Comment on “Apical Node Involvement Does Not Influence Prognosis After Potentially Curative Resection for Stage III Colorectal Cancer, A Competing Risks Analysis”

Abstract Adjuvant chemotherapy is the current standard treatment for stage III colorectal cancer after curative resection. However, the prognosis of stage III colorectal cancer is still poor even after curative resection and adjuvant chemotherapy. Several observational studies suggested that the anti-tumor effect of aspirin. Therefore, we planned a randomized double-blind placebo-controlled phase III trial, which commenced in Japan in March 2018, to confirm the superiority of aspirin over placebo added to adjuvant chemotherapy in terms of disease-free survival (DFS) for stage III colorectal cancer patients after curative resection. A total of 880 patients will be accrued from 20 Japanese institutions within 3 years. The primary endpoint is DFS and the secondary endpoints are overall survival, relapse-free survival, relative dose intensity, adverse events, and serious adverse events. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031180009 (https://jrct.niph.go.jp/detail/589).

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Plasma Prokineticin 1, a prognostic biomarker in colorectal cancer patients with curative resection: a retrospective cohort study

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02421-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Noriyuki Tagai ◽

Takanori Goi ◽

Michiaki Shimada ◽

Hidetaka Kurebayashi

Keyword(s):

Colorectal Cancer ◽

Survival Rate ◽

Cancer Patients ◽

Curative Resection ◽

Angiogenic Factor ◽

Stage Iii ◽

Primary Cancer ◽

Colorectal Cancer Patients ◽

Cancer Lesion ◽

Related Survival

Abstract Background Prokineticin 1 (PROK1) was reported as an angiogenic factor, which is associated with tumor progression, cell invasion, and metastasis in colorectal cancer. Although the association between PROK1 expression in primary cancer lesion and patient prognosis was reported, it is unclear whether plasma PROK1 concentration may be a predictive factor in colorectal cancer patients. This study investigated the association between PROK1 concentration in plasma and prognosis in colorectal cancer patients. Methods We measured preoperative PROK1 plasma levels using ELISA method, while PROK1 expression in primary cancer lesion was evaluated using immunohistochemistry (IHC). The association between plasma PROK1 levels and cancer-related survival rate (CRS) was evaluated. Additionally, we examined whether simultaneous PROK1 expression in both primary cancer lesions and plasma was correlated with CRS. The cancer-related survival rate was calculated using the Kaplan-Meier method, and survival estimates were compared using the log-rank test. Results We have gathered eligible 130 CRC patients retrospectively. Out of 130 patients, 61 (46.9%) were positive on IHC in primary cancer, and 69 (53.1%) were negative, while 43 (33.1%) had high-value PROK1 in plasma. Out of these 43, 30 (25.4%) also had concomitant higher IHC expression in primary cancer. The plasma PROK1 levels tended to increase with advancing stages. The plasma PROK1-positive group had a lower 5-year CRS than the negative group (63.6% vs. 88.2%; P = 0.006). Additionally, simultaneous PROK1 expression was associated with a more significant decrease of 5-year CRS than both negative groups in all stages (76.2% vs. 92.5%; P = 0.003) and stage III (59.3% vs. 84.5%; P = 0.047). Multivariate analysis showed simultaneous PROK1 expression was independently associated with worse CRS (HR, 1.97; 95% CI 1.20‑3.24, P < 0.01). Conclusion PROK1 expression in preoperative plasma reflects poor prognosis in patients undergoing curative resection for colorectal cancer. The plasma PROK1 level may be a potential predictive marker, especially in stage III colorectal cancer patients.

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Competing risks analysis of the association between perioperative blood transfusion and long‐term outcomes after resection of colorectal cancer

Colorectal Disease ◽

10.1111/codi.14970 ◽

2020 ◽

Vol 22 (8) ◽

pp. 871-884

Author(s):

O. F. Dent ◽

J. E. Ripley ◽

C. Chan ◽

M. J. F. X. Rickard ◽

A. Keshava ◽

...

Keyword(s):

Colorectal Cancer ◽

Blood Transfusion ◽

Competing Risks ◽

Long Term Outcomes ◽

Competing Risks Analysis ◽

Perioperative Blood Transfusion

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Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer

Annals of Oncology ◽

10.1093/annonc/mdy151.201 ◽

2018 ◽

Vol 29 ◽

pp. v56

Author(s):

K. Spring ◽

J. Toh ◽

P. Chapuis ◽

L. Bokey ◽

C. Chan ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor ◽

Microsatellite Instability ◽

Competing Risks ◽

Competing Risks Analysis

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Multicenter trial for assessing cytokine promoter gene polymorphism as a predictive parameter of PSK responder for curatively resected stage II or III colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.619 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 619-619

Author(s):

Shigefumi Yoshino ◽

Furuya Takumi ◽

Koichiro Sakata ◽

Ryoichi Shimizu ◽

Naoko Okayama ◽

...

