Importance:Optimizing treatment decisions in metastatic breast cancer (MBC) can alleviate patients' burden and improve quality of life. Whether 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can be used to better estimate outcomes is unknown. Objective:To evaluate clinical utility of early metabolic change on FDG-PET for improving outcome estimation compared with standard diagnostic evaluation in patients with newly diagnosed MBC. Design, Setting, and Participants:The multicenter IMPACT-MBC clinical cohort trial enrolled patients with nonrapidly progressive, newly diagnosed MBC from August 2013 to May 2018, before initiation of first-line systemic therapy. Baseline assessment included metastasis biopsy procedure and FDG-PET and CT imaging. Early FDG-PET was performed after 2 weeks of treatment, and CT response evaluation after 8 weeks. Clinical utility was defined as the ability of early FDG-PET to estimate progressive disease (PD) on CT, progression-free survival (PFS), and overall survival (OS). Data were analyzed from October 19, 2025, to February 13, 2026. Intervention:Early FDG-PET or standard-of-care (SOC) biopsy-based treatment. Main Outcomes and Measures:Clinical utility of molecular imaging to improve outcome estimation of standard diagnostics defined as the capacity to identify poor patient outcomes. Measures were PD at 8 weeks, PFS, and OS. Results:The analysis included 200 patients (median [range] age, 61 [32-84] years; 198 females [99%] and 2 males [1%]). Non-PD on early FDG-PET had a negative predictive value (NPV) of 94.7% (95% CI, 89.5%-97.4%) for non-PD on 8-week CT. This was similar in all MBC subtypes and bone-only disease. Patients with SOC treatment and non-PD on early FDG-PET (n = 133) had a median PFS of 19.4 (95% CI, 15.2-22.8) months and OS of 39.4 (95% CI, 33.7-48.3) months compared to 4.1 (95% CI, 3.3-15.5) months and 18.5 (95% 3 CI, 7.0-33.0) months, respectively (P < .001 for both). Patients with non-PD on 8-week CT but with PD on early FDG-PET had a median (IQR) PFS and OS of 9.5 (4.1-18.1) and 19.4 (8.7-33.0) months compared to 22.3 (15.3-96.1) months and 40.1 (23.4-72.7) months without PD. Conclusions and Relevance:In this clinical cohort trial of patients with nonrapidly progressive, newly diagnosed MBC before initiation of first-line systemic therapy, early FDG-PET after only 2 weeks of treatment identified patients with MBC with distinct long-term outcomes. Incorporating early FDG-PET can improve outcome estimation of standard CT assessment. Trial Registration:ClinicalTrials.gov Identifier: NCT01957332.

In the original publication [...].

