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• MDT decision-making for stage III NSCLC was studied between 2015–2017. • Surgery or chemo-radiotherapy were recommended in just 61 % of patients. • Deaths from NSCLC at ≤2 years were seen in 41–43 % after all treatments. • Better tolerated and more effective treatments are needed in stage III NSCLC. Treatment patterns in patients with stage III non-small cell lung cancer (NSCLC) vary considerably between countries, for reasons that are not well understood. We studied factors influencing treatment decision-making at thoracic multidisciplinary tumor boards (MDT's) and outcome for patients treated between 2015–2017, at a regional network comprising 5 hospitals. Details of all patients, including comorbidities, with stage III NSCLC were collected in an ethics-approved database. Weekly MDT's were conducted. The preferred radical intent treatments (RIT) for suitable patients were assumed to be concurrent chemoradiotherapy and/or surgery and other therapies were non-radical intent treatments (n-RIT). Of 197 patients identified, 95 % were discussed at an MDT. RIT were recommended in 61 % of patients, but only 48 % finally received RIT. The estimated median OS was significantly better for patients undergoing RIT (28.3 months, CI-95 % 17.3–39.3), versus those who did not (11.2 months, CI-95 % 8.0−14.3). Patient age ≥70 years and a WHO-PS ≥2 were the most important predictors of not recommending RIT. Deaths due to progressive lung cancer within 2 years were observed in 36, 26 and 29 % of patients who received RIT, sequential chemoradiotherapy or radical radiotherapy. Corresponding comorbidity related deaths within 2 years were 3, 12 and 38 %. A large number of patients who underwent MDT review were considered too old or not fit for RIT. More effective and better tolerated systemic treatments are required for patients presenting with stage III NSCLC. [ABSTRACT FROM AUTHOR]

We studied treatment patterns for adrenal metastases using surgery or SABR at a single institution during a 10-year period. The number of patients undergoing SABR doubled since 2016, without a change in numbers undergoing surgery. Both treatments resulted in low rates of acute toxicity and similar survivals. [ABSTRACT FROM AUTHOR]

Summary: Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, a study was performed in non-small cell lung cancer (NSCLC) patients using positron emission tomography (PET) and radiolabeled docetaxel ([11C]docetaxel). In NSCLC, bevacizumab reduced both perfusion and net influx rate of [11C]docetaxel within 5 hr. These effects persisted after 4 days. The clinical relevance of these findings is notable, as there was no evidence for a substantial improvement in drug delivery to tumors. These findings highlight the importance of drug scheduling and advocate further studies to optimize scheduling of anti-angiogenic drugs. [Copyright &y& Elsevier]

• 18F-afatinib PET/CT is a safe tool to quantify 18F-afatinib uptake in NSCLC tumors. • Tumor uptake of 18F-afatinib is higher in EGFR mutated NSCLC versus wild type EGFR. • There is no difference in tracer uptake between EGFR common and uncommon mutations. • A TBR_WB 60−90 value of ≥6 is predictive of response to treatment using afatinib. Non-small cell lung cancer (NSCLC) tumors harboring common (exon19del, L858R) and uncommon (e.g. G719X, L861Q) activating epidermal growth factor receptor (EGFR) mutations are best treated with EGFR tyrosine kinase inhibitors (TKI) such as the first-generation EGFR TKI erlotinib, second-generation afatinib or third-generation osimertinib. However, identifying these patients through biopsy is not always possible. Therefore, our aim was to evaluate whether 18F-afatinib PET/CT could identify patients with common and uncommon EGFR mutations. Furthermore, we evaluated the relation between tumor 18F-afatinib uptake and response to afatinib therapy. 18F-afatinib PET/CT was performed in 12 patients: 6 EGFR wild type (WT), 3 EGFR common and 3 EGFR uncommon mutations. Tumor uptake of 18F-afatinib was quantified using TBR_WB 60−90 (tumor-to-whole blood activity ratio 60−90 min post-injection) for each tumor. Response was quantified per lesion using percentage of change (PC): [(response measurement (RM)–baseline measurement (BM))/BM]×100. Statistical analyses were performed using t-tests, correlation plots and sensitivity/specificity analysis. Twenty-one tumors were identified. Injected dose was 348 ± 31 MBq. Group differences were significant between WT versus EGFR (common and uncommon) activating mutations (p = 0.03). There was no significant difference between EGFR common versus uncommon mutations (p = 0.94). A TBR_WB 60−90 cut-off value of 6 showed the best relationship with response with a sensitivity of 70 %, a specificity of 100 % and a positive predictive value of 100 %. 18F-afatinib uptake was higher in tumors with EGFR mutations (common and uncommon) compared to WT. Furthermore, a TBR_WB 60−90 cut-off of 6 was found to best predict response to therapy. 18F-afatinib PET/CT could provide a means to identify EGFR mutation positive patients who benefit from afatinib therapy. [ABSTRACT FROM AUTHOR]

