NIMG-06. CHARACTERIZATION OF LONG-TERM METABOLIC CHANGES OF IRRADIATED BRAIN METASTASES USING SERIAL DYNAMIC FET PET IMAGING

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi128-vi128
Author(s):  
Norbert Galldiks ◽  
Gabriele Stoffels ◽  
Jan Werner ◽  
Elena Bauer ◽  
Christian Baues ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Mri Findings ◽  
Fet Pet ◽  
Radiation Induced ◽  
Induced Changes ◽  
Pet Scans ◽  
Dynamic Fet Pet

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. PATIENTS AND METHODS From 2010-2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2-6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2-64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5-60 months). The overall median follow-up time was 26 months (range, 8-101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P< 0.001). CONCLUSIONS FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.

OS03.3.A Characterization of long-term metabolic changes of irradiated brain metastases using serial dynamic FET PET imaging

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
N Galldiks ◽  
G Stoffels ◽  
J Werner ◽  
E K Bauer ◽  
C Baues ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Mri Findings ◽  
Fet Pet ◽  
Radiation Induced ◽  
Induced Changes ◽  
Pet Scans ◽  
Dynamic Fet Pet

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. MATERIAL AND METHODS From 2010–2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2–6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2–64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5–60 months). The overall median follow-up time was 26 months (range, 8–101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P<0.001). CONCLUSION FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.

scholarly journals OTHR-14. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING FET PET IN PATIENTS WITH MELANOMA AND LUNG CANCER BRAIN METASTASES: INITIAL EXPERIENCES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i21-i21
Author(s):  
Norbert Galldiks ◽  
Diana Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Treatment Monitoring ◽  
Mri Findings ◽  
Fet Pet ◽  
Additional Information

Abstract BACKGROUND: Due to the lack of specificity of contrast-enhanced (CE) MRI, both the response assessment and differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (ICI) or targeted therapy (TT) may be challenging, especially when ICI or TT is applied in combination with radiotherapy (RT). Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) as a problem-solving tool in comparison to CE-MRI in patients with brain metastases (BM) secondary to malignant melanoma (MM) and NSCLC. METHODS: We retrospectively identified 31 patients with 74 BM secondary to MM (n=20 with 42 BM) and NSCLC (n=11 with 32 BM) who underwent 52 FET-PET scans during the course of disease. All patients had RT prior to ICI or TT initiation (61%) or RT concurrent to ICI or TT (39%). In 13 patients, FET-PET was performed for treatment response assessment of ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET-PET was used for the differentiation of progression from PsP related to RT plus ICI or TT. In all BM, metabolic activity on FET-PET was evaluated by calculation of tumor/brain ratios. FET-PET imaging findings were compared to CE-MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. RESULTS: In 4 of 13 patients (31%), FET-PET provided additional information for treatment response evaluation beyond the information provided by CE-MRI alone. Furthermore, responding patients on FET-PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE-MRI findings suggesting progression, FET-PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. CONCLUSIONS: FET-PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with ICI or TT.

Treatment monitoring of immunotherapy and targeted therapy using FET PET in patients with melanoma and lung cancer brain metastases: Initial experiences.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13525-e13525 ◽  
Author(s):  
Norbert Galldiks ◽  
Diana S.Y. Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Treatment Monitoring ◽  
Mri Findings ◽  
Fet Pet

e13525 Background: Due to the lack of specificity of contrast-enhanced (CE) MRI, the differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (IT) or targeted therapy (TT) may be challenging, especially when IT or TT is applied in combination with radiotherapy (RT). Similarly, for response assessment of RT plus IT or targeted therapy (TT), the use of CE MRI alone may also be difficult. For problem solving, the integration of advanced imaging methods may add valuable information. Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) in comparison to CE MRI for these important clinical situations in patients with brain metastases (BM) secondary to malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Methods: From 2015-2018, we retrospectively identified 31 patients with 74 BM secondary to MM (n = 20 with 42 BM) and NSCLC (n = 11 with 32 BM) who underwent 52 FET PET scans during the course of disease. All patients had RT prior to IT or TT initiation (61%) or RT concurrent to IT or TT (39%). In 13 patients, FET PET was performed for treatment response assessment of IT or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET PET was used for the differentiation of progression from PsP related to RT plus IT or TT. In all BM, metabolic activity on FET PET was evaluated by calculation of tumor/brain ratios. FET PET imaging findings were compared to CE MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. Results: In 4 of 13 patients (31%), FET PET provided additional information for treatment response evaluation beyond the information provided by CE MRI alone. Furthermore, responding patients on FET PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE MRI findings suggesting progression, FET PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. Conclusions: FET PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with IT or TT.

