Overcoming acquired osimertinib-resistance in EGFR-mutant advanced non-small lung cancer mediated by activating BRAF V600E mutation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20682-e20682 ◽  
Author(s):  
Diana S.Y. Abdulla ◽  
Matthias Scheffler ◽  
Carsten Kobe ◽  
Thorsten Persigehl ◽  
Matthias Schmidt ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Standard Dose ◽  
Resistance Mechanism ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Tumor Control ◽  
Egfr Inhibition ◽  
Pet Ct ◽  
Egfr Mutant ◽  
Fdg Pet Ct

e20682 Background: There is growing insight in the mechanisms underlying resistance to the 3rdgeneration EGFR inhibitor osimertinib. Unlike resistance to 1stgeneration inhibitors, these mechanisms not necessarily lead to sequential targeted therapy approaches. Here we report on the treatment of two patients with acquired resistance to osimertinib with a new detected BRAF V600E mutation as resistance mechanism. Methods: We identified two patients with EGFR-T790M-mutant advanced NSCLC with progression on osimertinib and detection of a new BRAFV600E mutation in a tumor rebiopsy by next-generation sequencing (NGS). No other known resistance mechanism beside T790M loss in one patient was found. Osimertinib was discontinued and BRAF-targeted combination therapy with dabrafenib and trametinib at standard dose was initiated. We monitored the clinical course with sequential 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) / computed tomography (CT) assessing maximum standard uptake value (SUVmax), sequencing based liquid biopsies and tumor marker assessment. Results: Patient (1) with EGFR del19 (E746_A750del), preserved T790M mutation and acquired BRAF V600E mutation showed reduction in FDG uptake of 18% after 2 weeks of dabrafenib/trametinib that demonstrated a slight increase of 12% in a FDG-PET/CT scan 4 weeks thereafter and combination treatment has been continued. Patient (2) with EGFR del19 (E746_A750del), T790M loss and new BRAF V600E mutation showed continuous metabolic (+8% and + 39%, respectively) and morphologic progression after 2 and 4 weeks of dabrafenib and trametinib. A tumor rebiopsy showed no additional molecular changes. We changed the treatment to osimertinib and dabrafenib combination and observed an impressive metabolic response (-33%) after 2 weeks by FDG-PET/CT. Conclusions: BRAF V600E mutation has recently been described as a novel molecular resistance mechanism in osimertinib-resistant EGFR-mutant NSCLC. We describe one patient where combined BRAF/MEK inhibition with no additional EGFR-inhibition resulted in a preliminary feasible tumor control, but confirmatory CT staging is pending. In a second patient, co-inhibition of EGFR and BRAF pathway with osimertinib and dabrafenib was needed to overcome BRAF-mediated osimertinib resistance resulting in an impressive early tumor response that was not observed to either single-target inhibition of EGFR or BRAF. FDG-PET/CT was able to monitor tumor dynamics. Updated data will be presented.

scholarly journals The Role of Staging Evaluation at Initial Diagnosis of Adult Patients with Clinically Isolated Pulmonary Langerhans Cell Histiocytosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 45-45
Author(s):  
Antonious Hazim ◽  
Gordon Ruan ◽  
Aishwarya Ravindran ◽  
Jithma P. Abeykoon ◽  
Caleb J Scheckel ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Fdg Pet ◽  
Braf V600e ◽  
Imaging Studies ◽  
Pet Ct ◽  
Extra Pulmonary ◽  
Fdg Pet Ct ◽  
Histopathologic Findings

