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Role of perilesional edema and tumor volume in the prognosis of non-small cell lung cancer (NSCLC) undergoing radiosurgery (SRS) for brain metastases

Rolle des perilesionalen Ödems und des Tumorvolumens bei der Prognose von nicht-kleinzelligem Lungenkrebs (NSCLC) nach einer Radiochirurgie (SRS) von Hirnmetastasen

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Abstract

Aim

To assess the role of perilesional edema (PE) in non-small cell lung carcinoma (NSCLC) brain metastases (BM) undergoing radiosurgery (SRS).

Methods

This series includes 46 patients with 1–2 BM treated with SRS, selected out of all patients referred for radiotherapy (RT) for BMs over 5 years (2013 to 2017). Both the PE and gross tumor volume (GTV) were contoured on MRI images, and the PE/GTV ratio and PE + GTV value (TV, total volume) were calculated. Our clinical endpoints were brain recurrence free-survival, divided into local brain control (in field, LBC) and distant brain control (out of field, DBC) and overall survival (OS). We analyzed the role of the previously described volumetric parameters and of known clinical prognosticators (disease specific GPA, DS-GPA; chemotherapy, CHT) with Cox regression analyses.

Results

Only four patients (9%) developed in-field progression, whereas 10 patients (22%) showed new out-of-field BM and thirty-eight patients died in the follow up (83%). In univariate analysis, both volumetric parameters and clinical parameters were correlated with DBC and OS, whereas we did not find any correlation with LBC. In the multivariate analysis of DBC, the significant parameters were PE/GTV ratio (HR 0.302), sex (HR 0.131), and DS-GPA (HR 0.261). The OS multivariate analysis showed that the only significant parameters were DS-GPA (HR 0.478) and TV (HR: 1.038).

Conclusion

Our study, although with the limitations of a monocentric retrospective study analyzing a small cohort of patients, suggests the role of PE/GTV ratio for the development of new BMs. TV also seems to be correlated with OS, together with known clinical prognosticators. These findings, if validated in a larger prospective dataset, could help in selecting patients for the most suitable RT modality (or systemic therapy approach).

Zusammenfassung

Ziel

Beurteilung der Rolle des perilesionalen Ödems (PE) bei der Radiochirurgie (SRS) von Hirnmetastasen (BM) beim nicht-kleinzelligen Lungenkarzinom (NSCLC).

Methoden

Diese Serie umfasst 46 Patienten mit 1–2 mit SRS behandelten BM, die aus allen Patienten ausgewählt wurden, bei denen über einen Zeitraum von 5 Jahren (2013–2017) eine Radiotherapie (RT) zur BM-Behandlung eingesetzt wurde. Sowohl das PE- als auch das Bruttovolumen des Tumors (GTV) wurde auf MRT-Bildern konturiert, um das PE/GTV-Verhältnis und den PE + GTV-Wert (TV, Gesamtvolumen) zu erhalten. Unsere klinischen Endpunkte waren die rezidivfreie Zeit des Gehirns, welche in die lokale Hirnkontrolle (LBC, „in field“) und die entfernte Hirnkontrolle (DBC, „out of field“) unterteilt wurde, sowie das Gesamtüberleben des Patienten (OS). Wir haben die Rolle der zuvor beschriebenen volumetrischen Parameter und der bekannten klinischen Faktoren (krankheitsspezifische GPA: DS-GPA, Chemotherapie: CHT) mit den Cox-Regressionsanalysen analysiert.

Ergebnisse

Nur 4 Patienten (9%) entwickelten eine In-field-Progression, wohingegen 10 Patienten (22%) neue Out-of-field-BM zeigten und 38 Patienten im Follow-up starben (83%). Bei der univariaten Analyse wurden sowohl die volumetrischen Parameter als auch die klinischen Parameter mit DBC und OS korreliert, wohingegen wir keine Korrelation mit LBC fanden. Bei der multivariaten DBC-Analyse waren das PE/GTV-Verhältnis (HR 0,302), das Geschlecht des Patienten (HR 0,131) und das DS-GPA (HR 0,261) signifikante Parameter.

Schlussfolgerung

Unsere Studie legt – trotz der Einschränkungen einer monozentrischen retrospektiven Studie, die eine kleine Patientengruppe analysiert – die Rolle des PE/GTV-Verhältnisses für die Entwicklung neuer BMs nahe. Das TV scheint auch mit OS, zusammen mit bekannten klinischen Faktoren, zu korrelieren. Diese Erkenntnisse könnten, wenn sie in einem größeren, prospektiven Datensatz validiert würden, bei der Auswahl der Patienten für die geeignetste RT-Modalität (oder den systemischen Therapieansatz) helfen.

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Authors and Affiliations

  1. Unit of Radiation Oncology, Ospedale del Mare, Viale della Metamorfosi, Naples, Italy

    Valerio Nardone MD & Cesare Guida

  2. Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy

    Sara Nanni, Pierpaolo Pastina & Paolo Tini

  3. Department of Medicine, Surgery and Neurosciences (Clinical Neurology and Neuro-metabolic Disorders), University of Siena, Siena, Italy

    Claudia Vinciguerra

  4. Unit of Neuro-Radiology, University Hospital of Siena, Siena, Italy

    Alfonso Cerase

  5. Unit of Medical Oncology, Grand Metropolitan Hospital “Bianchi Melacrino Morelli” Reggio Calabria, Reggio Calabria, Italy

    Pierpaolo Correale

  6. Sbarro Health Research Organization, Temple University, Philadelphia, PA, USA

    Antonio Giordano, Paolo Tini & Luigi Pirtoli

  7. Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA

    Antonio Giordano & Luigi Pirtoli

  8. Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Alfonso Reginelli & Salvatore Cappabianca

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  1. Valerio Nardone MD
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V. Nardone, S. Nanni, P. Pastina, C. Vinciguerra, A. Cerase, P. Correale, C. Guida, A. Giordano, P. Tini, A. Reginelli, S. Cappabianca, and L. Pirtoli declare that they have no competing interests.

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Nardone, V., Nanni, S., Pastina, P. et al. Role of perilesional edema and tumor volume in the prognosis of non-small cell lung cancer (NSCLC) undergoing radiosurgery (SRS) for brain metastases. Strahlenther Onkol 195, 734–744 (2019). https://doi.org/10.1007/s00066-019-01475-0

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