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Purpose This research work evaluates monotherapy with checkpoint inhibitors (CPI). as a neoadjuvant treatment for patients with Microsatellite Instability-High (MSI-H) locally advanced gastric cancer. Methods Here we present the results of the retrospective study from Napalkov Cancer Center over 4.5 years on patients with MSI-H locally advanced gastric cancer. A total of 566 patients were analyzed, 18 of whom were included in the research, focusing on clinical response rate, surgical pathology, 'watch and wait' strategy, and safety outcomes on an exploratory basis. Patients were assigned to four to eight neoadjuvant cycles of CPI, followed by surgery. Results The objective response to neoadjuvant CPI in patients with MSI-H gastric cancer was 77.8%. Complete response was achieved in five (27.8%) and partial response in nine (50%) patients, accordingly. Surgery was performed on 14 patients. Complete margin-free (R0) resection rates were 100%. Downstaging was observed in 12 out of 14 patients. Histopathologic complete response rates (pathologic complete response or Tumor Regression Grade-major response (TRG1)) were achieved in eight (57.1%) patients. No disease progression was detected with a median follow-up of 33.7 months (4.4-55.7 months). Clinically significant adverse events were not observed. Conclusion CPI in a neoadjuvant setting for patients with MSI-H locally advanced gastric cancer is highly effective and safe.
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This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene. Since the patient already developed contraindications to the standard chemotherapy, olaparib (300 mg twice a day) was given as a last hope option. The patient demonstrated a "Lazarus response": the performance status and the results of the biochemical tests went back to the norm within first two weeks of treatment. Positron emission tomography-computed tomography (PET-CT) was performed at one month after the start of olaparib therapy, and revealed complete metabolic response for all multiple metastatic lesions located in the liver, bones, small pelvis, lungs, mediastinum, retroperitoneum, etc. Cytotoxic therapy and poly ADP-ribose polymerase (PARP) inhibitors are known to have virtually identical mechanisms of tumor escape from the treatment, which are confined to the restoration of BRCA proficiency within cancer cells. The pronounced tumor response to the treatment in this patient can be attributed to the lack of recent exposure to standard cytotoxic treatment as well as to the inability of tumors with gross BRCA rearrangements to restore BRCA function via secondary mutation. This observation calls for comprehensive evaluation of PARP inhibitors in chemonaive patients with hereditary cancer.