The Role of 68 Ga-FAPI PET/CT in Breast Cancer Response Assessment and Follow-Up.

PURPOSE: 68 Ga-fibroblast activation protein inhibitor (FAPI), a new PET/CT radiotracer targeting cancer-associated fibroblasts in tumor microenvironment, can detect many types of cancer. We aimed to assess whether it can also be used for response assessment and follow-up. METHODS: We followed up patients with FAPI-avid invasive lobular breast cancer (ILC) before and after treatment changes and correlated qualitative maximal intensity projection images and quantitative tumor volume with CT results and blood tumor biomarkers. RESULTS: Six consenting ILC breast cancer patients (53 ± 8 years old) underwent a total of 24 scans (baseline for each patient and 2-4 follow-up scans). We found a strong correlation between 68 Ga-FAPI tumor volume and blood biomarkers ( r = 0.7, P < 0.01), but weak correlation between CT and 68 Ga-FAPI maximal intensity projection-based qualitative response assessment. CONCLUSIONS: We found a strong correlation between ILC progression and regression (as assessed by blood biomarkers) and 68 Ga-FAPI tumor volume. 68 Ga-FAPI PET/CT could possibly be used for disease response assessment and follow-up.

The Role of 68 Ga-FAPI PET/CT in Detection of Metastatic Lobular Breast Cancer.

PURPOSE: Invasive lobular breast cancer (ILC) may be hard to detect using conventional imaging modalities and usually shows less avidity to 18 F-FDG PET/CT. 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT has shown promising results in detecting non- 18 F-FDG-avid cancers. We aimed to assess the feasibility of detecting metastatic disease in patients with non- 18 F-FDG-avid ILC. METHODS: This prospective study included patients with metastatic ILC, infiltrative to soft tissues, which was not 18 F-FDG avid. The patients underwent 68 Ga-FAPI PET/CT for evaluation, which was correlated with the fully diagnostic CT performed at the same time. RESULTS: Seven women (aged 57 ± 10 years) were included. Among the 30 organs and structures found to be involved by tumor, the number of findings observed by FAPI PET/CT was significantly higher than that observed by CT alone ( P = 0.022), especially in infiltrative soft tissue and serosal locations. CONCLUSIONS: This small pilot trial suggests a role for 68 Ga-FAPI PET/CT in ILC, which needs to be confirmed by subsequent trials.

The Impact of Comprehensive Genomic Profiling (CGP) on the Decision-Making Process in the Treatment of ALK-Rearranged Advanced Non-Small Cell Lung Cancer (aNSCLC) After Failure of 2nd/3rd-Generation ALK Tyrosine Kinase Inhibitors (TKIs).

Background: The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable. Methods: We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2nd/3rd-generation ALK TKIs. Physician's choice of the most recommended next-line systemic treatment (NLST) was captured before and after receival of CGP results; the percentage of cases in which the NLST recommendation has changed was assessed along with the CGP turnaround time (TAT). Patients were divided into groups: patients in whom the NLST was initiated after (group 1) and before (group 2) receival of the CGP results. Time-to-treatment discontinuation (TTD) and overall survival (OS) with NLST were compared between the groups. Results: In 20 eligible patients (median [m]age 63 years [range, 40-89], females 75%, adenocarcinoma 100%, failure of alectinib 90%, FoundationOne Liquid CDx 80%), CGP has altered NLST recommendation in 30% of cases. CGP findings were as follows: ALK mutations 30% (l1171X 10%, G1202R, L1196M, G1269A, G1202R+l1171N+E1210K 5% each), CDKN2A/B mutation/loss 10%, c-met amplification 5%. CGP mTAT was 2.9 weeks [IQR, 2.4-4.4]. mTTD was 11.3 months (95% CI, 2.1-not reached [NR]) and 5.4 months (95% CI, 2.0-NR) in groups 1 and 2, respectively (p-0.34). mOS was 13.2 months (95% CI, 2.9-NR) and 13.0 months (95% CI, 6.0-NR) in groups 1 and 2, respectively (p-0.86). Conclusion: CGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2nd/3rd-generation ALK TKIs.

A Retrospective Analysis of the Safety and Activity of Lutetium-177-Prostate-Specific Membrane Antigen Radionuclide Treatment in Older Patients with Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Prostate cancer is a common malignancy of the elderly, and with the aging of the population, the need is growing for therapies suitable for this age group. Lutetium-177-prostate-specific membrane antigen (Lu-PSMA), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen, enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer (mCRPC). In a recent single-arm phase II trial and a subsequent expansion cohort, a prostate-specific antigen (PSA) decline of ≥50% was observed in approximately 60% of patients receiving Lu-PSMA. Taking into account the specific challenges and potential toxicities of Lu-PSMA administration in elderly men, we sought to retrospectively analyze the safety and activity of Lu-PSMA in men aged older than 75 years with mCRPC. PATIENTS AND METHODS: The electronic medical records of 24 patients aged older than 75 years treated with Lu-PSMA "off-trial" were reviewed, and clinical data were extracted. Clinical endpoints were toxicity and activity, defined as a PSA decline ≥50%. Descriptive statistics were performed using Excel. RESULTS: The median age at treatment start was 81.7 years (range 75.1-91.9). The median number of previous treatment lines was four. The number of treatment cycles ranged from one to four; the mean administered radioactivity was 6 GBq per cycle. Treatment was generally tolerable; side effects included fatigue (n = 8, 33%), anemia (n = 7, 29%), thrombocytopenia (n = 5, 21%), and anorexia/nausea (n = 3, 13%). Clinical benefit was observed in 12 of 22 patients (54%); PSA decline above 50% was observed in 11 patients (48%) and was associated with significantly longer overall survival. CONCLUSION: Our results indicate that Lu-PSMA is safe and active in elderly patients with mCRPC. IMPLICATIONS FOR PRACTICE: Lutetium-177-prostate-specific membrane antigen (Lu-PSMA), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen, enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer (mCRPC). The recently published single-arm phase II trial with Lu-PSMA, describing its safety and activity, did not include patients aged older than 75 years. In this study, Lu-PSMA activity was retrospectively analyzed in patients aged older than 75 years and results indicate that treatment was tolerable and similarly active in this age group, with no new emerging safety signals. Despite the small cohort size, this analysis suggests that Lu-PSMA can serve as an advanced palliative treatment line in mCRPC in elderly patients.