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Background: ImmunoPET is a multicentre, single arm, phase 0-1 study that aims to establish if 89 Zr-durvalumab PET/CT can be used to interrogate the expression of PD-L1 in larger, multicentre clinical trials., Methods: The phase 0 study recruited 5 PD-L1+ patients with metastatic non-small cell lung cancer (NSCLC). Patients received 60MBq/70 kg 89 Zr-durva up to a maximum of 74 MBq, with scan acquisition at days 0, 1, 3 or 5±1 day. Data on (1) Percentage of injected 89 Zr-durva dose found in organs of interest (2) Absorbed organ doses (µSv/MBq of administered 89 Zr-durva) and (3) whole-body dose expressed as mSv/100MBq of administered dose was collected to characterise biodistribution.The phase 1 study will recruit 20 patients undergoing concurrent chemoradiotherapy for stage III NSCLC. Patients will have 89 Zr-durva and FDG-PET/CT before, during and after chemoradiation. In order to establish the feasibility of 89 Zr-durva PET/CT for larger multicentre trials, we will collect both imaging and toxicity data. Feasibility will be deemed to have been met if more than 80% of patients are able complete all trial requirements with no significant toxicity., Ethics and Dissemination: This phase 0 study has ethics approval (HREC/65450/PMCC 20/100) and is registered on the Australian Clinical Trials Network (ACTRN12621000171819). The protocol, technical and clinical data will be disseminated by conference presentations and publications. Any modifications to the protocol will be formally documented by administrative letters and must be submitted to the approving HREC for review and approval., Trial Registration Number: Australian Clinical Trials Network ACTRN12621000171819., Competing Interests: Competing interests: FH-J has clinical trial funding, has received honoraria and participated in advisory boards for Astra Zeneca. She has received payments and honoria from BeiGene and MSD for lectures and presentations. Her work is supported by the Peter Mac Foundation and the Victorian Cancer Agency. SER and PSD are inventors on intellectual property relating to the use of DFOSq that have been licensed from the University of Melbourne to Telix Pharmaceuticals. TJ has received payments and honoraria from BMS and Astra Zeneca for lectures and presentations, and sits on Data Safety and Monitoring Boards or Advisory boards for Roche, BMS, Astra Zeneca, Novartis, Amgen, Puma, MSD and Merck. SF has received payments and honoraria from Astra Zeneca, Roche, Amgen, Novartis, Bayer, GSK, BMS, MSD and Janssen for lectures and presentations. KB has received payments and honoraria from Bayer and Abbvie for lectures and presentations and participates on Data Safety and Monitoring boards for Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to describe the longitudinal thromboembolism (TE) risk relative to the natural history of disease and clinical course of ROS1 rearranged non-small cell lung cancer (NSCLC)., Materials and Methods: Cases of ROS1-rearranged NSCLC from six Australian hospitals were pooled and evaluated for incidence, timing, predictors and outcomes of venous or arterial TE, as well as objective response rate (ORR) to active therapy and overall survival (OS)., Results: Of 42 patients recruited, 20 (48%) experienced TE; one (2%) arterial, 13 (31%) a pulmonary emboli (PE), and 12 (29%) a deep vein thrombosis. Among those with TE, six (30%) experienced multiple events, three as concurrent and three as recurrent diagnoses. The cumulative incidence of TE over time, adjusted for death as a competing risk factor, approached 50%. TE occurred prior to, during and post the peri-diagnostic period and occurred irrespective of treatment strategy. A thrombophilia was identified in n = 3/10 (30%) cases screened: in two factor V Leiden and in one anti-thrombin III (ATIII) deficiency. Median OS was 21.3 months in those with TE vs. 28.8 months in those without; hazard ratio 1.16 (95%CI 0.43-3.15). Respective ORR to first-line therapy with TE was 50% vs. 44% without TE in the chemotherapy arm and 67% vs. 50% in the targeted therapy arm., Conclusion: In the rare cancer subtype, ROS1, these real-world data demonstrate sustained TE risk beyond the diagnostic period irrespective of therapeutic strategy. High incidence of PE, concurrent TE, and recurrent TE warrant validation in larger cohorts. Consideration of primary thromboprophylaxis in ROS1 populations is recommended., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest directly related to this work however acknowledge the following associations outside the submitted work. Dr. Alexander has nothing to disclose. Dr. Pavlakis reports personal fees from Boerhinger Ingelheim, personal fees from Takeda, personal fees from Astra Zeneca, personal fees from BMS, personal fees from MSD, personal fees and other from Roche, grants and personal fees from Pfizer, personal fees from Novartis, personal fees from Amgen, personal fees from Merck KgA, personal fees from Merck Serono, grants from Bayer, personal fees from Ipsen, outside the submitted work. Dr. John reports personal fees from Ignyta, personal fees from Roche, personal fees from AstraZeneca, personal fees from Novartis, personal fees from Pfizer, personal fees from Merck, personal fees from BMS, outside the submitted work. Dr. O’Connell has nothing to disclose; Dr. Kao reports personal fees from Pfizer, personal fees from Novartis, personal fees from Roche, during the conduct of the study; personal fees from Boehringer, personal fees from BMS, personal fees from MSD, grants and personal fees from Astra Zeneca, outside the submitted work. Dr. Hughes reports personal fees from Pfizer, personal fees from Roche, personal fees from Merck Sharpe and Dohme, personal fees from Bristol Meyers Squibb, personal fees from AstraZeneca, grants from Amgen, outside the submitted work. Dr. Lee reports personal fees from Munipharma, outside the submitted work; Dr. Hayes has nothing to disclose. Dr. Howell has nothing to