Abscopal effect following nivolumab induction in a patient with metastatic renal cell carcinoma‑unique pathological features of the primary specimen: A case report

Abstract

The case of a patient with metastatic renal cell carcinoma who exhibited the abscopal effect following treatment by anti-programmed death-1 (PD-1) antibody is presented. A 40-year-old woman was diagnosed with an 8.2-cm renal tumor without distant metastases, and radical nephrectomy was subsequently performed. Pathological examination revealed a clear cell renal cell carcinoma. At 3 months after surgery, the patient developed one lung metastasis. Following treatment with interferon and three types of tyrosine kinase inhibitors, anti-PD1 antibody (nivolumab) was started. During the treatment, para-aortic/supraclavicular lymph nodes and several lung lesions remained, although other lesions decreased markedly. The patient was subsequently treated by palliative radiotherapy to the para-aortic and supraclavicular lymph nodes for pain control. After the radiotherapy, the lung lesions previously refractory to nivolumab started to decrease, probably due to an abscopal effect. Additionally, the laboratory data and Karnofsky Performance Status improved. Histological re-examination of the primary lesion revealed heterogeneity of the immunological microenvironment, which may be associated with the heterogeneity of treatment sensitivity.

Possible abscopal effect after discontinuation of nivolumab in metastatic renal cell carcinoma

“…The abscopal effect, which was first reported by Mole in 1953, is induced by local radiotherapy and shows the regression of non‐irradiated metastatic lesions that are distant from the irradiated site 12 . Although it is a rare phenomenon, to the best of our knowledge, there are five case reports on metastatic RCC treated with a combination of ICI and EBRT 3–7 . The exact mechanisms of abscopal effect have not been elucidated, but some are evident in recent studies 13,14 .…”

“…The primary application of conventional EBRT is in palliation of metastatic sites and local tumor growth. The phenomenon of tumor regression in distant lesions from the irradiated site is known as the “abscopal effect.” Although the abscopal effect is a rare phenomenon, to the best of our knowledge, there are five case reports on metastatic RCC treated with a combination of ICI and EBRT 3–7 . Such combination therapies are likely to provide optimal treatment options for advanced RCC.…”

Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

“…PD-L1 expression, may also serve to define the role of the RT in an AbE, however, the temporal and spatial heterogeneity of PD-L1 expression must also be taken into account [213]. Nonetheless, PD-L1 negative patients may also benefit from checkpoint therapy because PD-L1 expression in metastases do not correspond with the expression in the primary tumor [73,82,90]. A study of metastatic NSCLC demonstrated a substantial variation in the PD-L1 expression across different sites and clinical states.…”

“…The patient showed regression of a lung metastasis six months after RT and immunotherapy treatment. Nevertheless, only a part of the tumor was considered immunogenic before anti-PD-1 treatment [90]. Teulings et al performed a detailed immunological analysis of biopsies from a melanoma patient presenting AbE twelve months after irradiation of the axillary region and brain.…”

Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review

“…Another study reported the case of a 40-year-old woman who was diagnosed with renal cell carcinoma (RCC) at 3 months after RT, and the levels of C-reactive protein (CRP), hemoglobin (Hb), and platelet (Plt values) were found to be normalized [98]. Several prognostic markers have been reported in RCCs.…”