CASE PRESENTATION
A 55-year-old male patient presented with loss of appetite and icterus. Upper Gastrointestinal Scopy revealed gastric and duodenal ulcers with gastric obstruction. HPE of biopsied tumor tissue indicated Gastric Adenocarcinoma The patient underwent diagnostic laparoscopy which showed omental and peritoneal deposits which were confirmed by HPE as metastases. HER2 status was not evaluated by Immunohistochemistry. The patient received neoadjuvant Standard of Care chemotherapy with Docetaxel, Cisplatin and 5-Fluorouracil along with 50Gy/28 days of radiotherapy. Post chemoradiotherapy, PET-CT showed good response to the treatment with reduced wall thickening in stomach. The patient subsequently underwent Radical Distal Gastrectomy, with Roux-En-Y reconstruction. The pathological staging was pT3N0 with a moderately differentiated gastric adenocarcinoma. The patient received adjuvant 50.4 Gy #28 CTRT radiation therapy along with oral Tab Capecitabine till April 2018. On a follow up PET/CT scan at six months, there were deposits seen along the transverse colon and in the pelvic peritoneum along with ascites.
Due to disease progression, patient was offered Encyclopedic Tumor Analysis (ETA). The process and details of ETA have been previously described.12 Briefly, ETA includes Next Generation Sequencing based profiling of gene variants in tumor DNA using a targeted multigene variant panel, as well as evaluation of differentially expressed (>20000) transcripts in tumor RNA and finally in vitro chemoresponse evaluation of viable tumor tissue derived cells. NGS profiling identified mutations in NOTCH3 (p.G2218G), ATM (c.1236-2A>T;intronic) and GNAS (p.R201C), in addition to amplification of FGFR3 gene. In vitro chemoresponse profiling of viable tumor cells indicated very high sensitivity towards Gemcitabine, Pemetrexed and Doxoribicin and high sensitivity towards Topotecan and Epirubicin.
HER2 amplifications were not detected in NGS and HER2 status by IHC was not ascertainable due to insufficient biopsy (patient was unable to undergo a repeat biopsy). Prior FFPE blocks / slides were unavailable for evaluation. Based on ETA findings, the patient was then treated with a combination of Tab Pazopanib (400 mg, PO, 1 OD) IV Gemcitabine (800 mg, D1 and D8 of 21 Day cycle) and IV Pemetrexed (400 mg, D1 and D8 of 21 Day cycle).
The patient received 5 cycles of ETA guided treatment between Oct 2018 to Feb 2019. The patient underwent 4 follow-up radiological imaging scans between Oct 2018 and Apr 2019. Significant response to treatment was observed at day 28 as well as all subsequent imaging scans, with no new lesions. Thereafter the patient continued to receive maintenance treatment with Oral Tab Pazopanib. The patient tolerated the treatment regimen well with minimal and manageable profile of Adverse Events (AE), which included one Grade III incidence each of Fatigue, Thrombocytopenia, Sepsis and Pneumothorax. All AEs were transient (resolved within a week) and did not necessitate treatment suspension or dose modification. There were no Grade IV AEs.
Patient reported significant improvement in general health and reduction of symptoms. The patient continued the maintenance regimen for several months but declined further follow-up or imaging. Unfortunately, the patient passed away in March 2020 at the beginning of the COVID pandemic.
A clinical timeline of the patient including all the received treatments, is shown in figure 1-A, along with the PET CT scan in figure 1-B, showing a significant response to the ETA guided drug treatment.