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Linac-based stereotactic body radiation therapy for unresectable locally advanced pancreatic cancer: risk-adapted dose prescription and image-guided delivery

LINAC-basierte Körperstereotaxie beim nichtresektablen lokal fortgeschrittenen Pankreaskarzinom: Risikoadaptierte Dosisverordnung und bildgesteuerte Dosisverteilung

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Abstract

Background

Stereotactic body radiation therapy (SBRT) represents a new treatment option for locally advanced pancreatic cancer (LAPC). An accurate treatment planning with risk-adapted dose prescription with adherence to specific dose constraints for organs at risk (OARs) and the use of daily cone beam CT (CBCT) for image guidance could allow an effective and safe treatment delivery. Here, feasibility and efficacy of SBRT in LAPC treated in our cancer care center are reported.

Patients and methods

33 unresectable LAPC patients underwent SBRT. In order to respect OAR dose constraints, a risk-adapted dose prescription strategy was adopted, choosing between the following schedules: 42 Gy or 45 Gy in 6 daily fractions with a biologically effective dose (BED) > 70 Gy10 or 36 Gy/6 fractions (estimating a BED 57.6 Gy10). SBRT was delivered with volumetric modulated arc technique (VMAT) and flattening filter-free (FFF) mode. Image guidance was performed by means of CBCT before every treatment session. The patients were evaluated at the end of treatment for acute toxicity and at 3, 6, and 12 months for late toxicity and treatment response.

Results

At the time of analysis, the median follow-up was 18 months (range 5–34 months). Prior to SBRT, 24 out of 33 patients received induction chemotherapy. Although all patients were previously judged as unresectable, 6 out of 33 (18%) underwent surgery after SBRT; all of them received a BED > 70 Gy10. One-year LC and OS were 81% and 75%, respectively. A total of 12 patients (37%) had an extra-pancreatic progression. No cases of ≥G3 acute or late toxicity were reported.

Conclusion

In our experience, risk-adapted dose prescription and image-guided SBRT represents an effective treatment option for LAPC patients.

Zusammenfassung

Hintergrund

Stellt die Körperstereotaxie (SBRT) eine neue Behandlungsoption für lokal fortgeschrittene Pankreaskarzinome (LAPC) dar. Eine präzise Bestrahlungsplanung mit risikoadaptierten Dosiskonzepten und Einhaltung spezifischer Toleranzdosisgrenzen für Risikoorgane (OARs) sowie die Anwendung von täglicher Image-Guidance mittels Cone-beam-Computertomographie (CBCT) könnte eine effektive und sichere Behandlungsoption darstellen. Wir berichten über die Anwendbarkeit und Effektivität von SBRT bei LAPC-Patienten, die in unserem Krebszentrum behandelt wurden.

Patienten und Methoden

33 Patienten mit nichtresektablem LAPC wurden stereotaxiert. Um OAR-Toleranzwerte einzuhalten, wurde eine risikoadaptierte Dosisverordnung durchgeführt und zwischen den folgenden Dosiskonzepten gewählt: 42 Gy oder 45 Gy in 6 täglichen Fraktionen mit einer biologisch äquivalenten Dosis (BED) > 70 Gy10 oder 36 Gy in 6 Fraktionen (BED 57,6 Gy10). Die SBRT wurde mit volumenmodulierter Radiotherapie (VMAT) ohne Ausgleichsfilter („flattening filter-free“, FFF) durchgeführt. Vor jeder Behandlungseinheit erfolgte eine Image-Guidance mittels CBCT. Das Ansprechen sowie die Akut- und Spätnebenwirkungen wurden am Ende der Therapie sowie nach 3, 6 und 12 Monaten ausgewertet.

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 18 Monate (5–34 Monate). Vor der SBRT erhielten 24 von 33 Patienten eine Induktionschemotherapie. Obwohl alle Patienten zuvor als inoperabel eingestuft wurden, wurden 6 von 33 (18 %) nach SBRT operiert. Alle operierten Patienten hatten eine BED > 70 Gy10 erhalten. Lokoregionale Kontrolle (LC) und Gesamtüberleben (OS) nach einem Jahr waren 81 % und 75 %. Insgesamt erlitten 12 Patienten (37 %) eine distante Progression. Kein Patient entwickelte eine akute oder späte Grad-3-Toxizität.

Schlussfolgerung

Die bildgeführte SBRT mit risikoadaptierter Dosisverordnung stellt eine effektive Behandlungsoption für LAPC-Patienten dar.

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Abbreviations

BED:

Biologically effective dose

CT:

Computed tomography

CTV:

Clinical target volume

CR:

Complete response

Dx:

Dose per x cc

GTV:

Gross tumor volume

IMRT:

Intensity-modulated radiotherapy

IGRT:

Image-guided radiotherapy

LAPC:

Locally advanced pancreatic cancer

LC:

Local control

Linac:

Linear accelerator

OS:

Overall survival

OARs:

Organs at risk

PD:

Progressive disease

PERCIST:

PET Response Criteria in Solid Tumors

PET:

Positron-emission tomography

PR:

Partial response

PTV:

Planning target volume

RT:

Radiotherapy

RECIST:

Response Evaluation Criteria in Solid Tumors

SBRT:

Stereotactic body radiotherapy

SD:

Stable disease

Vx:

Volume receiving x Gy

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Authors and Affiliations

  1. Radiation Oncology, Sacro Cuore Don Calabria Hospital, Negrar-Verona, Italy

    Rosario Mazzola MD, Sergio Fersino, Ruggero Ruggieri & Filippo Alongi

  2. University of Brescia, Brescia, Italy

    Filippo Alongi

  3. Radiation Oncology School, University of Palermo, Palermo, Italy

    Dario Aiello

  4. Radiation Oncology School, University of Padua, Padua, Italy

    Fabiana Gregucci & Umberto Tebano

  5. Radiation Oncology, LMU Munich, Munich, Germany

    Stefanie Corradini

  6. University of Palermo, Palermo, Italy

    Gioacchino Di Paola

  7. Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar-Verona, Italy

    Massimo Cirillo

  8. Medical Oncology, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy

    Luca Tondulli

  9. Surgical Oncology, Sacro Cuore Don Calabria Hospital, Negrar-Verona, Italy

    Giacomo Ruffo

Authors
  1. Rosario Mazzola MD
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  2. Sergio Fersino
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  3. Dario Aiello
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  4. Fabiana Gregucci
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  7. Gioacchino Di Paola
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  8. Massimo Cirillo
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  9. Luca Tondulli
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  10. Giacomo Ruffo
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  11. Ruggero Ruggieri
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  12. Filippo Alongi
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Corresponding author

Correspondence to Rosario Mazzola MD.

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Conflict of interest

R. Mazzola, S. Fersino, D. Aiello, F. Gregucci, U. Tebano, S. Corradini, G. Di Paola, M. Cirillo, L. Tondulli, G. Ruffo, R. Ruggieri, and F. Alongi declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Mazzola, R., Fersino, S., Aiello, D. et al. Linac-based stereotactic body radiation therapy for unresectable locally advanced pancreatic cancer: risk-adapted dose prescription and image-guided delivery. Strahlenther Onkol 194, 835–842 (2018). https://doi.org/10.1007/s00066-018-1306-2

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