TOMMASO CORNALI

Dottore di ricerca

ciclo: XXXIII



Titolo della tesi: PROactive Management of ENdoperitoneal spreAD in colonic CancEr. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) and target organ resection for peritoneal spread at primary surgery in patients with colon cancer at high risk of peritoneal metastases; the PROMENADE randomized multicenter trial (NCT02974556)

Colorectal cancer is one of the leading causes of cancer death in developed countries. Despite recent advances in understanding the molecular pathogenesis and improvements in diagnosis and treatment, more than 1,2 million new cases and 600,000 deaths occur annually worldwide and cure rates remain low for patients with metastatic or recurrent disease. According to reports from the National Cancer Institute, cancer of the colon is a highly treatable and often curable disease when confined to the bowel. Surgery is the primary treatment and results in a cure rate of approximately 50% of the patients; however, recurrence following surgery is a major problem and is often the ultimate cause of death. In colon cancer locoregional recurrence (local recurrence and metachronous peritoneal spread), as the main site of recurrence, is less common (up to 10% of all recurrences) and generally occurs within 3 years of resection. An important concept is the origin of local recurrences and peritoneal metastases that have a common natural history. Specific features of the primary tumor like size and depth of bowel wall invasion (pT3-pT4), which determine a specific clinical evolution (obstruction, perforation with exfoliation of cancer cells) are responsible for endoperitoneal recurrence. Cytoreductive Surgery (CRS) defined as removal of macroscopic abdominal and peritoneal disease combined with Hyperthermic Perioperative Chemotherapy (HIPEC) is the treatment considered standard of care for selected patients with moderate to small volume peritoneal metastases secondary to colorectal cancer. Nevertheless treatment of locoregional recurrence and peritoneal metastases in colon cancer are disappointing first because only 30% of patients can be surgically treated and second because of this 30% only 15- 30% survive 5 years, leaving only 10% of patients with a chance of being cured. Furthermore the economic burden of metastatic colorectal cancer treatment is considerable including the common adverse events associated that increase healthcare resource utilization and considering the addition of biological drugs to standard treatment. An evaluation of CRS combined with HIPEC for peritoneal metastases of colorectal origin in the era of value-based medicine, showed an incremental cost respect to modern chemotherapy regimens of 44,217 US$ for life-year saved, making investment in prevention even more attractive. Despite screening for colorectal cancer in average-risk patients using colonoscopy was associated with a substantially reduced risk of diagnosis with new-onset primary late-stage tumors, colorectal cancer screening remains underused. Analyzing the recent surgical published series, the majority (around 70%), of patients with a diagnosis of colonic cancer operated with curative intent, have a pT3-4 tumor, which is exactly the high-risk class of patients for local recurrence and peritoneal metastases. In this scenario the most effective strategy to combat endoperitoneal recurrence seems prevention. Two previous studies performed in our Institution investigated how a proactive management of peritoneal metastases in colon cancer patients considered at high-risk for peritoneal recurrence according to depth of bowel wall invasion and specific histopathologic features (pT3, pT4 any N, M0, mucinous or signet ring cell pathology) influence outcome. A group of 25 patients for whom inclusion criteria were verified by intraoperative pathologic assessment, were submitted to a "proactive" treatment that included in addition to the standard surgical treatment, a greater omentectomy, appendectomy, exeresis of the liver round ligament and, in post-menopausal women, a bilateral oophorectomy. At the end of the operation, in these patients a HIPEC was performed with oxaliplatin and simultaneous iv infusion of 5-fluorouracil (FU) + leucovorin (LV). Short and long-term results showed that when compared to a control group (50 cases) of similar patients treated only by standard treatment in the same Institution, this group of patients had a statistically significant decreased incidence of peritoneal recurrence (4 vs. 28%) and an increase in overall and disease-free survival rates. These results should obviously validated by larger controlled studies, and this is the aim of the PROMENADE protocol, to verify if the treatment criteria applied in colorectal peritoneal metastases (Surgery combined with HIPEC) could represent a mean of tertiary prevention of endoperitoneal recurrence in high-risk colon cancer. However, simpler application criteria were needed for a large-scale study. For this reason histological typing have not been yet considered an inclusion criteria and will only represent a secondary outcome measure. Furthermore, also considering other experiences, the protocol will use an imaging technique (MDCT) for preoperative selection of high-risk T3 (>/= 5 mm tumor invasion beyond the muscularis propria) and T4 colon cancers, combined in patients with suspected systemic disease after MDCT with functional positron-emission tomography (PET), avoiding the need for an intra-operative frozen-sections pathologic assessment. The results of this study will hopefully confirm the therapeutic rationale that makes microscopic local seeding as the main reason for endoperitoneal recurrence. It will be also important to verify if, as demonstrated in our pilot study, a better loco-regional control of the disease will carry better long-term survival.

