Purpose. We assessed the outcome of 129 patients with primary adenoid cystic carcinoma (ACC) of the salivary glands treated with proton beam therapy (PBT) with curative intent at Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, between 2017 and 2022. Methods. This is an observational retrospective cohort study. A survival analysis was performed to assess clinical outcomes and prognostic factors. Toxicities were recorded and a literature review was performed. Results. Prior to PBT, 104 patients underwent surgery (18 with R0, 56 with R1, and 30 with R2 margins). The median total dose was 66 Gy(RBE). The median follow-up was 34 months. The 2-year PFS, LPFS, DMFS, and OS are 78.3%, 93.2%, 78.2%, and 94.2%, respectively. The 5-year PFS, LPFS, DMFS, and OS are 63.8%, 83.7%, 66.3%, and 86.8%, respectively. In the multivariable Cox regression analyses, the time to progression appears to be influenced by the T stage (p = 0.014) and the solid pattern (p = 0.005). The maximum acute and late toxicity grade was G4 (0.8% and 3.1%, respectively). A significant effect of the overall treatment time for the group of all operated patients on the time to progression (p = 0.009), time to local progression (p = 0.002), and time to distant progression (p = 0.009) is observed. Optimal cutoffs identified for the overall treatment time and the time from surgery to RT for this group of patients are 4.47 months and 3.23 months, respectively. When considering operated patients with only 1 surgery, the cutoffs are similar (4.47 and 3 months, respectively), but, for this group, no effect of the intervals of interest is observed in the univariable Cox analysis. Conclusion. We achieved good results in terms of locoregional control and overall survival, though distant metastases remain an important concern in the long-term management of patients with ACC. The treatment was well tolerated, also during follow-up. We confirm the prognostic significance of the solid variant at histology as well as of the T4 stage, while also underlining the negative impact of the T3 stage on survival curves. While surgery remains the gold standard approach in the initial management of ACC, and indeed, we found that operated patients perform better than non-operated ones in terms of failure rate, surgical margins do have an impact on prognosis. Finally, the only time interval found to be significant is the overall treatment time for the group of all operated patients, with an estimated optimal cutoff of 4.47 months. A larger patient sample size as well as multivariable analyses are needed, though, in order to determine the actual significance of this variable.
Obiettivo. Abbiamo valutato l’outcome di 129 pazienti con carcinoma adenoide cistico primario delle ghiandole salivari trattati con protonterapia con intento curativo presso CNAO, Pavia, tra il 2017 e il 2022. Metodi. Questo è uno studio di coorte osservazionale retrospettivo. E’ stata eseguita un’analisi di sopravvivenza per valutare gli outcome clinici e i fattori prognostici. Sono stati raccolti i dati relativi alle tossicità ed è stata eseguita una revisione della letteratura. Risultati. Prima della protonterapia, 104 pazienti sono stati sottoposti ad intervento chirurgico (18 con margini R0, 56 con R1, e 30 con R2). La dose totale mediana è stata di 66 Gy(RBE). La durata mediana del follow-up è stata di 34 mesi. PFS, LPFS, DMFS, ed OS a 2 anni sono, rispettivamente, 78.3%, 93.2%, 78.2%, e 94.2%. PFS, LPFS, DMFS, ed OS a 5 anni sono, rispettivamente, 63.8%, 83.7%, 66.3%, e 86.8%. Alle analisi multivariabili con modello di Cox, il tempo alla progressione risulta essere influenzato dallo stadio T (p = 0.014) e dal pattern solido (p = 0.005). Il grado massimo di tossicità acuta e tardiva è stato G4 (0.8% e 3.1%, rispettivamente). Si osserva un effetto significativo dell’overall treatment time per il gruppo di pazienti operati con ≥1 chirurgie sul tempo alla progressione (p = 0.009), sul tempo alla progressione locale (p = 0.002), e sul tempo alla progressione a distanza (p = 0.009). I cutoff ottimali individuati per l’overall treatment time e il time from surgery to RT per questo gruppo