Purpose. Page 2 of 24

Transcription

1 Accuracy of MDCT in the preoperative definition of peritoneal cancer index (PCI) in patients with advanced ovarian cancer who underwent peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) Poster No.: C-2069 Congress: ECR 2013 Type: Scientific Exhibit Authors: M. A. Mazzei, L. Khader, A. Cirigliano, N. Cioffi Squitieri, S. Guerrini, G. Imbriaco, A. Parrinello, F. G. Mazzei, L. Volterrani; Siena/IT Keywords: Genital / Reproductive system female, Oncology, Management, CT, Diagnostic procedure, Staging, Treatment effects, Neoplasia DOI: /ecr2013/C-2069 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 24

2 Purpose Due to the lack of specific symptoms and early tendency to peritoneal dissemination, epithelial ovarian cancer is most commonly detected in an advanced stage after it has spread into the peritoneal cavity (stage FIGO III), when the overall five-year survival rate is 30-40% [1]. Peritoneal carcinomatosis (PC) is a clinical entity with unfavourable prognosis that commonly characterises the terminal evolution of abdominopelvic neoplastic diseases. Being particularly difficult to treat, cancers with widespread peritoneal dissemination often cause their great morbidity and mortality through progressive involvement of the peritoneal surfaces [2]. The standard treatment of ovarian cancer with peritoneal dissemination involves optimal surgical cytoreduction (CRS) followed by platinum/taxane based chemotherapy. However, despite the notable chemosensitivity of this neoplasm, tumor recurrence occurs in most cases, particularly when extra-pelvic peritoneal dissemination is present, resulting in very low long-term survival probability [3]. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a locoregional treatment which involves the washing of peritoneal cavity with heated solutions and high drug concentrations [4-7]. The rationale for HIPEC is based on direct cytotoxicity of hyperthermia against malignant cells, combined with heat-related enhanced cytotoxic effects and pharmacokinetic advantages of the intraperitoneal route of anticancer drug. In the treatment of peritoneal carcinomatosis HIPEC is generally associated with surgical debulking and peritonectomy, with the aim to remove macroscopic tumor (Fig.1). Theoretically, CRS is performed to treat the macroscopic disease and HIPEC to treat the microscopic residual disease, eradicating neoplastic disease in a single procedure (Fig.2). This advanced multimodality treatment has shown significant improvement in long-term results with respect to the conventional treatment [4-6] (Fig.3-4). Preoperative imaging, essentially CT and MRI, that theoretically could assist not only in planning cytoreduction but also in preventing unwarranted laparotomy in patients with unresectable disease, are currently limited in the ability to reliably visualize localised peritoneal carcinomatosis, having decreased sensitivity for low-volume disease [8]. The extent of peritoneal dissemination at the time of surgery and HIPEC is generally scored according to the Peritoneal Cancer Index (PCI), described by Jacque and Sugarbaker, which is commonly used for the classification of peritoneal carcinomatosis from different diseases [9]. Page 2 of 24

3 The PCI has been shown to have prognostic value: it is a quantitative indicator of PC useful to guide selection of patients who are most likely to respond to the treatment and to exclude those who have little or no chance of benefiting [3], allowing to estimate with reasonable accuracy the probability of complete cytoreduction; proving to be a prognostic indicator for survival (Fig.5). The aim of our work has been to evaluate the accuracy of MDCT in the preoperative definition of PCI in patients with advanced ovarian cancer who underwent peritonectomy and HIPEC after neoadjuvant chemotherapy, in order to obtain a pre-surgery prognostic evaluation and a prediction of optimal cytoreduction. Page 3 of 24

4 Images for this section: Fig. 1: Intraoperative image representing CRS. In particular the picture shows the removal of a solid implant on an intestinal loop (then proved to be malignant after histological evaluation). Page 4 of 24

