scholarly journals Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients

Author(s):  
S. G. Larsen ◽  
M. A. Goscinski ◽  
S. Dueland ◽  
S. E. Steigen ◽  
E. Hofsli ◽  
...  

Abstract Background Patients with metastatic colorectal cancer (mCRC) carrying BRAF (mutBRAF) or KRAS mutation (mutKRAS) have an inferior prognosis after liver or lung surgery, whereas the prognostic role in the context of peritoneal metastasis (PM) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been less investigated. Methods In total, 257 patients with non-appendiceal PM-CRC were included from the Norwegian National Unit for CRS-HIPEC. Results In total, 180 patients received CRS-HIPEC with Mitomycin C, 77 patients received palliative surgery only. In the CRS-HIPEC group, mutBRAF was found in 24.7%, mutKRAS 33.9% and double wild-type 41.4% without differences in survival. MSI was found in 29.3% of mutBRAF cases. Patients with mutBRAF/MSI had superior 5-year survival compared to mutBRAF with MSS (58.3% vs 25.2%, P = 0.022), and better 3-year disease-free survival (DFS) compared to mutKRAS (48.6% vs 17.2%, P = 0.049). Peritoneal Cancer Index and the number of lymph node metastasis were prognostic for OS, and the same two, location and gender prognostic for DFS in multivariate analysis. Conclusions PM-CRC with CRS-HIPEC patients has a surprisingly high proportion of mutBRAF (24.7%). Survival was similar comparing mutBRAF, mutKRAS and double wild-type cases, whereas a small subgroup with mutBRAF and MSI had better survival. Patients with mutBRAF tumours and limited PM should be considered for CRS-HIPEC.

2020 ◽  
Vol 33 (06) ◽  
pp. 372-376
Author(s):  
Hideaki Yano

AbstractPeritoneal metastasis from colorectal cancer (PM-CRC) is used to be considered a systemic and fatal condition; however, it has been growingly accepted that PM-CRC can still be local disease rather than systemic disease as analogous to liver or lung metastasis.Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now considered an optimal treatment for PM-CRC with accumulating evidence. There is a good reason that CRS + HIPEC, widely accepted as a standard of care for pseudomyxoma peritonei (PMP), could be a viable option for PM-CRC given a similarity between PM-CRC and PMP.Recent years have also seen that modern systemic chemotherapy with or without molecular targeted agents can be effective for PM-CRC. It is possible that neoadjuvant or adjuvant chemotherapy combined with CRS + HIPEC could further improve outcomes.Patient selection, utilizing modern images and increasingly laparoscopy, is crucial. Particularly, diagnostic laparoscopy is likely to play a significant role in predicting the likelihood of achieving complete cytoreduction and assessing the peritoneal cancer index score.


2015 ◽  
Vol 100 (1) ◽  
pp. 21-28 ◽  
Author(s):  
David S. Sparks ◽  
Bradley Morris ◽  
Wen Xu ◽  
Jessica Fulton ◽  
Victoria Atkinson ◽  
...  

Abstract Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical but effective treatment option for select peritoneal malignancies. We sought to determine our early experience with this method for peritoneal carcinomatosis secondary to mucinous adenocarcinomas of appendiceal origin. As such, we performed a retrospective clinical study of 30 consecutive patients undergoing CRS with planned HIPEC at the Princess Alexandra Hospital, between June 2009 to December 2012, with mucinous adenocarcinomas of the appendix. CRS was performed in 30 patients, 13 received HIPEC intraoperatively and 17 received early postoperative intra-peritoneal chemotherapy (EPIC) in addition. Mean age was 52.3 years and median hospital stay was 26 days (range 12–190 days). Peritoneal cancer index scores were 0–10 in 6.7% of patients, 11–20 in 20% of patients and >20 in 73.3% of patients. Complete cytoreduction was achieved overall in 21 patients. In total, 106 complications were observed in 28 patients. Ten were grade 3-A, five were grade 3-B and one grade-5 secondary to a fatal PE on day 97. In patients who received HIPEC, there was no difference in disease-free survival (P = 0.098) or overall survival (P = 0.645) between those who received EPIC versus those who did not. This study demonstrates that satisfactory outcomes with regards to morbidity and survival can be achieved with CRS and HIPEC, at a single-centre institution with growing expertise in the technique. Our results are comparable with outcomes previously described in the international literature.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tuanhe Sun ◽  
Kang Li ◽  
Gang Xu ◽  
Kun Zhu ◽  
Qiong Wang ◽  
...  