• Salvage surgery for local recurrence should be considered in selected patients. • Salvage pneumonectomy is associated with minimal morbidity and mortality. • DFS and OS are better in patients in whom an R0 resection was performed. • Recurrence and subsequent surgery more than 12 months after CRT seem to do better. Locoregional recurrence and persistent/progressive disease after curative-intent definitive chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is challenging to manage, as salvage options are limited. Selected patients might be candidates for resection. This study evaluated the outcomes of patients after salvage surgery for locoregional recurrence, focusing specifically on morbidity and mortality after salvage pneumonectomy. This retrospective study included patients from 2 tertiary referral hospitals who underwent salvage pulmonary resection for locoregional recurrence or disease persistence/progression >12 weeks after completion of curative intent high dose (>60 Gy) CRT. Disease-free (DFS) and overall survival (OS) were estimated and the influence of patient and treatment characteristics on these endpoints was assessed. A total of 30 patients treated between 2015–2017 were identified with a median age of 60 years (range 42–72 years), 67 % were male. Median follow-up was 47 months (95 % CI 46-NR). Pneumonectomy was performed in 13/30 (43 %) patients and lobectomy in 17/30 (57 %). Median DFS and OS after pneumonectomy/lobectomy were 14/6 and NR/17 months, respectively. 30 and 90-day mortality for pneumonectomy/lobectomy were 0/12 % and 0/24 % respectively. More favorable survival was seen after pathologically radical resection, i.e. R0, and when surgery was performed more than 12 months after completion of CRT. Salvage surgery, including pneumonectomy is associated with acceptable outcomes in selected patients with recurrent or persistent/progressive NSCLC after curative-intent high dose CRT. Patients should be assessed for the probability of an R0 resection, and patients with a locoregional recurrence more than 12 months after treatment with CRT may benefit most from salvage surgery. [ABSTRACT FROM AUTHOR]

• ctDNA testing of NSCLC patients with complex treatment history in clinical setting. • A trend between ctDNA detection and progression under osimertinib in 2nd / 3rd line. • Monitoring response with ctDNA may benefit patients following previous EGFR-TKIs. Circulating tumor (ct)DNA analysis is rapidly gaining acceptance as a diagnostic tool to guide clinical management of advanced non-small cell lung cancer (NSCLC). Clinically-actionable EGFR mutations can be detected in ctDNA before or after first-line EGFR-Tyrosine Kinase Inhibitor (TKI) treatment, but data are limited for patients with a complex treatment history. This study aimed to explore the feasibility of ctDNA testing in a clinical setting of NSCLC patients receiving osimertinib as a second or third line EGFR-TKI. Twenty EGFR T790M-positive NSCLC patients, who had received osimertinib as a second or third line EGFR-TKI and had donated blood samples while attending routine follow-up consultations between April and November 2016, were retrospectively selected to test plasma cfDNA for tumor-guided EGFR mutations. We used EGFR mutations previously identified in tumor-tissue to retrospectively test plasma ctDNA from 20 patients who had received osimertinib as a second or third line EGFR-TKI. Both EGFR-TKI sensitising and T790 M resistance mutations were analysed by droplet digital PCR (ddPCR) in plasma taken alongside routine consultations and ctDNA detection was correlated with response under osimertinib. Follow-up solid-tissue biopsies were obtained after disease progression. CtDNA was detected under osimertinib treatment in four out of the eight patients (50 %) who showed no response, two out of the seven (29 %) who showed an initial response and none of the five patients (0 %) who showed an ongoing response. The fraction of EGFR -mutant ctDNA in plasma tended to be higher in non-responders (0.1–68 %), compared to the initial responders (0.2–1.1 %). Blood samples were donated up to 34, 27 and 49 weeks after the start of osimertinib for the non-, initial and ongoing responders, respectively. These findings support a potential role for ctDNA analysis in response monitoring of NSCLC patients with a complex EGFR-TKI treatment history. The weak trend between ctDNA detection and disease progression warrants larger studies to further investigate potential clinical utility. [ABSTRACT FROM AUTHOR]

