e13001 Background: Molecular profiling of cancer can guide treatment decision, monitor response and predict clinical outcome in the era of precision medicine and individualized treatment. Emerging evidence has suggested that ctDNA change correlates with treatment response and predates radiological relapse. Thus, we aim to provide real-world data regarding the dynamic changes of ctDNA level measured via Guardant 360 Response in advanced solid cancer correlates with clinical outcome. Methods: We retrospectively reviewed data of patients with advanced solid cancer and had at least 2 timepoints of Guardant 360 Response test at Houston Methodist Cancer center from 1/1/2014- 2 /1/2022. Data collected included age, gender, type of solid cancer, mutational values, treatment started date and type of systemic therapy. Personalized mutational profiles derived from tumor tissue via whole-exome sequencing were used to design patient-specific ctDNA assays for variant detection in plasma samples. Blood samples taken at baseline and 8 weeks were analyzed to a 70-gene next-generation sequencing panel. On-therapy changes in circulating tumor DNA levels (molecular response) were measured using a ratio computation, with response defined as a decrease in mean variant allele fraction of 50% or more. Apart from ctDNA analysis, patients were also monitored using tumor markers and radiological imaging. Results: : Of 267 patients, only 93 were met the inclusions criteria with age 58.66 (±12.95) and female were the most with 77 (82.80%). Patients with breast cancer were the dominant with 62 (66.67%), Lung adenocarcinoma 20 (21.51%), Uveal Melanoma 4 (4.30%), Colorectal Cancer and Lung Squamous Cell Carcinoma 2 (2.15 %) each, Large Cell Lung Carcinoma, Sarcoma and Thymic Carcinoma were 1(1.07%) each. Patients who received Chemotherapy /Immunotherapy were 38 (41.30%), Chemotherapy/Immunotherapy/Radiation therapy were 29 (31.52%), Immunotherapy 9 (9.78%), Chemotherapy/Immunotherapy/Targeted Therapy 2 (2.17%) and Targeted Therapy /Chemotherapy 3 (3.26%).Patients samples who correlated with clinical data were 89 (95.70%) and only 4 (4.30%) were not .Follow-up time 2.15 (interquartile range: 1.10-4.12) years, patients who still alive are 24 (25.81%), median survival time 2.4 (95% CI: 1.78-2.76) years. Conclusions: Our data demonstrated that molecular response evaluation using circulating tumor DNA as a noninvasive predictor of response to systemic therapy in addition to standard of care imaging in some solid cancer. Further prospective studies are needed to confirm the validation.
2525 Background: Immune checkpoint inhibitors (ICIs) can cause a variety of inflammatory autoimmune tissue damage, referred to as immune-related adverse events (irAEs). COVID-19 is associated with increased amounts of proinflammatory cytokines, which may synergistically affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Methods: We retrospectively analyzed adult patients with malignant solid tumors treated with ICIs at AdventHealth Orlando between August 2020 and August 2021. All COVID-19 infections were confirmed by PCR. Patients who had the most recent ICI treatment over one month before or after the positive COVID-19 test were excluded from the study. For COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. Results: A total of 579 patients were included in our study, with 46 (7.9%) in COVID-19 positive group, and 533 (92.1%) in COVID-19 negative group. The baseline characteristics of patients in the two groups were similar in terms of age, ethnicity, ECOG, cancer histology, and type of ICI. With a median follow-up of 10 months (1-73 months), no differences in the time from ICI initiation to irAE onset, corticosteroid use, or additional immunosuppressant use were seen. A trend in higher incidence of all-grade diarrhea/colitis (8.7% vs. 3.0%, p=0.07) and grade 3 and 4 hepatitis (4.3% vs. 0.8%, p=0.08) was noted in the COVID-19 positive group, however the difference was not statistically significant. No significant difference in the incidence of pneumonitis (2.2% vs. 1.1%, p=0.44), nephritis (2.2% vs. 0.8%, p=0.34) or dermatitis (6.5% vs. 6.4%, p=1.00) were noted between COVID-19 positive and negative groups. We noticed a higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, p=0.18), but the difference was not statistically significant. The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, p=0.02). Nine COVID-19 related death occurred while no irAE-related death was noted in the entire cohort. Conclusions: Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possible delaying ICI administration could be considered when cancer patients were infected with COVID-19. [Table: see text]
