Jeong JH, et al. J Korean Med Sci. 2023 Jul;38(32):e244. https://doi.org/10.3346/jkms.2023.38.e244

Introduction: Although pirfenidone slows disease progression in patients with idiopathic pulmonary fibrosis (IPF), in clinical practice, patients often cannot tolerate the recommended dose because of several adverse events. This study aimed to investigate adverse events associated with pirfenidone and factors associated with dose reduction. Methods: This single-center retrospective cohort study included 156 consecutive patients with IPF who received pirfenidone. Demographic characteristics, pulmonary function, and pirfenidone-related adverse events were investigated. We compared patients who received standard and reduced doses of pirfenidone. Results: The mean patient age was 69.7 years. The median follow-up duration was 243 days. The low-dose group (n = 73) included older patients (71.0 years vs. 67.4 years, p = 0.016), fewer smokers (80.8% vs. 96.4%, p = 0.008), and patients with a lower body mass index (BMI; 24.1 kg/m² vs. 25.7 kg/m², p = 0.027) than the standard dose group (n = 57). Multivariate logistic regression analysis revealed that older age (odds ratio = 1.066, p = 0.016) was significantly associated with dose reduction of pirfenidone after adjusting for sex, smoking history, emphysema, and BMI. No significant difference was found in the rates of a reduced forced vital capacity and diffusing capacity for carbon monoxide between the two groups. Conclusions: Although older patients are more likely to undergo dose reduction of pirfenidone, low-dose pirfenidone might be effective for treating patients with IPF. Low-dose pirfenidone could be considered an effective treatment option for older patients with IPF.

Rationale: Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory condition that can lead to ureteral obstruction and renal dysfunction. While most cases are idiopathic, secondary causes including malignancies should be considered. RPF secondary to gastric cancer is extremely rare, with only a few cases reported. Patient concerns: A 56-year-old woman presented with generalized edema, decreased urine output, and nausea that had begun 7 days prior. Laboratory tests revealed acute kidney injury, and imaging showed bilateral hydronephrosis. Diagnoses: Further evaluation through abdominal-pelvic computed tomography and esophagogastroduodenoscopy revealed a depressed ulcerative gastric lesion. Histopathological examination confirmed poorly differentiated gastric adenocarcinoma. Intraoperative biopsy of retroperitoneal fibrotic tissue showed malignant cell infiltration, confirming RPF secondary to gastric cancer. Interventions: The patient underwent subtotal gastrectomy and bilateral percutaneous nephrostomy for urinary diversion. Antibiotics were administered postoperatively for urinary tract infection. She was discharged with a plan for adjuvant chemotherapy. Outcomes: Urine output and renal function normalized following percutaneous nephrostomy insertion. The patient’s infection resolved with antibiotic therapy, and she remained clinically stable at discharge. Lessons: This case illustrates a rare presentation of gastric cancer manifesting as malignancy-associated RPF. Clinicians should maintain a high index of suspicion for occult malignancy in patients with bilateral ureteral obstruction of unclear cause. Early imaging and histological evaluation are critical for diagnosis and appropriate management.

Background: As the outcome of immunotherapy can be improved when concurrently or sequentially combined with cytotoxic chemotherapy or radiotherapy, we investigated the efficacy of immunotherapy maintenance following platinum‐based chemotherapy in epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) after EGFR‐tyrosine kinase inhibitor (EGFR‐TKI) failure.Methods: In this prospective, open‐label, single arm phase 2 trial, we enrolled patients aged 18 years or older with EGFR‐mutant NSCLC, which progressed after first‐ or second‐line EGFR‐TKI. Patients received platinum‐based chemotherapy followed by nivolumab maintenance therapy. They were intravenously administered 240 mg of nivolumab every 2 weeks for 3 months followed by 480 mg every 4 weeks until disease progression or unacceptable toxic effects occurred. The primary endpoint was progression‐free survival (PFS). Secondary outcomes were overall survival (OS) and incidence of grade 3–4 treatment‐related adverse events (AEs).Results: We enrolled 26 patients between May 2020 and July 2021. The median PFS was 1.7 months (95% CI: 0.401–2.999 months). The median OS was 21.4 months (95% CI: 18.790–24.010 months) with 6‐ and 12‐month OS rates of 96.2% and 76.9%, respectively. The objective response rate was 7.7% (2/26) and disease control rate, 11.5% (3/26). The tumor mutational burden by next‐generation sequencing in blood was not related to the treatment outcomes. Grade 3–4 treatment‐related AEs occurred in four (15.4%) patients; the most frequent AE was increased alanine aminotransferase (7.7%).Conclusion: Nivolumab maintenance following platinum‐based chemotherapy did not show clinical benefits after EGFR‐TKI failure in patients with EGFR‐mutant NSCLC.

