PRaG Therapy of Refractory Metastatic Gastric Cancer: A Case Report

Abstract

Patients with metastatic gastric cancer had limited treatments and often had a somber prognosis, especially when patients were unable to tolerate high-intensity cytotoxic treatment due to poor physical condition or organ dysfunction after the failure of standard therapy. Here, we reported a metastatic and proficient mismatch repair (pMMR) gastric adenocarcinoma patient with the Eastern Cooperative Oncology Group (ECOG) performance status score of 2 associated with hypoproteinemia and fatigue, and poor appetite that was unable to tolerate high-intensity therapy after several chemotherapy regimens and anti-angiogenic therapy. After receiving novel triple-combination therapy, which consists of PD-1 inhibitor, Radiotherapy and Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy (PRaG for short), the patient achieved a complete response (CR) with a progression-free survival time of 14 months, and ECOG performance status score improved from 2 to 0. A significant systemic effect was observed in this case and the PRaG triple-combination therapy might provide a novel treatment strategy for metastatic pMMR gastric cancer patients.

Keywords: GM-CSF; case report; gastric cancer; immunotherapy; pMMR; radiotherapy.

Figure 1

(A–F, H) Pathological and immunohistochemical staining of gastric cancer biopsy specimens from this patient. (A) Gastric adenocarcinoma (hematoxylin and eosin). (B) The tumor cells were strongly positive (3+) for HER2/neu immunostain. The expression of MLHI (C), MSH2 (D), MSH6 (E), and PMS2 (F) was preserved in tumor cells. (G)There were no tumor cells in the pelvic effusion. (H) showed positivity for PD-LI CPS 60.

Figure 2

Timeline of the whole treatment process for the patient. The patient experienced PD with the new emergence of enlarged paratracheal lymph nodes during postoperative adjuvant chemotherapy on 26 August 2020. Two months after apatinib was combined with chemotherapy, the subcarinal LN, right upper paratracheal LN, and left lower paratracheal LN were detected by CT scan on 06 November 2020, and the patient developed PI) again, After 4 cycles of PRaG therapy, the sum of diameters of the unirradiated target metastases decreased by 45% from baseline, and the right upper paratracheal LN almost disappeared. The patient was assessed as PR on 24 March 2021.18F FDG PET-CT on 10 June 2021, most LNs disappeared and one shrunk to normal size with normal FDG uptake. Therefore the patient achieved CR. Although the patient unfortunately suffered PD again on 21 January 2022 (new metastatic LNs appeared), he obtained 14 months of PFS from the start of PRaG therapy on 19 November 2020. PRaG therapy: The patient was treated with subcutaneous GM-CSF (200 gg once daily, d4-17) after the completion of radiotherapy (15Gy/3f, d1-3) and received a PD-I inhibitor (toripalimab 240mg, d4.The PRaG regimen was repeated every three weeks, and different mediastinal lymph nodes were irradiated during the PRaG treatment, with each cycle delivered to one metastatic site. After four cycles of PRaG therapy, maintenance treatment ofPD-1 monotherapy was administered every three weeks. Until 21 January 2022, when the patient suffered PD again, Each cycle of the above has a duration of 21 days. LN, lymph node; PD, progressive disease; PR, partial response; CR, complete response; PFS, progression-free survival.

Figure 3

Trends of CEA and CA724 levels. The CA724 level was reduced to normal on 07 January 2021 after 2 cycles of PRaG therapy. The CEA level was decreased to normal on 22 March 2021 after 4 cycles of PRaG therapy. There was a fluctuating increase in both biomarkers from 6 August 2021 to 3 1 December 2021, but the disease remained stable after CT evaluation. On 20 January 2022, a multifold increase in the two biomarkers was detected, at which time the patient was assessed as progressive disease (PD) by CT scans.

Figure 4

CT scans before (2020-11.06), during (2021-01-08), and after (2121-03-24, 2021-05-12) the PRaG therapy. Right upper paratracheal (A) and subcarinal lymph node (B) were the two irradiated lesions that gradually shrunk significantly after the PRaG therapy, One of the left lower paratracheal lymph nodes (C) progressively shrunk and the other (D) rapidly shrunk and disappeared after PRaG therapy. (E) shows that pelvic effusion gradually decreased and disappeared, The yellow arrow indicated the irradiated lesions, and the blue arrow indicated the unirradiated ones; all assessed lesions were circled with orange lines.