Resiliency among Older Adults Receiving (Roar) Lung Cancer Treatment: A Feasibility Study

PURPOSE/HYPOTHESIS: Poor physical performance and negative mood are two risk factors for functional decline among older adults with lung cancer. Yet, targeted interventions to maintain independence prevent functional decline are not well studied. Our primary objective was to assess the feasibility of a novel virtual health physical therapy (PT) plus progressive muscle relaxation (PMR) intervention with longitudinal microbiome biospecimen collection delivered to older adults with advanced lung cancer. Secondary objectives were to characterize functional status and clinical factors pre and post-study intervention. NUMBER OF SUBJECTS: We accrued adults aged >=60 years with advanced non-small cell or extensive-stage small cell lung cancer receiving treatment at The Ohio State University James Comprehensive Cancer Center (OSU-JCCC) in the Thoracic Oncology department (N=22). There were no exclusion criteria pertaining to Eastern Cooperative Oncology Group (ECOG) performance status, laboratory values, prior cancer diagnoses, presence of comorbidities, or brain metastases. MATERIALS AND METHODS: Participants were asked about functional status, symptoms, mood through the PHQ-9, GAD-7, POMS, and acceptability questions about the program. PT evaluation and assessment included SPPB and 2- or 6-minute walk test outcomes. The study sought to collect gut microbiome samples for every in-person visit and activity monitoring data (Actigraph) on a subset. Feasibility was defined as successfully collecting specimens, wearing an Actigraph activity monitor, and adhering to the intervention. PT and psychologists evaluated participants in-person at the first and final visit. The rest of the 12-week intervention was conducted via virtual health. Physical therapy intervention consisted of endurance, strength, and flexibility exercises. RESULT(S): In total, 22 patients consented and 18 started the intervention (81.8%). Seven microbiome samples were collected from four participants. Six patients collected activity monitoring data. Among the 18 participants, 11 participants (61.1%) completed 70% or more of all the intervention visits. The SPPB data show a moderate effect size (Cohen's d=0.24) from pre- to post-data. On average patients improved by 1.8 total points on the SPPB. Patients demonstrated improvement on timed walk tests throughout intervention from an average of 108 feet pre-intervention to an average of 138.4 feet post intervention. CONCLUSION(S): Despite the challenges of the COVID-19 pandemic, longitudinal biospecimen and correlative data collection were feasible in the context of PT and PMR intervention among older adults with advanced lung cancer. Virtual physical therapy interventions can be safely delivered to improve physical performance as demonstrated by a moderate effect size for the SPPB in this patient population. CLINICAL RELEVANCE: Based on the feasibility study results, delivering a virtual PT intervention to older patients with lung cancer can improve SPPB score leading to decreased frailty and improve quality of life among patients.

Melanoma of unknown primary: a case series and review of the literature

Melanoma of unknown primary (MUP) was originally defined in 1963 as melanoma in the subcutaneous tissue, lymph nodes or visceral organs without the presence of a cutaneous, ocular or mucosal primary. The incidence of MUP is reported to be between 1% and 8% of all melanomas. MUP can be divided into lymph node involvement only and organ metastases. The aetiology of MUP is elusive. Possibilities proffered include an unrecognized melanoma, a previously excised melanoma that was misdiagnosed as benign, a primary melanoma that has completely regressed or the de novo malignant transformation of an aberrant melanocyte within a lymph node. We report our experience in a single tertiary referral centre. A database of all melanomas diagnosed between January 2018 and December 2021 was analysed for MUP. The total number of melanomas diagnosed in that timeframe was 298. Six patients (three males, three females) were identified as having MUP, with an incidence of 2%. Median age was 63.3 years (range 45-84). One (17%) presented with primary dermal metastatic deposits, 67% (n = 4) presented with isolated lymph node metastases, 0% presented with visceral metastases and 17% (n = 1) presented with isolated brain metastases. All six patients were reviewed by dermatology and ophthalmology. Fifty per cent (n = 3) were reviewed by ENT. One (17%) was referred to gynaecology. No primary melanoma was identified in any of the patients. All patients underwent a positron emission tomography-computed tomography (CT) scan to investigate for further metastases, and all underwent dedicated brain imaging via CT and magnetic resonance imaging. All patients underwent surgical resection of their MUP, and all were reviewed by medical oncology, with 83% (n = 5) undergoing treatment with immunotherapy. There have been no associated deaths to date. In five patients (83%) the MUP was diagnosed in 2021, and one (17%) was diagnosed in 2018. Recent studies have shown the impact of the COVID- 19 pandemic on the presentation of cutaneous melanoma, including an increased Breslow thickness at the time of presentation vs. a similar period pre-COVID-19. Our data indicate an increased rate of MUP presenting after the onset of the COVID-19 pandemic;however, given the low number overall, no conclusions can be drawn. There is no current literature regarding the increased rate of MUP since the COVID-19 pandemic. Further studies are required to investigate this. Recommendations for the evaluation of those with MUP include a full skin examination by a dermatologist and ocular examination to exclude primary melanoma. Patients should undergo imaging of the brain, thorax, abdomen and pelvis to assess disease burden. Referral to otorhinolaryngology can be considered to assess for mucosal melanoma of the nasopharynx. Gynaecology referral should be considered for those with inguinal lymphadenopathy. MUP is rare. Guidelines for the investigation of MUP are currently lacking and are needed to ensure the delivery of consistent evidence-based care for patients.