8578 Background: Immune-checkpoint inhibitors (ICI) are part of first-line treatment concepts for most patients with metastatic non-small cell lung cancer (NSCLC) without targetable driver mutations. Still, long-term response is rare and data on predictive biomarkers limited. Methods: As part of the Daiichi Sankyo ENDEAVOUR programme supporting young LC researchers, the ENDEAVOUR-IMIGO working group aims to explore novel predictive biomarkers for ICI response with a focus on imaging data. We present the baseline characteristics of first-line ICI “super-responders” with PFS ≥24 months, derived from three independent cohorts from Austria, Italy and the Netherlands. Also, an exploratory single-center analysis compared ICI super- to non-responders (PFS<6M) matched for age, sex, histology, PD-L1 positivity, stage and ECOG performance status. Results: The Linz (Austria) cohort reported 50 (12.4%) super-responders out of a total of 402 patients, the Milan cohort (Italy) 45 out of 283 (15.9%), and the Groningen cohort (Netherlands) 46 (10.7%) out of 428. As shown in table 1, all cohorts had a high prevalence of adenocarcinomas, with KRAS mutations present in nearly half of patients and a mean PD-L1 expression of approximately 50%. In the Austrian cohort, matched baseline data showed a higher frequency of systemic steroids among non-responders, and lower absolute neutrophil count as well as neutrophil-to -lymphocyte ratio in super-responders. Conclusions: Baseline characteristics of ICI super-responders were similar in three European cohorts, with a majority of high-PD-L1 expressing adenocarcinomas. Exploratory matched analyses from one cohort showed implications of baseline systemic steroid treatment as well as of differential blood cell count. Linz Milan Groningen PFS < 6M n = 50(matched) PFS ≥ 2Y n = 50 p value < 6M vs. ≥ 2Y PFS ≥ 2Y n = 45 PFS ≥ 2Y n = 46 Male sex, n (%) 24 (48) 25 (50) 0.841 34 (75.5) 22 (48) Age <70, n (%) 14 (28) 15 (30) 0.826 15 (33.3) 34 (74) ECOG, n (%) 0 25 (50) 24 (48) 0.768 21 (47) 18 (39) 1 16 (32) 19 (38) 23 (51) 23 (50) 2+ 9 (18) 7 (14) 1 (2) 5 (11) Histological subtype, n (%) Adenocarcinoma 36 (72) 36 (72) 0.341 30 (67) 33 (72) Squamous cell carcinoma 12 (24) 14 (28) 6 (13) 7 (15) Other 2 (4) 0 (0) 9 (20) 6 (13) PD-L1 expression %, mean (SD) 41.9 (36.8) 48.9 (38.8) 0.403 52.3 (35.4) 54.0 (39.0) Brain metastases, n(%) 16 (32) 13 (26) 0.509 14 (31) 7 (15) KRAS mutation, n (%) 12 (35) 18 (50) 0.214 19 (42) 23 (50) Treatment, n (%) Chemo-ICI combination 29 (58) 38 (76) 0.056 18 (40) 19 (41) ICI-monotherapy 21 (42) 12 (24) 27 (60) 27 (59) Systemic steroid treatment, n(%) 17 (34) 6 (12) 0.009 12 (27) 8 (17) Absolute neutrophil count (G/L), mean (SD) 11.5 (8.7) 7.7 (2.9) 0.015 6.8 (3.2) 7.3 (2.6) Absolute lymphocyte count (G/L), mean (SD) 1.7 (3.7) 1.4 (0.7) 0.071 1.9 (0.7) 1.6 (0.7) Neutrophil-to-lymphocyte ratio, mean (SD) 13.4 (11.0) 7.2 (5.2) 0.006 4.4 (3.6) 5.9 (4.0)

Little is known regarding tumour target saturation by the programmed death-ligand (PD-L1) antibody atezolizumab. Therefore, tumour saturation by the PD-L1 antibody atezolizumab in patients with advanced solid tumours was assessed using 89Zr-atezolizumab PET imaging. Patients received 10 mg 89Zr-atezolizumab after the initial 2 cycles of 1200 mg atezolizumab, followed by PET/CT scans. Tracer uptake was calculated as tumour standardized uptake value (SUV)max, normal tissues SUVmean, and tumour-to-background ratio SUVmax/SUVmax tumour. Tumour biopsies were obtained around day 7 of both cycles for autoradiography and PD-L1 immunohistochemistry. Findings were compared with previously reported pretreatment 89Zr-atezolizumab PET/CT data. Geometric mean tumour SUVmax day 7 was similar between cycle 1 (5.5, 95% CI, 4.4–6.9) and 2 (5.4, 95% CI, 4.3–6.8, N = 13, P = 0.88). Geometric mean tumour-to-background ratio was 1.67 (95% CI, 1.15–2.41) and 1.53 (N = 11, 95% CI, 1.05–2.21, P = 0.32), respectively. Higher tumour-to-background ratios showed a positive trend with best overall response ptrend 0.069. Autoradiography signal was present in tumour biopsies. On-treatment uptake was lower in the lesions and spleen, with a higher blood pool SUVmean than pre-treatment. Compared to earlier reported pre-treatment 89Zr-atezolizumab PET/CT results, 89Zr-atezolizumab tumour uptake during treatment is lower, suggesting partial PD-L1 tumour saturation during atezolizumab treatment. NCT02453984, NCT02478099

