Purpose: A growing interest has recently raised around the role of Normal Tissue Control Probability (NTCP) models in supporting clinical decisions. Due to promising role of PT in reducing treatment related toxicities, the current work aims to apply the model-based approach, referring to a set of toxicities (dysphagia and xerostomia), in a cohort of patients treated with radical radiotherapy (VMAT) for HPV-related Oropharyngeal Squamous Cell Carcinomas (OPSCC). An in-silico planning comparison was performed in order to quantify the potential benefit of IMPT compared to VMAT in a multicenter setting. Materials and methods: IMPT and VMAT plans were optimized for a cohort of 41 HPV+ OPC patients treated from February 2017 to January 2024 in 5 different Italian centers. Organs at risk (OARs) were contoured according to the international consensus guidelines for CT-based delineation of OARs in the head and neck region. Target coverage was defined as at least 95% of the Clinical Target Volume (CTV) covered by 98% of the prescribed dose. Regarding OARs a dose-volume comparison was performed, particularly focusing on the parotid glands, brainstem, spinal cord, mandible, oral cavity, pharyngeal constrictors muscles and larynx. According to the Dutch National Indication Protocol for Proton therapy (NIPP) two NTCP models were selected, and a comparative analysis was performed for all 82 plans (VMAT and IMPT). Patients could be qualified for proton therapy in case the ΔNTCPx-p thresholds are: (1) ≥ 10% for toxicities grade ≥2, (2) ≥ 5% for toxicities grade ≥ 3, (3) ≥ 15% for the summed ΔNTCP of toxicities grade ≥ 2 (with a minimum of ≥ 5% for each) or (4) ≥ 5% for the summed ΔNTCP of toxicities grade ≥ 3 (with a minimum of ≥ 3.75% for each), with specific reference to dysphagia and xerostomia. Results: A dose per fraction of 2.12 Gy was prescribed for most plans (51%). The median prescription dose to HD-PTV was 69,96 Gy. Average HD-PTV D95 was 66,25 Gy with IMRT and 66,37 Gy RBE with IMPT. Average HD-PTV D98 was 65,07 Gy in IMRT plans and 65,31 Gy RBE in IMPT plans. A lower Dmean to the majority of OARs of interest was obtained with IMPT versus VMAT with statistically significance (p value < .05), except for PCMsup, PCMinf, mandible and left parotid. According to NIPP ΔNTCP thresholds, of 41 patients eligible for the analysis, 15 patients (37%) would benefit from proton therapy. These patients were selected based on the ΔNTCPx-p values in terms of toxicities for dysphagia and xerostomia. The average NTCP value for xerostomia grade 2 was 35,24% with the photon plan, and 30,15% for the proton plan, while for xerostomia grade 3 was 9,45% and 7,86%, respectively, with an average ΔNTCPp-x value of -5,1% for grade 2 toxicity and -1,6% for grade 3. On the other hand, the average NTCP value for dysphagia grade 2 was 19,55% with the photon plan, and 13,11% for the proton plan, while for dysphagia grade 3 was 5,53% and 2,81%, respectively, with an average ΔNTCPp-x value of -6,4% for grade 2 toxicity and -2,7% for grade 3. Conclusions: In the current study, the model-based approach referring to a set of toxicities (dysphagia and xerostomia) was applied to a cohort of patients treated with radical radiotherapy (VMAT) for HPV+ OPC, and planning comparison was feasible. Among 41 patients, 15 (37%) resulted eligible for protons and they are the most likely to benefit from IMPT in terms of prevention of dysphagia and xerostomia. Moreover, a dosimetric analysis demonstrated advantage in IMPT plans, with equal target coverage versus VMAT plans.