di pazienti sono di 4.47 mesi and 3.23 mesi, rispettivamente. Quando si considerano i pazienti operati con 1 solo intervento chirurgico, i cutoff sono simili (4.47 e 3 mesi, rispettivamente), ma, per questo gruppo, non si osserva alcun effetto di tali intervalli all’analisi univariabile. Conclusione. Abbiamo ottenuto risultati favorevoli in termini di controllo locoregionale e di sopravvivenza globale; tuttavia, le metastasi a distanza restano un problema importante nella gestione a lungo termine dei pazienti con ACC. Il trattamento è stato ben tollerato, anche durante il follow-up. Confermiamo il significato prognostico della variante solida all’istologia e dello stadio T4, evidenziando tuttavia anche l’impatto negativo dello stadio T3 sulle curve di sopravvivenza. Mentre la chirurgia resta il primo approccio all’ACC, e infatti abbiamo determinato che i pazienti operati hanno una risposta migliore in termini di tasso di progressione, i margini chirurgici hanno un impatto sulla prognosi. Infine, l’unico intervallo di tempo risultato significativo è l’overall treatment time riferito ai pazienti operati con ≥1 chirurgie, con un cutoff ottimale di 4.47 mesi. Un numero maggiore di pazienti e analisi multivariabili sono tuttavia necessari per determinare il significato effettivo di questo fattore.
PROTON THERAPY FOR ADENOID CYSTIC CARCINOMA OF THE HEAD AND NECK: RESULTS OF A SINGLE-CENTRE EXPERIENCE
BRIGHENTI, LAURA
2023/2024
Abstract
Purpose. We assessed the outcome of 129 patients with primary adenoid cystic carcinoma (ACC) of the salivary glands treated with proton beam therapy (PBT) with curative intent at Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, between 2017 and 2022. Methods. This is an observational retrospective cohort study. A survival analysis was performed to assess clinical outcomes and prognostic factors. Toxicities were recorded and a literature review was performed. Results. Prior to PBT, 104 patients underwent surgery (18 with R0, 56 with R1, and 30 with R2 margins). The median total dose was 66 Gy(RBE). The median follow-up was 34 months. The 2-year PFS, LPFS, DMFS, and OS are 78.3%, 93.2%, 78.2%, and 94.2%, respectively. The 5-year PFS, LPFS, DMFS, and OS are 63.8%, 83.7%, 66.3%, and 86.8%, respectively. In the multivariable Cox regression analyses, the time to progression appears to be influenced by the T stage (p = 0.014) and the solid pattern (p = 0.005). The maximum acute and late toxicity grade was G4 (0.8% and 3.1%, respectively). A significant effect of the overall treatment time for the group of all operated patients on the time to progression (p = 0.009), time to local progression (p = 0.002), and time to distant progression (p = 0.009) is observed. Optimal cutoffs identified for the overall treatment time and the time from surgery to RT for this group of patients are 4.47 months and 3.23 months, respectively. When considering operated patients with only 1 surgery, the cutoffs are similar (4.47 and 3 months, respectively), but, for this group, no effect of the intervals of interest is observed in the univariable Cox analysis. Conclusion. We achieved good results in terms of locoregional control and overall survival, though distant metastases remain an important concern in the long-term management of patients with ACC. The treatment was well tolerated, also during follow-up. We confirm the prognostic significance of the solid variant at histology as well as of the T4 stage, while also underlining the negative impact of the T3 stage on survival curves. While surgery remains the gold standard approach in the initial management of ACC, and indeed, we found that operated patients perform better than non-operated ones in terms of failure rate, surgical margins do have an impact on prognosis. Finally, the only time interval found to be significant is the overall treatment time for the group of all operated patients, with an estimated optimal cutoff of 4.47 months. A larger patient sample size as well as multivariable analyses are needed, though, in order to determine the actual significance of this variable.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/17570