disclose. Dr. Clarke has nothing to disclose. Dr. Millward reports personal fees from Pfizer, during the conduct of the study; personal fees from Astra-Zeneca, personal fees from Bristol Myers Squibb, personal fees from Roche, personal fees from Merck Sharp & Dohme, outside the submitted work. Dr. Burbury has nothing to disclose. Dr. Solomon reports personal fees from Pfizer, personal fees from Roche/Genetech, personal fees from Novartis, personal fees from Merck, personal fees from Bristol Myers Squibb, personal fees from AstraZeneca, personal fees from Loxo Oncology, outside the submitted work. Dr. Itchins reports personal fees from Pfizer, personal fees from Roche, outside the submitted work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Non-small-cell lung cancer outcomes are poor but heterogeneous, even within stage groups. To improve prognostic precision we aimed to develop and validate a simple prognostic model using patient and disease variables., Methods: Prospective registry and study data were analysed using Cox proportional hazards regression to derive a prognostic model (hospital 1, n=695), which was subsequently tested (Harrell's c-statistic for discrimination and Cox-Snell residuals for calibration) in two independent validation cohorts (hospital 2, n=479 and hospital 3, n=284)., Results: The derived Lung Cancer Prognostic Index (LCPI) included stage, histology, mutation status, performance status, weight loss, smoking history, respiratory comorbidity, sex, and age. Two-year overall survival rates according to LCPI in the derivation and two validation cohorts, respectively, were 84, 77, and 68% (LCPI 1: score⩽9); 61, 61, and 42% (LCPI 2: score 10-13); 33, 32, and 14% (LCPI 3: score 14-16); 7, 16, and 5% (LCPI 4: score ⩾15). Discrimination (c-statistic) was 0.74 for the derivation cohort, 0.72 and 0.71 for the two validation cohorts., Conclusions: The LCPI contributes additional prognostic information, which may be used to counsel patients, guide trial eligibility or design, or standardise mortality risk for epidemiological analyses.

Introduction: We addressed the uncertainty of comorbidity as a prognosticator by evaluating comorbidity and the Simplified Comorbidity Score (SCS) as predictors of overall survival in non-small cell lung cancer (NSCLC)., Methods: A prospective study included patients in whom NSCLC was diagnosed at an Australian cancer hospital between 2012 and 2014. Patients were assessed for SCS at recruitment and followed up every 3 months until death., Results: The cohort included 633 patients; their median age was 67 years (range 28-93), 63% were male, and 86% were ever-smokers. The median SCS at enrolment was 8 (range 0-19); 20% had an SCS higher than 9, and 11% had an SCS of 0. An SCS higher than 9 was associated with male sex, age older than 75 years, an Eastern Cooperative Oncology Group performance status of 2 or higher, and fewer cancer treatments. The 1-year overall survival rate was 62% (95% confidence interval: 58-66). In multivariate analysis, the strongest associations with mortality were metastatic disease (hazard ratio [HR] = 2.8, p < 0.01), Eastern Cooperative Oncology Group performance status of 2 or higher (HR = 2.0, p < 0.01), male sex (HR = 1.6, p < 0.01), more than 10% weight loss at diagnosis (HR = 1.5, p < 0.01), and age older than 75 years (HR = 1.5, p = 0.01). An SCS higher than 9 was not associated with overall survival (HR = 1.0, p = 0.8), and the effect of continuous SCS (HR = 1.1, p < 0.01) was explained by smoking status., Conclusions: In this cohort of patients with NSCLC the SCS was not a clinically significant predictor of overall survival over and above basic patient and disease factors., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)-positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility., Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status., Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age., Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Thromboembolism is common in lung cancer. Current thromboprophylaxis guidelines lack specific recommendations for appropriate strategies in this high thrombotic risk patient cohort. We profiled lung cancer patients receiving anti-cancer therapy. Thromboembolism incidence and thromboembolism-related mortality rates are reported and we explored patient, disease, and treatment-related risk factors associated with higher thrombotic rates., Methods: Retrospective review of lung cancer patients referred to a Comprehensive Cancer Centre between 01/07/2011 and 30/06/2012 for anti-cancer therapy. Data were collected from medical, pharmacy, pathology and diagnostic imaging electronic records., Results: After a median follow up of 10 months (range: 0.03-32 months), 24/222 patients (10.8%) had developed radiologically confirmed thromboembolism; 131 events per 1000 person-years (95%CI 87-195). Thromboembolism occurred equally in patients with non-small cell and small cell lung cancer (10.8% and 10.5% respectively), and more frequently among patients with adenocarcinoma compared to squamous cell carcinoma (14.7% and 5.3% respectively). Chemotherapy-treated patients experienced thromboembolism more often than patients who did not receive chemotherapy (HR 5.7 95%CI 2.2-14.8). Radiotherapy was also associated with more frequent thromboembolism (HR 5.2 95%CI 2.0-13.2). New lung cancer diagnosis, presence of metastatic disease, second primary malignancy and Charlson Index ≥ 5 were also associated with higher rates of thromboembolism. Importantly, pharmacological thromboprophylaxis (P-TP) was not routinely or systematically prescribed for ambulant lung cancer patients during any treatment phase, at this institution. The majority (83%) of thromboembolic events occurred in the ambulatory care setting., Conclusion: Morbidity and mortality from thromboembolism occurs frequently in lung cancer. Thromboprophylaxis guidelines should be developed for the ambulatory care setting., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)