Case Report

Osteoblastic Flare During Chemo-Immunotherapy in Small Cell Lung Cancer: Do Not Be Misleaded!

Bertolini Federica1, Cabitza Eleonora1*, Trudu Lucia2, Guaitoli Giorgia2, Greco Stefano1, Fontana Annalisa1, Casari Federico3, Sabbatini Roberto1Dominici Massimo1, Maur Michela1

1Division of Oncology, Department of Oncology and Hematology, University of Modena & Reggio Emilia and University Hospital of Modena, Modena, Italy

2PhD Program Clinical and Experimental Medicine, University of Modena & Reggio Emilia, Modena, Italy

3Radiology Department, University of Modena & Reggio Emilia and Modena University Hospital, Modena, Italy

*Corresponding author: Cabitza Eleonora, Division of Oncology, Department of Oncology and Hematology, University of Modena & Reggio Emilia and University Hospital of Modena, Modena, Italy

Received Date: 26 March 2023

Accepted Date: 30 March 2023

Published Date: 03 April 2023

Citation: Bertolini F, Cabitza E, Trudu L, Guaitoli G, Greco S, et al (2023) Osteoblastic Flare During Chemo-Immunotherapy in Small Cell Lung Cancer: Do Not Be Misleaded!. Ann Case Report. 8: 1244. https://doi.org/10.29011/2574-7754.101244

Abstract

Introduction: “Osteoblastic flare” is defined as a temporary increase in bone tracer uptake associated with therapy response in patients without previously detected bone metastases. Hypothetically these apparently “new osteoblastic” lesions are not visible at baseline and are radiologically detected only after a bone sclerotic healing reaction has appeared, for this reason it does not indicate disease progression, but the healing of previously inconspicuous lesions. This phenomenon has been described in several solid tumours as response to antineoplastic treatments; however, it had never been reported in patients with ES-SCLC treated with chemo-immunotherapy.

Methods: The Computed Tomography scans (CTs) of five patients with ES-SCLC treated with first-line chemo-immunotherapy with Atezolizumab, Carboplatin and Etoposide, were retrospectively reviewed to analyse the bone response to treatment compared with the response of the visceral tumour.

Results: On reassessment CTs the development of new onset osteoblastic lesions was associated with a partial response in the other disease sites. In each case, osteoblastic lesions, developed during therapy, were considered as a response reflecting bone repair and efficacy of the treatment. Therefore, the maintenance therapy was continued obtaining a temporary stability of the disease. In view of the increasing use of chemo-immunotherapy in this setting, it is important not to confuse this phenomenon with disease progression, in order to avoid discontinuation of the maintenance immuno-therapy treatment, which the patient could benefit from.

Keywords: Chemo-Immunotherapy; ES-SCLC; Osteoblastic-

Flare

Introduction

Small cell lung cancer (SCLC) represents approximately 1316% of annual lung cancer diagnoses world-wide. The ability of SCLC tumour cells to disseminate early explains why 60-70% of cases presents with extensive stage (ES) disease, with bone and liver being predominant sites for metastatic involvement. Reliable detection of bone and bone marrow metastases, which affect 4060% of patients, remains an unsolved issue in SCLC staging. The prognosis of ES-SCLC is dismal, with 5-year overall survival (OS) less than 7% [1,2]. The life expectancy of ES-SCLC patients had not improved in the last three decades, till the publication of two recent clinical trials (CASPIAN and Impower-133) showed how the addition of anti-programmed death ligand (PD-L1) therapy to chemotherapy led to a modest OS benefit over chemotherapy alone [3,4]. In the past decades, the appearance of bone metastases (either osteolytic or osteoblastic) during treatment was usually qualified as disease progression. More recently, bone flare reaction, including the onset of new osteoblastic lesions, has been redefined as a sign of response to antineoplastic treatment. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course eventually giving a negative effect on patients’ clinical outcome. To our best knowledge, bone flare reaction had never been reported in patients with ES-SCLC treated with chemo-immunotherapy. Thus, we retrospectively reviewed the computed tomography scans of five patients with ES-SCLC treated with first-line Atezolizumab, Carboplatin and Etoposide at the Division of Oncology of Modena University Hospital evaluating bone and visceral tumour response to treatment.

Figure 1: Base-line contrast-enhanced CT-scan showed a solid expansive hilar process on the right (A), liver (C) and brain (E) lesions (arrows), while no bone metastases were detected (G). The revaluation CT-scan after 4 courses of chemo-immunotherapy showed the reduction of the pulmonary (B), liver (D) and brain (F) lesions (arrows), but the onset of osteoblastic lesions (H) in the dorso-lumbar vertebrae (arrow). (CT: Computed Tomography).

Case 1

On February 2021, a former smoker 68-year-old white man was diagnosed with ES-SCLC (liver, nodes and brain metastases). Bone metastases could not be detected at diagnosis [Figure 1]. He received four courses of first-line chemo-immunotherapy followed by Atezolizumab as maintenance immunotherapy. After first cycle patient underwent surgery to reduce a pertrochanteric fracture (consequence of accidental fall). Neoplastic cell infiltration was not detected on the surgical specimen. At first evaluation, after three months of chemo-immunotherapy, and before the beginning of immunotherapy maintenance computed tomography (CT) scans showed the onset of multiple osteoblastic lesions that were not confirmed by 18-fluorodeoxyglucose PET (18-FDG-PET). A marked reduction in all the previously identified metastases, included disseminated brain lesions, were reported [Figure 1]. In view of the good response elsewhere, the osteoblastic lesions were considered an osteoblastic response to treatment and immunotherapy maintenance was continued until august 2021 when brain progression was documented, and the patient died shortly after.

Figure 2: Base-line contrast-enhanced CT-scan showed a solid expansive hilar process on the right (A), a smaller one at the homolateral lower lobe (C) and liver (E) lesions (arrows), while no bone metastases were detected (G). The revaluation CT-scan after 4 courses of chemo-immunotherapy showed the reduction of the pulmonary (B, D) and liver (F) lesions (arrows), but the onset of osteoblastic lesions (H) in the dorso-lumbar vertebrae (arrows). (CT: Computed Tomography).

Case 2

On February 2021 an active smoker 74-year-old woman was diagnosed with an ES-SCLC (liver, pleural effusion and adrenal glands). No bone metastases were detected at diagnosis. She underwent first-line chemo-immunotherapy followed by Atezolizumab maintenance. At first evaluation, after 3 months of chemo-immunotherapy, computed tomography scans showed the onset of osteoblastic lesions [Figure 2]. All phosphocalcic metabolites on blood tests were normal. A significant reduction in all the previously identified metastatic sites was described [Figure 2]. To better define the nature of the new bone lesions, 18-FDG-PET imaging was performed with no increase of tracer uptake reported in the multiple vertebral lesions. Due to worsening back-pain, a spinal Magnetic Resonance Imaging (MRI) was performed which demonstrated D12 vertebral-collapse and osteothickening lesions of D11, and L2-L5. After neuroradiologist image revision, the palliative radiotherapy program was excluded as the bone lesions seemed to be related to osteoporosis. Thus, the patient underwent D12 vertebroplasty. Also, L3 bone biopsy was performed but no tumour cells were detected on histological specimen. The second evaluation by CT scan, performed 3 months later after 4 courses of immunotherapy maintenance, showed a substantial stable disease, so the patient continued maintenance with Atezolizumab for a total of 12 courses until progression was detected in January 2022.