Background: Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder that is now recognized as a neoplasm by the World Health Organization. It is generally classified based on the site and extent of disease involvement (single system or multisystem). Pulmonary LCH (pLCH), an uncommon interstitial lung disease associated with smoking, often presents as isolated pulmonary disease. It is unclear whether patients with clinically isolated pLCH have extra-pulmonary lesions at diagnosis or during the course of their disease. The role of [18F] fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) in the staging of pLCH remains unclear. Our study aims to better characterize the utility of radiographic staging studies at time of diagnosis and prevalence of extrapulmonary disease at follow up in pLCH. Methods: We conducted a retrospective study of patients presenting with clinical findings consistent with isolated pLCH seen at the Mayo Clinic from January 2000 to January 2020. All patients had a diagnosis of pLCH determined by chest imaging studies [computed tomography (CT) or high-resolution CT (HRCT)] or by histopathologic findings from surgical or transbronchial lung biopsy. Histopathologic findings for the diagnosis of pLCH required the presence of Langerhans cells (S100+/CD1a+/Langerin+). Patients were excluded if they had clinically apparent extra-pulmonary organ involvement at the time of diagnosis. BRAF V600E mutation was determined by immunohistochemistry (IHC) or cell-free DNA (cfDNA). Staging was defined as FDG-PET-CT or whole body CT imaging obtained within 3 months of diagnosis of pLCH. Extra-pulmonary LCH involvement was determined by imaging characteristics or by histopathologic findings. Descriptive statistics and overall survival (OS) were analyzed with JMP software, version 14 (SAS Institute Inc., Cary, NC). Results: A total of 112 patients with clinically isolated pLCH were identified. The median age at diagnosis was 45 years (range 21-73), and 48 (43%) were male. The majority (n=110, 99%) were former or current smokers with a median pack year of 25 (range 1-57). Three (3%) patients were noted to have occupational industrial exposure. Nine patients had a history of another cancer prior to their diagnosis and staging of pLCH [lung (n=4), breast (n=2), neuroendocrine (n=2), thyroid (n=1)]. Presenting symptoms included dyspnea on exertion 49 (44%), cough 18 (16%), chest pain 14 (13%), and 29 (28%) were incidentally discovered on imaging studies. On HRCT, the following characteristics were observed: 42 (38%) cystic, 32 (29%) cystic and nodular, 37 (33%) nodular, 1 (<1%) ground glass opacities. Seventy (63%) patients had lung biopsy confirmation, of which 11 (16%) patients underwent BRAF V600Emutation testing (7 by IHC, 4 by cfDNA). Six (55%) of these 11 patients were positive for BRAF V600E mutation. 34 (30%) patients underwent radiographic staging studies within 3 months of diagnosis of pLCH (25 FDG-PET-CT and 9 whole-body CT), and none of these imaging studies showed evidence of extra-pulmonary disease. Of the patients who had at least one year of follow-up (n=52), one (2%) developed extra-pulmonary disease. This patient did not undergo initial staging studies, developed headaches and was found to have a large calvarial lytic lesion within 2 months of pLCH diagnosis (BRAF V600E+). Among those who did not undergo staging at diagnosis (n=78), long term (>5 years) follow up data were available for 23 (29%), and none developed extra-pulmonary disease as determined by clinical notes or imaging studies. No patient had evidence of new extra-pulmonary involvement or second malignancy at the time of last known follow-up. After a median follow-up duration of 2.4 years (95% CI: 1.5-3.6, range: 0.1-17) ten (9%) patients died, of which 5 died of pLCH related complications. The median OS for entire cohort was 15 years (95% CI 9.1-not reached, Figure 1). Conclusion: Our study shows that adult patients with clinically isolated pLCH rarely present with extra-pulmonary manifestations at diagnosis or at follow up. These findings suggest a limited role of routine radiographic staging studies in pLCH unless clinically indicated. Studies on longer follow up of this cohort would provide further insights into the natural history of pLCH and are underway. Disclosures Bennani: Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board; Kite/Gilead: Research Funding; Affimed: Research Funding. Shah:Dren Bio: Consultancy.

PET Scan Results of NCCTG N0489: Epratuzumab and Rituximab in Combination with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone Chemotherapy (ER-CHOP) in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 137-137 ◽  
Author(s):  
Ivana N. Micallef ◽  
Matthew J. Maurer ◽  
Thomas E. Witzig ◽  
Daniel Nikcevich ◽  
Paul Kurtin ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Aggressive Lymphoma ◽  
Pet Ct ◽  
Intent To Treat ◽  
Fdg Pet Ct ◽  
Pet Scans