Oncological emergencies in lung cancer patients during 2019 and SARS-CoV-2 pandemic year

Lung cancer (LC) is frequently related to oncological emergencies (OE). We performed a retrospective analysis to characterize OE in LC from 2019 to 2020 and to determine the effects of SARS-CoV-2 pandemic. T-test or Mann- Whitney was used to compare independent continuous variables. Comparison between proportions was tested through Chi-square. The association between clinical variables and 6-months mortality was tested through uni and multivariable logistic regression.82 patients were admitted due to OE. The median age was 66 years old and 73.1% were male. The two most frequent OE were brain metastasis (45.1%) and vena cava syndrome (15.8%). OE was the first manifestation of LC in 45.2% of cases and only 24.4% were alive 6 months after the OE. Neurological OE was associated with lower risk of 6-months mortality compared to cardiovascular and respiratory OE, regardless of gender, age, stage, histology, smoking status and cancer treatment [OR 0.255 (CI 0.72-0.90), p=0.035)]. SCLC had shorter time between diagnosis and OE compared to NSCLC (p=0.016), as well as patients with distant metastasis compared to local disease (p=0.02) and in those without previous cancer treatment (p<0.001). When comparing patients admitted with OE in 2019 and 2020, there were no differences in the following variables: 6-months mortality (p=0.741), OE as first manifestation of LC (p=0.913), time between diagnosis and OE (p=0.670), stage (p=0.276) and type of OE (p=0.733). In this study, SCLC, metastatic disease and no previous cancer treatment were associated with lesser time until OE and brain metastasis was associated with better prognosis. There were no differences in relevant clinical variables between 2019 and 2020.

Impact of COVID infection on brain metabolism: the revealing role of 18F-FDG PET/CT

Aim/Introduction: In SARS-CoV2 outbreak scenario, many considerations about possible long-term effects of this infection can be made. Early evidences reported in literature about the relation between long-COVID disease and brain involvement in patients with persistent neurological symptoms, found brain hypometabolism on 18F-FDG PET/CT. Our study aims to evaluate the impact of SARSCoV2 infection on brain metabolism in a long-term setting, also in asymptomatic patients. Material(s) and Method(s): Brain PET scans of 48 patients with documented previous SARS-CoV2 infection (COVID-group), performed from January to December 2021, were analysed and compared with brain PET scans of 48 patients, controlled for age and sex, who didn't experience the infection (control-group) using a quantitative software-aided approach. Patients with documented brain metastases or neurodegenerative diseases were excluded. No patient had neurological symptoms at the time of PET. CortexID Suite software (GE Healthcare) was applied for a segmentation analysis reporting Z score (ZS) values for each brain area in both groups. Basing on hypometabolism severity, the sample was divided as follows: normal (>=-1 ZS), mild (between -1 and -2 ZS), severe (<=-2 ZS). For COVID-group, time intercurred from infection to PET was recorded. Differences between ZS per areas between the two groups were evaluated using Mann-Withney-U test. Considering hypometabolism severity, Chi-Square test was applied to evaluate differences between groups. Finally, Pearson's test was used to correlate COVID-group ZS and time intercurred from infection. Result(s): Mean age of patients was 63.2 and 63.6 years old in the COVID-and control-group respectively. In both groups, 22/48 were male. In COVID-group 27/48 patients have had symptoms (cough, fever, dyspnoea) during SARS-CoV2 infection. The majority of brain areas showed a statistically significant difference in ZS values between groups. According to hypometabolism severity, left pre-frontal medial (p=0.032), right sensory-motor (p=0.014), right inferior parietal (p=0.001) and right lateral temporal (p=0.002) areas showed a statistically significant difference between COVIDand control-group with a prevalence in COVID-group of mild and severe brain hypometabolism. Lower ZS values were observed in patients with a longer time intercurred from infection to PET/CT scan. Conclusion(s): Our preliminary results confirm the impact of SARS-CoV2 infection on brain metabolism, consisting mostly in a mild hypometabolism. The presence of this metabolic pattern in patients without neurological symptoms suggests a devious action of the infection. Further studies, also using serial PET, are necessary to explore whether these metabolic alterations are transient or predictive of a future clinical manifestation.

Nivolumab (NIVO) + chemotherapy (chemo) vs chemo in patients (pts) with EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) with disease progression after EGFR tyrosine kinase inhibitors (TKIs) in CheckMate 722