Importance Optimizing treatment decisions in metastatic breast cancer (MBC) can alleviate patients’ burden and improve quality of life. Whether 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) can be used to better estimate outcomes is unknown. Objective To evaluate clinical utility of early metabolic change on FDG-PET for improving outcome estimation compared with standard diagnostic evaluation in patients with newly diagnosed MBC. Design, Setting, and Participants The multicenter IMPACT-MBC clinical cohort trial enrolled patients with nonrapidly progressive, newly diagnosed MBC from August 2013 to May 2018, before initiation of first-line systemic therapy. Baseline assessment included metastasis biopsy procedure and FDG-PET and CT imaging. Early FDG-PET was performed after 2 weeks of treatment, and CT response evaluation after 8 weeks. Clinical utility was defined as the ability of early FDG-PET to estimate progressive disease (PD) on CT, progression-free survival (PFS), and overall survival (OS). Data were analyzed from October 19, 2025, to February 13, 2026. Intervention Early FDG-PET or standard-of-care (SOC) biopsy-based treatment. Main Outcomes and Measures Clinical utility of molecular imaging to improve outcome estimation of standard diagnostics defined as the capacity to identify poor patient outcomes. Measures were PD at 8 weeks, PFS, and OS. Results The analysis included 200 patients (median [range] age, 61 [32-84] years; 198 females [99%] and 2 males [1%]). Non-PD on early FDG-PET had a negative predictive value (NPV) of 94.7% (95% CI, 89.5%-97.4%) for non-PD on 8-week CT. This was similar in all MBC subtypes and bone-only disease. Patients with SOC treatment and non-PD on early FDG-PET (n = 133) had a median PFS of 19.4 (95% CI, 15.2-22.8) months and OS of 39.4 (95% CI, 33.7-48.3) months compared to 4.1 (95% CI, 3.3-15.5) months and 18.5 (95% 3 CI, 7.0-33.0) months, respectively ( P < .001 for both). Patients with non-PD on 8-week CT but with PD on early FDG-PET had a median (IQR) PFS and OS of 9.5 (4.1-18.1) and 19.4 (8.7-33.0) months compared to 22.3 (15.3-96.1) months and 40.1 (23.4-72.7) months without PD. Conclusions and Relevance In this clinical cohort trial of patients with nonrapidly progressive, newly diagnosed MBC before initiation of first-line systemic therapy, early FDG-PET after only 2 weeks of treatment identified patients with MBC with distinct long-term outcomes. Incorporating early FDG-PET can improve outcome estimation of standard CT assessment. Trial Registration ClinicalTrials.gov Identifier: NCT01957332

Background: Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was conducted to address this. Materials and Methods: Brain metastasis patients showing progression on MRI according to response assessment in neuro-oncology brain metastases criteria after starting ICI therapy were included, irrespective of prior irradiation. Lesions were classified as tumour progression (TP) or pseudoprogression based on three-month radiological follow-up or histopathology. TP was assigned if progression was again shown at three months. Pseudoprogression was assigned if lesions showed stability, partial, or complete response at three months. ‘Non-classified’ lesions were those with new or changed treatment during follow-up. Results: A cohort of 98 patients with 233 lesions was included over a 13-year period; 170 lesions were considered non-classified, and 41 and 22 lesions were classified as TP and pseudoprogression respectively. This resulted in a lesion- and patient-specific incidence for pseudoprogression of 9.4% and 17.3% respectively. Due to the large number of lesions that could not be classified, as is the case in clinical practice, the reported incidence in this study is likely an underestimation and can be seen as a ‘minimum’ incidence rate. Ten pseudoprogression (45.5%) and 13 (31.7%) TP lesions were previously irradiated. Pseudoprogression occurred at a median of 2.7 months after starting ICI therapy. The only clinical feature distinguishing patients with TP from pseudoprogression was that TP patients were more likely to need dexamethasone for neurological symptoms. Conclusions: Pseudoprogression has a lesion-specific incidence rate of at least 9.4% and occurs at a median of 2.7 months after starting ICI therapy. Severe neurological symptoms requiring dexamethasone may be a clinical feature typical for TP.

