Predictors of undergoing multivisceral resection, margin status and survival in Dutch patients with locally advanced colorectal cancer

Nes, Lindsey C. F. de; Heijden, J. Van Der; Verstegen, Moniek; Drager, Luuk D.; Tanis, Pieter J.; Verhoeven, Rob H.A.; Wilt, Johannes H. W. de

doi:10.1016/j.ejso.2021.11.004

Cited by 8 publications

(10 citation statements)

References 32 publications

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“…In our study, clinicopathological biomarkers showed consistent reliability in prognostic prediction before chemotherapy in patients with LACC [ 4 , 9 , 24 , 54 , 55 ]. On the other hand, the predictive value of molecular or serum biomarkers appeared to be more effective in certain tumor stage or treatment phases [ 17 , 49 , 51 , 85 , 88 , 91 , 92 , 94 , 95 ].…”

Section: Discussionmentioning

confidence: 78%

“…An observational study including 15,489 patients with stage IIB/C disease reported a median survival of 122.6 months for stage IIB/C and the retrieval of ≥12 LNs following adjuvant chemotherapy, 72.5 months for stage IIB/C and the retrieval of <12 LNs following adjuvant chemotherapy, and only 46.5 months for stage IIB/C without chemotherapy [ 54 ]. A Dutch study including 10,878 patients with LACC indicated that old age (≥70 year), incomplete resection margin, and nodal positivity status were significantly associated with poor survival [ 4 ]. The site of colon cancer development is another key prognostic factor for LACC ( Figure 2 ) [ 55 , 56 , 57 , 58 ].…”

Section: Role Of Biomarkers In Lacc Treatmentmentioning

confidence: 99%

“…Leijssen et al indicated that even in curative resection, a radial margin of <1 cm and LN involvement were independent predictors of poor DFS [ 24 ]. Furthermore, a Dutch study reported that multivisceral resection (MVR) was independently associated with less incomplete resection but not with survival [ 4 ]. Likewise, adjuvant chemotherapy in the regimen of oxaliplatin and fluoropyrimidine (FOLFOX or CAPOX) prevents recurrence by eradicating minimal residual disease and has been approved as a standard treatment for stage III colon cancer [ 21 ].…”

Section: Role Of Biomarkers In Lacc Treatmentmentioning

confidence: 99%

“…According to the World Health Organization Global Cancer Observatory report, more than 1.9 million new CRC cases occurred in 2020 worldwide, and among them, 1,148,515 were estimated to be diagnosed as having colon cancer [ 1 ]. Approximately 10–15% of patients with colon cancer are diagnosed late as having locally advanced colon cancer (LACC), which has poor prognosis [ 2 , 3 , 4 , 5 ]. LACC is defined as primary stage T4 colon cancer with direct invasion of surrounding organs or extensive regional lymph node (LN) involvement.…”

Section: Introductionmentioning

confidence: 99%

“…Risk factors, including cT4, cN+, and poor or undifferentiated pathology of LACC, significantly reduce the possibility of R0 resection [ 4 , 24 ]. Neoadjuvant chemotherapy can enhance tumor shrinkage, eradicate micrometastases, and prevent tumor cell shedding during surgery.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

Chuang

Tsai

Chen

et al. 2022

Cells

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Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC.

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Section: Discussionmentioning

confidence: 78%

Section: Role Of Biomarkers In Lacc Treatmentmentioning

confidence: 99%

Section: Role Of Biomarkers In Lacc Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

Chuang

Tsai

Chen

et al. 2022

Cells

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PD‐1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer

Pei,

He,

Duan

et al. 2024

Cancer Medicine

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BackgroundPatients with DNA mismatch repair‐proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti‐PD‐1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies.MethodsIn this pilot study, we administered six preoperative doses of each 2‐week cycle of the anti‐PD‐1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5‐FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics.ResultsBy the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow‐up was 24.7 months (IQR: 21.1–26.1). All patients underwent R0 surgical resection without treatment‐related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence‐free. Treatment‐related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10−8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non‐pCR tumors (p = 0.038 and p = 0.015, respectively).ConclusionsNeoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non‐pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD‐1 blockade‐enhanced targeted chemotherapy require further investigation.

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Narrative review of neoadjuvant therapy in patients with locally advanced colon cancer

Chuang,

Chen,

Wang

2024

The Kaohsiung J of Med Scie

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Colorectal cancer is a leading cause of cancer‐related morbidity and mortality worldwide, with more than 1.9 million new cases reported in 2020, and is associated with major survival challenges, particularly in patients with locally advanced colon cancer (LACC). LACC often involves T4 invasion or extensive nodal involvement and requires a multidisciplinary approach for management. Radical surgery followed by adjuvant chemotherapy remains the primary treatment strategy for LACC. However, achieving complete tumor resection (R0) is challenging because locally advanced colon tumors typically infiltrate adjacent organs or nodes. Advancements in LACC treatment have involved neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiotherapy (NACRT), and neoadjuvant immunotherapy (NAIT). Studies such as FOxTROT and PRODIGE 22 have demonstrated that NACT, particularly with FOLFOX or CAPOX, can lead to major tumor downstaging, improved survival rates, and increased R0 resection rates. Predictive biomarkers, such as mismatch repair (MMR) status and T stage, are crucial in identifying candidates who may benefit from NACT. NACRT has demonstrated promise in enhancing tumor regression, particularly in patients with rectal cancer, underscoring its potential for use with LACC. NAIT, particularly for deficient MMR tumors, has emerged as a novel approach, with studies such as NICHE‐2 and NICHE‐3 reporting excellent pathologic responses and pathologic complete responses. Integrating these therapies can enhance the surgical and survival outcomes of patients with LACC, highlighting the importance of personalized treatment strategies based on tumor characteristics and response to neoadjuvant interventions. This review discusses the evolving landscape of LACC management, focusing on optimizing treatment approaches for improved patient outcomes.

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Predictors of undergoing multivisceral resection, margin status and survival in Dutch patients with locally advanced colorectal cancer

Cited by 8 publications

References 32 publications

Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

PD‐1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer

Narrative review of neoadjuvant therapy in patients with locally advanced colon cancer

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