5 Fig. 2: HIPEC Surgical Procedure (Video). Page 5 of 24

6 Fig. 3: Progression-free survival for HIPEC-paclitaxel and control group. Kim JH, Lee JM, Ryu KS, Lee YS, Park YG, Hur SY, Lee KH, Lee SH, Kim SJ. Consolidation Hypertermic Intraperiotoneal Chemotherapy using Paclitaxel in patients with Epithelial Ovarian cancer. J Surg Oncol : Page 6 of 24

7 Fig. 4: Overall survival for HIPEC- Paclitaxel and control group. Kim JH, Lee JM, Ryu KS, Lee YS, Park YG, Hur SY, Lee KH, Lee SH, Kim SJ. Consolidation Hypertermic Intraperiotoneal Chemotherapy using Paclitaxel in patients with Epithelial Ovarian cancer. J Surg Oncol : Page 7 of 24

8 Fig. 5: Kaplan-Meier survival curves according to the peritoneal cancer index (PCI) at the time of surgery. The difference of the three groups is statistically significant (log-rank test: P = 0.003, Chi-square 11.72, df:2). Roviello F, Pinto E, Corso G, Pedrazzani C, Caruso S, Filippeschi M, Petrioli R, Marsili S, Mazzei MA, Marrelli D. Safety and potential benefit of hypertermic intraperitoneal chemotherapy (HIPEC) in peritoneal carcinomatosis from primary or recurrent ovarian cancer. J Surg Oncol : Page 8 of 24

9 Methods and Materials Patients Between March 2001 and June 2012, pre-hipec CT examinations of 43 patients were evaluated. Among 43 patients included in this study 27 had a first diagnosis of ovarian cancer (OC) and 16 had a recurrent ovarian cancer (ROC). Mean age was 58 years (range: 30-76). The patients were staged with the international Federation of Gynaecology and Obstetrics (FIGO) Classification; 41/43 (95,3%) were in stage IIIC, 1/43 (2,3%) were in stage IIIB and 1/43 (2,3%) in stage IV (Tab.1, Tab.2). Inclusion Criteria were: - First diagnosis of OC or ROC; - CT imaging performed in our department; - Patients underwent CT examinations within a maximum period of 45 days from HIPEC. CT Examinations All the CT examinations were performed with a MDCT system using unenhanced and multiphasic post-contrast spiral scans, associated to multiplanar reconstructions. The MDCT systems used were: - CT 4 rows (LightSpeed Plus, GE Healthcare, Milwaukee, USA); - CT 16 rows (LightSpeed 16 Pro, GE Healthcare, Milwaukee, USA); - CT 64 rows (VCT, GE Healthcare, Milwaukee, USA). All the technical parameters used for the acquisition are shown in Tab.3. Imaging Analysis The PCI was scored following the Sugarbaker classification (Fig.6) [9] but, with the advantage of the 2D analysis proper of CT examination (Fig.7). Infact it is a widely cited and one of the most accurate system of staging PC from different diseases, based on quantification and distribution of peritoneal implants. It quantitatively determines the distribution and implant size of the cancer throughout 13 abdominopelvic regions, of which 4 refer to small bowel (regions 9 and 10 correspond to upper and lower portions Page 9 of 24

10 of the jejunum, regions 11 and 12 the upper and lower portions of ileum). The lesion size (LS) of the largest implants is scored (0 trough 3) for each abdominopelvic region. The sum of each region's numerical score results in the PCI total score, that varies from 1 to 39. Preliminary Statistical Analysis Pre-surgery CT examinations were evaluated, retrospectively and in a blind fashion, by a Radiologist with expertise in the oncologic field. The results were compared with macroscopic and histologic data after peritonectomy. 1) PATIENT-LEVEL ANALYSIS: For each patient the positive or negative PCI CT value (in terms of presence/absence of disease) were compared with histologic results. 2) REGION-LEVEL ANALYSIS: For each region the positive or negative CT results (in terms of presence/absence of disease) were compared with histologic and macroscopic results. 3) PCI GRADING: The PCI values were stratified in three groups (grade 1: PCI = 0; grade 2: 1# PCI < 6; grade 3: PCI # 6) to standardize the PCI prognostic value for survival. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were also calculated. Page 10 of 24

