Further studies are needed to elucidate the molecular and immunological bases of HPD to improve the management of patients receiving ICI therapy. 3.1. shown clear survival benefits as single-agent or combination therapy when compared with standard chemotherapy in treatment-naive or previously treated patients.[1C7] However, increasing evidence has shown that these new immunotherapy drugs are associated with some novel tumor response patterns, such as delayed responses, pseudoprogressions, and hyperprogressive disease (HPD).[8C9] Although the definition and incidence of HPD varied across studies, it always resulted in a dismal prognosis.[10C13] However, the management of HPD has not been specifically addressed. Here, we present a heavily pretreated lung cancer patient who experienced HPD during ICI therapy and was successfully treated with iodine-125 (125I) radioactive particle implantation. 2.?Case presentation In August 2017, a 47-year-old nonsmoking Chinese man was referred to our hospital with a hard, immovable, and non-tender mass in the right supraclavicular fossa, approximately 2??2?cm in size. The patient had an Eastern Cooperative Oncology Group performance status W-2429 score of 0. Rabbit Polyclonal to ATP5S He reported no systemic disease. A contrast-enhanced total-body computed tomography (CT) scan (head to pelvis) revealed a mass and obstructive pneumonia in the upper lobe of the right lung. Along with this, lymphadenopathy (short axis? ?15?mm) in the right upper mediastinum, supraclavicular fossa, and posterior cervical triangle and an osteolytic lesion in the right fifth rib were also seen. CT-guided biopsy of the lung mass revealed poorly differentiated adenocarcinoma. The adenocarcinoma cells were positive for CKpan, CK7, CD56 (focal), and CK5 (focal), but negative for TTF-1, CgA, Syn, P63, and P40. The positive expression rate of ki67 was 80% to 90%. Genomic analysis revealed no sensitizing mutations in the epidermal growth factor receptor gene or in the anaplastic lymphoma kinase gene. Starting in September 2017, he received 3 lines of systemic chemotherapy before ICI treatment (paclitaxel and carboplatin plus bevacizumab for 6 cycles, followed by 4 cycles of bevacizumab monotherapy with partial response and a progression-free survival of 6 months, pemetrexed and cisplatin for 6 cycles with partial response and a progression free W-2429 survival of 4 months, and anlotinib for 157 days with subsequent progressive disease). In addition, he also received brachytherapy with 125I radioactive particle implantation in the primary lung mass. The response evaluation criteria for solid tumors 1.1 was referred. In March 2019, a contrast-enhanced total-body CT scan (head to pelvis) demonstrated partial response of the primary lung mass after 125I radioactive particle implantation, stable disease of the right fifth rib metastasis, and progression disease of the axillary W-2429 lymph node metastases. Given the patient’s performance status (Eastern Cooperative Oncology Group performance status 1), palliative treatment with docetaxel and toripalimab, the first domestic recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody approved for use in refractory metastatic melanoma in China on December 17, 2018, was planned. Docetaxel and toripalimab were administered at 75?mg/m2 and 240?mg, respectively, every 3 weeks. After administration of the first dose, the patient began to experience a gradual worsening of his persistent right-sided chest pain. Two weeks later, a physical examination revealed a palpable right-sided chest wall mass. An enhanced CT scan showed progression of the rib metastasis. The metastatic tumor cells widely infiltrated the thoracic wall, invading the subcutaneous tissue (Fig. ?(Fig.1,1, 1st evaluation). Biopsy of the lesion revealed a poorly differentiated adenocarcinoma. Next-generation sequencing showed no targetable oncogenic alterations. Immunohistochemical analysis of programmed death-ligand 1 expression using the murine 22C-3 antibody revealed a tumor proportion score (TPS) of 0%. The primary lung tumor and metastatic lymph nodes remained stable..