e20531 Background: One-third of patients with newly diagnosed non-small cell lung cancer (NSCLC) present at an early stage. Surgical resection remains the standard of care for medically fit patients. Adjuvant chemotherapy has shown benefit in stage II and III disease, but with the advent of immune checkpoint inhibition and targeted therapy, the adjuvant setting is now evolving. In 2017, all hospitals in the Houston Methodist Hospital (HMH) system approved reflex molecular testing at the time of diagnosis for all new cases of NSCLC, regardless of the clinical or pathologic stage. We performed a retrospective analysis of patients with NSCLC who underwent reflex molecular within the HMH system. Here we report outcomes for patients with early-stage EGFR-mutated NSCLC. Methods: Data was collected from a network of 7 hospitals for patients who underwent reflex molecular testing from 1/1/2017 to 8/31/2022. Patients diagnosed with stage I-II NSCLC and molecularly confirmed EGFR mutations were included. Baseline characteristics included age at diagnosis, sex, race, smoking status, performance status, and comorbidities. Pathologic assessment included histologic subtype, molecular results, and time from diagnosis to results of reflex molecular testing. Treatment information included initial surgery, radiation, and adjuvant therapy if given. Recurrence free survival (RFS) and overall survival (OS) were reported using Kaplan Meier methodology. Results: There were 37 patients included, with a median age at diagnosis of 71.2 (48-85) years. Of these, 26 (70.3%) were females, 21 (56.8%) were non-Hispanic Caucasian, and 16 (43.2%) were current/former smokers. All cases were histologically confirmed adenocarcinoma and 29 (78.4%) were stage I disease. Thirteen (35.1%) patients had exon 19 deletion, 17 (45.9%) had exon 21 L858R, and 3 (8.1%) had two synchronous EGFR mutations. Median time from diagnosis to EGFR results was 18 (5-134) days. Reflex test resulting time from 2017-2018 and 2019-2021 was 22 (5-134) and 16 (8-96) days, respectively. Thirty-four (91.9%) patients who underwent surgical resection and 3 (8.1%) received radiation. Five (13.5%) patients received adjuvant chemotherapy and 5 (13.5%) received EGFR-targeted therapy. At last follow-up, 7 (18.9%) patients had recurred and 4 (10.8%) died. RFS at 3 and 5 years was 68.2% and 56.9%, respectively. OS at 3 and 5 years was 88.7% and 82.8%, respectively. Conclusions: Reflex molecular testing at our institution has allowed for insight into outcomes of patients with early-stage NSCLC harboring EGFR mutations. With the adjuvant landscape evolving, broader adoption of reflex molecular testing in early-stage lung cancer should be implemented. Our analysis shows improvement in resulting time for molecular testing, along with similar DFS and OS reported in other studies.
e21507 Background: Metastatic uveal melanoma carries a poor prognosis, especially for patients who are not eligible for Tebentafusp. Unlike cutaneous melanoma, checkpoint inhibitors have limited effect on uveal melanoma. The observation of Abscopal effect has inspired this study of adding radiotherapy to boost the efficacy of immunotherapy. Methods: We performed a retrospective study in Houston Methodist Hospital to evaluate the efficacy of combining immunotherapy with radiotherapy including either SBRT or Y-90 treatment. Clinical outcomes were determined by assessing best overall response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), progression-free survival(PFS) and overall survival. Results: A total of 8 patients were included for this study, among which one patient had previously progressed on immunotherapy. The median follow-up period was 19 months. The best overall response rate (ORR) and disease control rate (DCR) were 25% and 75% in patients received dual-modality combination treatment (including one complete response and one partial response). The PFS and overall survival in dual-modality combination treatment group were 5.4 months (95% CI, 1.1 to 14.9 months) and 18.7 month (95% CI, 11.1 to 23.9 months), respectively. Fifty percent of patients experienced grade 3-4 treatment-related adverse events. Conclusions: The combination of radiotherapy and immunotherapy is active in metastatic uveal melanoma with sustained response in selected patients. A randomized prospective trial may be required to confirm the benefits of dual-modality combination treatment.[Table: see text]
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