11 Images for this section: Table 1: Clinical and pathological characteristics of 43 patients with PC from primary or recurrent ovarian cancer at the time of enrollment in the study. PC = Peritoneal Carcinomatosis. Table 2: Surgical procedures performed at the time of HIPEC in 43 patients. HIPEC = Hypertermic Intraperitoneal Chemotherapy. Table 3: Technical parameters used for the acquisitions in 43 patients. RI = Reconstruction Interval; IV = Intra Venous. Page 11 of 24

12 Fig. 6: PCI staging system for PC [2]. PCI = Peritoneal Cancer Index; PC = Peritoneal Carcinomatosis. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. In: Sugarbaker PH, editor. Peritoneal carcinomatosis: principles of management. Boston, USA: Kluwe Academic Publishers 1996; Page 12 of 24

13 Fig. 7: CT representation of Sugarbaker Classification scheme. Page 13 of 24

14 Results At the time of diagnosis of ovarian cancer extra pelvic peritoneal dissemination of the disease was present in all cases: most patients (41 cases, 95,3%) were classified in stage IIIC, and the remaining 2 (4,7%) in stages IIIB and IV, according to the FIGO classification. All patients were treated by systemic chemotherapy (generally 6 cycles) before being submitted to surgery and HIPEC with the aim of downstaging the peritoneal disease. Infact CT examinations evaluated the Post-CHT FIGO stages (Tab.4) showing significant downstaging, predominantly among IIIC FIGO patients. PATIENT LEVEL ANALYSIS: The patient level analysis tested the accuracy of CT to detect peritoneal disease (represented by PCI positive or negative values, respectively), comparing for each patient CT examination with histologic results. Among the 43 patients enrolled in the study CT and histologic results correlated for presence of disease (PCI positive values) in 38/43 cases (88,3%); for absence of disease (PCI negative values) in 2/43 (4,6%). In the remaining 3 patients CT and histology were not concordant thus showing a sensitivity of 100%, a specificity of 40%, PPV 92%, NPV 100% and an accuracy of 93% (Tab.5). REGION LEVEL ANALYSIS: The region level analysis, according to Sugarbaker classification, tested the correlation between CT and histology and between CT and macroscopic score for OC (Tab.6) and ROC (Tab.7), in both positive and negative sense for each region, obtaining for the correlation between CT and histology a sensitivity of 72%, a specificity of 80%, PPV 66%, NPV 84% and an accuracy of 77% (Tab.8). As for the correlation between CT and macroscopic scores we found a sensitivity of 62%, a specificity of 79%, VPP of 68%, VPN 74% with an accuracy of 72% (Tab.9). Some examples of minimal PC in different regions, correctly identified at CT examination, are shown in Fig.8. PCI GRADING: Furthermore the correlations between the PCI scores extrapolated with MDCT and both histologic and macroscopic PCI scores were calculated, according to PCI grading (Tab.10). Page 14 of 24

15 Images for this section: Table 4: Initial and post-cht FIGO stages in 43 patients. The table shows disease downstaging after 6 CHT cycles. Reference: Pecorelli S, Benedet JL, Creasman WT, Shepherd JH. FIGO staging of gynaecologic cancer FIGO Committee on Gynecologic Oncology. International Federation of Gynecology and Obstetrics. Int J Gynaecol Obstet : Page 15 of 24

16 Table 5: The diagnostic results of CT versus histologic analysis, at the patient level. The accuracy was 93%. NOTE: FN = False- Negative results; FP = False-Positive results; TN = True-Negative results; TP = True-Positive results; PPV = Positive Predictive Value; NPV = Negative Predictive Value. Table 6: Concordance of Disease distribution at the region level in OC patients, in terms of presence (+)/absence (-) of disease between CT scans and histology and between CT and macroscopic score. Page 16 of 24

