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Role of upper abdominal reirradiation for gastrointestinal malignancies: a systematic review of cumulative dose, toxicity, and outcomes on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Die Rolle der oberen abdominalen Rebestrahlung bei gastrointestinalen Malignomen: Ein systematischer Review über kumulative Dosen, Toxizität und Outcome im Auftrag der Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

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Abstract

Purpose

Abdominal recurrences of gastrointestinal malignancies are common. Evidence in clinical studies has shown that re-irradiation (Re-I) is tolerable and efficient in different tumor locations. In contrast, little clinical data are available on normal long-term Re‑I tolerance doses. A systematic review of upper abdominal Re‑I was performed with the aim of exploring the cumulative dose, toxicity, and outcomes.

Methods

A computerized search was undertaken in MEDLINE, EMBASE, OVID, and the Cochrane database. Only studies reporting toxicity and/or outcomes were taken into consideration. To improve the comparability of the different Re‑I regimens and assess the relationship between Radiotherapy (RT) dose and toxicity, the equivalent dose in 2‑Gy fractions was calculated according to the linear quadratic model.

Results

Sixteen studies met the inclusion criteria, with the total patients numbering 408. Median follow-up Re‑I ranged from 5.9 to 45 months. The median time elapsed since previous RT treatment was 15 months (2–162 months). Re‑I prescription doses were variable (22.5 Gy in 3 fractions to 126.5 Gy with 125I). Cumulative doses calculated for acute- and late-responding tissues ranged from 67.25 to 136 Gy and 30.3 to 188.38 Gy, respectively. Comprehensively, the pooled ≥G3 toxicity was 12% (95%CI: 7.6–19%). The overall 1‑year survival and local recurrence-free survival rates were 53.7% (95%CI: 45.6–63.2%) and 66.5% (95% CI: 58.7–75.4%), respectively. Pain improvement was reported in 66.9% of patients.

Conclusion

Due to limited evidence as a result of the retrospective design of the majority of the studies, our review suggests that upper abdominal Re‑I is effective in terms of local control and palliation, with a moderate rate of severe toxicities.

Zusammenfassung

Zweck

Bei gastrointestinalen Malignomen sind abdominale Rezidive häufig. Klinische Studien haben belegt, dass eine Re-I-Bestrahlung (Re-I) bei verschiedenen Tumorlokalisationen tolerierbar und wirksam ist. Dagegen liegen nur wenige klinische Daten über langfristige normale Re-I-Toleranzdosen vor. Es wurde eine systematische Überprüfung der Oberbauch-Re‑I durchgeführt, mit dem Ziel, kumulative Dosis, Toxizität und Ergebnisse zu untersuchen.

Methoden

Eine computergestützte Suche wurde anhand von MEDLINE, EMBASE, OVID und der Cochrane-Datenbank durchgeführt. Es wurden nur Studien mit Angabe der Toxizität und/oder Gefahrlosigkeit als Ergebnis berücksichtigt. Um die Vergleichbarkeit der verschiedenen Re-I-Regime zu verbessern und den Zusammenhang zwischen Strahlentherapie(RT)-Dosis und Toxizität zu beurteilen, wurde die Äquivalentdosis in 2‑Gy-Fraktionen nach dem linear-quadratischen Modell berechnet.

Ergebnisse

Sechzehn Studien erfüllten die Einschlusskriterien bei einer Gesamtzahl von 408 Patienten. Das mediane Follow-up-Re-I-Range betrug 5,9–45 Monate. Die seit der vorhergehenden RT verstrichene mediane Zeit betrug 15 Monate (Spanne 2–162 Monate). Die Re-I-Verschreibungsdosen waren variabel (22,5 Gy in 3 Fraktionen bis 126,5 Gy mit 125I). Die für akutes und spät ansprechendes Gewebe berechneten kumulativen Dosen lagen zwischen 67,25 und 136 Gy bzw. 30,3 und 188,38 Gy. Insgesamt betrug die gepoolte >G3-Toxizität 12% (95%-Konfidenzintervall [KI] 7,6–19%). Die auf 1 Jahr bezogene Gesamtüberlebensrate und die lokale rezidivfreie Überlebensrate betrugen jeweils 53,7% (95%-KI 45,6–63,2%) bzw. 66,5% (95%-KI 58,7–75,4%). Bei 66,9% der Patienten wurde eine Verbesserung der Schmerzsituation verzeichnet.

Schlussfolgerung

Trotz der Einschränkungen aufgrund weniger Beweise und aufgrund der vorwiegend retrospektiv gestalteten Studien spricht unsere Überprüfung dafür, dass Oberbauch-Re‑I durchführbar ist, was schwere Toxizität bei guter lokaler Kontrolle und Linderung der Symptome anbelangt.

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Acknowledgements

The authors wish to thank the Scientific Commission of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for the revision of the manuscript.

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Authors and Affiliations

  1. Radiation Oncology Unit, “SS Annunziata” Hospital, “G. D’Annunzio” University, Via Dei Vestini, 66100, Chieti, Italy

    Luciana Caravatta M.D., Consuelo Rosa & Domenico Genovesi

  2. Department of Radiation Oncology and Nuclear Medicine, State Hospital Mater Salutis AULSS 9, 37045, Legnago (VR), Italy

    Francesco Fiorica

  3. UOC Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy

    Luca Boldrini, Anna Rita Alitto, Alessia Nardangeli & Mariangela Massaccesi

  4. Proton Therapy Unit, Department of Oncology, Azienda Provinciale per i Servizi Sanitari, APSS, 38123, Trento, Italy

    Francesco Dionisi

  5. Department of Radiotherapy, Azienda U. S. L. della Valle d’Aosta, 11100, Aosta, Italy

    Lavinia Bianco & Fernando Munoz

  6. Radiation Oncology Section, University of Perugia and Perugia General Hospital, 06156, Perugia, Italy

    Marco Lupattelli

  7. Department of Oncology and Radiotherapy, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy

    Giovanna Mantello

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  1. Luciana Caravatta M.D.
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  2. Francesco Fiorica
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  9. Fernando Munoz
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  13. Mariangela Massaccesi
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Consortia

Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Contributions

L. Caravatta and M. Massaccesi designed and coordinated the study and the analysis. L. Boldrini, A. Nardangeli, and A.R. Alitto performed the literature search and selected included studies. F. Dionisi revised the literature search and performed data extraction. C. Rosa, F. Munoz, and L. Bianco checked data extraction. F. Fiorica and L. Caravatta finally reviewed and approved the literature selection and data extraction. F. Fiorica performed statistical data analysis. F. Fiorica and L. Caravatta performed the main data analysis and provided graphics. F. Fiorica, L. Caravatta, A.R. Alitto, and C. Rosa drafted the manuscript. M. Massaccesi, M. Lupattelli, D. Genovesi, and G. Mantello critically revised the study and the manuscript. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Luciana Caravatta M.D..

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Conflict of interest

L. Caravatta, F. Fiorica, C. Rosa, L. Boldrini, A.R. Alitto, A. Nardangeli, F. Dionisi, L. Bianco, F. Munoz, M. Lupattelli, G. Mantello, D. Genovesi, and M. Massaccesi declare that there is no conflict of interest regarding the publication of this article.

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Caravatta, L., Fiorica, F., Rosa, C. et al. Role of upper abdominal reirradiation for gastrointestinal malignancies: a systematic review of cumulative dose, toxicity, and outcomes on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Strahlenther Onkol 196, 1–14 (2020). https://doi.org/10.1007/s00066-019-01519-5

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