Background: Treatment (tx) options are limited for pts with EGFR-mutated (mut) mNSCLC who experience disease progression following EGFR TKIs. CheckMate 722 (NCT02864251) is a randomized, open-label, phase 3 study of NIVO + chemo vs chemo in pts with EGFR-mut mNSCLC after progression on EGFR TKIs. Method(s): Pts with EGFR-mut mNSCLC (including uncommon mutations) with disease progression on 1 or 2 prior lines of EGFR TKI tx (including 1st or 2nd generation TKI for those with no T790M mutation and/or osimertinib regardless of T790M mutation) were stratified by tumor PD-L1, presence of brain metastases, smoking history, and prior osimertinib. Pts were randomized 1:1 to receive NIVO 360 mg Q3W + chemo (platinum + pemetrexed) Q3W or chemo for <= 4 cycles;pts without progression received NIVO + pemetrexed or pemetrexed, respectively, until disease progression, unacceptable toxicity or <= 2 y for NIVO. Primary endpoint: PFS. Secondary endpoints: OS, ORR, DOR, and 9- and 12-mo PFS rates. Result(s): In all, 294 pts were randomized;baseline characteristics were well balanced between treatment arms. At final analysis (minimum follow-up: 18.2 mo), there was no statistically significant improvement in PFS with NIVO + chemo vs chemo (HR [95% CI]: 0.75 [0.56-1.00];P = 0.053). No difference in PFS was seen between treatment arms across most subgroups except in pts with sensitizing EGFR mutations (n = 269) and 1 prior line of EGFR TKI tx (n = 248);HR (95% CI) was 0.72 (0.54-0.97) for both. Other efficacy results are presented (Table). Grade 3-4 treatment-related AEs occurred in 45% (NIVO + chemo) vs 29% (chemo) of pts. [Formula presented] Conclusion(s): NIVO + chemo did not show statistically significant improvement in PFS in pts with EGFR-mut mNSCLC after progression on EGFR TKIs;however, a trend of benefit was seen in pts with sensitizing EGFR mutations and in those with 1 prior line of EGFR TKI tx. No new safety signals were identified. Clinical trial identification: NCT02864251. Editorial acknowledgement: All authors contributed to and approved the ;writing and editorial assistance were provided by Thai Cao, MS, of Envision Pharma Group, funded by Bristol Myers Squibb. Legal entity responsible for the study: Bristol Myers Squibb (Princeton, NJ). Funding(s): Bristol Myers Squibb (Princeton, NJ) and Ono Pharmaceutical Company Ltd. (Osaka, Japan). Disclosure: T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi-Aventis, Takeda, PER, Daz Group, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Merck Pharmaceuticals HK Ltd, MiRXES, Novartis, OrigiMed Co. Ltd., Pfizer, Shanghai BeBirds Translation & Consulting Co., Ltd., Taiho Pharmaceutical Co., Ltd, AstraZeneca;Financial Interests, Personal, Advisory Board: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science, Bayer Healthcare Pharmaceuticals Ltd., Covidien LP, C4 Therapeutics, Cirina Ltd., Da Volterrra, F. Hoffmann-La Roche Ltd / Genentech, Gilead Sciences, Lucence Health Inc., Medscape LLC / WebMD, MiRXES, OSE Immunotherapeutics, Pfizer, SFJ Pharmaceutical Ltd., Synergy Research, Tigermed, Vertex Pharmaceuticals, Berry Oncology, D3 Bio Ltd., Lakeshore Biotech;Financial In erests, Personal, Invited Speaker, Former known as Hutchison Chi-Med: HutchMed;Financial Interests, Personal, Officer, Chairman: ACT Genomics-Sanomics Group;Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca;Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed;Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology;Non-Financial Interests, Personal, Advisory Role: geneDecode;Non-Financial Interests, Personal, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.;Non-Financial Interests, Personal, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO);Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen's College & Prep. School (Hong Kong);Non-Financial Interests, Personal, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO);Non-Financial Interests, Personal, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC). K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co.,Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, YODOSHA CO., LTD., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., TAIYO Pharma Co., Ltd.;Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K.;Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.;Financial Interests, Institutional, Research Grant: PAREXEL International Corp., PRA HEALTHSCIENCES, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co.,Ltd., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services JAPAN K.K., SYNEOS HEALTH CLINICAL K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., SRL, Inc. K. Park: Financial Interests, Personal, Advisory Board: JNJ, Astra Zeneca, Daiichi Sankyo, BMS, Takeda;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim;Financial Interests, Personal, Other, DMC member: BeiGene, Incyte;Financial Interests, Personal, Other, Advisor/Consultant: Genius, IMBdx;Financial Interests, Institutional, Research Grant: AstraZeneca, MSD. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, ONO, BMS, Eli Lilly, Boehringer Ingelheim, Takeda, MSD, Novartis;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Celltrion, Amgen, Nippon Kayaku, Takeda, Pfizer, ONO, Janssen, AnHeart Therapeutics Inc;Financial Interests, Institutional, Invited Speaker: AstraZeneca, Eli Lilly, Janssen, Amgen;Financial Interests, Personal and Institutional, Invited Speaker: Takeda, ONO;Non-Financ al Interests, Personal, Leadership Role: JSMO, JLCS, JCOG;Non-Financial Interests, Personal, Member: ASCO. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly;Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda;Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG);Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC;Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). J.F. Gainor: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Genentech/Roche, Takeda, Lilly, Moderna, AstraZeneca, Pfizer, Novartis, iTeos, Karyopharm, Silverback Therapeutics, GlydeBio, BeiGene;Financial Interests, Personal, Stocks/Shares, Immediate family member is an employee. Note: Ironwood Pharmaceuticals is not involved in any oncology drug development. It is focused on gastroenterology.: Ironwood Pharmaceuticals;Financial Interests, Personal and Institutional, InvitedSpeaker: Novartis;Financial Interests, Institutional, Invited Speaker: Genentech, Bristol Myers Squibb, Merck, AstraZeneca, Moderna, Jounce, Alexo. X. Zhang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Sylvester: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S. Li: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J.C. Yang: Financial Interests, Institutional, Advisory Board: Astrazeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen;Financial Interests, Institutional, Invited Speaker: Astrazeneca, Boehringer Ingelheim, Novartis, Astrazeneca, MSD, Ipsen, Takeda Oncology;Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals;Financial Interests, Personal, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen;Non-Financial Interests, Personal, Leadership Role, Board of Director: IASLC;Non-Financial Interests, Personal, Member: ASCO. All other authors have declared no conflicts of interest. Copyright © 2022

Early-Term Outcomes of Pulmonary Embolism Response Team

Background: Treatment of pulmonary embolism, which is a life-threatening clinical condition, varies according to the different clinical presentations and experiences of the healthcare centers. Pulmonary embolism response teams (PERT) might improve outcomes of pulmonary embolism with faster evaluation and increases the usage of advanced treatment methods. In this study, the effects of PERT in the treatment of pulmonary embolism were investigated. Method(s): Patients diagnosed with pulmonary embolism in our hospital between 01.03.2019 and 28.02.2022 were retrospectively analyzed. Patients, who were diagnosed with PE for the first time and over 18 years of age, were included in the study. The data of the patients was obtained from the patient files. Hospitalization rates, referral rates, treatment approaches, and early-term outcomes were evaluated. Result(s): Nine-eight patients with pulmonary embolism were evaluated by the PERT during the study period. The mean age was 62.8+16.4 years and 59% were male. Nine patients had a history of fracture twelve patients had recently had Covid-19 infection and 6 patients had a history of long-term traveling. Twenty-nine patients had a proven deep venous thrombosis.All patients with intermediate-low risk were treated medically. 59.2% of the patients were hospitalized. The rate of catheterdirected thrombolysis was 37.8% (n=37). Systemic thrombolytic therapy was performed on two patients. One patient with a metastatic brain tumor was treated with low-molecular-weight heparin. Catheter-directed procedures were performed in 37 patients. The time from diagnosis to reperfusion was 243 minutes. There was one pericardial effusion and onemortality. In the 30-day follow- up there was no re-hospitalization and mortality. Conclusion(s): Treatment of pulmonary embolism still varies according to clinical experience. PERT might help with early triage and treatment of patients with pulmonary embolism. Experienced specialists in this team might contribute to clinical recovery by performing advanced treatment methods and decreasing the risk of chronic thromboembolic pulmonary hypertension in the long term and improving the clinical outcomes by increasing quality of life.

