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CYTOREDUCTIVE SURGERY IS SUFFICE

CYTOREDUCTIVE SURGERY IS SUFFICE. Dr Selcuk Seber NKU/SUAMON 2018. A major difference between AJCC-7th, and AJCC-8th is that the CRC staging system was revised to include a new stage involving peritoneal metastasis (named stage IVC). Peritoneal metastasis occur in %1 - %4 of patients.

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CYTOREDUCTIVE SURGERY IS SUFFICE

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  1. CYTOREDUCTIVE SURGERY IS SUFFICE Dr Selcuk Seber NKU/SUAMON 2018

  2. A major difference between AJCC-7th, and AJCC-8th is that the CRC staging system was revised to include a new stage involving peritoneal metastasis (named stage IVC). Peritoneal metastasis occur in %1 - %4 of patients

  3. Full thickness invasion of the bowel wall • In metastatic cases;%15 - %25 cases it is only site of metastatic disease • right colon • young age • poor differentiation • T4 tumor • Node positive • musinous LYMPHATIC COLON CANCER CELL HEMATOGENOUS transcoelomic During / after surgery in transit tumor cells escape from dissected LN or blood spill from surgical field

  4. Tran B, Kopetz S, Tie J et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 2011; 117: 4623–4632 So are we talking about the same disease, does BRAF mutant and BRAF negative cases of PC patients react differently to treatment modalities ? poor differentiation more aggressive signet cell PIK3CA mutation

  5. Cytoreduction is a personal matter Peritoneal carcinomatosis index: evaluating the size of peritoneal lesions in each of 13 abdominopelvic regions.and Lesion size (LS) is scored in each of the 13 regions and summed to yield a score from 0 to 39. Cytoreductive surgery: visceral resections such as those of the stomach, colon, ovary, uterus, spleen, gallbladder, and small bowel. In addition, parietal peritonectomy, greater omentectomy, and lesser omentectomy were performed. Completeness of cytoreduction : CCO score: 0 - 3 CC-1, CC-2, and CC-3 indicate residual tumor nodules measuring < 2.5 mm, between 2.5 mm and 2.5cm, and >2.5 cm

  6. Lin EK, Hsieh MC, Chen CH, Lu YJ, Wu SY. Outcomes of cytoreductive surgery andhyperthermic intraperitoneal chemotherapy for colorectal cancer with peritonealmetastasis. Medicine (Baltimore). 2016 Dec;95(52):e5522 Taipei University Hospital 1999 - 2014 33 patients retrospective analysis selected group of patients cytoreductive surgery followed by HIPEC The mean peritoneal cancer index (PCI) was 16.2. The major risk factors for death in these patients were a total PCI score > 20, total PPCI score > 0, and CC score ≥ 2 (P = 0.022, 0.031, and 0.0001, respectively; log-rank test). Multivariate analysis revealed that the total PPCI score was the strongest predictor of death following cytoreductive surgery and HIPEC in these patients. More than %70 of the patients received TPN, preoperative K.therapy, postop K.therapy.

  7. What we learn from this small retrospective study • this is the largest study conducted in Asia to examine the outcomes of cytoreductive surgery and HIPEC for treating colorectal cancer with peritoneal metastasis. • All patients had primary colorectal cancer with peritoneal metastasis. • The 2- and 5-year overall survival rates following cytoreductive surgery and HIPEC were 57% and 38%, respectively. • This is the first study reporting factors related to poor prognosis following HIPEC in patients with colorectal cancer and peritoneal metastasis. • Although mounting data suggest that long-term survival can be achieved in a low number of patients by using aggressive surgical cytoreduction followed by HIPEC, it remains unclear whether these outcomes are more favorable compared with those achieved using modern oxaliplatin- and irinotecan-based systemic chemotherapy with or without biological agents.

  8. HIPEC was not performed HIPEC was not administered if the risk of postoperative complications was high. who had poor preoperative performance status, poor laboratory data, excessive intraoperative bleeding in those who underwent extremely aggressive surgical procedures.

  9. What the guideline says /ESMO 2018: read between the lines cytoreductive surgery and HIPEC for patients with peritoneal metastases In selected patients with peritoneal metastasis, complete cytoreduc- tive surgery and HIPEC may provide prolonged survival when carried out in experienced high-volume centres (in view of the relatively high morbidity associated with the procedure) [228–230]. The efficacy of this multimodality treatment depends on the extent of peritoneal dissemination and is scored using the peritoneal cancer index (PCI), which is the main prognostic factor [231]. Involvement of the lower ileum is a negative prognostic factor. Cytoreductive surgery is particularly effective in patients with low-volume peritoneal disease (a PCI <12 is often suggested) With recommendations on stan- dardising the delivery of HIPEC in patients with CRC [232]and evaluation of oxaliplatin versus mitomycin C for HIPEC [233], cytoreductive surgery and HIPEC is on the verge of becoming the accepted standard treatment approach for patients with peritoneal metastases

  10. What if we prefer chemotherapy as the sole therapy for therapy for PC ? Of a total of 2,101 patients were included; Patients with pcCRC as the sole presentation of mCRC were uncommon in this patient population(n = 44, 2.1%).