BACKGROUND:Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). Although guidelines recommend baseline BM screening in asymptomatic patients, its benefit remains unproven. Routine imaging burdens healthcare systems and patients. Immune checkpoint inhibitors (ICI) show similar intra-and extracranial response percentages, supporting deferral of local BM treatment and possibly screening. However, dissociated responses occur. Therefore, patients newly diagnosed with BM during first-line ICI probably would have benefited most from baseline (and follow-up) screening. Identifying high-risk patients for BM progression or development during first-line ICI-based therapy is crucial to optimize screening. METHODS:Retrospective multicenter cohort study of patients with stage IV NSCLC without known baseline BM, treated with first-line (chemo-)ICI between 2018-2021. Incidence, timing, and symptom burden of newly diagnosed BM were analyzed. Cox regression identified predictive factors, and a nomogram was developed. RESULTS:Among 589 patients, BM were diagnosed during therapy in 9.0 %, 88.7 % occurred within the first year. Most cases (90.6 %) were symptomatic. Four factors predicted higher BM risk: age < 65 years (HR 2.66; 95 % CI: 1.49-4.74), T4 stage (HR 2.08; 95 % CI: 1.18-3.65), M1c stage (HR 2.19; 95 % CI: 1.22-3.94) and PD-L1 < 50 % (HR 2.03; 95 % CI: 1.16-3.54). The nomogram showed good performance (C-index 0.70). Twelve-month cumulative incidence was 11.7 % (95 % CI: 8.5-14.9 %). CONCLUSION:BM detection during first-line (chemo-)ICI is relatively low in patients with stage IV NSCLC without known baseline BM, but the burden (symptoms) is high. Upon validation, the identified risk factors may support selective brain imaging in high-risk patients, avoiding routine screening in low-risk patients.

Understanding which patients with human epidermal growth factor receptor 2 (HER2)-negative or -low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on 89Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization.89Zr-trastuzumab uptake was quantified as SUVmax and SUVmean HER2 immunohistochemistry was related to the quantitative 89Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, 89Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUVmax of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79-0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy.

1019 Background: Optimizing patient outcome prediction in metastatic breast cancer (MBC) can potentially reduce patients’ and healthcare burden. Molecular imaging to visualize early metabolic change, baseline whole-body human epidermal growth factor receptor-2 (HER2) and estrogen receptor (ER) expression might achieve this. In the prospective multicenter IMPACT study, we evaluated the clinical utility of molecular imaging to improve standard diagnostics in patients with newly diagnosed MBC of all subtypes. Methods: Patients underwent extensive workup, including baseline metastasis biopsy, [18F]FDG-PET, [89Zr]trastuzumab-PET (HER2-PET), [18F]FES-PET, and early [18F]FDG-PET after 2 weeks. Treatment was based on HER2 or ER subtype determined in biopsy (immunohistochemistry, IHC; standard-of-care) or PET findings (HER2- and [18F]FES-PET; investigational) in case of negative biopsy but positive HER2 and/or [18F]FES-PET scan. Clinical utility of molecular imaging was defined as the capacity to identify poor patient outcome, measured as progressive disease (PD) on CT at 8 weeks, progression-free survival (PFS), and overall survival (OS). Results: Two hundred patients were included. Progression on early [18F]FDG-PET was related to poor outcome in all subtypes (median PFS 4.1 versus 19.4 months, OS 19.4 versus 45.0 months). Early [18F]FDG-PET correctly predicted non-PD on 8 week CT (specificity 90.5%, negative predictive value 94.1%), but sensitivity and positive predictive value for PD was low (50 and 37.5%, respectively). However, early [18F]FDG-PET related better to long-term outcome than CT: patients with non-PD on 8 week CT, but with progression on early [18F]FDG-PET, had a median PFS and OS of 9.5 and 22.3 months respectively, compared to 19.4 and 50.1 months without [18F]FDG-PET progression (PFS HR 1.76 (95%CI 1.0 – 2.9), OS HR 1.93 (1.0 – 3.5)). HER2 or ER subtype was discrepant between biopsy and PET in 52 out of 200 (26%) patients, yielding investigational PET-based treatment options in 41 (21%) patients. In patients with HER2-positive biopsy IHC disease who received standard HER2-targeting treatment, median PFS with positive- versus negative HER2-PET was 23.2 and 4.5 months, respectively. In patients with biopsy IHC HER2-negative disease but positive HER2-PET, median PFS was with investigational HER2-targeted treatment 11.4 months, without 7.4 months. The pattern was similar in ER-positive disease, although less pronounced for biopsy- and PET-based subtypes. Conclusions: This study supports the clinical utility of molecular imaging with [18F]FDG-PET, HER2-PET, and [18F]FES-PET, to improve standard diagnostics for outcome and subtype assessment in patients with newly diagnosed MBC. Clinical trial information: NCT01957332 .