Mechanisms of primary and secondary resistance to RET inhibitors in patients with RET-positive advanced NSCLC

Background: RET fusions are found in 1-2% of patients (pts) with advanced non-small cell lung cancer (aNSCLC). Targeted therapy with RET inhibitors (RETi) significantly improved prognosis. Molecular mechanisms of resistance are still incompletely characterized. Methods: This multicentric retrospective study included 24 centres. Eligible pts had a RET+ aNSCLC, were treated with a RETi and had at least one molecular profile by next-generation sequencing (NGS), performed before and/or after RETi, on tissue and/or plasma samples. Primary resistance under RETi was defined as disease progression (PD) within 6 months of therapy. Results: 95 patients were included with 112 biopsies: 93 at baseline, 19 at PD. 17 patients had paired NGS (baseline and PD). Median age was 65 years (range 56-72);62% were female, 54% were never smokers, 17% had brain metastasis (BM) at diagnosis. 55 patients received pralsetinib, 36 selpercatinib, 4 other RETi. Overall, median PFS under RETi was 17.1 months (95%CI 12.6-28). Primary resistance to RETi occurred in 22 (23%) patients. Primary resistant versus durable responders to RETi had non-adenocarcinoma histology in 9% vs 46% (p=0.61), smoking history in 57% vs 40% (p=0.21), BM in 5% vs 21% (p=0.1), TP53 mutations in 37% vs 22% (p=0.23). KRAS G12V mutation and SMARCA4 alterations were found only in poor responders (4.5% vs 0%, p=0.2;and 25% vs 0%, p=0.04, respectively). Among biopsies at PD (N=19, 13 liquid and 6 tissue biopsies), 7/13 (54%) liquid biopsies failed due to insufficient ctDNA. In 12 evaluable pts, 3 (25%) acquired secondary RET mutations (2 G810S and 1 S904F), 3 (25%) had novel RET rearrangements (2 in intron 11, 1 RET-DOCK1, 1 RET-CSGALNACT2) and 3 (25%) pts had off-target alterations (2 MET and 1 MYC amplification). Three pts (25%) developed novel TP53 mutations, while 3 (25%) had no novel identifiable alterations at PD. Conclusions: SMARCA4 and KRAS co-mutations may have a role in primary resistance to RETi. Secondary RET mutations, novel RET rearrangements and MET/MYC amplifications were identified after treatment with RETi. More than half of pts had insufficient ctDNA at PD, making tissue biopsy essential to identify resistance mechanisms. Legal entity responsible for the study: Institut Gustave Roussy. Funding: Has not received any funding. Disclosure: V. Fallet: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Takeda, Roche, Pfizer, Sanofi, Sandoz, Jansen;Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Takeda, Pfizer, MSD;Financial Interests, Personal, Expert Testimony: GSK, Boehringer. C. Audigier-Valette: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Eli Lilly, Novartis, Pfizer, and Roche. A. Russo: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, MSD, Novartis;Financial Interests, Personal, Writing Engagements: AstraZeneca, Novartis. A. Calles Blanco: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, Lilly, Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Takeda, Sanofi;Financial Interests, Personal, Other, Speaker honoraria: Bayer;Financial Interests, Institutional, Research Grant, Drug-only for Investigator-initiated trial: Merck Sharp & Dohme. P. Iranzo Gomez: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb Recipient, F. Hoffmann, La Roche AG, Merck Sharp & Dohme, Boehringer Ingelheim, MSD Oncology, Rovi, Yowa Kirin, Grunenthal Pharma S.A., Pfizer. M. Tagliamento: Financial Interests, Personal, Other, medical writer: Novartis, Amgen;Financial Interests, Personal, Invited Speaker, travel/accommodation: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. C. Lindsay: Financial Interests, Institutional, Principal Investigator: Roche, Amgen, BI;Financial Interests, Personal, Advisory Role: CBPartners, Amgen. S. Ponce: Financial Interests, Institutional, Principal Investigator: Merck Sharp and Dohme, F. Hoffmann-La Roche, Foundation Medicine, PharmaMar. Personal fees: Merck Sharp and Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche, Foundation Medicine, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Pfizer, Amgen, Celgene.;Financial Interests, Personal, Advisory Board: Merck Sharp and Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche, Foundation Medicine, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Pfizer, Amgen, Celgene.;Non-Financial Interests, Personal, Other: Merck Sharp and Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche. M. Aldea: Financial Interests, Personal, Invited Speaker, travel/accommodation: Sandoz. All other authors have declared no conflicts of interest.