Introduction Erlotinib is a tyrosine kinase inhibitor prescribed for non-small cell lung cancer (NSCLC) patients bearing epidermal growth factor receptor mutations in the kinase domain. The objectives of this study were to (1) establish a human dosimetry profile of [ 11 C]erlotinib and (2) assess the consistency of calculated equivalent dose across species using the same dosimetry model. Methods Subjects examined in this multi-species study included: a stage IIIa NSCLC patient, 3 rhesus macaque monkeys, a landrace pig, and 4 athymic nude-Fox1nu mice. [ 11 C]erlotinib PET data of the whole body were acquired dynamically for up to 120 min. Regions of interest (ROIs) were manually drawn to extract PET time activity curves (TACs) from identifiable organs. TACs were used to calculate time-integrated activity coefficients (residence times) in each ROI, which were then used to calculate the equivalent dose in OLINDA. Subject data were used to predict the equivalent dose to the organs of a 73.7 kg human male. Results In three of four species, the liver was identified as the organ receiving the highest equivalent dose (critical organ). The mean equivalent doses per unit of injected activity to the liver based on human, monkey, and mouse data were 29.4 μSv/MBq, 17.4 ± 6.0 μSv/MBq, and 5.27 ± 0.25 μSv/MBq, respectively. The critical organ based on the pig data was the gallbladder wall (20.4 μSv/MBq) but the liver received a nearly identical equivalent dose (19.5 μSv/MBq). Conclusions (1) When designing PET studies using [ 11 C]erlotinib, the liver should be considered the critical organ. (2) In organs receiving the greatest equivalent dose, mouse data underestimated the dose in comparison to larger species. However, the effective dose of [ 11 C]erlotinib to the whole body of a 73.7 kg man was predicted with good consistency based on mice (3.14 ± 0.05 μSv/MBq) or the larger species (3.46 ± 0.25 μSv/MBq). [ABSTRACT FROM AUTHOR]

Objectives Development of leptomeningeal metastasis (LM) in non-small cell lung cancer (NSCLC)-patients is associated with a poor prognosis. It has been suggested that LM-patients with epidermal growth factor receptor mutated ( EGFR +) NSCLC have a superior prognosis compared to EGFR -wild type NSCLC. Studies in EGFR + NSCLC-patients with LM are scarce. We retrospectively evaluated a multi-institutional cohort of EGFR + NSCLC-patients for LM to assess clinical outcome in relation to patient characteristics and treatment modalities. Material and methods Medical records of advanced-stage EGFR + NSCLC-patients (diagnosed between August 2000 and June 2014) from 11 Dutch hospitals were evaluated for LM as diagnosed by MRI and/or cytopathological liquor analysis. Data on patient characteristics, treatment and outcome were collected. Results Thirty-two of 356 (9.0%) advanced-stage EGFR + NSCLC-patients (median follow-up 21.0 months), were diagnosed with LM between 2006 and 2014. LM was diagnosed by MRI (59.4%), liquor analysis (9.4%) or by both MRI and liquor analysis (31.3%). Median survival after LM-diagnosis was 3.1 months (95% CI: 0.0–7.3). Six- and 12-month survival rates were 43.8% and 18.8%, respectively. Patients with performance status (PS) 0–1 at time of diagnosis of LM had a significantly higher chance to be alive after 6 months and had a significantly longer survival after diagnosis of LM compared to patients with PS ≥ 2. Age, treatment with high-dose EGFR-TKI, radiotherapy and whether LM was the only site of progressive disease did not influence survival after LM-diagnosis. Conclusion Although median survival after LM-diagnosis in EGFR -mutated NSCLC-patients was poor, a substantial part of the patients had a prolonged survival of more than 6 months. PS of 0–1 at time of diagnosis of LM was associated with prolonged survival. No other patient- or treatment-related characteristics were identified. Further research is warranted to identify treatment strategies that improve survival in EGFR + NSCLC-patients with LM. [ABSTRACT FROM AUTHOR]