Should We Be Doing Cytoreductive Surgery with HIPEC for Signet Ring Cell Appendiceal Adenocarcinoma? A Study from the US HIPEC Collaborative

Levinsky, Nick C.; Morris, Mackenzie C.; Wima, Koffi; Sussman, Jeffrey J.; Ahmad, Syed A.; Cloyd, Jordan M.; Kimbrough, Charles W.; Fournier, Keith F.; Lee, Andrew; Dineen, Seán; Dessureault, Sophie; Veerapong, Jula; Baumgartner, Joel M.; Clarke, Callisia N.; Zaidi, Mohammad Y.; Staley, Charles A.; Maithel, Shishir K.; Leiting, Jennifer L.; Grotz, Travis E.; Lambert, Laura; Hendrix, Ryan J.; Ronnekleiv‐Kelly, Sean M.; Pokrzywa, Courtney; Raoof, Mustafa; Eng, Oliver S.; Johnston, Fabian M.; Greer, Jonathan B.; Patel, Sameer H.

doi:10.1007/s11605-019-04336-4

Cited by 28 publications

(24 citation statements)

References 23 publications

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“…Well-established predictors of long-term survival following CRS/HIPEC include tumor burden measured by peritoneal cancer index (PCI), optimal cytoreduction, and absence/low percentage of goblet or signet ring cell histology. [8][9][10][11] While these prognostic tools are useful, they have limited utility before CRS/HIPEC since they are most accurately determined intraoperatively or postoperatively. Currently, there is a need for reliable preoperative tools in APM that can predict the benefit of surgical management before CRS/HIPEC surgical intervention.…”

Section: Introductionmentioning

confidence: 99%

Exploring the prognostic and therapeutic utility of expanded mutation profiling in appendix peritoneal metastasis managed with CRS/HIPEC

Zhang

Plambeck

Craig

et al. 2021

Journal of Surgical Oncology

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Introduction: Interrogation of cancers with next-generation sequencing (NGS) mutation panels has become widely utilized, identifying prognostic and actionable mutations. This study explored the value of expanded mutation analysis in appendix peritoneal metastases (APM). Methods: Forty-eight APM patients treated 2013-2018 were retrospectively collected from a registry. Fifty-gene NGS analysis was performed in CLIA approved lab to obtain mutation profiles. All patients underwent cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C. Peritoneal cancer index (PCI), optimal CRS, survival (overall survival [OS] and progression-free survival [PFS]) data were collected. Survival analyses were performed on all APM, high-grade (HG), and low grade (LG) subsets, evaluating the impact of specific mutations on the outcome.Results: Eighty-three percent of APM had a mutation identified. KRAS was most frequent, 65% (88% LG 42% HG) with GNAS identified in 92% of LG-APM. SMAD4 and/or TP53 mutations occurred in 25% of APM with observed decreased OS (46 vs. 81 months p = .0029); worse in HG-APM (26 vs. 49 months p = .0451).SMAD4 was associated with the most significant reduction in PFS in APM (p = .0085). Actionable mutations were identified in 73% of APM patients.Conclusions: Most frequent mutations were KRAS, TP53, and SMAD4, and actionable mutation detection was common. SMAD4 and TP53 were associated with decreased OS. NGS mutation profiling has potential utility in APM.

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Section: Introductionmentioning

confidence: 99%

Exploring the prognostic and therapeutic utility of expanded mutation profiling in appendix peritoneal metastasis managed with CRS/HIPEC

Zhang

Plambeck

Craig

et al. 2021

Journal of Surgical Oncology

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“…Munoz-Zuluaga et al 33 reported median OS of 90 months for patients with high-grade mucinous carcinoma peritonei versus 26.4 months for those with high-grade Mucinous Carcinoma Peritonei with Signet Ring Cells (MCP-S), with a HR of 2.9 ( P < 0.001). Multicentre studies 38 , 39 based on large databases obtained similar results: 16.2 (ref. 38) and 32 (ref.…”

