PET/CT to CT increases lesion detection compared to CT alone in newly diagnosed good and intermediate prognosis mccRCC patients eligible for watchful waiting. Electronic supplementary material The online version of this article (10.1007/s00259-019-04358-9) contains supplementary material, which is available to authorized users.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have shown promising results in patients with various advanced stage solid tumors; however, response is limited to a subset of patients. Although the number of clinical studies with ICIs is rapidly increasing, there is still an unmet need for a robust biomarker to optimize response. PD-1/PD-L1 imaging using radiolabeled antibodies allows in vivo quantification of whole-body PD-1/PD-L1. Clinical PD-1/PD-L1 imaging can contribute to a better understanding of the dynamic complexity of PD-1/PD-L1 in the tumor microenvironment.

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3573 Background: Immune checkpoint inhibitors (ICI) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have shown activity in R/M squamous cell carcinoma of the head and neck (SCCHN). Positron-emission-tomography (PET) with 89Zr-labeled anti-PD-L1 antibodies could aid in predicting response to ICI. We present the dose-finding results of the first-in-human 89Zr-durvalumab PD-L1 PET-imaging in patients with SCCHN participating in the ongoing phase II PINCH study (NCT03829007). Methods: Following baseline [18F]FDG-PET and CT/MRI imaging, patients with incurable R/M SCCHN received 37 MBq 89Zr-durvalumab and protein dose 2mg, 10mg or 50mg durvalumab. 89Zr-durvalumab PD-L1 PET-scan was acquired day 5 post-injection. Plasma pharmacokinetic analyses were performed at day 0 and 5. Standardized uptake values (SUV, mean ± SD) were measured in [18F]FDG-positive tumor lesion, liver, spleen, bone marrow and bloodpool. PD-L1-expression was assessed on archival tumor tissue using the Ventana PD-L1 (SP263) assay. Results: 14 patients were enrolled and no adverse events were reported. High tracer-retention was observed in liver and spleen, most prominent in patients receiving 2 or 10mg durvalumab. 89Zr-durvalumab accumulation within tumors and between patients was heterogeneous and not all [18F]FDG-positive lesions showed 89Zr-durvalumab uptake. Tumor lesions were visualized best using 10 or 50mg durvalumab (SUVpeak 2mg: 3.86 ± 0.79, 10mg: 7.46 ± 2.18, 50mg: 5.57 ± 1.74). Tumor-to-blood-ratios for 10mg durvalumab were highest (2mg: 2.27 ± 0.33, 10mg: 3.44 ± 0.76, 50mg: 1.73 ± 0.99; p = 0.019). PK-analyses confirmed visual prolonged tracer-retention in bloodpool with increasing protein dose. PD-L1-expression was equally distributed amongst dose-groups. Conclusions: This is the first study to show feasibility of 89Zr-durvalumab PD-L1 PET in SCCHN patients, demonstrating the highest tumor-to-blood radio with a total dose of 10mg durvalumab. So far, no correlation of tumor PD-L1 expression with 89Zr-durvalumab-uptake and PD-L1 expression on archival tissue was found. Next step will be to correlate 89Zr-durvalumab PD-L1 PET tumor uptake with durvalumab treatment response in the phase 2 part of the PINCH study. Clinical trial information: NCT03829007 .