Il ruolo della terapia ossea durante il trattamento con inibitori...

LA RICERCA

The role of bone radiotherapy

during immune checkpoint

inhibitors treatment

of non-small-cell lung cancer:

a single-institution

experience

Di:

Ivan Facilissimo, Guido Natoli,

Fabio Gaspari, Tiziana Comandone,

Diego Bongiovanni, Paola Gollini,

Claudia Provenza, Alessandro Comandone

ABSTRACT

Background: Immune checkpoint inhibitors (ICIs) represent a keystone of cancer treatment, including non-small-cell lung cancer (NSCLC). Unfortunately, the efficacy of ICIs remains poor in patients with bone metastases from NSCLC. Recently, several case reports have suggested the clinical benefit of radiotherapy in advanced NSCLC patients. However, whether this positive effect is applicable during ICI treatment of NSCLC involving bones remains to be established.

Methods: We retrospectively reviewed the records of patients with bone metastases who received ICIs as monotherapy (anti-PD1 or anti-programmed death-ligand 1) as well as in combination with platinum-based-chemotherapy (carboplatin or cisplatin). We next analyzed the presence or the absence of radiotherapy targeting bone metastases (RT) among these patients during immunotherapy.

Results: A total of 40 patients were included in this study; among them, 10 (25%) received palliative RT for symptomatic bone metastases during cancer immunotherapy treatment with ICIs (RT group); the remaining 30 (75%) patients did not receive bone irradiation (Non-RT group). We observed that the RT group had a significantly longer overall survival (OS) than the Non-RT group, with a median survival of 16 months in the RT group versus 3 months in the Non-RT group (log-rank test p < 0.048; hazard ratio (HR) for OS = 0.44; 95% confidence interval (CI): 0.18–1.00). Similar results were observed with respect to progression-free survival (PFS; log-rank test p < 0.016; HR for PFS = 0.34; 95% CI: 0.15–1.00).

Conclusion: Our results suggest that radiotherapy to bone metastases may improve ICIs efficacy in patients with bone metastatic NSCLC.

Keywords: abscopal effect, bone metastasis, bystander effect, immune checkpoint inhibitors, immunotherapy, non-small-cell lung cancer, radiotherapy

Introduction

Lung cancer is the second most common cancer in both men and women and is the leading cause of cancer-related death worldwide. Fortunately, the overall survival (OS) rate of patients with metastatic non-small-cell lung cancer (NSCLC) has improved in recent years and such improvement is probably due to the advent of immun checkpoint inhibitors (ICIs)._¹ Several biomarkers (e.g., programmed death-ligand 1 (PD-L1), tumor mutation burden) and clinical characteristics (e.g., gut microbiota, performance status, neutrophil to lymphocyte ratio) have helped us to identify which patients could benefit the most from ICIs treatment.^₂ Nevertheless, there is still a significant percentage of patients with little chance to be cured. In fact, the life expectancy is particularly disappointing among NSCLC patients with bone metastases,_³ despite the aforementioned advent of ICIs._⁴ Palliative bone radiation therapy (RT) may help to mitigate the magnitude of the bone pain._⁵ Pre-specified subgroup analysis focusing “ad hoc” on bone metastatic patients is lacking in immunotherapy clinical trials,_^6–9 as well as in two meta-analyses._^10,11 Thus, the appropriate clinical management of NSCLC patients with bone metastases remains an open issue. In this retrospective analysis, we explored the potential role of concomitant treatment with palliative bone RT and ICIs in a mono-institutional cohort of 40 patients with bone metastases from NSCLC. We also examined, in both a univariate way and multivariate way, other clinicopathological characteristics associated with the prognosis of this peculiar subset of metastatic NSCLC patients.

CONTINUA...

Correspondence to:

Guido Natoli

Division of Oncology, San Giovanni Bosco Hospital, Piazza del Donatore di Sangue 3, Torino 10154, Italy

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Ivan Facilissimo - Fabio Gaspari - Alessandro Comandone

Division of Oncology, San Giovanni Bosco Hospital, Torino, Italy

Tiziana Comandone

Pharmacology, University of Turin, Torino, Italy

Diego Bongiovanni

Division of Radiation Oncology, San Giovanni Antica Sede Hospital, Torino, Italy

Paola Gollini