Fatal Interstitial lung disease induced by Osimertinib: a case report

Introduction: Osimertinib is a selective third-generation EGFR-TKI inhibitor with an inhibitory effect on the T790M mutation. Interstitial lung disease (ILD) occurred in 3.9% of the Osimertinib-treated patients (with 0.4% fatal cases). Methods: Case report of fatal ILD induced by Osimertinib in a patient with metastatic lung adenocarcinoma. Results: We present the case of an 81-year-old female patient diagnosed with stage IVB lung adenocarcinoma (May 2020) with pulmonary, adrenal, and brain metastasis. Genetic sequencing showed an exon 19 deletion. She started erlotinib until documentation of disease progression in January 2021. In this context, she performed a liquid biopsy with the detection of a T790M resistance mutation. She started Osimertinib in February 2021. Her past medical history showed diabetes and dyslipidemia. Two months after starting Osimertinib, she went to the emergency department (ER) with a one-week evolution with progressive dyspnea, cough, and fever. Upon admission to the ER, she was conscious and cooperative, with respiratory distress signs, normal blood pressure, and hypoxemia. She had decreased breath sounds, and coarse crackles were audible bilaterally. In the blood sampling, Haemoglobin was 7.7 mmol/L, creatinine 0.08 mmol/L, platelets 257000x10ˆ9/L, C-reactive protein 28.6 nmol/L, and NT-proBNP 98 pmol/L. Rt-PCR for sars-CoV-2 detection was negative. X-ray showed bilateral diffuse infiltrates. She started oxygen therapy via nasal cannula at 3l/min and IV antibiotics. ABG values were pH 7.44, pCO2 37 mmHg, pO2 69 mmHg, HCO3 26 mEq/L, sO2 94%. On reassessment after 3 hours, she presented worsening dyspnea and dizziness, with higher oxygen needs (venturi mask, 60%). Chest CT angiography showed extensive bilateral diffuse ground-glass densification with crazy-paving areas. It also showed no signs of pulmonary embolism. We admitted her to a level 2 ICU unit for surveillance. Due to suspected drug toxicity, she started Methylprednisolone pulses (1000mg/3days). Six hours after admission, due to hypoxemia worsening, non-invasive ventilation was started with the need to escalate oxygen therapy to 100% FiO2. At 24h, she showed clinical and blood analysis improvement. Nonetheless, she still needed 100% fiO2 to maintain >92% oxygen saturation. On the 4th day of hospitalization, she was hypotensive, prostrated, and with little reaction to painful stimulation. She started palliative treatment and died on the same day. Conclusions: ILD is a rare adverse effect of the treatment with Osimertinib, and fatal ILD is even rarer. The time from starting Osimertinib to this side effect is variable between patients. Awareness is necessary for a rapid diagnosis and early treatment. [Formula presented] Keywords: Osimertinib, Intersticial Lung Disease, Adverse effect

A Phase II Study of Metformin with Pemetrexed/Carboplatin in Patients with Metastatic Non-Squamous Non-Small Cell Lung Cancer

Introduction: There is a subset of NSCLC patients ineligible for benefit from TKIs/Immunotherapy (e.g. STK11 mutation conferring resistance to Immunotherapy). Besides, many patients cannot afford these therapies. Metformin has anticancer properties acting both on glycolytic metabolism and tumor microenvironment. In vitro studies suggest synergism between metformin and pemetrexed. STK11 deficient cell lines are more sensitive to metformin. Clinical studies combining metformin with chemotherapy are limited by small sample size. We conducted an exploratory phase-2 clinical trial of metformin with pemetrexed/carboplatin in advanced non-squamous NSCLC. Methods: This was a single center, open label, single arm phase 2 clinical trial with a Simon’s two stage design. The null hypothesis was that the combination would not improve the 6-month PFS rate by 15%, from 50%. Treatment-naive, non-diabetic patients aged 18-75 years with NSCLC (adenocarcinoma/not-otherwise-specified) with stage IV disease having ECOG PS 0-2 with unmutated EGFR/ALK and without brain metastasis or with asymptomatic brain metastases were treated with pemetrexed-carboplatin chemotherapy and metformin for six months. The primary outcome was 6-month progression free survival (PFS) rate. Secondary outcomes were safety, overall survival (OS), overall response rate (ORR), proportion of STK 11 mutation and effect of STK 11 mutation on 6-month PFS rate. PFS and OS were estimated using the Kaplan-Meier method. Targeted sequencing was attempted for available tissue specimens. Results: The first interim analysis was performed after enrollment of 26 patients for the first stage (before the target accrual of first stage was reached) due to slow accrual, in view of COVID pandemic. The study was terminated after first stage for futility. The median age of patients in the study was 52 years (range, 30 to 68) and 18 patients (69.0%) were males. Half of the patients had ECOG-PS 2. Brain metastases were present in eight (31%) patients and among these four (50%) were symptomatic at presentation. The median follow-up time was 25 months. The median PFS was four months. 6-month PFS rate was 28% (95% CI - 0.12 to 0.46). Of the 25 evaluable patients, five (20%) had a partial response, and eight (32%) had stable disease;13 (52%) of the patients had disease control. The median OS was 16 months. During combined therapy, 14 (54%) and 3 (11%) patients had any grade and grade 3 anemia respectively. One patient had grade 3 neutropenia. Among non-hematological toxicities, gastrointestinal toxicities (nausea, vomiting and diarrhea) were the most common. No grade 4 toxicities were reported. There were no treatment discontinuations, however treatment delay due to grade three toxicities was present in two patients. Dose modification for Metformin was required in four patients. Targeted Sequencing was possible in nine cases. Two of these patients had STK11 mutation and an associated bad outcome (PFS < 2 months). Conclusions: We could not demonstrate the benefit of combination of Metformin with pemetrexed-carboplatin in terms of improvement in 6-month PFS rate. The addition of metformin to pemetrexed-carboplatin has an acceptable safety profile. Future trials should test metformin in specific subsets (STK11 mutated) and in combination with immunotherapy and TKIs. Keywords: Metformin, NSCLC, STK11

A phase 1/2 trial of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): The LUPER study