Abstract Abstract 137 Background: FDG-PET/CT after 2–4 cycles of chemotherapy has been shown to be predictive of outcome in patients with aggressive lymphoma. This multicenter NCCTG phase II study was carried out to assess efficacy of ER-CHOP in newly diagnosed DLBCL; functional response as measured by FDG-PET/CT was done after 2 cycles and after 6 cycles of therapy. Methods: Patients received immunochemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard dose CHOP every 3 weeks for 6 cycles. FDG-PET/CT was done after 2 cycles and again after 6 cycles of therapy. All PET scans were centrally reviewed by an expert in nuclear medicine who was blinded to the outcome of the patients. Results: 107 patients were accrued from Feb 2006 to Aug 2007. 27 patients were ineligible resulting in 80 eligible patients. Baseline patient characteristics for the eligible patients included median age 60 (range 21–82); 56% were male. 80% had advanced stage; 73% had an elevated LDH. Performance score was 0–1 in 71 pts and 2–3 in 9 pts. IPI was 0–1 in 18 pts (23%), 2 in 22 pts (28%), 3 in 29 pts (36%) and 4–5 in 11 pts (14%). PET scans were available on 76 patients (95%); 3 patients completed treatment but scans were unavailable and 1 died prior to cycle 2 PET. The PET CR rate after 2 cycles was 79%. The PET CR rate after 6 cycles was 90%. Using an intent to treat (ITT) analysis, 67 patients (87%) achieved PET CR of which 61 (79%) also completed all 6 cycles of treatment. Based on interim PET after 2 cycles, the EFS at 24 months (EFS24) was 73% for the PET negative patients vs 60% for the PET positive patients (p=0.25); OS at 24 months (OS24) was 83% vs 73% for the PET negative and positive pts, respectively (p=0.17). In comparison, EFS24 for patients with a negative PET after 6 cycles was 80% vs 57% for those with a positive PET (p=0.11); OS24 was 92% vs 57%, respectively (p=0.01). In intent to treat (ITT) analysis, patients that achieved a functional CR had improved overall survival (OS24 = 84%) and event free survival (EFS24 = 74%) compared to patients that failed to achieve a functional CR (OS24 = 50%, EFS24 = 40%, p=0.01 and p=0.006 respectively). Conclusions: ER-CHOP every 21 days × 6 cycles results in a functional CR rate of 87%. Early PET scan during therapy does not significantly predict outcome. Achievement of PET negativity by completion of therapy is associated with a good outcome Disclosures: No relevant conflicts of interest to declare.

Inter/intra-tumoral dose response variations assessed using FDG-PET/CT feedback images: Impact on tumor control and treatment dose prescription

2021 ◽  
Vol 154 ◽  
pp. 235-242
Author(s):  
Di Yan ◽  
Shupeng Chen ◽  
Daniel J. Krauss ◽  
Rohan Deraniyagala ◽  
Peter Chen ◽  
...  
Keyword(s):  
Dose Response ◽  
Fdg Pet ◽  
Tumor Control ◽  
Pet Ct ◽  
Treatment Dose ◽  
Fdg Pet Ct

scholarly journals P3.13-004 Prospective Study of Sequential Ultra-Low then Standard Dose 18F-FDG PET/CT Scans for Lung Lesion Detectability

2017 ◽  
Vol 12 (11) ◽  
pp. S2316-S2317
Author(s):  
J. Schaefferkoetter ◽  
D. Townsend ◽  
M. Conti ◽  
X.M. Shi ◽  
R. Soo ◽  
...  
Keyword(s):  
Prospective Study ◽  
Fdg Pet ◽  
Standard Dose ◽  
Lung Lesion ◽  
Ct Scans ◽  
Lesion Detectability ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

scholarly journals Artificial intelligence for reduced dose 18F-FDG PET examinations: A real-world deployment through a standardized framework and business case assessment

2020 ◽  
Author(s):  
Katia Katsari ◽  
Daniele Penna ◽  
Vincenzo Arena ◽  
Giulia Polverari ◽  
Annarita Ianniello ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Real World ◽  
Fdg Pet ◽  
Standard Dose ◽  
Acquisition Time ◽  
Reduced Dose ◽  
Pet Ct ◽  
Significant Difference ◽  
18F Fdg ◽  
Fdg Pet Ct

