Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative method of delivering chemotherapy drugs by dispersing them as an aerosol under pressure directly into the abdominal cavity. Through clinical trials, PIPAC has demonstrated numerous advantages, including improved drug uptake by peritoneal tumor nodules, enhanced coverage of the peritoneal surface, increased drug penetration, favorable pharmacokinetics, and optimal biodistribution. Furthermore, PIPAC allows for more frequent administration compared to other intraperitoneal chemotherapy treatments. As a result, this novel technique exhibits promising potential in effectively managing peritoneal carcinomatosis. Methods: A systematic review of the English-language literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The online databases PubMed, Scopus, and Cochrane Library were screened to identify clinical trials assessing the use PIPAC in women with peritoneal carcinomatosis from gynecologic malignancies. 652 articles were identified by the literature search, and, after the exclusion of duplicates, 569 records were subjected to abstract screening. 65 articles were subject to full-text screening to assess for eligibility. Finally, 14 studies fulfilled all inclusion criteria and were considered for the analysis. Primary outcomes were represented by disease response, overall survival (OS) and progression-free (PFS) survival in patients undergoing PIPAC. Secondary outcomes were represented by quality of life (QoL), performance status (PS), and post-treatment complications’ rate. A proportional meta-analysis was performed addressing the effectiveness of PIPAC on the mean OS of platinum resistant OC patients. Results: 14 articles were considered eligible: 4 case reports, 7 retrospective cohort studies, one phase I study, and two phase II studies. A total of 224 patients were analyzed (208 with ovarian cancer, 16 with endometrial cancer). The collective number of PIPAC cycles performed across these patients was 545. Data on OS was reported by 10 studies, with a total of 78 patients still alive at the 12-month mark. Only three studies provided information on PFS. Six studies reported on the number of patients who remained free from progression at 6 months, which amounted to 30 patients. Pathological response to treatment was discussed in six studies. Only the case report by Solass et al. included information on PS change: the Karnofsky index of the patient improved from 40% to 90% after six PIPAC cycles. Three studies reported on the QoL during PIPAC treatment, all indicating an improvement in scores. AEs were documented in 9 studies: among 545 PIPAC procedures, 185 (34%) were followed by G1 events, 96 (17.6%) procedures were followed by G2 events, 32 (5.9%) procedures were followed by G3 events, and finally, 4 (0.7%) procedures were followed by G4 events. A proportional meta-analysis was performed addressing the effectiveness of PIPAC on the mean OS of platinum resistant OC patients, which was 15.9 months (95% CI 8,5 - 29,8 random effects). As expected, I^2 (79,85%, 95% CI 52,43 - 91,46) was high, but it did not necessarily mean that data were inconsistent. Conclusions: Experimental and clinical evidence attest to the safety and efficacy of PIPAC in treating peritoneal cancer arising from gynecological cancer metastasis. Furthermore, studies indicate that PIPAC-treated patients experience a more favorable quality of life compared to those undergoing traditional systemic chemotherapy. However, case control studies and randomized control trials are an urgent need in the field of PIPAC for gynecological cancers because the absence of high-quality studies that compare PIPAC and standard treatment precludes the definitive establishment of this novel technique as a recognized therapeutic modality.
Background: La chemioterapia aerosol intraperitoneale pressurizzata (PIPAC) è un metodo innovativo di somministrazione dei farmaci chemioterapici mediante dispersione in forma di aerosol direttamente nella cavità addominale. La PIPAC ha dimostrato numerosi vantaggi, tra cui miglior assorbimento dei farmaci da parte dei noduli tumorali, maggiore copertura del peritoneo, maggiore penetrazione dei farmaci, farmacocinetica favorevole e biodistribuzione ottimale. Inoltre, la PIPAC consente una somministrazione più frequente rispetto ad altri trattamenti di chemioterapia intraperitoneale. Di conseguenza, questa nuova tecnica mostra un grande potenziale nell'affrontare in modo efficace la carcinomatosi peritoneale. Metodi: È stata condotta una revisione sistematica della letteratura in lingua inglese in conformità alle linee guida PRISMA. Sono stati esaminati i database online PubMed, Scopus e Cochrane Library per individuare gli studi clinici che valutano l'uso del PIPAC nelle donne affette da carcinomatosi peritoneale da neoplasie ginecologiche. Sono stati identificati 652 articoli e, dopo l'esclusione dei duplicati, 569 articoli sono stati sottoposti a screening degli abstract. 65 articoli sono stati sottoposti a una valutazione completa del testo. Infine, 14 studi hanno soddisfatto tutti i criteri di inclusione e sono stati considerati per l'analisi. I risultati primari sono rappresentati dalla risposta alla malattia, dalla sopravvivenza complessiva (OS) e dalla sopravvivenza libera da progressione (PFS). I risultati secondari sono rappresentati dalla qualità della vita (QoL), dallo performance status (PS) e dal tasso di complicanze (AEs) post- trattamento. In assenza di studi comparativi, è stata eseguita una metanalisi proporzionale per valutare l'efficacia del PIPAC sulla sopravvivenza complessiva. Risultati: Sono stati considerati idonei 14 articoli: 4 casi clinici, 7 studi di coorte retrospettivi, uno studio di fase I e due studi di fase II. In totale sono state analizzate 224 pazienti (208 con cancro ovarico, 16 con cancro endometriale). Il numero totale di cicli di PIPAC eseguiti è di 545. I dati sull’OS sono stati