Background: L is a novel anticancer agent that inhibits trans-activated transcription and modulates the tumor microenvironment. L is approved by the FDA for metastatic SCLC patients (pts) with progressive disease (PD) on or after platinum-based chemotherapy (CT). The LUPER study is assessing the safety, tolerability, and preliminary efficacy of L+P as second-line regimen for SCLC pts after failure of platinum- based CT. Phase 1 data are presented here. Methods: In this phase 1/2 trial (NCT04358237), adult pts with histologically confirmed SCLC, PD to a previous CT-containing regimen (≥4 weeks before study initiation), no prior exposure to immunotherapy, ECOG PS of 0-1, and measurable disease as per RECIST 1.1 are eligible. Pts with treated, stable, and asymptomatic brain metastases (BMs) are allowed. A 3+3 dose-escalation was done to determine the recommended phase 2 dose (RP2D) of L+P. L was dosed at 2.4 mg/m2 and 3.2 mg/m2 IV Q3W in the dose level (DL)1 and 2, respectively, in combination with fixed dose of P (200 mg IV Q3W). The RP2D was the highest DL at which 0/3 pts or ≤1/6 pts experienced dose-limiting toxicities (DLTs) during the first cycle. Treatment was administered until PD, unacceptable toxicity, or consent withdrawal. Secondary endpoints include safety as per CTCAE 5.0, preliminary efficacy, and pharmacokinetics. Results: Thirteen pts were enrolled across 3 hospitals in Spain (DL1, n = 7;DL2, n = 6). Median age was 66 (range 43-78) years, 46.2% were female, 61.5% had ECOG PS of 1, 38.5% had platinum-free interval < 90 days, 30.8% had LDH > upper normal limit, and 15.4% had BMs. One DLT (G3 asthenia) and one G4 neutropenia lasting > 3 days (controlled with G-CSF prophylaxis upon C2, without requiring dose delay or modification) occurred in the DL1. No DLT were reported in the DL2. The RP2D was identified as 3.2 mg/m2 L and 200 mg P IV Q3W. At data cutoff (Jan 21, 2022), 5 (38.4%) pts remained on treatment (1 pt in DL1 discontinued due to COVID-19 in cycle 1). Median duration of treatment was 2.1 (0-11.8) months, 5 (38.5%) pts had ≥8 cycles, and median relative dose intensity of L and P were 91.1% and 95.7%, respectively. Immune-related AEs (G2 pneumonitis;G3 ALT increased) led to P discontinuation in 2 (15.4%) pts. Responses were shown in both DLs, with ORR of 30.8% (1 confirmed complete response and 3 partial responses);3 pts had stable disease (SD;including 1 patient with SD > 12 weeks) and 5 (38.5%) pts experienced PD. Conclusions: This is the first report to demonstrate a manageable safety profile and preliminary efficacy of second-line L+P for relapsed SCLC pts. This combination warrants further confirmation in the ongoing expansion phase 2.

Our Experience in Palliative Radiotherapy During the COVID-19 Pandemic

Background/aims: Radiotherapy is an effective palliative treatment for metastatic disease. The current COVID-19 pandemic has led us to consider shorter courses, new guidelines and prioritize cases clinically urgent. The purpose of this study is to analyze our practice in palliative treatment, new potential strategies and hypofractionation. Methods: 252 patients who receive palliative radiation treatment from March 2020 to March 2021 were reviewed. We analyze how the treatment line has been modified throughout the 1 year of the pandemic and other items related to the different therapeutic options as mortality, reirradiation, primary localization and intention. Results: Median age was 68 years (range 33-95y), 66% males, 34% females. Main primary tumors were 30% lung, 12% prostate and 10% breast. 65% patients had painful bone metastases, 15% brain metastases, 14% cord compression, 4% bleeding and 2% superior vena cava obstruction. Advanced disease was detected in 12% as debut. Half of patients were treated in the two first months of the pandemic than later. Treatment provided was: 8 patients required reirradiation. Currently, 66% died. Conclusions: Radiotherapy plays a critical role improving quality of life in patients with advanced disease, even in the midst of the COVID-19 pandemic. During the first months of confinement, short radiation therapy cycles prevailed over the long ones, as the normal schemes of fractionation coinciding with a greater number of sessions gained importance as time went on. (Table Presented).

A case of brain metastases masquerading as cognitive decline

Introduction: Cognitive decline in the elderly is a diagnostic challenge - one that must consider numerous differential diagnoses, including dementia. Given the profound impact of one's cognition on functional status and quality of life, early recognition of reversible and treatable causes of cognitive decline, especially when it occurs at a rate faster than expected, is critical. Case Presentation: An 86-year-old female was admitted from long-term care for a 2-week history of cognitive decline, hypoxia, and vomiting that began after receiving the second dose of the COVID vaccine. Her past medical history was significant for dementia, right middle cerebral artery stroke, benign left parietal neoplasm under surveillance, and pulmonary emboli. Investigations for her hypoxia were unremarkable;thus, it was thought to be due to aspiration from emesis. Initially, the patient's cognitive decline was presumed to be secondary to her dementia, which has been progressive for the past 5 years, leading to her eventual admission to long-term care. However, it was highlighted that the patient's cognition rapidly declined in a period of weeks. Despite her dementia, at baseline, the patient could engage in full conversations. However, over the past few weeks, the patient could only communicate with a few words and became newly dependent with ADLs. The patient was not delirious, given the non-fluctuating cognitive decline with normal attention and level of consciousness. Laboratory studies, including TSH and vitamin B12, were normal. CT Brain was completed given patient's history of parietal neoplasm, demonstrating a new left occipital lobe lesion with vasogenic edema. The patient was started on dexamethasone given the size of the lesion and edema. With this, her cognition significantly improved over days, allowing the patient to be involved in the decision-making of her care. Unfortunately, the patient had an aspiration event during her admission. As per her wishes, she was discharged to long-term care with symptom-focused, comfort care. Discussion: In this case, we discuss our approach to cognitive decline and highlight the importance of maintaining a broad differential, even in the face of known dementia. Finding reversible causes of cognitive decline can not only improve quality of life, but as seen in our patient, it can allow individuals to participate in meaningful decisions regarding their goals of care.