Abstract Background To determine whether artificial intelligence (AI) processed PET/CT images of reduced by 33% administered 18-F FDG activity acquired in a single center, were non-inferior to native scans and if so to assess the potential impact of commercialization. Methods SubtlePET™ AI was introduced in a PET/CT center in Italy. Eligible patients referred for 18F-FDG PET/CT were prospectively enrolled. Administered 18F-FDG was reduced to two-thirds of standard dose. Patients underwent one low-dose CT and two sequential PET scans; ‘PET-processed’ with reduced dose and standard acquisition time, and ‘PET-native’ with an elapsed time to simulate standard acquisition time and dose. PET-processed images were reconstructed using SubtlePET™. PET-native images were defined as the standard of reference. The datasets were anonymized and independently evaluated in random order by four blinded readers. The evaluation included subjective image quality (IQ) assessment, lesion detectability and assessment of business benefits. Results From February to April 2020, 61 patients were prospectively enrolled. Subjective IQ was not significantly different between datasets (4.62±0.23, p=0.237) for all scanner models, with ‘almost perfect’ inter-reader agreement. There was no significant difference between datasets in lesions’ detectability, target lesion mean SUVmax value and liver mean SUVmean value (182.75/181.75 [SD:0.71], 9.8/11.4 [SD:1.13], 2.1/1.9 [SD:0.14] respectively). No false-positive lesions were reported in PET-processed examinations. Agreed SubtlePET™ price per examination was 15-20% of FDG savings. Conclusion This is the first real-world study to demonstrate the non-inferiority of AI processed 18F-FDG PET/CT examinations obtained with 66% standard dose and a methodology to define the AI solution price.

Predictive role of 18F-FDG-PET/CT 1 month before and after hypofractionated stereotactic body radiation therapy for stage I non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7569-7569
Author(s):  
S. Song ◽  
J. Ryu ◽  
S. Lee ◽  
S. Ahn ◽  
J. Kim ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Local Tumor Control ◽  
Chest Ct ◽  
Stage I ◽  
Tumor Control ◽  
Tumor Diameter ◽  
Local Tumor ◽  
Pet Ct ◽  
Before And After ◽  
Fdg Pet Ct

7569 Background: To know the predictive role of 18F-FDG-PET/CT 1month before and after stereotactic body radiation therapy (SBRT) to stage I non-small cell lung cancer (NSCLC). Methods: Between 2004 and 2007, 20 patients received SBRT with 48 Gy for 4 consecutive days and checked two times of FDG- PET/CT and chest CT with contrast-enhancement at 1 month before and after SBRT. Change of maximal SUV (SUVmax) on FDG-PET/CT and the longest tumor diameter on chest CT before and after SBRT was measured. Patients only with high FDG uptake, SUVmax 3.0 or above, on FDG-PET/CT before SBRT and tumor diameter below 5 cm were analyzed in this study. Change of tumor diameter was classified to PR (partial response), SD (stable disease), and DP (disease progression) as RECIST criteria and change of SUVmax was described as % change. Chest CT was checked at every 3 or 6 months during follow-up. Results: Mean time intervals from SBRT to FDG-PET/CT and chest CT were 32 and 30 days respectively. Mean longest tumor diameter was changed from 2.59 cm (1.36–3.93) to 2.17 cm (1.18–3.41), and its reduction rate was -16.2%. By RECIST criteria, 4 patients showed PR, 15 patients showed SD, and other 1 patient showed DP. Mean decrease rate of SUVmax on FDG-PET/CT was -52.1% and its mean value was changed from 7.1 (3.2–13.1) to 3.4 (0.3–9.8). Median follow-up time was 16 months. Local tumor progression developed in 2 (10%) patients and time to progression was 3.4, 6.1 months. Tumor responses on post-SBRT chest CT were PR in 1 and SD in the other 1 patient, and SUVmax changes were -31.9%, -25.5% in each. Most of patients showing no response, SD or DP, didn't recur after SBRT, and so chest CT at 1 month could not predict actuarial tumor response. On the contrary to chest CT, no patients showing SUVmax decreases over 40% experienced tumor progression after SBRT. High decrease rate of SUVmax over 40% decrease on FDG-PET/CT 1 month after SBRT could warrant good actuarial local tumor control earlier. Conclusions: Change of SUVmax on FDG-PET/CT 1 month before and after SBRT could predict actuarial local tumor control of stage I NSCLC earlier and 1 month after SBRT was adequate timing for the earlier evaluation of tumor response. No significant financial relationships to disclose.

scholarly journals Artificial Intelligence for Reduced Dose 18F-FDG PET Examinations: A Real-World Deployment Through a Standardized Framework and Business Case Assessment