17 Table 7: Concordance of Disease distribution at the region level in ROC patients, in terms of presence (+)/absence (-) of disease between CT scans and histology and between CT and macroscopic score. Table 8: The diagnostic results of CT versus histologic analysis, at the region level. The accuracy was 77%. NOTE: FN = False- Negative results; FP = False-Positive results; TN = True-Negative results; TP = True-Positive results; PPV = Positive Predictive Value; NPV = Negative Predictive Value. Page 17 of 24

18 Table 9: The diagnostic results of CT versus macroscopic score, at the region level. The accuracy was 72%. NOTE: FN = False- Negative results; FP = False-Positive results; TN = True-Negative results; TP = True-Positive results; PPV = Positive Predictive Value; NPV = Negative Predictive Value. Fig. 8: Some examples of minimal PC in different regions, correctly identified at CT examination. Page 18 of 24

19 Table 10: Concordance between CT and histological/macroscopic PCI scores, according to PCI prognostic grading, for OC, ROC and total (OC+ROC) patients. *0/1= one patient OC with MACROSCOPIC PCI=0 but both CT and HISTOLOGIC PCI = 2 **0/2= two patients ROC, one with CT PCI=1 and the other one with CT PCI = 4 but both with HISTOLOGIC PCI = 0. Page 19 of 24

20 Conclusion - MDCT is an accurate technique to obtain an appropriate preoperative definition of PCI and therefore a pre-surgery prognostic evaluation in patients with ovarian cancer. - CT examination with fluid distension of the bowel loops can therefore improve diagnostic performance. - CT examination can provide a substantial improvement in pre-surgery patients selection and in treatment planning. - The PCI value at CT may have the potential to serve as prognostic biomarker in patients with advanced ovarian cancer. Page 20 of 24

21 References 1. Sant M, Allemani C, Santaquilani M, et al. Survival of cancer patients diagnosed in Results and commentary. Eur J Cancer 2009; 45: Roviello F, Caruso S, Marrelli D, et al. Treatment of peritoneal carcinomatosis with cytoreductive surgery and hypertermic intraperitoneal chemotherapy: state of the art and future developments. Surg Oncol 2011; 20:e Roviello F, Pinto E, Corso G, et al. Safety and potential benefit of hypertermic intraperitoneal chemotherapy (HIPEC) in peritoneal carcinomatosis from primary or recurrent ovarian cancer. J Surg Oncol 2010; 102: Glehen O, Mohamed F, Gilly FN. Peritoneal carcinomatosis from digestive tract cancer: New management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol 2004; 5: Yan TD, Black D, Savady R, et al. A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol 2007; 14: Verwaal VJ, Bruin S, Boot H, et al. 8-year follow-up of randomized trial: Cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patient with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol 2008; 15: Chua TC, Robertson G, Liauw W, et al. Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian cancer peritoneal carcinomatosis: Systemic review of current results. J Cancer Res Clin Oncol 2009; 135: th 8. Stewart 4 JH, Shen P, Levine EA, Intraperitoneal Hyperthermic chemotherapy for peritoneal surface malignancy: current status and future directions. Ann Surg Oncol 2005; 12: Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. In: Sugarbaker PH, editor. Peritoneal carcinomatosis: principles of management. Boston, USA: Kluwe Academic Publishers 1996; Page 21 of 24

22 Page 22 of 24

23 Personal Information Maria Antonietta Mazzei, MD, Assistant Professor of Radiology. University of Siena, Department of Medical, Surgical and Neuro Sciences, section of Radiological Sciences. Viale Bracci 10, Siena, 53100, Italy. Telephone: +39 (0) ; Fax: +39 (0) ; Page 23 of 24

24 Images for this section: Fig. 9: The Authors Page 24 of 24