Section: Discussionmentioning

confidence: 55%

Defining stage in mucinous tumours of the appendix with peritoneal dissemination: the importance of grading terminology: systematic review

et al. 2021

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Background Mucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but no universally accepted histological grading has been established. The aim of this systematic review was to provide historical insight to understand current grading classifications, basic histopathological features of each category, and to define which classification correlates best with prognosis. Methods MEDLINE and the Cochrane Library were searched for studies that reported survival across different pathological grades in patients with mucinous neoplasm of the appendix with PD treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PRISMA guidelines were followed. Results Thirty-eight studies were included. Ronnett’s classification was the most common (9 studies). Classifications proposed by the Peritoneal Surface Oncology Group International (PSOGI) (6 studies) and the seventh or eighth edition of the AJCC (7 studies) are gaining in popularity. Nine studies supported a two-tier, 12 a three-tier, and two a four-tier classification system. Three studies demonstrated that acellular mucin had a better prognosis than low-grade pseudomyxoma peritonei in the PSOGI classification or M1bG1 in the eighth edition of the AJCC classification. Four studies demonstrated that the presence of signet ring cells was associated with a worse outcome than high-grade pseudomyxoma peritonei in the PSOGI classification and M1bG2 in the eighth edition of the AJCC. Conclusion There is a great need for a common language in describing mucinous neoplasms of the appendix with PD. Evolution in terminology as a result of pathological insight turns the four-tiered PSOGI classification system into a coherent classification option.

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“…As such, NAC may be better reserved for high‐risk situations, such as aggressive tumor biology or high PCI with low chance of complete cytoreduction. In a previous study from our collaborative, the use of NAC compared with SF was not associated with improved outcomes among high‐risk appendiceal cancer patients with SRC 33 . Future research should highlight the diversity of appendiceal cancers to design personalized treatment approaches tailored to individual clinical and molecular features.…”

Section: Discussionmentioning

confidence: 78%

“…While current guidelines recommend using chemotherapy regimens commonly used for colon cancer, appendiceal cancers have different genetic compositions, including greater KRAS and GNAS mutations and fewer phosphatidylinositol 3‐kinase‐AKT and TP53 mutations 30,31 . Further, appendiceal tumors have great molecular and histopathologic heterogeneity with unique gene expressions, protein regulation, tumor behavior, treatment regimens, and prognostic implications 32,33 . As such, NAC may be better reserved for high‐risk situations, such as aggressive tumor biology or high PCI with low chance of complete cytoreduction.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of neoadjuvant chemotherapy before CRS‐HIPEC for patients with appendiceal cancer

Chen

Beal

Hays

et al. 2020

Journal of Surgical Oncology

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Background Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is indicated for patients with peritoneal dissemination of appendiceal cancer. The role of neoadjuvant chemotherapy (NAC) before CRS‐HIPEC remains controversial. Methods A retrospective review of adult patients who underwent CRS ± HIPEC for metastatic appendiceal cancer between 2000‐2017 was performed. Patients who received NAC followed by surgery were compared with those who underwent surgery first (SF) with and without 1:1 propensity score matching (PSM). Results Among 803 patients with appendiceal cancer who underwent CRS ± HIPEC, 225 (28%) received NAC, and 578 (72%) underwent SF. After PSM (n = 186), median overall survival (OS) did not differ (NAC: 40 vs SF: 56 months; P = .210) but recurrence‐free survival (RFS) was worse among patients who received NAC (14 vs 22 months; P = .007). NAC was independently associated with worse OS (hazards ratio [HR], 1.81; 95% confidence interval [CI], 1.03‐3.18) and RFS (HR, 1.93; 95% CI, 1.25‐2.99). Conclusion In this multi‐institutional retrospective analysis of patients with peritoneal dissemination from appendiceal cancer, the use of NAC before CRS‐HIPEC was associated with worse OS and RFS even after PSM and multivariable regression. Immediate surgery should be considered for patients with disease amenable to complete cytoreduction.

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Should We Be Doing Cytoreductive Surgery with HIPEC for Signet Ring Cell Appendiceal Adenocarcinoma? A Study from the US HIPEC Collaborative

Cited by 28 publications

References 23 publications

Exploring the prognostic and therapeutic utility of expanded mutation profiling in appendix peritoneal metastasis managed with CRS/HIPEC

Exploring the prognostic and therapeutic utility of expanded mutation profiling in appendix peritoneal metastasis managed with CRS/HIPEC

Defining stage in mucinous tumours of the appendix with peritoneal dissemination: the importance of grading terminology: systematic review

Outcomes of neoadjuvant chemotherapy before CRS‐HIPEC for patients with appendiceal cancer

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