Obiettivo: Il ruolo dei modelli di probabilità d'insorgenza di una complicanza dei tessuti sani (NTCP) a supporto delle decisioni cliniche è un argomento di interesse crescente. Essendo la protonterapia ad intensità modulata (IMPT) promettente nel ridurre le tossicità correlate al trattamento, il presente studio è volto ad applicare l’approccio model-based (MBA) in riferimento ad un set di tossicità (disfagia e xerostomia) in una coorte di pazienti trattati con radioterapia convenzionale (IMRT) radicale per carcinomi squamocellulari dell’orofaringe (OPC) HPV-relati. Un confronto in-silico dei piani è stato effettuato per quantificare il potenziale beneficio della IMPT rispetto alla IMRT in un setting multicentrico. Materiali e metodi: I piani IMPT e IMRT sono stati ottimizzati per un campione di 41 pazienti affetti da HPV+ OPC trattati dal 2017 al 2024 in 5 diversi centri italiani. Gli organi a rischio (OAR) sono stati contornati sulle TAC nel distretto cervico-cefalico secondo le linee guida internazionali. La copertura del target è stata definita come almeno il 95% del CTV coperto dal 98% della dose prescritta. In merito agli OAR, un confronto dose-volume è stato realizzato, con attenzione particolare per le ghiandole parotidi, il tronco encefalico, il midollo spinale, la mandibola, il cavo orale, i muscoli costrittori faringei e la laringe. Secondo il Protocollo Nazionale olandese di Indicazione alla Protonterapia (NIPP) due modelli NTCP sono stati selezionati, e un’analisi comparativa è stata compiuta per tutti gli 82 piani (IMRT e IMPT). I pazienti sono risultati qualificabili alla protonterapia nei casi di livelli di ΔNTCPx-p qui riportati: ≥ 10% per le tossicità di grado ≥2; ≥ 5% per le tossicità di grado ≥ 3; ≥ 15% per la ΣΔNTCP delle tossicità di grado ≥ 2 (con un minimo di ≥ 5% ciascuno) o ≥ 5% per la ΣΔNTCP ≥ 3 (con un minimo di ≥ 3.75% ciascuno), in riferimento a disfagia e xerostomia. Risultati: Una dose per frazione di 2.12 Gy è stata prescritta nella maggior parte dei piani (51%). La dose mediana di prescrizione ai HD-PTV era di 69,96 Gy. La media della HD-PTV D95 era 66,25 Gy con IMRT e 66,37 Gy RBE con IMPT. La media delle HD-PTV D98 era invece 65,07 Gy con IMRT e 65,31 Gy RBE con IMPT. E’ stata riscontrata una dose media inferiore con IMPT rispetto a IMRT con rilevanza statistica (p value <.05) nella maggior parte degli OAR d’interesse, ad eccezione di muscoli costrittori faringei superiori e inferiori, mandibola e parotide sinistra. Secondo i livelli di ΔNTCP stabiliti dal NIPP, su un totale di 41 pazienti coinvolti nell’analisi, 15 (il 37%) trarrebbero vantaggio dalla protonterapia. Questi pazienti sono stati selezionati sulla base dei valori ΔNTCPx-p per disfagia e xerostomia. Il valore medio di NTCP per la xerostomia di grado 2 era 35,24% per il piano a fotoni, e 30,15% per quello a protoni, mentre per la xerostomia di grado 3 era 9,45% e 7,86%, rispettivamente, con un valore ΔNTCPp-x medio di -5,1% per tossicità G2 e di -1,6% per G3. Considerando invece il valore medio di NTCP per la disfagia G2, risulta essere 19,55% con IMRT, e 13,11% con IMPT, mentre per la disfagia G3 era 5,53% e 2,81, rispettivamente, con un valore ΔNTCPp-x medio di -6,4% per tossicità G2 e di -2,7% per G3. Conclusioni: Nel presente studio, l’approccio MBA per un set di tossicità è stato applicato ad un campione di pazienti trattati con la IMRT radicale per il carcinoma dell’orofaringe HPV-relato, ed è stata effettuata l’analisi comparativa tra i piani. Su un totale di 41 pazienti, 15 (il 37%) sono risultati eleggibili per la protonterapia e rappresentano quindi coloro che hanno più probabilità di trarre beneficio dalla IMPT in termini di prevenzione di disfagia e xerostomia. Inoltre, l’analisi dosimetrica ha dimostrato il vantaggio dei piani IMPT, a parità di copertura di target rispetto ai piani IMRT.