Patient Satisfaction with Novel Telemedicine Platform Applied to Neuro-oncology

Introduction: The COVID-19 outbreak led to the rapid adoption of telemedicine by many specialties, including neurosurgery. Despite several telemedicine options currently available, the assessments that are specific to patients with neurological diagnoses and cranial nerve deficits remain limited. Our group has developed a novel telemedicine platform that enables patients to undergo cranial nerve and neuro-ophthalmic testing on any personal computer from their own home. In this study, we provide a detailed account of our experience using the Myelin Analytics proprietary platform in a high-volume neuro-oncology practice and share the patient satisfaction results. Methods: This is a prospective, pragmatic, non-randomized controlled study using the Myelin Analytics telemedicine platform to perform cranial nerve and neuro-ophthalmic testing in patients greater than 18 years of age diagnosed with a brain tumor who received care at our institution from June to September 2021. The investigational arm included patients who underwent the novel Myelin Analytics assessment during their inpatient stay or outpatient visit. The control arm included patients with the diagnosis of a brain tumor using conventional telemedicine provided by Teladoc Health for their outpatient visit in the same neuro-oncology practice. Both arms were asked to complete the validated 21-question Telehealth Usability Questionnaire (TUQ) after a telehealth clinic visit. The TUQ used a Likert scale ranging from Strongly Agree to Strongly Disagree to grade patient responses. Patient satisfaction was dichotomized into favorable (included strongly agree and agree responses), and unfavorable (included somewhat agree to strongly disagree). Results: A total of 42 patients met the inclusion criteria for the investigational arm and 34 patients for the control arm. The patients in the investigational and control arms were on average 52.2 ± 15.3 (range: 21-79) and 58 ± 13 years old (range: 29-76), respectively. The most common primary diagnoses were pituitary adenoma, cerebral metastasis, and vestibular schwannoma. Of the 42 patients that used the Myelin Analytics platform, 29 (69%) patients completed the patient satisfaction survey. The Myelin cohort achieved favorable patient satisfaction significantly more frequently in regards to access to healthcare (Q1: 96.6 vs. 73.5%, p = 0.013), clear communication with provider (Q12: 50.0 vs. 23.5%, p = 0.037) and expressing oneself effectively (Q13: 57.7 vs. 32.4%, p = 0.050). Discussion: Current telemedicine tools focus on audiovisual communication but lack the functionalities needed to perform a comprehensive neurological examination. This novel platform enables patients to undergo cranial nerve and neuroophthalmic testing remotely, obviating the need for in-person examination. Our feasibility study demonstrates promising.

Use of Novel Telemedicine Software to Automate Cranial Nerve and Neuro-Ophthalmic Remote Testing

INTRODUCTION: Despite the rapid surge in telemedicine use due to the COVID-19 pandemic, there is still a paucity of telemedicine tools for the remote assessment of patients with neurological diagnoses. Current telemedicine platforms lack the capabilities to perform thorough cranial nerve and neuro-ophthalmic testing. To address this need, we developed a novel software that patients can use to undergo cranial nerve and neuro-ophthalmic testing remotely via their own personal computer. METHODS: We conducted a pilot study of patients above 18 years old diagnosed with a brain tumor who receive their care at our institution. Ten patients were enrolled to undergo a comprehensive cranial nerve and neuro-ophthalmic testing using our proprietary telemedicine software. We assessed visual acuity, visual fields, extraocular movements, facial sensitivity, facial symmetry, hearing, uvula/palatal movement, shoulder elevation, tongue deviation, and speech. Their performance on the telemedicine software to physical examination by their treating physician. All patients were given a patient satisfaction survey upon completion of the telemedicine visit. RESULTS: Ten patients have been enrolled so far with a mean age of 47±14.3 years old (4 males, 6 females). Diagnoses included brain metastases, pituitary adenoma, craniopharyngioma and meningiomas. Visual acuity, facial sensitivity, facial symmetry, shoulder elevation, tongue deviation were consistent with physical examination findings in all six patients. Extraocular movements were consistent in 80% of patients. Assessment of the uvula was the most challenging, comparable to physical examination in only 20% of patients. Visual fields were equivalent in 80% of patients and superior than confrontation testing in 10% of patients. CONCLUSION: While this is a very early experience with a new telemedicine software, we demonstrate the feasibility of performing comprehensive cranial nerve and neuro-ophthalmic testing. We provide a detailed account of the challenges encountered, the patient experience and satisfaction results.

Brain surgical tissue for advanced tumour models in precision medicine: Developing the brain-stat pathway

AIMS: There are approximately four thousand neuro-oncology procedures in the UK per annum. Many of these result in tissue and biofluid specimens that are surplus to diagnostic requirement and can be collected as standard of clinical care. However, developing technologies and treatments for precision medicine require access to a range of individualised biospecimens paired with deep clinical phenotyping data. Here, we present Brain Surgical Tissue for Advanced Tumour Models (BRAINSTAT) programme, an infrastructure that has been established between Queen Elizabeth Hospital, Birmingham and the University of Birmingham, to collect, structure and store these resources and also maximise their value for research over the long-term. Using this approach our aim is to provide high-quality, annotated resources to help develop novel treatments for patients with brain tumours. METHOD: BRAINSTAT infrastructure allows: Prospective consent Biospecimens, including tumour tissue (brain and other primary in the case of metastasis), cyst fluid, dura, skin, CSF, blood (matched "germ-line" and for circulating cell free tumour DNA analysis), urine and saliva can be collected. Consent for long term follow-up, is either via clinic or NHS digital. More limited consent for non-oncological neurosurgical cohorts (e.g. epilepsy or vascular) and healthy volunteers allow healthy access-tissue and biofluids to be collected. B. Rapid transfer of fresh surgical tissue samples: Strong collaborative links and close physical proximity between operating theatre and laboratory allows rapid transfer of biospecimens minimising transit time. C. Standardised annotation across disciplines The RedCAP database system allows granular control over data-access, and each specialist research team is provided access only to the sub-sections relevant to them. All users must have Good Clinical Practice certification and GDPR training, prior to access of the BRAINSTAT database. RESULTS: Between 25/11/2019-16/03/2020 and 27/07/2020-16/11/2020, 65 patients were consented for BRAINSTAT at the weekly neurosurgical oncology clinic. (Recruitment gaps due to the SARS-COVID 19 pandemic). Pathological diagnosis of surplus tissue collected included: 37 high grade glioma, 3 low grade glioma and 16 brain metastasis including: (6 lung, 6 breast, 2 colorectal, 1 oesophageal, 1 endometrial). Meningioma (5 WHO I;1 WHO III) 1 patient undergoing anterior temporal lobectomy for hippocampal sclerosis contributed access tissue from the lateral neocortex. 1 patient had a non-neoplastic, non-diagnostic sample. All patients had matched "germline" blood samples. Median time from resection to arrival in the laboratory was 10 minutes (range 4-31). Standardised operating protocols to optimise this have been developed. Glioblastoma and breast-brain metastasis tumourspheres and cerebral organoids are currently being validated. CONCLUSION: Despite the challenges of the pandemic we have established a viable tissue pipeline from neurosurgical operating theatre to our university laboratories. We are developing clinically annotated human brain tumour cell lines, stem cells and 3D organoid models, principally for commonly encountered brain tumours such as glioma and metastasis. The research sets the foundation for a multitude of downstream applications including:-Building more complex organoid cultures e.g. by including other cell types such as healthy brain cells and endothelial cells allowing future experiments to more accurately model tumour growth.-Developing high-throughput, patient-specific drug screens of novel drugs and drug combinations using these 3D tumour models aiming to more effectively treat tumour proliferation and spread. These patient avatars will help inform and test more "stratified" personal medical treatments and will provide opportunities to allow earlier intervention with the aim of improving survival, coupled with a better quality of life.