Background: In metastatic breast cancer (MBC), [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [18F]FDG uptake in corresponding metastases. Patients and Methods: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [18F]FDG-PET. Biopsies were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (ER, PR, HER2); Ki-67; and histological subtype. [18F]FDG uptake was expressed as maximum standardized uptake value (SUVmax) and results were expressed as geometric means. Results: Of 200 patients, 188 had evaluable metastasis biopsies, and 182 of these contained tumor. HER2 positivity and Ki-67 ≥ 20% were correlated with higher [18F]FDG uptake (estimated geometric mean SUVmax 10.0 and 8.8, respectively; p = 0.0064 and p = 0.014). [18F]FDG uptake was lowest in ER-positive/HER2-negative BC and highest in HER2-positive BC (geometric mean SUVmax 6.8 and 10.0, respectively; p = 0.0058). Although [18F]FDG uptake was lower in invasive lobular carcinoma (n = 31) than invasive carcinoma NST (n = 146) (estimated geometric mean SUVmax 5.8 versus 7.8; p = 0.014), the metastasis detection rate was similar. Conclusions: [18F]FDG-PET is a powerful tool to detect metastases, including invasive lobular carcinoma. Although BC histopathological characteristics are related to [18F]FDG uptake, [18F]FDG-PET and biopsy remain complementary in MBC staging (NCT01957332).