Produzione scientifica

  • 11573/380115 - 2011 - E-cadherin expression in peritoneal carcinomatosis from ovarian cancer: clinical and prognostic role (04b Atto di convegno in volume)
    ACCARPIO, FABIO; SIBIO, SIMONE; BIACCHI, DANIELE; CARDI, MAURIZIO; CORNALI, TOMMASO; DI GIORGIO, ANGELO; SAMMARTINO, PAOLO
  • 11573/380309 - 2011 - Prevention of peritoneal carcinomatosis (PC) from colorectal cancer in high risk patients : preliminary results of surgery plus prophylactic hipec. (04a Atto di comunicazione a congresso)
    SAMMARTINO, PAOLO; SIBIO, SIMONE; ACCARPIO, FABIO; BIACCHI, DANIELE; CARDI, MAURIZIO; BACCHESCHI, ANNA MARIA; CORNALI, TOMMASO; DI GIORGIO, ANGELO
  • 11573/445424 - 2011 - Metastasis of Pleural Mesothelioma Presenting as Bleeding Colonic Polyp (01a Articolo in rivista)
    SIBIO, SIMONE; SAMMARTINO, PAOLO; ACCARPIO, FABIO; BIACCHI, DANIELE; CORNALI, TOMMASO; CARDI, MAURIZIO; DI GIORGIO, ANGELO
  • 11573/480151 - 2012 - Prevention of Peritoneal Metastases from Colon Cancer in High-Risk Patients: Preliminary Results of Surgery plus Prophylactic HIPEC (01a Articolo in rivista)
    SAMMARTINO, PAOLO; SIBIO, SIMONE; BIACCHI, DANIELE; CARDI, MAURIZIO; ACCARPIO, FABIO; MINGAZZINI, PIETRO; ROSATI, MARIA SOFIA; CORNALI, TOMMASO; DI GIORGIO, ANGELO
  • 11573/515758 - 2013 - Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases (01a Articolo in rivista)
    DI GIORGIO, ANGELO; CARDI, MAURIZIO; BIACCHI, DANIELE; SIBIO, SIMONE; ACCARPIO, FABIO; CIARDI, ANTONIO; CORNALI, TOMMASO; FRAMARINO DEI MALATESTA, MARIALUISA; SAMMARTINO, PAOLO
  • 11573/226259 - 2010 - Predominant Brenner Tumor Combined with Struma Ovarii Containing a Papillary Microcarcinoma Associated with Benign Peritoneal Strumosis: Report of a Case and Histologic Features (01a Articolo in rivista)
    SIBIO, SIMONE; BORRINI, FEDERICO; SAMMARTINO, PAOLO; ACCARPIO, FABIO; BIACCHI, DANIELE; BACCHESCHI, ANNA MARIA; CORNALI, TOMMASO; DI GIORGIO, ANGELO
  • 11573/604592 - 2014 - Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases (01a Articolo in rivista)
    SAMMARTINO, PAOLO; SIBIO, SIMONE; BIACCHI, DANIELE; CARDI, MAURIZIO; MINGAZZINI, PIETRO; ROSATI, MARIA SOFIA; CORNALI, TOMMASO; SOLLAZZO, BIANCA MARIA; DI GIORGIO, ANGELO
  • 11573/655429 - 2014 - Patient Selection for Treatment (02a Capitolo o Articolo)
    SAMMARTINO, PAOLO; ACCARPIO, FABIO; SOLLAZZO, BIANCA MARIA; IMPAGNATIELLO, ALESSIO; CORNALI, TOMMASO; BIACCHI, DANIELE
  • 11573/650484 - 2014 - Other primary peritoneal surface malignancies (02a Capitolo o Articolo)
    SAMMARTINO, PAOLO; ACCARPIO, FABIO; CORNALI, TOMMASO; IMPAGNATIELLO, ALESSIO; SOLLAZZO, BIANCA MARIA; FRAMARINO DEI MALATESTA, MARIALUISA
  • 11573/934678 - 2012 - Prevention of Peritoneal Carcinomatosis from Colon Cancer in High-Risk Patients. (04f Poster)