  11. Chua and colleagues metaanalysis, 2, 492 patients,1995 and 2009. They reported survival rate of33 months (20–63) for patients with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus only12.5 months (5–24) • for patients having palliative surgery and/or systemic chemotherapy [11]. • However, none of the trials on systemic therapies have reported the peritoneum as a site of metastasis in patients entered into the trials. This highlights the difficulties of applying the RECIST criteria. PC is an exclusion criteria • Patients who fail to undergo a complete cytoreduction, be it due to the extensiveness of peritoneal implants or the lack of technical skills, the survival outcome is dismal with a median overall survival of 8 months with majority of patients succumbing to disease within a year. This is similar to the survival outcomes of the group of patients who underwent palliative surgery and/or systemic chemotherapy

  12. When the data of the patients who underwent cytoreduction followed by HIPEC were further analyzed, they showed that patients with 6-7 regions still had a very poor survival (median, 5.4 months) compared with those with zero to five regions involved (median, 29 months) • Eighty percent of all incidences of grade 4 toxicity (postoperative complications included) and all treatment-related deaths were in this patient group. These are the same patients in whom we failed to obtain a complete cytoreduction. These patients have clearly not benefited from cytoreduction and HIPEC • THİS İS THE GROUP THAT WE SHOULD AVOID CRS in PATIENTS with PC

  13. no important ascites, and no bulky clinical or radiological PC. Any patient presenting a rapid progression of PC under systemic chemotherapy was excluded.They were included in the study only after complete resection of the PC .

  14. Obtaining a 60% 2-year survival rate based on complete macroscopic resection of colorectal PC was the most important and unexpected result of this trial • “They were very disappointed to hear that EPIC was given in our institution only on a randomized trial basis.”

  15. CONCLUSION: 48 patients, Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%. • no huge and symptomatic PC, no extra-abdominal malignancy, a good general status and younger than 66 years old, and no disease progression after 2 to 3 months of neoadjuvant chemotherapy. To classify the extension of the PC, the abdominopelvic cavity was divided into five regions that included the four abdominal quadrants plus the pelvis.9 Before CRS, the distribution of PC was noted: one or two regions invaded defined limited PC, whereas three or more regions defined extended PC. To our knowledge, this is the first study to assess the efficacy of cytoreduction plus HIPEC versus modern chemotherapy.

  16. Two hundred thirty-two patients (47%) had received postoperative adjuvant systemic chemotherapy when they achieved an objective response to preoperative chemotherapy (if administered) or when they exhibited poor prognostic factors (CCR-1 or -2 status, invaded lymph nodes, or liver metastases).Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, Second, there is a strong correlation between the PCI (ie, extent of peritoneal disease), the completeness of CRS, and also morbidity and mortality it was surprising to discover that there was no statistical difference in survival rates between HIPEC or EPIC.

  17. The ASPSM conducted a retrospective review of patients with colorectal cancer and peritoneal dissemination. Multicenter, 584 included in the study underwent treatment of peritoneal dissemination from colorectal cancer with CRS and HIPEC with Oxaliplatin or MMC. • The Peritoneal Surface Disease Severity Score (PSDSS): I =/<4; II=/>4–7; III =/>8–10; and IV=/>10 • A complete cytoreductions (CC‐0/CC‐1) was achieved in 547 (93.7%) patients. There were 62 (12.6%), 258 (52.4%), 66(13.4%) and 106 (21.5%) patients with PSDSS I, II, III, and, IV respectively • Median OS for PSDSS I, II, III and IV were >76, 36.1, 23.9, and 18.5 months, respectively • Median OS for patients having a complete CRS for PSDSS I, II, III, and, IV were >76, 36.1, 24.0, and 19.0 months, respectively

  18. prospective, two databases containing 345 patients • To examine whether patients who developed PM after adjuvant chemotherapy had worse outcomes, patients were divided into four groups based on administration of adjuvant chemotherapy (yes vs. no) and time to diagnosis of PM after primary tumor resection (within 1 year vs. after more than 1 year). DFS OS

  19. PRODİGE 7 • multicenter randomized study involving patients with isolated PC, between 2008 - 2014 • To be included in the analysis, patients were required to achieve macroscopically complete surgical resection (R0/R1) or resection with ≤1 mm residual tumor tissue (R2). • all groups received chemo for 6 months • median follow up of 63.8 months, median overall survival – the primary endpoint of the study – was “completely comparable” at 41.7 and 41.2 months, respectively, in 133 patients randomized to receive HIPEC with oxaliplatin after cytoreductive surgery and 132 randomized to the cytoreductive surgery–Median overall relapse-free survival was 13.1 and 11.1 months in the groups, respectively • complete resection rate over 90 percent • The postoperative mortality rate was 1.5% at 30 days in both groups • the 60-day complication rate was nearly double in the HIPEC group vs. the no-HIPEC group (24.1% vs. 13.6%). • Conclusion: colorectal cancer patients with a isolated peritoneal carcinomatosis should therefore be considered for surgery if they qualify the criteria for CRC

  20. the rate of peritoneal relapse %33 at both study arms median OS rate at3 years %80 and %79

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