riportati in 10 studi, con 78 pazienti ancora in vita al termine dei 12 mesi. Solo tre studi hanno fornito informazioni sul PFS. Sei studi hanno riportato il numero di pazienti che sono rimaste libere da progressione a 6 mesi, che è stato di 30 pazienti. La risposta patologica al trattamento è stata discussa in sei studi. Il caso Solass et al. ha fornito informazioni sul cambiamento del PS: l'indice di Karnofsky della paziente è migliorato dal 40% al 90% dopo sei cicli di PIPAC. Tre studi hanno riportato la QoL durante il trattamento con PIPAC, tutti indicando un miglioramento dei punteggi. Gli AEs sono stati documentati in 9 studi: su 545 procedure di PIPAC, 185 sono state seguite da eventi di grado 1, 96 da eventi di grado 2, 32 da eventi di grado 3, 4 da eventi di grado 4. È stata eseguita una meta-analisi proporzionale che ha valutato l'efficacia del PIPAC sulla sopravvivenza complessiva media delle pazienti con carcinoma ovarico resistente al platino, che è stata di 15,9 mesi (95% CI 8,5 - 29,8). Come previsto, I^2 (79,85%, 95% CI 52,43 - 91,46) è risultato elevato, ma ciò non significa che i dati siano inconsistenti. Conclusioni: Evidenze sperimentali e cliniche attestano la sicurezza ed efficacia della PIPAC nel trattamento del cancro peritoneale derivante da metastasi dei tumori ginecologici. Inoltre, gli studi indicano che i pazienti trattati con PIPAC hanno una migliore QoL rispetto a quelli sottoposti alla chemioterapia sistemica tradizionale. Tuttavia, sono necessari studi caso- controllo e studi randomizzati controllati nel campo della PIPAC per i tumori ginecologici, poiché l'assenza di studi di alta qualità che confrontino PIPAC con il trattamento standard impedisce l'instaurazione definitiva di questa nuova tecnica come modalità terapeutica riconosciuta.
PRESSURIZED INTRAPERITONEAL AEROSOL CHEMOTHERAPY (PIPAC): A NOVEL TREATMENT IN PALLIATION FOR PERITONEAL CARCINOMATOSIS
BOLOGNA, CAROLINA
2022/2023
Abstract
Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative method of delivering chemotherapy drugs by dispersing them as an aerosol under pressure directly into the abdominal cavity. Through clinical trials, PIPAC has demonstrated numerous advantages, including improved drug uptake by peritoneal tumor nodules, enhanced coverage of the peritoneal surface, increased drug penetration, favorable pharmacokinetics, and optimal biodistribution. Furthermore, PIPAC allows for more frequent administration compared to other intraperitoneal chemotherapy treatments. As a result, this novel technique exhibits promising potential in effectively managing peritoneal carcinomatosis. Methods: A systematic review of the English-language literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The online databases PubMed, Scopus, and Cochrane Library were screened to identify clinical trials assessing the use PIPAC in women with peritoneal carcinomatosis from gynecologic malignancies. 652 articles were identified by the literature search, and, after the exclusion of duplicates, 569 records were subjected to abstract screening. 65 articles were subject to full-text screening to assess for eligibility. Finally, 14 studies fulfilled all inclusion criteria and were considered for the analysis. Primary outcomes were represented by disease response, overall survival (OS) and progression-free (PFS) survival in patients undergoing PIPAC. Secondary outcomes were represented by quality of life (QoL), performance status (PS), and post-treatment complications’ rate. A proportional meta-analysis was performed addressing the effectiveness of PIPAC on the mean OS of platinum resistant OC patients. Results: 14 articles were considered eligible: 4 case reports, 7 retrospective cohort studies, one phase I study, and two phase II studies. A total of 224 patients were analyzed (208 with ovarian cancer, 16 with endometrial cancer). The collective number of PIPAC cycles performed across these patients was 545. Data on OS was reported by 10 studies, with a total of 78 patients still alive at the 12-month mark. Only three studies provided information on PFS. Six studies reported on the number of patients who remained free from progression at 6 months, which amounted to 30 patients. Pathological response to treatment was discussed in six studies. Only the case report by Solass et al. included information on PS change: the Karnofsky index of the patient improved from 40% to 90% after six PIPAC cycles. Three studies reported on the QoL during PIPAC treatment, all indicating an improvement in scores. AEs were documented in 9 studies: among 545 PIPAC procedures, 185 (34%) were followed by G1 events, 96 (17.6%) procedures were followed by G2 events, 32 (5.9%) procedures were followed by G3 events, and finally, 4 (0.7%) procedures were followed by G4 events. A proportional meta-analysis was performed addressing the effectiveness of PIPAC on the mean OS of platinum resistant OC patients, which was 15.9 months (95% CI 8,5 - 29,8 random effects). As expected, I^2 (79,85%, 95% CI 52,43 - 91,46) was high, but it did not necessarily mean that data were inconsistent. Conclusions: Experimental and clinical evidence attest to the safety and efficacy of PIPAC in treating peritoneal cancer arising from gynecological cancer metastasis. Furthermore, studies indicate that PIPAC-treated patients experience a more favorable quality of life compared to those undergoing traditional systemic chemotherapy. However, case control studies and randomized control trials are an urgent need in the field of PIPAC for gynecological cancers because the absence of high-quality studies that compare PIPAC and standard treatment precludes the definitive establishment of this novel technique as a recognized therapeutic modality.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.
Per maggiori informazioni e per verifiche sull'eventuale disponibilità del file scrivere a: unitesi@unipv.it.
https://hdl.handle.net/20.500.14239/16075