Abstract Background The prognosis of patients with colorectal cancer and peritoneal metastasis (CRC-PM) after incomplete cytoreductive surgery (CRS) or palliative surgery is poor. Novel and effective therapies are urgently needed. This study aimed to assess the effects of palliative postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with CRC-PM. Methods This retrospective study included patients with CRC-PM at the First Affiliated Hospital of Xi’an Jiaotong University in 05/2014–05/2019. Observation indicators included overall survival (OS), ascites-free survival, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). Kaplan-Meier survival curves and multivariable Cox regression models were used to determine the factors associated with OS and ascites-free survival. The ascites-specific quality of life (QoL) was measured using the Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI). Results Eighty-two patients were included, including 37 and 45 in the HIPEC and non-HIPEC groups, respectively. Mean OS was 10.3±3.7 (95% CI 9.5–11.2) months. Multivariable Cox proportional hazard regression suggested that PCI (HR=6.086, 95% CI 3.187–11.620, P < 0.0001) was independently associated with OS. The degree of ascites (HR=2.059, 95% CI 1.412–3.005, P < 0.0001), PCI (HR=6.504, 95% CI 2.844–14.875, P < 0.0001), and HIPEC (HR=0.328, 95% CI 0.191–0.562, P < 0.0001) were independently associated with ascites-free survival. In patients with survival >6 months, postoperative ascites-specific QoL was significantly improved after HIPEC compared with the non-HIPEC group (P < 0.001). Oxaliplatin-based HIPEC significantly increased the rates of neutropenia and peripheral neurotoxicity (both P < 0.05). Conclusion These data indicate that postoperative oxaliplatin-based HIPEC might help increase ascites-free survival in CRC-PM patients after incomplete CRS or palliative surgery, with improved QoL after 6 months of follow-up.


2015 ◽  
Vol 100 (6) ◽  
pp. 1033-1039 ◽  
Author(s):  
Christos Mavroudis ◽  
Leonidas Alevizos ◽  
Konstantinos M. Stamou ◽  
Theodosia Vogiatzaki ◽  
Savvas Eleftheriadis ◽  
...  

Cytoreductive surgery with HIPEC has provided a chance for long-term survival in selected patients. However, perioperative management remains a challenge for the anesthesiology team. The aim of this study was to evaluate the changes in hemodynamic parameters during hyperthermic intraperitoneal chemotherapy (HIPEC) using the FloTrac/Vigileo system. Forty-one consecutive patients undergoing cytoreductive surgery and HIPEC were enrolled. Heart rate (HR), esophageal temperature, and cardiac output (CO) steadily increased until the end of HIPEC. In the first half of HIPEC, systolic blood pressure (SBP) and central venous pressure (CVP) increased whereas systemic vascular resistance (SVR) decreased; SVR stabilized in the second half. Diastolic blood pressure (DBP), mean arterial pressure (MAP), and stroke volume (SV) showed no significant variation. Male gender was related to increased CVP, CO, and SV, and decreased SVR; age &gt;55 years was related to increased SBP, and peritoneal cancer index (PCI) was correlated with HR, DBP, and SV. PCI &gt;14 was associated with increased HR and decreased DBP and MAP. American Society of Anesthesiologists score &gt;1 was related to decreased CO and SV. Patients undergoing HIPEC develop a hyperdynamic circulatory state because of the increased temperature, characterized by a steady decrease in SVR and continuous increase in HR and CO. FloTrac/Vigileo system may provide an easy-to-handle, noninvasive monitoring tool.


2019 ◽  
Vol 37 (23) ◽  
pp. 2028-2040 ◽  
Author(s):  
Pierre-Emmanuel Bonnot ◽  
Guillaume Piessen ◽  
Vahan Kepenekian ◽  
Evelyne Decullier ◽  
Marc Pocard ◽  
...  