Keyword(s):

Colorectal Cancer ◽

Curative Resection ◽

Cytokine Production ◽

Prospective Trial ◽

Disease Recurrence ◽

Multicenter Trial ◽

Stage Ii ◽

Stage Iii ◽

Tnf Α ◽

Promoter Gene

619 Background: Polysaccharide-K (PSK), a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor, is an immunomodulator widely used in colorectal cancer in Japan. PSK has immunological actions including enhancement or inhibition of cytokine production. It has been reported that levels of cytokine production are influenced by polymorphisms in the promoters of cytokine genes. We hypothesized that cytokine promoter gene polymorphisms may be responsible for genetic susceptibilities to immunological effect of PSK. Methods: This is a multicenter prospective trial. One hundred and ten patients with stage II or III colorectal cancer were enrolled. All patients received adjuvant immnochemotherapy after curative resection using UFT (stage II) or UFT/LV (stage III) combined with PSK (3.0 g/day, p.o.) for 1 year. Post-operative survey of recurrence was followed with CT scan at 6-month intervals during the first 2 years after surgery and at 1-year intervals thereafter until 5 year after surgery. DNA was extracted from peripheral blood cells in all patients. The following polymorphisms of the patients were genotyped: TNF-α-1031T/C, IL-1ß-511C/T, IL-6-634C/G, IL-10-819T/C. Results: Twenty (6 in stage II, 14 in stage III) out of 110 patients showed recurrence after more than 5 years survey. Fifteen out of 74 patients with TNF-α-1031 TT genotype and 5 out of 36 with TNF-α-1031 CC or CT showed disease recurrence. Five out of 39 patients with IL-1ß-511 CC and 15 out of 71 with IL-1ß-511 CT or TT showed disease recurrence. Eleven out of 61 patients with IL-6-634 CC and 9 out of 49 with IL-6-634 CG or GG showed disease recurrence. No association between genotype frequency and disease recurrence was observed for TNF-α, IL-1ß, IL-6. Fifteen out of 61 patients with IL-10-819 CC or CT genotype showed disease recurrence, whereas only 5 out of 49 with IL-10-819 TT showed tumor recurrence (p=0.052). Especially, significant association with disease recurrence was found in stage III patients (12/30 vs 2/17, p=0.042). Conclusions: It is suggested that colorectal cancer patients with IL-10-819 TT genotype could be PSK responder after curative resection.

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Efficacy of aspirin for stage III colorectal cancer: A randomized double-blind placebo-controlled trial (JCOG1503C, EPISODE-III trial).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps3623 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS3623-TPS3623

Author(s):

Atsuo Takashima ◽

Kenichi Miyamoto ◽

Yuya Sato ◽

Natsuko Okita ◽

Manabu Shiozawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Events ◽

Curative Resection ◽

Phase Iii ◽

Stage Iii ◽

Double Blind ◽

Free Survival ◽

Double Blind Placebo ◽

Aspirin Group

TPS3623 Background: Adjuvant chemotherapy is the current standard treatment for stage III colorectal cancer after curative resection. However, the prognosis of stage III colorectal cancer is still poor even after curative resection and adjuvant chemotherapy. Recently, several observational studies suggested the anti-tumor effect of aspirin for advanced colorectal cancer. The main mechanism of the anti-tumor effect by aspirin may be to suppress cyclooxygenase activity in the arachidonic acid cascade and to inhibit the production of prostaglandins involved in tumor growth. So far, aspirin showed a prolongation of survival for colorectal cancer in several retrospective studies. However, in these studies, aspirin was given not to be evaluated the effect on prognosis of colorectal cancer in adjuvant setting but to prevent cardiovascular event. In addition, baseline patient characteristics were imbalanced between aspirin group and non-aspirin group and both dosage amount and dosing period of aspirin were different among patients. Methods: We planned a randomized double-blind placebo-controlled phase III trial commenced in Japan in March 2018 to confirm the superiority of aspirin in terms of disease-free survival (DFS) over placebo for stage III colorectal cancer patients after curative resection. Patients receive aspirin (100 mg/day) or placebo for 3 years with the standard adjuvant chemotherapy of mFOLFOX6, CAPOX or capecitabine until relapse or unacceptable toxicities. The primary endpoint is DFS and the secondary endpoints are overall survival, relapse-free survival, relative dose intensity, adverse events, and serious adverse events. We assumed the 3-year DFS of aspirin arm as 74% based on two previous trials conducted by JCOG and expected a 6% increase in the 3-year DFS with aspirin adding to standard adjuvant chemotherapy after curative surgery. A total of 880 patients will be accrued from 20 Japanese institutions within 3 years, and 47 patients were enrolled as of Jan 31, 2019. Both aspirin and placebo are provided by Bayer Yakuhin Ltd. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031180009 (https://jrct.niph.go.jp/detail/589). Clinical trial information: jRCTs031180009.

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