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.