Primary Tumor Sidedness is Predictive of Survival in Colon Cancer Patients Treated with Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy: A US HIPEC Collaborative Study

Kotha, Nikhil V.; Baumgartner, Joel M.; Veerapong, Jula; Cloyd, Jordan M.; Ahmed, Ahmed; Grotz, Travis E.; Leiting, Jennifer L.; Fournier, Keith F.; Lee, Andrew; Dineen, Seán; Dessureault, Sophie; Clarke, Callisia N.; Mogal, Harveshp; Zaidi, Mohammad Y.; Russell, Maria C.; Patel, Sameer H.; Sussman, Jeffrey J.; Dhar, Vikrom K.; Lambert, Laura; Hendrix, Ryan J.; Abbott, Daniel E.; Pokrzywa, Courtney; Lafaro, Kelly J.; Lee, Byrne; Greer, Jonathan B.; Fackche, Nadege; Lowy, Andrew M.; Kelly, Kaitlyn J.

doi:10.1245/s10434-019-07373-0

Cited by 16 publications

(10 citation statements)

References 17 publications

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“…[23][24][25][26][27][28][29][30] Analogously, primary tumor sidedness correlated with prognosis in two American series but not in one French series. [31][32][33][34] Our findings strongly suggest that both BRAF mutations and right-sided primary have to be taken into consideration, not only as prognostic factors in patients undergoing curative-intent treatment but also as stratification factors in future clinical trials.…”

Section: Discussionmentioning

confidence: 74%

Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metastases

et al. 2020

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Background. Selecting patients with colorectal cancer peritoneal metastases (CRC-PMs) for surgery is still a concern. Biological features have the potential to improve prognostic stratification, but their significance in this clinical setting is still unclear. We assessed the prognostic impact of primary side and KRAS/NRAS/BRAF/PIK3CA mutations in patients treated with either cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) or CRS alone. Methods. We reviewed a prospective database of 152 CRC-PM patients selected to undergo perioperative systemic chemotherapy and CRS with or without HIPEC. Extensive mutational analysis of KRAS, NRAS, BRAF, and PIK3CA was performed by polymerase chain reaction (PCR). In 68 patients, Ion Torrent next-generation sequencing technology was used to characterize the hotspot regions of 50 genes. Results. The primary tumor was right-sided in 61 patients (40.1%) and left-sided in 91 patients (59.9%). Right-sided primaries were associated with mutated KRAS (p = 0.01) and normal carcinoembryonic antigen (CEA; p = 0.03). KRAS was mutated in 71/152 patients (46.7%), NRAS in 7/152 patients (4.6%), BRAF in 10/152 patients (6.6%), PIK3CA in 17/78 patients (25.0%), TP53 in 37/68 patients (54.4%), APC in 25/68 patients (36.7%), SMAD4 in 13/68 patients (19.1%), and FBXW7 in 5/68 patients (7.4%). Median follow-up was 54.9 months and median survival from PM diagnosis was 45.1 months. The right-sided primary (hazard ratio [HR] 1.62, 95% confidence interval [CI] 0.43-0.89; p = 0.011), BRAF mutations (HR 2.21, 95% CI 1.05-4.63; p = 0.038), and Peritoneal Cancer Index (HR 1.47, 95% CI 1.03-2.10; p = 0.036) independently correlated with poorer survival, while APC mutations univariately correlated with better survival (p = 0.03). Conclusions. BRAF mutations and right-sided primary are adverse prognostic factors that may be used to optimize therapeutic strategies. APC may be involved in CRC-PM development and progression. Peritoneal metastases (PMs) from colorectal cancer (CRC) are still a significant healthcare problem and an important cause of disease-related death following liver and lung metastases. 1,2 Because of the current limitation of imaging in detecting small-volume peritoneal disease, CRC-PMs are frequently diagnosed at an advanced stage. 3

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Section: Discussionmentioning

confidence: 74%

Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metastases

et al. 2020

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“…On the other hand, other retrospective studies with a smaller patient population reported worse prognosis of RCC after CRS plus HIPEC. A retrospective cohort study from the US in 2019 with 336 patients with peritoneal metastases from CRC reported a significantly shorter OS for RCC compared to LCC (median 30 months versus 45.4 months, P = 0.028), and RCC was an independent predictor of worse DFS and OS on multivariate analysis (47). A retrospective study from the US in 2019 with 115 patients with peritoneal metastases from CRC who underwent CRS plus HIPEC showed the same result of significantly inferior DFS (HR = 2.27, 95% CI 1.09-4.76, P = 0.029) and OS (HR = 2.57, 95% CI 1.13-5.84, P = 0.021) in RCC compared to LCC (48).…”

Section: Ptl and Surgical Outcome In Peritoneal Metastases From Crcmentioning

confidence: 99%

The primary tumor location in colorectal cancer: A focused review on its impact on surgical management

Nagai

Kiyomatsu

Gohda

et al. 2021

GHM

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The primary tumor location (PTL) has attracted increasing attention in recent years for colorectal cancer (CRC) patients. Although the underlying mechanisms for differences caused by PTL remain still unclear, right-sided colon (RCC) and left-sided colon (LCC) are now considered as distinct entities because of their different molecular profile and clinical response to surgery and chemotherapy. In this article, we review the influence of PTL particularly on surgical management of primary and metastatic CRC settings. For nonmetastatic CRC, RCC could be a slightly superior prognostic factor after curative resection in stage I-II CRC, while RCC could be an inferior prognostic factor in stage III CRC with worse survival after recurrence, suggesting the oncological aggressiveness of recurrent RCC. For metastatic CRC, RCC could be a predictor of worse survival after hepatectomy of liver metastases from CRC with aggressive recurrence pattern and lower chance of re-resection. In lung metastases from CRC, the role of PTL still remains uncertain because of the limited number of studies. As to the impact of PTL on survival outcome after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal metastases from CRC, a discrepancy exists among studies and further investigation will be needed. The very simple clinical factor of PTL could provide important information for the prediction of the survival outcome after surgery in CRC. Further clinical and basic research will facilitate the clinical application of PTL in a more specified and personalized manner.

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“…[20][21][22][23][24] However, little is known about the role of primary tumor location in patients with PM, and patients with PM undergoing CRS-HIPEC. 25,26 The aim of this study was to assess the impact of the primary tumor location in all patients with PM of colon cancer on a population-based level.…”

Section: Introductionmentioning

confidence: 99%

A population‐based study on the prognostic impact of primary tumor sidedness in patients with peritoneal metastases from colon cancer

et al. 2020

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Primary Tumor Sidedness is Predictive of Survival in Colon Cancer Patients Treated with Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy: A US HIPEC Collaborative Study

Cited by 16 publications

References 17 publications

Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metastases

Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metastases

The primary tumor location in colorectal cancer: A focused review on its impact on surgical management

A population‐based study on the prognostic impact of primary tumor sidedness in patients with peritoneal metastases from colon cancer

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