Abstract Background: Anti-HER2 antibody drug conjugates (ADCs) can assert an effect in part of patients with HER2-low breast cancer. In light of patient burden and financial sustainability, biomarkers to select responding patients are urgently needed, but so far, none have been identified. In the IMPACT trial (NCT01957332), patients with newly diagnosed and non-rapidly progressive metastatic breast cancer (MBC) of all subtypes (including HER2-negative, -low, and –positive disease) were included. We assessed the performance of Zirconium-89 (89Zr)-trastuzumab positron emission tomography (HER2-PET) in HER2-low and negative MBC. Methods: All patients received extensive workup, including a metastasis biopsy and HER2-PET at baseline. HER2 status was determined by immunohistochemistry (IHC) and in situ hybridization. ⁸⁹Zr-trastuzumab uptake was quantified as maximum and mean standardized uptake values (SUVmax, SUVmean) in metastases and healthy background tissue. Quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, was related to HER2 IHC status. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases. With increasing HER2 IHC status, uptake was higher (geometric mean SUVmax 7.0, 7.6, 7.3, and 17.4 with HER2 IHC 0, 1, 2, or 3+, in respectively 71, 71, 20, and 24 biopsied metastases (P  0.001 between IHC 0 and 3+). SUVmax in lesions was heterogeneous within and between patients for all HER2 IHC groups. All HER2 IHC groups, also HER2-negative and -low, had uptake exceeding that of the healthy background (geometric mean tumor-to-background ratio SUVmax >1 in all groups, increasing with higher HER2 IHC). Of patients with a HER2 IHC 0 biopsy, 27.8% had at least one metastasis elsewhere in the body, with uptake exceeding the overall 90th SUVmax percentile of 14.6; in HER2 low IHC1+ and 2+, this was 31.9% and 30%. Conclusions: In this largest series with HER2-PET in patients with MBC, we show that ±30% of patients with HER2-low or -negative IHC in the biopsy, in fact, have metastases with high HER2 uptake elsewhere in the body. This spatial heterogeneity provides novel insights into HER2-negative and -low disease compared to standard HER2 IHC of a single biopsy. As HER2-PET uptake is related to ADC response in HER2 positive MBC1, HER2-PET is a potential biomarker for anti-HER2 ADC effect in HER2-low and -negative MBC as well. Reference: 1. Gebhart G, et al. Ann Oncol 2016;27(4): 619-624. Supported by the Dutch Cancer Society grant 2012-5565 Citation Format: Carolien Schroder, Jasper van Geel, Bertha Eisses, Adrienne Brouwers, Sjoerd Elias, Frederike Bensch, Evelien Kuip, Agnes Jager, Andor Glaudemans, Bert van der Vegt, Willemien Menke-van der Houven van Oordt, Elisabeth de Vries. Spatial HER2 heterogeneity on HER2-PET in HER2-low and negative disease: potential biomarker for antibody-drug conjugate effect [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-13-03.

BACKGROUND:The number of solitary pulmonary nodules to be evaluated is expected to increase and therefore we need to improve diagnostic and therapeutic tools to approach these nodules. To prevent patients from futile invasive procedures and receiving treatment without histological confirmation of cancer, we evaluated the value of virtual bronchoscopy navigation to obtain a diagnosis of the solitary pulmonary nodule in a real-world clinical setting.METHODS:In the NAVIGATOR single center, prospective, observational cohort study patients underwent a virtual bronchoscopy navigation procedure with or without guide sheet tunnelling to assess a solitary pulmonary nodule. Nodules were considered not accessible if a diagnosis could not be obtained by either by CT-guided transthoracic biopsy or conventional bronchoscopy.RESULTS:Between February 2021 and January 2022 35 patients underwent the virtual bronchoscopy navigation procedure. The overall diagnostic yield was 77% and was dependent on size of the nodule and chosen path, with highest yield in lesions with an airway path. Adverse events were few and manageable.CONCLUSION:Virtual bronchoscopy navigation with or without sheet tunnelling is a new technique with a good diagnostic yield, also in patients in whom previously performed procedures failed to establish a diagnosis and/or alternative procedures are considered not feasible based on expected yield and/or safety. Preventing futile or more invasive procedures like surgery or transthoracic punctures with a higher complication rate is beneficial for patients, and allowed treatment adaptation in two-third of the analyzed patient population.