PURPOSE Gastric cancer (GC) with peritoneal metastases (PMs) is a poor prognostic evolution. Cytoreductive surgery (CRS) yields promising results, but the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. Here we aimed to compare outcomes between CRS-HIPEC versus CRS alone (CRSa) among patients with PMs from GC. PATIENTS AND METHODS From prospective databases, we identified 277 patients with PMs from GC who were treated with complete CRS with curative intent (no residual nodules > 2.5 mm) at 19 French centers from 1989 to 2014. Of these patients, 180 underwent CRS-HIPEC and 97 CRSa. Tumor burden was assessed using the peritoneal cancer index. A Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used to assess the effect of HIPEC and account for confounding factors. RESULTS After IPTW adjustment, the groups were similar, except that median peritoneal cancer index remained higher in the CRS-HIPEC group (6 v 2; P = .003). CRS-HIPEC improved overall survival (OS) in both crude and IPTW models. Upon IPTW analysis, in CRS-HIPEC and CRSa groups, median OS was 18.8 versus 12.1 months, 3- and 5-year OS rates were 26.21% and 19.87% versus 10.82% and 6.43% (adjusted hazard ratio, 0.60; 95% CI, 0.42 to 0.86; P = .005), and 3- and 5-year recurrence-free survival rates were 20.40% and 17.05% versus 5.87% and 3.76% ( P = .001), respectively; the groups did not differ regarding 90-day mortality (7.4% v 10.1%, respectively; P = .820) or major complication rate (53.7% v 55.3%, respectively; P = .496). CONCLUSION Compared with CRSa, CRS-HIPEC improved OS and recurrence-free survival, without additional morbidity or mortality. When complete CRS is possible, CRS-HIPEC may be considered a valuable therapy for strictly selected patients with limited PMs from GC.


2019 ◽  
Vol 26 (13) ◽  
pp. 4835-4842 ◽  
Author(s):  
Malin Enblad ◽  
Wilhelm Graf ◽  
Alexei Terman ◽  
Pascal Pucholt ◽  
Björn Viklund ◽  
...  

Abstract Purpose Genetic alterations in colorectal peritoneal metastases (PM) are largely unknown. This study was designed to analyze whole-genome copy number alterations (CNA) in colorectal PM and to identify alterations associated with prognosis after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods All patients with PM, originating from a colorectal adenocarcinoma, who were treated with CRS and HIPEC in Uppsala Sweden, between 2004 and 2015, were included (n = 114). DNA derived from formalin-fixed paraffin-embedded (FFPE) specimens were analyzed for CNA using molecular inversion probe arrays. Results There were extensive but varying degrees of CNA, ranging from minimal CNA to total aneuploidy. In particular, gain of parts of chromosome 1p and major parts of 15q were associated with poor survival. A combination of gains of 1p and 15q was associated with poor survival, also after adjustment for differences in peritoneal cancer index and completeness of cytoreduction score [hazard ratio (HR) 5.96; 95% confidence interval (CI) 2.19–16.18]. These patients had a mean copy number (CN) of 3.19 compared with 2.24 in patients without gains. Complete CN analysis was performed in 53 patients. Analysis was unsuccessful for the remaining patients due to insufficient amounts of DNA and signals caused by interstitial components and normal cells. There was no difference in survival between patients with successful and unsuccessful CN analysis. Conclusions This study shows that gains of parts of chromosome 1p and of major parts of chromosome 15q were significantly associated with poor survival after CRS and HIPEC, which could represent future prognostic biomarkers.


2012 ◽  
Vol 78 (9) ◽  
pp. 942-946 ◽  
Author(s):  
Rolando GarcÍA-Matus ◽  
Carlos Alberto HernÁNdez-HernÁNdez ◽  
Omar Leyva-GarcÍA ◽  
Sergio Vásquez-Ciriaco ◽  
Guillermo Flores-Ayala ◽  
...  

Peritoneal carcinomatosis (PC) has been traditionally considered a terminal disease with median survivals reported in the literature of 6 to 12 months. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are playing an ever increasing role in the treatment of these patients. Excellent results have been achieved in well-selected patients but there is a very steep learning curve when starting a new program. A program for peritoneal surface malignancies in which patients with PC of gastrointestinal or gynecological origin were treated using multi-modality therapy with combinations of systemic therapy, cytoreductive surgery (CRS), and HIPEC was initiated in December 2007 at “Hospital Regional de Alta Especialidad de Oaxaca,” Mexico. We present the results of our initial experience. From December 2007 to February 2011, 26 patients were treated with CRS and HIPEC. There were 21 female patients. Most common indication (46%) was recurrent ovarian cancer. Mean duration of surgery was 260 minutes. Mean Peritoneal Cancer Index was 9. Twenty-three (88.5%) patients had a complete cytoreduction. Major morbidity and mortality rates were 19.5 and 3.8 per cent, respectively. Mean hospital stay was 8 days. At a mean follow-up of 20 months, median survival has not been reached. Rigorous preoperative workup, strict selection criteria, and mentoring from an experienced cytoreductive surgeon are mandatory and extremely important when starting a center for PC.


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