Background: Epithelial ovarian cancer represents the sixth cause of cancer-related death in women in Italy. The introduction of PARP inhibitors into clinical practice has revolutionized the treatment of advanced-stage ovarian cancer. Recent studies have reported an improvement in clinical outcome with the use of stereotactic radiotherapy in the treatment of disease recurrence in some solid tumors. The combination of these two therapeutic strategies could open new perspectives in the clinical management of patients with oligometastatic/oligorecurrent ovarian cancer. Aim of the Study: The aim of this observational, retrospective study is to evaluate the effectiveness and safety of radiation treatment, delivered both with stereotactic radiotherapy (Stereotactic Body Radiation Therapy SBRT) and with non-stereotactic radiotherapy (Non-Stereotactic Radiation Therapy NSRT), on of disease progression in patients with metastatic, oligopersistent, oligorecurrent or oligoprogressive ovarian cancer, during maintenance therapy with PARP inhibitors. This preliminary study aims to be preparatory to the drafting of a similar multicenter research protocol. Material and Methods: The study included patients over 18 years of age and diagnosed with oligometastatic ovarian cancer with evidence of disease progression of up to 5 lesions, during maintenance therapy with PARP inhibitors, in simultaneous treatment with stereotactic radiotherapy or non-stereotactic fractionated radiotherapy. The patients will be enrolled from the Radiotherapy center of the Veneto Oncology Institute in Padua. At the end of radiotherapy all patients were restaged with Computed Tomography (CT) or Positron Emission Tomography (PET) and the response to radiation treatment was assessed according to the RECIST (1.1) and PERCIST criteria. Acute and late toxicity will also be assessed according to the CTCAE scale. Patient characteristics were summarized using descriptive statistics methods. Continuous variables were summarized using medians and interquartile range, categorical variables were summarized using absolute and relative frequencies. Results: The study included 15 patients and, regarding radiation treatment, a total of 22 lesions were treated. If we consider the documented radiological response of the lesions regardless of the type of fractionation used, it can be observed that 9 lesions (42.9%) had a complete response, 7 (31.8%) had a partial response, only 1 lesion (4.6%) underwent disease progression, while 5 lesions (22.7%) remained stable. Among clinical and treatment parameters, only age ≤ 60 and lymph nodal disease emerged as independent predictors of high probabilities of complete response. All patients continued therapy with PARP inhibitors without interruption during the radiation treatment performed; furthermore, the addition of PARP inhibitors does not cause cumulative toxicities. The effectiveness of radiation therapy is accompanied by a low toxicity profile in our series, thus creating a favourable cost-effectiveness ratio; in particular, although 53.8% of patients presented acute toxicity, this was exclusively low grade (G1-G2). Conclusions: Our single-center retrospective study confirms the activity and safety of radiotherapy in patients with oligometastatic ovarian cancer and identifies clinical and treatment parameters capable of predicting the CR rate. Optimal SBRT and NSBRT programs should be defined considering the need to ensure the best personalized radiation dose for the individual patient.
Background: Il carcinoma ovarico epiteliale rappresenta la sesta causa di morte correlata ai tumori nel sesso femminile in Italia. L’introduzione dei PARP inibitori nella pratica clinica ha rivoluzionato il trattamento del carcinoma ovarico in stadio avanzato. Recenti studi hanno riportato un miglioramento dell'outcome clinico con l’utilizzo della radioterapia stereotassica nel trattamento di recidive di malattia in alcuni tumori solidi. La combinazione di queste due strategie terapeutiche potrebbe aprire nuove prospettive nella gestione clinica delle pazienti con carcinoma ovarico oligometastatico/ oligoricorrente. Scopo dello studio: Lo scopo di questo studio osservazionale, retrospettivo, è quello di valutare l’efficacia e la sicurezza del trattamento radiante, erogato sia con radioterapia stereotassica (Stereotactic Body Radiation Therapy SBRT) sia con radioterapia non stereotassica (Non Stereotactic Radiation Therapy NSRT), su sedi di progressione di malattia in pazienti affette da carcinoma dell’ovaio metastatico, oligopersistente, oligoricorrente o oligoprogressivo, in corso di terapia di mantenimento con PARP inibitori. Tale studio preliminare vuole essere propedeutico alla stesura di un analogo protocollo di ricerca multicentrico. Materiali e Metodi: Lo studio ha incluso pazienti con età superiore a 18 anni e diagnosi di carcinoma ovarico oligometastatico con evidenza di progressione di malattia fino a 5 lesioni, durante terapia di mantenimento con PARP inibitori, in contemporaneo trattamento con radioterapia stereotassica o radioterapia frazionata non stereotassica. Le pazienti sono arruolate dal centro di Radioterapia dell’Istituto Oncologico Veneto nella sede di Padova. Al termine della radioterapia tutte le pazienti sono state ristadiate con Tomografia Computerizzata (TC) o Tomografia a Emissione di Positroni (PET) e la risposta al trattamento radiante è stata valutata secondo i criteri RECIST (1.1) e PERCIST. Verrà inoltre valutata la tossicità acuta e tardiva secondo la scala CTCAE. Le