2020 ◽  
Author(s):  
Daniele Penna ◽  
Katia Katsari ◽  
Vincenzo Arena ◽  
Giulia Polverari ◽  
Annarita Ianniello ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Real World ◽  
Fdg Pet ◽  
Standard Dose ◽  
Acquisition Time ◽  
Reduced Dose ◽  
Pet Ct ◽  
Significant Difference ◽  
18F Fdg ◽  
Fdg Pet Ct

Abstract BackgroundTo determine whether artificial intelligence (AI) processed PET/CT images of reduced by 33% administered 18-F FDG activity acquired in a single center, were non-inferior to native scans and if so to assess the potential impact of commercialization. MethodsSubtlePET™ AI was introduced in a PET/CT center in Italy. Eligible patients referred for 18F-FDG PET/CT were prospectively enrolled. Administered 18F-FDG was reduced to two-thirds of standard dose. Patients underwent one low-dose CT and two sequential PET scans; ‘PET-processed’ with reduced dose and standard acquisition time, and ‘PET-native’ with an elapsed time to simulate standard acquisition time and dose. PET-processed images were reconstructed using SubtlePET™. PET-native images were defined as the standard of reference. The datasets were anonymized and independently evaluated in random order by four blinded readers. The evaluation included subjective image quality (IQ) assessment, lesion detectability and assessment of business benefits. ResultsFrom February to April 2020, 61 patients were prospectively enrolled. Subjective IQ was not significantly different between datasets (4.62±0.23, p=0.237) for all scanner models, with ‘almost perfect’ inter-reader agreement. There was no significant difference between datasets in lesions’ detectability, target lesion mean SUVmax value and liver mean SUVmean value (182.75/181.75 [SD:0.71], 9.8/11.4 [SD:1.13], 2.1/1.9 [SD:0.14] respectively). No false-positive lesions were reported in PET-processed examinations. Agreed SubtlePET™ price per examination was 15-20% of FDG savings. ConclusionThis is the first real-world study to demonstrate the non-inferiority of AI processed 18F-FDG PET/CT examinations obtained with 66% standard dose and a methodology to define the AI solution price.

scholarly journals Artificial intelligence for reduced dose 18F-FDG PET examinations: a real-world deployment through a standardized framework and business case assessment

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Katia Katsari ◽  
Daniele Penna ◽  
Vincenzo Arena ◽  
Giulia Polverari ◽  
Annarita Ianniello ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Real World ◽  
Fdg Pet ◽  
Standard Dose ◽  
Acquisition Time ◽  
Reduced Dose ◽  
Pet Ct ◽  
Significant Difference ◽  
18F Fdg ◽  
Fdg Pet Ct

Abstract Background To determine whether artificial intelligence (AI) processed PET/CT images of reduced by one-third of 18-F-FDG activity compared to the standard injected dose, were non-inferior to native scans and if so to assess the potential impact of commercialization. Materials and methods SubtlePET™ AI was introduced in a PET/CT center in Italy. Eligible patients referred for 18F-FDG PET/CT were prospectively enrolled. Administered 18F-FDG was reduced to two-thirds of standard dose. Patients underwent one low-dose CT and two sequential PET scans; “PET-processed” with reduced dose and standard acquisition time, and “PET-native” with an elapsed time to simulate standard acquisition time and dose. PET-processed images were reconstructed using SubtlePET™. PET-native images were defined as the standard of reference. The datasets were anonymized and independently evaluated in random order by four blinded readers. The evaluation included subjective image quality (IQ) assessment, lesion detectability, and assessment of business benefits. Results From February to April 2020, 61 patients were prospectively enrolled. Subjective IQ was not significantly different between datasets (4.62±0.23, p=0.237) for all scanner models, with “almost perfect” inter-reader agreement. There was no significant difference between datasets in lesions’ detectability, target lesion mean SUVmax value, and liver mean SUVmean value (182.75/181.75 [SD:0.71], 9.8/11.4 [SD:1.13], 2.1/1.9 [SD:0.14] respectively). No false-positive lesions were reported in PET-processed examinations. Agreed SubtlePET™ price per examination was 15-20% of FDG savings. Conclusion This is the first real-world study to demonstrate the non-inferiority of AI processed 18F-FDG PET/CT examinations obtained with 66% standard dose and a methodology to define the AI solution price.

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