Charles Honoré

Outcome Prediction in Primary Resected Retroperitoneal Soft Tissue Sarcoma: Histology-Specific Overall Survival and Disease-Free Survival Nomograms Built on Major Sarcoma Center Data Sets

PURPOSE Integration of numerous prognostic variables not included in the conventional staging of retroperitoneal soft tissue sarcomas (RPS) is essential in providing effective treatment. The purpose of this study was to build a specific nomogram for predicting postoperative overall survival (OS) and disease-free survival (DFS) in patients with primary RPS. PATIENTS AND METHODS Data registered in three institutional prospective sarcoma databases were used. We included patients with primary localized RPS resected between 1999 and 2009. Univariate (Kaplan and Meier plots) and multivariate (Cox model) analyses were carried out. The a priori chosen prognostic covariates were age, tumor size, grade, histologic subtype, multifocality, quality of surgery, and radiation therapy. External validation was performed by applying the nomograms to the patients of an external cohort. The models discriminative ability was estimated by means of the bootstrap-corrected Harrell C statistic. RESULTS In all, 523 patients were identified at the three institutions (developing set). At a median follow-up of 45 months (interquartile range, 22 to 72 months), 171 deaths were recorded. Five- and 7-year OS rates were 56.8% (95% CI, 51.4% to 62.6%) and 46.7% (95% CI, 39.9% to 54.6%. Two hundred twenty-one patients had disease recurrence. Five- and 7-year DFS rates were 39.4% (95% CI, 34.5% to 45.0%) and 35.7% (95% CI, 30.3% to 42.1%). The validation set consisted of 135 patients who were identified at the fourth institution for external validation. The bootstrap-corrected Harrell C statistics for OS and DFS were 0.74 and 0.71 in the developing set and 0.68 and 0.69 in the validating set. CONCLUSION These nomograms accurately predict OS and DFS. They should be used for patient counseling in clinical practice and stratification in clinical trials.

Results of Systematic Second-look Surgery Plus HIPEC in Asymptomatic Patients Presenting a High Risk of Developing Colorectal Peritoneal Carcinomatosis

Purpose: To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). Patients and Methods: From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). Results: PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9–109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). Conclusion: Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.

Variability in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients From the Multi-institutional Collaborative RPS Working Group

Background:Retroperitoneal sarcomas (RPS) are rare tumors composed of several well defined histologic subtypes. The aim of this study was to analyze patterns of recurrence and treatment variations in a large population of patients, treated at reference centers. Methods:All consecutive patients with primary RPS treated at 6 European and 2 North American institutions between January 2002 and December 2011 were included. Five, 8, and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariate analyses for OS, CCI of LR, and DM were performed. Results:In all, 1007 patients were included. Median follow-up was 58 months (first and third quartile range 36–90). The 5, 8, and 10-year OS were 67% [95% confidence interval (CI), 63, 70), 56% (95% CI, 52, 61), and 46% (95% CI, 40, 53). The 5, 8, and 10-year CCI of LR and DM were 25.9 (95% CI, 23.1, 29.1), 31.3 (95% CI, 27.8, 35.1), 35% (95% CI, 30.5, 40.1), and 21% (95% CI, 18.4, 23.8%), 21.6 (95% CI, 19.0, 24.6), and 21.6 (95% CI, 19.0, 24.6), respectively. Tumour size, histologic subtype, malignancy grade, multifocality, and completeness of resection were significant predictors of outcome. Patterns of recurrence varied depending on histologic subtype. Different treatment policies at participating institutions influenced LR of well differentiated liposarcoma without impacting OS, whereas discrepancies in adjuvant systemic therapies did not impact LR, DM, or OS of leiomyosarcoma. Conclusions:Reference centers are critical to outcomes of RPS patients, as the management strategy requires specific expertise. Histologic subtype predicts patterns of recurrence and should inform management decision. A prospective international registry is under preparation, to further define our understanding of this disease.

Transanal endoscopic total mesorectal excision combined with single-port laparoscopy.

