Overall survival of pseudomyxoma peritonei and peritoneal mesothelioma patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy can be predicted by computed tomography quantified sarcopenia.

BACKGROUND: Malnutrition is associated with increased postoperative morbidity in abdominal surgery. This study aimed to determine if sarcopenia and/or abdominal fat composition could predict postoperative outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for pseudomyxoma peritonei (PMP) and peritoneal mesothelioma (PM). METHODS: All patients who underwent a complete CRS-HIPEC for PMP and PM, between January 2009 and September 2017, were retrospectively studied. Preoperative computed tomography (CT) was used to measure the cross-sectional surface of skeletal muscle mass and adipose tissue (visceral and subcutaneous), at the level of the third lumbar vertebrae, to assess for sarcopenia and abdominal fat composition. RESULTS: Among 115 patients, 82 were treated for PMP and 33 for PM. 64 patients (55.7%) were sarcopenic on the preoperative imagery. Major postoperative complications occurred in 63 patients (54.8%), without observable difference between sarcopenic and non-sarcopenic patients (56.2% vs. 52.9%; p = 0.723). The median overall survival (OS) was 73.3 for the patients with a normal muscle mass and 57.2 months for the sarcopenic patients (p = 0.05). CONCLUSION: CT measured sarcopenia is an independent predictive factor for overall survival in patients treated for PMP and PM with CRS-HIPEC, but cannot predict postoperative morbidity.

Preoperative nutritional risk assessment in patients undergoing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for colorectal carcinomatosis.

BACKGROUND: Malnutrition is associated with increased postoperative morbidity in colorectal surgery. This study aimed to determine if preoperative nutritional markers could predict postoperative outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal metastasis (PM) of colorectal origin. METHODS: All patients who underwent a complete CRS-HIPEC for colorectal PM between January 2009 and December 2014 were evaluated. Preoperative clinical and biological nutritional factors, including Body Mass Index (BMI), preoperative albumin and prealbumin levels were analysed. Preoperative computed tomography was used to measure the cross-sectional surface of the visceral and subcutaneous adipose tissue, at the third lumbar vertebrae, to assess the abdominal fat composition. Skeletal muscle mass was measured to assess for sarcopenia. RESULTS: Among 214 patients, 14 (6.5%) had a BMI ≥ 35 kg/m2, 90 (42%) were sarcopenic, 19 (9%) presented albumin <35 g/L and 2 (1%) had pre-albumin <20 mg/dL. Median values for visceral and subcutaneous fat surfaces were 99.2 cm2 and 198 cm2, respectively. Hypoalbuminemia was associated with worse overall survival (23 vs. 59 months, p = 0.015). The other nutritional factors did not impact overall or progression free survival after CRS-HIPEC for colorectal PM. In multivariate analysis, major post-operative complication and hypoalbuminemia were independently associated with decreased overall survival. CONCLUSIONS: Hypoalbuminemia appears as a strong predictive factor for decreased overall survival in patients presenting PM of colorectal origin undergoing CRS-HIPEC.

Survival and prognostic factors after adjuvant 131iodine-labeled lipiodol for hepatocellular carcinoma: a retrospective analysis of 106 patients over 20 years.

OBJECTIVE: Hepatocellular carcinoma (HCC) has high recurrence rate after curative treatment. The aim of the present study was to report our experience with adjuvant use of 131I-lipiodol after curative treatment of HCC in terms of recurrence and survival in a large cohort of patients with a long follow-up. METHODS: All patients treated with 131I-lipiodol after curative treatment of HCC in two French centers from 1991 to 2009 were included in a retrospective cohort study. RESULTS: One hundred and six patients were included. The median (range) follow-up was 6 years (0.3-22). Forty-three patients (41%) had cirrhosis. Recurrence-free survival rates at 1, 2, 5, 10, and 20 years were 73, 57, 40, 30, and 14%, respectively. Cirrhosis was an independent predictive factor of recurrence [RR = 1.18, 95% CI (1.11-3.02), p = 0.019]. Overall, survival rates at 1, 2, 5, 10, and 20 years were 90, 83, 59, 37, and 23%, respectively. Prognostic factors were recurrence [RR = 2.73, 95% CI (1.35-5.54); p = 0.005], age over 60 years (RR = 1.91, 95% CI [1.02-3.61]; p = 0.044), and tumor number over 3 [RR = 3.31, 95% CI (1.25-8.77); p = 0.016]. CONCLUSION: Our results suggest that the effect of 131I-lipiodol after curative treatment of HCC could be related to a beneficial impact on risk factors of early tumor recurrence. This could be evaluated in further studies using modern radioembolization methods.

EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib.

AIM: This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177). PATIENTS & METHODS: About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off). RESULTS: Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified. CONCLUSION: Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.

Multiparameter Phase I trials: a tool for model-based development of targeted agent combinations--example of EVESOR trial.

