Spine eburnation in a metastatic lung cancer patient treated with immunotherapy and radiotherapy. The first case report of bystander effect on bone

Introduction Metastatic non-small cell lung cancer (NSCLC) is nowadays treated with a multimodal therapeutic approach including immunotherapy, targeted therapy and radiotherapy. Radiation therapy, in addition to immune checkpoint inhibitors, gives rise to a particular radiobiological effect known as “bystander effect” consisting of the radiation-induced damage in nearby unirradiated cells. Case report We report a case of a 79-year-old female patient with stage IV NSCLC treated with concomitant immuno-radiotherapy who showed a bystander effect on bone. Management and outcome: Primary tumour biopsy revealed an adenocarcinoma with a PDL1 expression >50%, while staging exams showed a right pulmonary lesion with a partial involvement of the contiguous rib and a single brain metastasis. The patient refused chemotherapy, so that Pembrolizumab 2 mg/Kg was administered every 3 weeks. After two administrations, the single brain metastasis was treated using stereotactic radiosurgery while the site of primitive lung cancer received an 8 Gy-single fraction 3 D-conformal radiotherapy. Three months after irradiation a chest CT showed a radiological remission of about 10% of the GTV and a partial eburnation of the vertebra located nearby the target volume. The CT images of a PET/CT at six months showed a complete vertebral eburnation. At the last follow-up, the patient was free of disease (brain MRI, spinal MRI and PET/CT). Discussion The present case alerts for unusual side effects provoked by bystander phenomenon in patients treated with a combination of immunotherapy and irradiation. Immune activation exacerbates the bystander effect causing normal tissues toxicities beyond what immunotherapies are causing by themselves.

The Effects of Postoperative Neurological Deficits on Survival in Patients With Single Brain Metastasis

BACKGROUND The prognosis for brain metastasis is poor, and surgical resection is part of the standard of care for these patients as it has been shown to improve median overall survival. Development of neurological deficits after surgical resection has been associated with worsened outcomes in patients with glioblastoma. The effect of postoperative neurological deficits on survival in patients with single brain metastasis has not been studied to date. OBJECTIVE To evaluate the association between postoperative neurological deficits and median overall survival. METHODS A single-institution retrospective cohort study was performed on all patients with single brain metastasis undergoing surgical resection by a single neurosurgeon. RESULTS A total of 121 patients met the inclusion criteria for this study. Among them 61% of patients presented with a preoperative deficit, and 26% of patients had a new postoperative deficit. However, most postoperative deficits resolved and only 3.3% of patients developed a new permanent postoperative deficit. Median overall survival in patients with a new postoperative deficit was 2.4 mo, whereas mOS in patients without a postoperative deficit was 12.6 mo (P < .0001). CONCLUSION This study suggests that a new neurological deficit is associated with worsened outcomes after surgical resection of a single brain metastasis. This finding has potential implications for patient selection and counseling as the patients most likely to benefit from surgical resection are the patients who are most likely to have resolution of a preoperative deficit.