caratteristiche dei pazienti sono state sintetizzate utilizzando metodi di statistica descrittiva. Le variabili continue sono state riassunte utilizzando mediane e intervallo interquartile, le variabili categoriali sono state riassunte utilizzando frequenze assolute e relative. Risultati: Lo studio ha incluso 15 pazienti e, per quanto riguarda il trattamento radiante, sono state trattate 22 lesioni in totale. Se consideriamo la risposta radiologica documentata delle lesioni indipendentemente dal tipo di frazionamento utilizzato, si può osservare che 9 lesioni (42.9%) sono andate in risposta completa, 7 (31.8%) hanno avuto una risposta parziale, unicamente 1 lesione (4.6%) è andata incontro a progressione di malattia, mentre 5 lesioni (22.7%) sono rimaste stabili. Tra i parametri clinici e di trattamento, solo età ≤ 60 e malattia linfonodale sono emersi come predittori indipendenti di elevate probabilità di risposta completa. Tutte le pazienti hanno continuato la terapia con PARP inibitori senza interruzioni durante il trattamento radiante eseguito, inoltre, l'aggiunta degli inibitori di PARP non dà tossicità cumulative. L’efficacia della terapia radiante è accompagnata da un basso profilo di tossicità nella nostra casistica, configurando così un rapporto costo-efficacia favorevole; in particolare, sebbene il 53.8% delle pazienti abbia presentato tossicità acuta, questa è stata esclusivamente di basso grado (G1-G2). Conclusioni: Il nostro studio retrospettivo monocentrico conferma l’attività e la sicurezza della radioterapia nelle pazienti con carcinoma ovarico oligometastatico e identifica parametri clinici e di trattamento in grado di predire il tasso di CR. I programmi SBRT e NSBRT ottimali dovrebbero essere definiti tenendo conto della necessità di garantire la migliore dose di radiazioni personalizzata per la singola paziente.
Radioterapia e PARP inibitori in pazienti affette da carcinoma ovarico oligometastatico
CREANZA, ANTONELLA
2023/2024
Abstract
Background: Epithelial ovarian cancer represents the sixth cause of cancer-related death in women in Italy. The introduction of PARP inhibitors into clinical practice has revolutionized the treatment of advanced-stage ovarian cancer. Recent studies have reported an improvement in clinical outcome with the use of stereotactic radiotherapy in the treatment of disease recurrence in some solid tumors. The combination of these two therapeutic strategies could open new perspectives in the clinical management of patients with oligometastatic/oligorecurrent ovarian cancer. Aim of the Study: The aim of this observational, retrospective study is to evaluate the effectiveness and safety of radiation treatment, delivered both with stereotactic radiotherapy (Stereotactic Body Radiation Therapy SBRT) and with non-stereotactic radiotherapy (Non-Stereotactic Radiation Therapy NSRT), on of disease progression in patients with metastatic, oligopersistent, oligorecurrent or oligoprogressive ovarian cancer, during maintenance therapy with PARP inhibitors. This preliminary study aims to be preparatory to the drafting of a similar multicenter research protocol. Material and Methods: The study included patients over 18 years of age and diagnosed with oligometastatic ovarian cancer with evidence of disease progression of up to 5 lesions, during maintenance therapy with PARP inhibitors, in simultaneous treatment with stereotactic radiotherapy or non-stereotactic fractionated radiotherapy. The patients will be enrolled from the Radiotherapy center of the Veneto Oncology Institute in Padua. At the end of radiotherapy all patients were restaged with Computed Tomography (CT) or Positron Emission Tomography (PET) and the response to radiation treatment was assessed according to the RECIST (1.1) and PERCIST criteria. Acute and late toxicity will also be assessed according to the CTCAE scale. Patient characteristics were summarized using descriptive statistics methods. Continuous variables were summarized using medians and interquartile range, categorical variables were summarized using absolute and relative frequencies. Results: The study included 15 patients and, regarding radiation treatment, a total of 22 lesions were treated. If we consider the documented radiological response of the lesions regardless of the type of fractionation used, it can be observed that 9 lesions (42.9%) had a complete response, 7 (31.8%) had a partial response, only 1 lesion (4.6%) underwent disease progression, while 5 lesions (22.7%) remained stable. Among clinical and treatment parameters, only age ≤ 60 and lymph nodal disease emerged as independent predictors of high probabilities of complete response. All patients continued therapy with PARP inhibitors without interruption during the radiation treatment performed; furthermore, the addition of PARP inhibitors does not cause cumulative toxicities. The effectiveness of radiation therapy is accompanied by a low toxicity profile in our series, thus creating a favourable cost-effectiveness ratio; in particular, although 53.8% of patients presented acute toxicity, this was exclusively low grade (G1-G2). Conclusions: Our single-center retrospective study confirms the activity and safety of radiotherapy in patients with oligometastatic ovarian cancer and identifies clinical and treatment parameters capable of predicting the CR rate. Optimal SBRT and NSBRT programs should be defined considering the need to ensure the best personalized radiation dose for the individual patient.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/65843