P14.79 Differentiation of treatment-related changes from tumor progression following brachytherapy in patients with WHO II and III gliomas using FET PET

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii53-ii53
Author(s):  
E K Bauer ◽  
J Werner ◽  
A Brunn ◽  
M Deckert ◽  
D Ruess ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Mri Findings ◽  
Who Grade ◽  
Fet Pet ◽  
Diagnostic Uncertainty ◽  
Radiation Induced ◽  
Grade Ii ◽  
Induced Changes

Abstract BACKGROUND Following brachytherapy, the differentiation of radiation-induced changes (e.g., radiation necrosis) from actual tumor progression using MRI is challenging. To overcome this diagnostic uncertainty, we evaluated the diagnostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in glioma patients treated with brachytherapy. MATERIAL AND METHODS From 2006–2019, we retrospectively identified WHO grade II or III glioma patients (i) treated with brachytherapy using Iodine-125 seeds, (ii) equivocal or progressive MRI findings inside the radiation field, and (iii) additional FET PET imaging for diagnostic evaluation. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBR) and dynamic FET PET parameters (i.e., time-to-peak, slope) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses and Fisher’s exact test. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS Following brachytherapy, suspect MRI findings occurred after a median time of 33 months (range, 5–111 months). In 10 of 21 patients (WHO grade II, n=5; WHO grade III, n=16), treatment-related changes were diagnosed. The best diagnostic performance for identification of treatment-related changes was obtained using maximum TBRs (threshold <3.20; accuracy, 86%; sensitivity, 100%; specificity, 73%; P=0.007). Mean TBRs reached an accuracy of 76% (threshold <2.05; sensitivity, 89%; specificity, 64%; P=0.010). Dynamic PET parameters did not reach statistically significant results. CONCLUSION Our data suggest that static FET PET parameters add valuable diagnostic information to diagnose radiation-induced changes in glioma patients treated with brachytherapy.

NIMG-20. DIFFERENTIATION OF TREATMENT-RELATED CHANGES FROM TUMOR PROGRESSION FOLLOWING BRACHYTHERAPY IN PATIENTS WITH WHO II AND III GLIOMAS USING FET PET

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi132-vi132
Author(s):  
Elena Bauer ◽  
Jan Werner ◽  
Anna Brunn ◽  
Martina Deckert ◽  
Daniel Ruess ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Mri Findings ◽  
Who Grade ◽  
Fet Pet ◽  
Diagnostic Uncertainty ◽  
Radiation Induced ◽  
Grade Ii ◽  
Induced Changes

Abstract BACKGROUND Following brachytherapy, the differentiation of radiation-induced changes (e.g., radiation necrosis) from actual tumor progression using MRI is challenging. To overcome this diagnostic uncertainty, we evaluated the diagnostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in glioma patients treated with brachytherapy. MATERIAL AND METHODS From 2006-2019, we retrospectively identified WHO grade II or III glioma patients (i) treated with brachytherapy using Iodine-125 seeds, (ii) equivocal or progressive MRI findings inside the radiation field, and (iii) additional FET PET imaging for diagnostic evaluation. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBR) and dynamic FET PET parameters (i.e., time-to-peak, slope) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses and Fisher’s exact test. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS Following brachytherapy, suspect MRI findings occurred after a median time of 33 months (range, 5-111 months). In 10 of 21 patients (WHO grade II, n=5; WHO grade III, n=16), treatment-related changes were diagnosed. The best diagnostic performance for identification of treatment-related changes was obtained using maximum TBRs (threshold < 3.20;accuracy, 86%; sensitivity, 100%; specificity, 73%; P=0.007). Mean TBRs reached an accuracy of 76% (threshold < 2.05; sensitivity, 89%; specificity, 64%; P=0.010). Dynamic PET parameters did not reach statistically significant results. CONCLUSION Our data suggest that static FET PET parameters add valuable diagnostic information to diagnose radiation-induced changes in glioma patients treated with brachytherapy.

Gamma Knife surgery for arteriovenous malformations in children

2010 ◽  
Vol 6 (5) ◽  
pp. 426-434 ◽  
Author(s):  
Chun Po Yen ◽  
Stephen J. Monteith ◽  
James H. Nguyen ◽  
Jessica Rainey ◽  
David J. Schlesinger ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Arteriovenous Malformations ◽  
Cyst Formation ◽  
Gamma Knife Surgery ◽  
Neurological Deficits ◽  
Secondary Tumors ◽  
Radiation Induced ◽  
Induced Changes

Object The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS). Methods Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm3 at the time of GKS, and a mean prescription dose of 21.9 Gy was used. Results After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career. Conclusions Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

Long-term radiosurgery effects in the treatment of temporal lobe epilepsy

2012 ◽  
Vol 117 (5) ◽  
pp. 962-969 ◽  
Author(s):  
Fernando L. Vale ◽  
Ali M. Bozorg ◽  
Mike R. Schoenberg ◽  
Kondi Wong ◽  
Thomas C. Witt
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mesial Temporal Sclerosis ◽  
Complication Rates ◽  
Mri Findings ◽  
Radiation Induced ◽  
Mesial Temporal Lobe ◽  
Mri Study