Background/Objectives: Surgical resection of non-small-cell lung cancer (NSCLC) often results in temporary suppression of natural killer cell activity (NKA), potentially increasing the risk of recurrence. This study aimed to evaluate whether multivitamin and mineral complexes containing Agaricus blazei could support postoperative immune recovery. Methods: In this randomized, double-blind, placebo-controlled multicenter pilot trial, 66 patients with stage I–III NSCLC received either a supplement or a placebo for 28 days post-surgery. NKA was assessed using an interferon-γ release assay preoperatively, on postoperative days (POD) 1–4, and on POD 30. Immune cell subsets, cytokine levels, clinical parameters, and quality of life were evaluated. Results: Both groups showed a postoperative decline in NKA, with recovery observed by POD 30. Although the increase in NKA was not statistically significant, the treatment group showed a greater relative recovery (17.8% vs. 9.9%, p = 0.104). Immune profiling demonstrated significantly better preservation of T cells (p = 0.026) and B cells (p = 0.001) as well as a greater reduction in monocytes (p = 0.031) in the treatment group. No significant differences were observed in cytokine levels, body mass index, Eastern Cooperative Oncology Group Performance Status, or patient-reported outcomes. Conclusions: Supplementation with a multivitamin and mineral complex containing Agaricus blazei may contribute to favorable immune modulation in patients undergoing curative surgery for NSCLC. Larger long-term trials are warranted to confirm these findings and facilitate clinical application.

Although mesenchymal–epithelial transition proto-oncogene (MET) amplification is a common resistance mechanism in targeted therapy for lung cancer, rapid disease progression associated with this resistance mechanism in patients with epidermal growth factor receptor (EGFR) mutation has scarcely been reported. Herein, we report a fatal case of lung adenocarcinoma that rapidly progressed after failure of EGFR-tyrosine kinase inhibitor treatment following the emergence of MET amplification. A 62-year-old man was diagnosed with metastatic lung adenocarcinoma containing mutations in EGFR exon L858R and RNA-binding motif 10. He received afatinib as frontline treatment and showed a partial response; however, the right lung lesion progressed after 14 months of treatment. Although the drug was maintained after salvage segmentectomy of the lesion, lung nodules and pleural effusion developed shortly thereafter. Because EGFR testing using resected tissue showed only the original mutation, we switched his regimen to pemetrexed and carboplatin. However, the disease rapidly progressed with a very large mass in the right lung and massive pleural effusion, which led to death within 7 weeks of treatment. Next-generation sequencing was performed at the time of first progression and second progression revealed acquired MET amplification (copy number gain 15.5 and 9.1, respectively) in addition to baseline mutations. Although an association between MET amplification and rapidly progressive lung cancer has been predicted previously, to the best of our knowledge, this is the first report on the potential contribution of other mutations, such as those in RNA-binding motif 10, during MET-driven rapid progression. Our report highlights the importance of more active utilization of molecular profiling for the emergence of resistance during tyrosine kinase inhibitor use and the early identification of MET amplification and timely initiation of MET-targeted therapy, such as MET inhibitors in combination with EGFR-TKIs, to potentially mitigate rapid disease progression and clinical deterioration.