    LUCIANI, CLAUDIO; AMORE BONAPASTA, STEFANO; CORNALI, TOMMASO; SIBIO, SIMONE; ACCARPIO, FABIO; CARDI, MAURIZIO; SAMMARTINO, PAOLO; DI GIORGIO, ANGELO
  • 11573/494273 - 2008 - LA peritonectomia con chemioipertermia intraperitoneale (HIPEC) nel trattamento della carcinosi peritoneale diffusa da carcinoma ovarico (04c Atto di convegno in rivista)
    SAMMARTINO, PAOLO; SIBIO, SIMONE; ACCARPIO, FABIO; BIACCHI, DANIELE; CORNALI, TOMMASO; DI GIORGIO, ANGELO
  • 11573/493740 - 2009 - 8032 Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer (04c Atto di convegno in rivista)
    SAMMARTINO, PAOLO; SIBIO, SIMONE; BIACCHI, DANIELE; ACCARPIO, FABIO; CORNALI, TOMMASO
  • 11573/900381 - 2016 - Proactive Management for Gastric, Colorectal and Appendiceal Malignancies: Preventing Peritoneal Metastases with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) (01a Articolo in rivista)
    SAMMARTINO, PAOLO; BIACCHI, DANIELE; CORNALI, TOMMASO; CARDI, MAURIZIO; ACCARPIO, FABIO; IMPAGNATIELLO, ALESSIO; SOLLAZZO, BIANCA MARIA; DI GIORGIO, ANGELO
  • 11573/175234 - 2009 - Surgery in Multimodal Treatment of Cancer: Peritoneal Carcinomatosis (04b Atto di convegno in volume)
    DI GIORGIO, ANGELO; ACCARPIO, FABIO; SIBIO, SIMONE; BIACCHI, DANIELE; BACCHESCHI, ANNA MARIA; CORNALI, TOMMASO; DI SERI, MARISA; CERBONE, LINDA; SAMMARTINO, PAOLO
  • 11573/833182 - 2016 - Computerized system for staging peritoneal surface malignancies (01a Articolo in rivista)
    SAMMARTINO, PAOLO; BIACCHI, DANIELE; CORNALI, TOMMASO; ACCARPIO, FABIO; SIBIO, SIMONE; LURASCHI, BERNARD STEPHANE C.; IMPAGNATIELLO, ALESSIO; DI GIORGIO, ANGELO
  • 11573/1117149 - 2018 - Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for patients with peritoneal metastases from endometrial cancer (01a Articolo in rivista)
    CORNALI, TOMMASO; SAMMARTINO, PAOLO; FRAMARINO DEI MALATESTA, MARIALUISA; SPAGNOLI, ALESSANDRA; CIARDI, ANTONIO; BIACCHI, DANIELE
  • 11573/1670758 - 2017 - Treatment of peritoneal metastases from breast cancer by maximal cytoreduction and HIPEC (02a Capitolo o Articolo)
    SAMMARTINO, PAOLO; CARDI, MAURIZIO; CORNALI, TOMMASO; SOLLAZZO, BIANCA MARIA; MARCELLINARO, ROSA; IMPAGNATIELLO, ALESSIO; DI GIORGIO, ANGELO
  • 11573/380116 - 2011 - Surgical strategies for colorectal resection during perritonectomy plus hipec in patients with ovarian cancer. (04a Atto di comunicazione a congresso)
    SIBIO, SIMONE; ACCARPIO, FABIO; CARDI, MAURIZIO; BIACCHI, DANIELE; BACCHESCHI, ANNA MARIA; CORNALI, TOMMASO; DI GIORGIO, ANGELO; SAMMARTINO, PAOLO
  • 11573/493748 - 2009 - surgery in multimodal treatment of cancer: peritoneal carcinomatosis (02a Capitolo o Articolo)
    DI GIORGIO, ANGELO; ACCARPIO, FABIO; SIBIO, SIMONE; BIACCHI, DANIELE; CORNALI, TOMMASO; DI SERI, MARISA; SAMMARTINO, PAOLO

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