BACKGROUND: Rectal dissection using a conventional multiport laparoscopic approach involves risks due to technical difficulties, particularly in patients with a low tumor, a narrow pelvis, or obesity. OBJECTIVE: We describe a technique of transanal endoscopic low and middle rectal dissection with subsequent coloanal anastomosis via single-port laparoscopy, with the aim of reducing technical problems, increasing safety, and improving cosmesis after resection of rectal cancer. DESIGN AND SETTING: This was an observational study conducted in a large, tertiary care cancer center in France. PATIENTS: Consecutive patients with rectal adenocarcinoma requiring total mesorectal excision with a coloanal anastomosis were evaluated for eligibility to undergo the procedure. Patients were selected if they had 1 or more of the following risk factors: narrow pelvis, a voluminous prostate, or obesity. INTERVENTION: After an anal mucosectomy, the rectal wall was circumferentially transected above the external sphincter and a transanal trocar was introduced. The dissection of the mesorectum was completely performed via endoscopy up to the Douglas rectovesical pouch. A single port was inserted at the future site of the transient ileostomy, and a left colectomy and a lymphadenectomy were performed. The upper rectum dissection enabled joining the transanal rectal plane of dissection. Then the splenic flexure was completely mobilized and the specimen was extracted through the site of the future ileostomy. OUTCOME MEASURES: Operative time, blood loss, duration of hospital stay, and histopathologic variables (margins, number of harvested lymph nodes, grade of the mesorectal fascia dissection) were recorded, and the quality of the surgical plane was assessed. The Cleveland Clinic Florida (Wexner) fecal incontinence questionnaire was administered after ileostomy closure. RESULTS: Four consecutive male patients with rectal cancer in a narrow pelvis were treated with this new approach. No conversion (by laparotomy or multiport laparoscopy) was necessary. The pathologic variables were satisfactory and the Wexner scores indicated no severe incontinence after ileostomy closure. The postoperative follow-up was uneventful except for an anastomotic fistula which developed in 1 patient and was treated without reoperation. LIMITATIONS: The study was limited by the small number of patients and the fact that no women and no obese patients were included. CONCLUSIONS: Rectal resection via the transanal approach combined with single-port laparoscopic assistance may be easier and safer than the traditional approach, especially in male patients who have a narrow pelvis. More data are needed in order to draw conclusions concerning oncologic results and before selecting the most appropriate indications for this technique.

Should patients with peritoneal carcinomatosis of colorectal origin with synchronous liver metastases be treated with a curative intent? A case-control study.

Objective:This study aimed to assess the prognostic impact of liver metastases (LM) in patients with colorectal peritoneal carcinomatosis (PC) who underwent complete cytoreductive surgery and resection of LM, followed by intraperitoneal chemotherapy. Background:Synchronous surgical treatment of PC and LM with curative intent remains controversial. Methods:From a prospective database, all patients with PC and synchronous LM who had undergone cytoreductive surgery and LM resection followed by intraperitoneal chemotherapy were matched with patients with PC alone according to the following criteria: age, peritoneal cancer index (PCI), site and lymph node involvement (pN) of primary cancer, and postoperative chemotherapy. Results:From 1993 to 2009, 37 patients with PC and LM were matched with 61 patients with PC alone. After a mean follow-up of 36 months, 3-year overall survival (OS) and disease-free survival rates were significantly lower in patients with PC and LM, respectively, 40% and 66% (P = 0.04) and 6% and 27% (P = 0.001). A PCI of 12 or more [odds ratio (OR): 4.6], a pN+ status (OR: 3.3), no adjuvant chemotherapy (OR: 3.0), and presence of LM (OR: 2.0) were identified as independent factors for poor OS. Three groups were singled out: (1) patients with a low PCI (<12) and no LM (median OS: 76 months); (2) patients with a low PCI (<12) and 1 or 2 LM (median OS: 40 months); and (3) patients with a high PCI (≥12) or patients with 3 LMs or more (median OS: 27 months). Conclusions:This case-control study seems to confirm that prolonged survival can be achieved in highly selected patients operated on for limited PC and fewer than 3 LM.

Prognostic similarities and differences in optimally resected liver metastases and peritoneal metastases from colorectal cancers.

PURPOSE To analyze and compare survival in patients operated for colorectal liver metastases (LM) with that in patients optimally resected for peritoneal metastases (PM). PATIENTS AND METHODS This study concerns 287 patients with LM and 119 patients with PM treated with surgery plus chemotherapy between 1993 and 2009, excluding patients presenting both LM and PM. RESULTS Mortality (respectively, 2.7% and 4.2%), morbidity (respectively, 11% and 17%), and 5-year overall survival (OS) rates (respectively, 38.5% and 36.5%) were not statistically different between the LM group and the PM group. Multivariate analysis showed that the extent of the disease was the main prognostic factor, which led us to divide the population into 5 subgroups. The best 5-year OS rate (72.4%) was obtained in patients with minimal peritoneal disease [peritoneal cancer index (PCI) ≤5]. OS was similar for the patients with less than 10 LM and those with a PCI between 6 and 15 (respectively, 39.4% and 38.7%). Five-year OS was lower in patients with more than 10 LM (18.1%), and dramatically low for patients with a PCI > 15 (11.8%). CONCLUSIONS This study underlines the prognostic impact of the tumor burden in metastatic colorectal disease. In selected patients, similar survival rates can be obtained after optimal treatment of LM and PM. As the role of optimal surgical resection of LM is widely accepted, our results confirm that an optimal attitude should also be adopted to treat PM with a PCI < 16, particularly in patients with very low PCI (<5) where survival could be better than LM.

Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin

BACKGROUND Complete cytoreductive surgery (CCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is on the verge of becoming the gold standard treatment for selected patients presenting peritoneal metastases (PM) of colorectal origin. PM is scored with the peritoneal cancer index (PCI), which is the main prognostic factor. However, small bowel (SB) involvement could exert an independent prognostic impact. AIM To define an adequate cut-off for the PCI and to appraise whether SB involvement exerts an impact on this cut-off. PATIENTS AND METHODS Patients (n = 139) treated with CCRS plus HIPEC were prospectively verified and retrospectively analyzed. One hundred presented with SB involvement of different extents and at different locations. RESULTS All the patients with a PCI ≥ 15 exhibited SB involvement. Five-year overall survival was 48% when the PCI was <15 vs 12% when it was ≥ 15 (p < 0.0001. The multivariate analysis retained two prognostic factors: PCI ≥ 15 (p = 0.02, HR = 1.8), and the involvement of area 12 (lower ileum) (p = 0.001, HR = 3.1). When area 12 was invaded, it significantly worsened the prognosis: 5-year overall survival of patients with a PCI <15 and area 12 involved was 15%, close to that of patients with a PCI ≥ 15 (12%) and far lower than that of patients with a PCI <15 and no area 12 involvement (70%). CONCLUSION A PCI greater than 15 appears to be a relative contraindication for treatment of colorectal PM with CCRS + HIPEC. Involvement of the lower ileum is also a negative prognostic factor to be taken into consideration.

Sporadic extra abdominal wall desmoid-type fibromatosis: Surgical resection can be safely limited to a minority of patients

BACKGROUND To analyse the natural history of extra-abdominal wall desmoid-type fibromatosis (DF) and compare outcome in patients who underwent initial surgery with those who did not. PATIENTS AND METHODS All consecutive patients affected by primary sporadic extra-abdominal wall DF observed between January 1992 and December 2012 were included. Patients were divided into surgical (SG) or non-surgical groups (NSG) according to initial treatment. Relapse free survival was calculated for SG, and crude cumulative incidence (CCI) of switching to surgery or other treatments for NSG. RESULTS 216 patients were identified, 94 in SG (43%), 122 in NSG (57%). A shift towards a more systematic use of a conservative approach (78% of all comers) was observed in the latter years (2006-2012), although a small proportion of patients (28%) had been offered the conservative strategy even in the early period (1992-2005). Median follow-up (FU) was 49 mo. (interquartile (IQ), 20-89 mo.), 76 months for SG and 39 months for NSG. 5-year relapse-free survival (RFS) for SG was 80% (95% confidence interval (CI), 72-89%). For the NSG, 5-year CCI of switching to surgery was 5% (95% CI: 1.7%, 14%), and 51% to other treatments (95% CI: 41%, 65%). 27 (20%) NSG patients underwent spontaneous regression. CONCLUSION A non-surgical approach to extra-abdominal wall DF allowed surgery to be avoided in the majority of patients. This approach can be safely proposed and surgery offered as an option in selected cases.

Post‐relapse outcomes after primary extended resection of retroperitoneal sarcoma: A report from the Trans‐Atlantic RPS Working Group

Despite a radical surgical approach to primary retroperitoneal sarcoma (RPS), many patients experience locoregional and/or distant recurrence. The objective of this study was to analyze post‐relapse outcomes for patients with RPS who had initially undergone surgical resection of their primary tumor at a specialist center.

External validation of a multi-institutional retroperitoneal sarcoma nomogram

A multi‐institutional nomogram for predicting disease‐free survival (DFS) and overall survival (OS) in patients with primary retroperitoneal sarcoma (RPS) incorporating relevant prognostic factors not included in the American Joint Committee on Cancer staging system for soft tissue sarcoma has been reported. The authors validated this nomogram with an independent, transatlantic cohort.