Optimal development of targeted drug combinations is one of the future challenges to be addressed. Computerization and mathematical models able to describe biological phenomena and to simulate the effects of changes in experimental conditions may help find solutions to this issue. We propose the concept of 'multiparameter trials', where biological, radiological and clinical data required for modeling purpose are collected and illustrated by the ongoing academic EVESOR trial. The objective of the model-based work would be the determination of the optimized doses and dosing schedules of everolimus and sorafenib, offering the maximization of the predicted modeled benefit/toxicity ratio in patients with solid tumors. It may embody the 'proof of concept' of model-based drug development of anticancer agent combinations.

Adjuvant Intraarterial Lipiodol or ¹³¹I-Lipiodol After Curative Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial.

UNLABELLED: The prevention of tumor recurrence after curative treatment of hepatocellular carcinoma (HCC) is unresolved. Postoperative intraarterial injection of (131)I-labeled lipiodol has been proposed as adjuvant treatment. The aim of this prospective randomized trial was to evaluate if a single dose of postoperative adjuvant intraarterial (131)I-lipiodol (vs. unlabeled lipiodol) could reduce the rate of intrahepatic recurrence at 2 y. METHODS: Patients who underwent curative treatment for HCC and recovered within 6 wk were randomly assigned to receive a single 2,200-MBq (131)I-lipiodol dose or a single unlabeled lipiodol dose on a 1:1 basis. Recurrence-free and overall survival rates were analyzed. RESULTS: Between June 2005 and February 2009, we included 58 patients (median age of 63 y [range, 23-85 y]): 29 received intraarterial (131)I-lipiodol and 29 received lipiodol adjuvant treatment. At 2 y after treatment, the rate of patients with intrahepatic recurrence was 28% in the (131)I-lipiodol group and 56% in the lipiodol group (P = 0.0449). The Kaplan-Meier analysis confirmed this result, with a 2-y recurrence-free survival in the (131)I-lipiodol and lipiodol groups of 73% and 45%, respectively (P = 0.0259). The 5-y recurrence-free survival rates in the (131)I-lipiodol and lipiodol groups were 40% and 0%, respectively (P = 0.0184). The overall and specific survivals were not significantly different between groups (P = 0.9378 and P = 0.1339, respectively). (131)I-lipiodol had no severe toxic effects. CONCLUSION: After curative treatment of patients with HCC, one 2,200-MBq dose of intraarterial (131)I-lipiodol significantly decreased the rate of intrahepatic recurrence but failed to improve overall or specific survival.

Assessment of water enema computed tomography: an effective imaging technique for the diagnosis of colon cancer: Colon cancer: computed tomography using a water enema.

AIM: The aim of this study was to assess the accuracy of water enema computed tomography (WECT) for the diagnosis of colon cancer. METHODS: A total of 191 patients referred for clinically suspected colon cancer were prospectively evaluated by WECT in a multicenter trial. Examination was contrast enhanced helical CT after colon filling through a rectal tube. For all the cases, final diagnosis was obtained by colonoscopy and/or surgery. CT data were interpreted both locally and at a centralized site by a specialized and general radiologist. RESULTS: Seventy-one patients were diagnosed with colon cancer. Overall, WECT sensitivity and specificity were 98.6 and 95.0%, respectively. Positive and negative predictive values were 92.1 and 99.1%, respectively. In a subgroup of 33 patients with unclean bowel, the sensitivity and specificity of WECT were 95.0 and 92.3%, respectively. The correlation between local radiologists and the specialized radiologist was excellent (Kappa = 0.87) as was the correlation between the general radiologist and the specialist (Kappa = 0.92). CONCLUSION: This prospective analysis demonstrates that WECT is an effective, safe, and simple imaging technique for the diagnosis of colon cancer and can be proposed when a strong clinical suspicion of colon cancer is present, especially in frail patients.

Water enema computed tomography: diagnostic tool in suspicion of colorectal tumor.

OBJECTIVES: The aim of this study was to assess the accuracy of water enema multi-row computed tomography for detecting clinically suspected colorectal tumor. PATIENTS AND METHODS: A water enema multi-row computed tomography (WE-MR-CT) was performed in 128 consecutive patients (71 women, mean age 67.7 years) referred for suspicion of colorectal cancer. We defined at least one centimeter size of the lesion as the threshold of detection. The results of WE-MR-CT were compared with the diagnosis obtained by colonoscopy, pathology or clinical follow-up. RESULTS: The overall sensitivity and specificity of water enema multi-row CT in identifying patients with colorectal lesions were 95.5% and 93.5%, respectively. The negative predictive value was 98.8% for a 10-mm threshold lesion size. WE-MR-CT allowed identifying synchronous lesions in three cases. CONCLUSIONS: WE-MR-CT can accurately detect supracentimetric colorectal tumors. The performance of this technique should be further evaluated in prospective studies.