Epilepsy surgery is an effective treatment for medically resistant temporal lobe epilepsy (TLE). To minimize complication rates and potentially improve neuropsychology outcomes, stereotactic radiosurgery (SRS) has been explored as an alternative. Two pilot trials have demonstrated the effectiveness of SRS for the treatment of medically resistant TLE, with seizure-free outcomes for approximately 65% of patients at last follow-up. Despite encouraging results, no conclusive long-term outcomes are available for SRS. This article discusses a single patient who presented with recurrent seizures, worsening headaches, and persistent abnormal MRI findings 7 years and 8 months after SRS. This 29-year-old woman with a history of medically refractory complex partial seizures since childhood was referred for evaluation. Medical management had failed in this patient. The workup was compatible with left mesial temporal lobe onset, with MRI findings suggestive of mesial temporal sclerosis. In 2003, at the age of 23 years, she underwent Gamma Knife surgery (GKS) targeting the left temporal mesial area with a dose of 24 Gy at the 50% marginal isodose line. After GKS, the patient's seizures decreased in frequency over several months, but auras were persistent. Nine months after treatment, she developed worsening headaches. A follow-up MRI study demonstrated a thick, irregular, enhancing lesion in the medial part of the temporal lobe. She was placed on corticosteroids, with resolution of her headaches. Her seizures and headaches recurred in March 2010. An MRI study showed a 2.2-cm, ill-defined, enhancing cystic lesion in the left mesial temporal lobe with T2 and FLAIR hyperintensity, which was presumably radiation induced. At that time, the patient opted for left temporal lobe resection to control her seizures. Histological examination showed moderately severe, remote, longstanding sclerosis at the level of the hippocampus. A vascular lesion was identified, and it was most consistent with radiation-induced capillary hemangioma. The entorhinal region was severely damaged, with hemorrhage, necrosis, neuronal loss, astrogliosis, and hemosiderin deposition. There was evidence of radiation vasculopathy. Radiation-induced lesions after SRS for the treatment of epilepsy are not well documented. Although GKS is a promising technique for the treatment of medically resistant TLE, the ideal candidate is not yet well defined. The selection of the appropriate technical parameters to obtain a desirable functional effect without histological damage to the surrounding neural tissue remains a challenge. This case illustrates the need for long-term follow-up when radiosurgery is used for epilepsy.

scholarly journals 11C-methyl-L-methionine PET measuring parameters for the diagnosis of tumour progression against radiation-induced changes in brain metastases

2021 ◽  
pp. 20210275
Author(s):  
Chris W Govaerts ◽  
Drs Bart RJ van Dijken ◽  
Drs Gilles N Stormezand ◽  
Drs Hiske L van der Weide ◽  
Dr Michiel Wagemakers ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Diagnostic Performance ◽  
Tumour Progression ◽  
Tumour Volume ◽  
Pet Scan ◽  
Metabolic Tumour Volume ◽  
Radiation Induced ◽  
Induced Changes ◽  
Met Pet

Objectives: Radiation-induced changes (RIC) secondary to focal radiotherapy can imitate tumour progression in brain metastases and make follow-up clinical decision making unreliable. 11C-methyl-L-methionine-PET (MET-PET) is widely used for the diagnosis of RIC in brain metastases, but minimal literature exists regarding the optimum PET measuring parameter to be used. We analysed the diagnostic performance of different MET-PET measuring parameters in distinguishing between RIC and tumour progression in a retrospective cohort of brain metastasis patients. Methods: 26 patients with 31 metastatic lesions were included on the basis of having undergone a PET scan due to radiological uncertainty of disease progression. The PET images were analysed and methionine uptake quantified using standardised-uptake-values (SUV) and tumour-to-normal tissue (T/N) ratios, generated as SUVmean, SUVmax, SUVpeak, T/Nmean, T/Nmax-mean and T/Npeak-mean. Metabolic-tumour-volume and total-lesion methionine metabolism were also computed. A definitive diagnosis of either RIC or tumour progression was established by clinicoradiological follow-up of least 4 months subsequent to the investigative PET scan. Results: All MET-PET parameters except metabolic-tumour-volume showed statistically significant differences between tumour progression and lesions with RIC. Receiver-operating-characteristic curve and area-under the-curve analysis demonstrated the highest value of 0.834 for SUVmax with a corresponding optimum threshold of 3.29. This associated with sensitivity, specificity, positive predictive and negative predictive values of 78.57, 70.59%, 74.32 and 75.25% respectively. Conclusions: MET-PET is a useful modality for the diagnosis of RIC in brain metastases. SUVmax was the PET parameter with the greatest diagnostic performance. Advances in knowledge: More robust comparisons between SUVmax and SUVpeak could enhance follow-up treatment planning.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

scholarly journals SAT0540 ONE-YEAR OUTCOMES AFTER RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS FROM CHECKPOINT INHIBITORS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.2-1227
Author(s):  
E. Berard ◽  
T. Barnetche ◽  
L. Rouxel ◽  
C. Dutriaux ◽  
L. Dousset ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Symptomatic Treatment ◽  
Musculoskeletal Symptoms ◽  
Day Range ◽  
One Year

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared

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