Small-cell lung cancer: envafolimab response complicated by immune-related diabetes, pneumonitis, and later submandibular progression

What happened, in summary

This 63-year-old man was admitted in April 2023 with newly diagnosed small-cell lung cancer. He had smoked about 20 cigarettes per day for 40 years and also had a long history of heavy alcohol intake. Brain MRI and whole-body bone scan showed no brain or bone metastases. Liver MRI initially raised concern for a lesion in segment S8, but later contrast CT scans showed only hepatic cysts without abnormal enhancement, so the likelihood of liver metastasis was considered low and the disease was later treated as limited-stage SCLC, cT2N2M0 / Stage IIIB. Treatment began with envafolimab, carboplatin, and etoposide. After 2 cycles, he achieved a sustained partial response. In August 2023, he started thoracic radiotherapy to the right hilar mass, mediastinal lymph nodes, and lymphatic drainage areas, delivered as 45 Gy in 30 fractions twice daily. His course then became complicated. He developed immune-checkpoint-inhibitor diabetes requiring insulin. In July 2024, biopsy of an enlarging left submandibular mass confirmed metastatic small-cell carcinoma, while other lesions remained in partial response. The submandibular metastasis was treated with iodine-125 seed implantation, and envafolimab was initially continued. Later, diffuse lung opacities were considered a combination of checkpoint-inhibitor pneumonitis and radiation pneumonitis, improving rapidly with methylprednisolone and prednisone. Envafolimab was permanently stopped. Topotecan was started but discontinued after 1 month because of cost. In June 2025, the left submandibular mass progressed again, and anlotinib was started after neurologic stabilization. He also needed ongoing insulin management after stopping insulin led to diabetic ketosis, and he experienced acute cerebral infarction requiring neurologic treatment. The latest cancer picture was mixed: most original lesions stayed in partial response, but the submandibular disease progressed and drove a new treatment line.