Clinical presentation of neuroendocrine cancer metastasis to an anterior clinoid process meningioma invading superior orbital fissure. A case report.

Metastasis to a meningioma is an uncommon phenomenon however reported in the literature. Meningiomas are common primary intracranial tumours which most frequently occur to be a recepient of metastases. A 66-year-old female presented with rapid development of visual acuity and visual field loss in the right eye with ipsilateral oculomotor nerve palsy. Magnetic resonance imaging (MRI) showed well-defined tumour intensely enhanced with contrast like a typical skull base meningioma. The neuropathological examination revealed two different morphological fragments of the tumour. In the cell-rich part of the tumour, immunopositivity for CK, chromogranin, and SY were detected. The less cellular portion of the tumour, immunopositivity to epithelial membrane antigen (EMA) and vimentin were detected. To our knowledge, we present the first rare metastasis of neuroendocrine carcinoma to the medial sphenoid meningioma that preceded the clinical symptoms of systemic neuroendocrine carcinoma.

US Food and Drug Administration regulatory updates in neuro-oncology.

OBJECTIVE: Contemporary management of patients with neuro-oncologic disease requires an understanding of approvals by the US Food and Drug Administration (FDA) related to nervous system tumors. To summarize FDA updates applicable to neuro-oncology practitioners, we sought to review oncology product approvals and Guidances that were pertinent to the field in the past year. METHODS: Oncology product approvals between January 1, 2020, and December 31, 2020, were reviewed for clinical trial outcomes involving tumors of the nervous system. FDA Guidances relevant to neuro-oncology were also reviewed. RESULTS: Five oncology product approvals described outcomes for nervous system tumors in the year 2020. These included the first regulatory approval for neurofibromatosis type 1: selumetinib for children with symptomatic, inoperable plexiform neurofibromas. Additionally, there were 4 regulatory approvals for non-central nervous system (CNS) cancers that described clinical outcomes for patients with brain metastases. These included the approval of tucatinib for metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer including patients with brain metastases, brigatinib for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), and pralsetinib and selpercatinib for RET fusion-positive NSCLC. Finally, two FDA Guidances for Industry, "Cancer Clinical Trial Eligibility Criteria: Brain Metastases" and "Evaluating Cancer Drugs in Patients with Central Nervous System Metastases" were published to facilitate drug development for and inclusion of patients with CNS metastases in clinical trials. CONCLUSIONS: Despite the challenges of the past year brought on by the COVID-19 pandemic, progress continues to be made in neuro-oncology. These include first-of-their-kind FDA approvals and Guidances that are relevant to the management of patients with nervous system tumors.

Hsa-miR-217 Inhibits the Proliferation, Migration, and Invasion in Non-small Cell Lung Cancer Cells Via Targeting SIRT1 and P53/KAI1 Signaling

Background: Brain metastasis is a major cause of cancer death in patients with lung cancer. Sirtuin 1 and hsa-miR-217 have been identified to mediate the development of non-small cell lung cancer. Aims: To investigate the roles of hsa-miR-217, its target sirtuin 1, and the P53/KAI1 axis in the brain metastasis from non-small cell lung cancer. Study Design: Cell culture study. Methods: Human pulmonary adenocarcinoma brain metastasis cell line PC-14/B were incubated and treated with constructed lentiviral plasmids expressing miR-217 and/or sirtuin 1. BEAS-2B cell line was used as a control. The targeted regulation of miR-217 to sirtuin 1was examined using a dual-luciferase reporter assay. Cell proliferation, migration, invasion, and related protein expression were detected to examine the effect of the miR-217/sirtuin 1 expression on metastasis. Results: PC-14/B cells expressed higher sirtuin 1 and lower P53 and KAI1 compared with BEAS-2B control cells (p<0.05). Sirtuin 1 was a direct target of miR-217. MiR-217 expression suppressed PC-14/B cell invasion (p=0.004), migration (p=0.001), and proliferation (p<0.05), whereas sirtuin 1 overexpression reversed all processes. sirtuin 1 expression inhibited P53, KAI1/CD82, matrix metalloproteinase-9, and ß-catenin but upregulated E-cadherin protein. MiR-217 overexpression induced reverse changes. Conclusion: Hsa-miR-217 and its target sirtuin 1 acted as metastasis suppressor and promoter gene in non-small cell lung cancer, respectively. The hsa-miR-217/sirtuin 1/P53/KAI1 metastasis regulatory pathway showed novel and crucial roles in brain metastasis from non-small cell lung cancer. This axis might be a potential target for the treatment of brain metastasis of lung cancer.

Inpatient and outpatient case prioritization for patients with neuro-oncologic disease amid the COVID-19 pandemic: general guidance for neuro-oncology practitioners from the AANS/CNS Tumor Section and Society for Neuro-Oncology.

The Coronavirus pandemic has created unprecedented strain on medical resources at health care institutions around the world. At many institutions, this has resulted in efforts to prioritize cases with an attempt to balance the acuity of medical needs with available resources. Here, we provide a framework for institutions and governments to help adjudicate treatment allocations to patients with neuro-oncologic disease.