Aim: Retrospective analysis of the safety and efficacy of extended interval dosing (EI) ICI compared to standard dose (SD) schedules. Results: 117 patients received EI dosing and 88 SD. In the EI dosing cohort was no increase in toxicity leading to dose reduction and/or discontinuation of treatment. Furthermore, efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seem a safe and effective strategy and should be continued also beyond the COVID-19 pandemic. Introduction: Extended interval (EI) dosing for immune checkpoint inhibitor (ICI) mono- or consolidation therapy initiated due to the COVID-19 pandemic led to a significant reduction in ICI-related site visits for patients with stage III and IV non-small cell lung cancer. Here we report the safety and efficacy compared to standard dose (SD) schedules. Method: In this retrospective analysis, patients who received ICI mono- or consolidation therapy, or adjuvant ICI therapy were assessed. Safety and efficacy of EI dosing with data of SD schedules were compared. Results: One hundred seventeen patients received EI dosing for ICI and 88 patients SD. Patient characteristics were comparable. We observed 237 adverse events in the EI dosing cohort versus 118 in the SD group (P = .02). Overall, there was no difference in the occurrence of grade >= 3 adverse events (EI dosing: 21/237 [8.9%]; SD group: 20/118 [17.0%], P = .42), except for the pembrolizumab EI dosing cohort. Of all patients who received an EI dosing schedule, however, only 8 (6.8%) were reduced to SD because of toxicity. In 5 (4.3%) patients ICI was permanently stopped because of severe toxicity compared to 11 (12.5%) discontinuations in the SD group. Short-term treatment interruption occurred with similar frequencies in both groups. Progression-free survival and overall survival were comparable in patients receiving pembrolizumab and in those receiving adjuvant durvalumab. Progression-free survival and OS were better in the EI dosing cohort of nivolumab. Conclusion: EI dosing for ICI did not lead to an increase of clinically relevant toxicities resulting in dose reduction and/or treatment discontinuation. Efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seems a safe and effective strategy. (C) 2021 The Authors. Published by Elsevier Inc.

The COVID-19 pandemic forced all oncologists worldwide to reduce patient contacts to decrease risk of exposure to the virus, and to reallocate resources to provide necessary COVID-19 care. We realized such a reduction of site-visits in our center by adapting the dosing schedules of nivolumab and pembrolizumab monotherapy and consolidation therapy or adjuvant durvalumab for patients with stage III and IV non-small cell lung cancer (NSCLC). Here we report the toxicity of the adapted dose versus the standard dose schedule in a real-world NSCLC population.

It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by 18F-FDG PET instead of 99mTc bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by 18F-FDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and 18F-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either 18F-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 102 evaluated patients (39% by ceCT, 26% by BS, and 87% by 18F-FDG PET). Additional bone lesions on 18F-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%-24%). BS also changed management compared with 18F-FDG PET in 1 patient (1%; 95% CI, 0%-5%). In 26% (95% CI, 19%-36%) of patients, an additional 18F-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, 18F-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for 18F-FDG PET. On the basis of these data, 18F-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC.

In-vivo quantification of tumor uptake of 89-zirconium (89Zr)-labelled monoclonal antibodies (mAbs) with PET provides a potential tool in strategies to optimize tumor targeting and therapeutic efficacy. A specific challenge for 89Zr-immuno-PET is low tumor contrast. This is expected to result in interobserver variation in tumor delineation. Therefore, the aim of this study was to determine interobserver reproducibility of tumor uptake measures by tumor delineation on 89Zr-immuno-PET scans. Data were obtained from previously published clinical studies performed with 89Zr-rituximab, 89Zr-cetuximab and 89Zr-trastuzumab. Tumor lesions on 89Zr-immuno-PET were identified as focal uptake exceeding local background by a nuclear medicine physician. Three observers independently manually delineated volumes of interest (VOI). Maximum, peak and mean standardized uptake values (SUVmax, SUVpeak and SUVmean) were used to quantify tumor uptake. Interobserver variability was expressed as the coefficient of variation (CoV). The performance of semi-automatic VOI delineation using 50% of background-corrected ACpeak was described. In total, 103 VOI were delineated (3–6 days post injection (D3-D6)). Tumor uptake (median, interquartile range) was 9.2 (5.2–12.6), 6.9 (4.0–9.6) and 5.5 (3.3–7.8) for SUVmax, SUVpeak and SUVmean. Interobserver variability was 0% (0–12), 0% (0–2) and 7% (5–14), respectively (n = 103). The success rate of the semi-automatic method was 45%. Inclusion of background was the main reason for failure of semi-automatic VOI. This study shows that interobserver reproducibility of tumor uptake quantification on 89Zr-immuno-PET was excellent for SUVmax and SUVpeak using a standardized manual procedure for tumor segmentation. Semi-automatic delineation was not robust due to limited tumor contrast.