Proton therapy for HPV-related oropharyngeal cancer patients using normal tissue complication probability (NTCP) model-based strategy: an italian multicenter retrospective cross-sectional study - PROPHETIC
BERTULESSI, ALESSIA
2023/2024
Abstract
Purpose: A growing interest has recently raised around the role of Normal Tissue Control Probability (NTCP) models in supporting clinical decisions. Due to promising role of PT in reducing treatment related toxicities, the current work aims to apply the model-based approach, referring to a set of toxicities (dysphagia and xerostomia), in a cohort of patients treated with radical radiotherapy (VMAT) for HPV-related Oropharyngeal Squamous Cell Carcinomas (OPSCC). An in-silico planning comparison was performed in order to quantify the potential benefit of IMPT compared to VMAT in a multicenter setting. Materials and methods: IMPT and VMAT plans were optimized for a cohort of 41 HPV+ OPC patients treated from February 2017 to January 2024 in 5 different Italian centers. Organs at risk (OARs) were contoured according to the international consensus guidelines for CT-based delineation of OARs in the head and neck region. Target coverage was defined as at least 95% of the Clinical Target Volume (CTV) covered by 98% of the prescribed dose. Regarding OARs a dose-volume comparison was performed, particularly focusing on the parotid glands, brainstem, spinal cord, mandible, oral cavity, pharyngeal constrictors muscles and larynx. According to the Dutch National Indication Protocol for Proton therapy (NIPP) two NTCP models were selected, and a comparative analysis was performed for all 82 plans (VMAT and IMPT). Patients could be qualified for proton therapy in case the ΔNTCPx-p thresholds are: (1) ≥ 10% for toxicities grade ≥2, (2) ≥ 5% for toxicities grade ≥ 3, (3) ≥ 15% for the summed ΔNTCP of toxicities grade ≥ 2 (with a minimum of ≥ 5% for each) or (4) ≥ 5% for the summed ΔNTCP of toxicities grade ≥ 3 (with a minimum of ≥ 3.75% for each), with specific reference to dysphagia and xerostomia. Results: A dose per fraction of 2.12 Gy was prescribed for most plans (51%). The median prescription dose to HD-PTV was 69,96 Gy. Average HD-PTV D95 was 66,25 Gy with IMRT and 66,37 Gy RBE with IMPT. Average HD-PTV D98 was 65,07 Gy in IMRT plans and 65,31 Gy RBE in IMPT plans. A lower Dmean to the majority of OARs of interest was obtained with IMPT versus VMAT with statistically significance (p value < .05), except for PCMsup, PCMinf, mandible and left parotid. According to NIPP ΔNTCP thresholds, of 41 patients eligible for the analysis, 15 patients (37%) would benefit from proton therapy. These patients were selected based on the ΔNTCPx-p values in terms of toxicities for dysphagia and xerostomia. The average NTCP value for xerostomia grade 2 was 35,24% with the photon plan, and 30,15% for the proton plan, while for xerostomia grade 3 was 9,45% and 7,86%, respectively, with an average ΔNTCPp-x value of -5,1% for grade 2 toxicity and -1,6% for grade 3. On the other hand, the average NTCP value for dysphagia grade 2 was 19,55% with the photon plan, and 13,11% for the proton plan, while for dysphagia grade 3 was 5,53% and 2,81%, respectively, with an average ΔNTCPp-x value of -6,4% for grade 2 toxicity and -2,7% for grade 3. Conclusions: In the current study, the model-based approach referring to a set of toxicities (dysphagia and xerostomia) was applied to a cohort of patients treated with radical radiotherapy (VMAT) for HPV+ OPC, and planning comparison was feasible. Among 41 patients, 15 (37%) resulted eligible for protons and they are the most likely to benefit from IMPT in terms of prevention of dysphagia and xerostomia. Moreover, a dosimetric analysis demonstrated advantage in IMPT plans, with equal target coverage versus VMAT plans.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/20.500.14239/17484