A Systematic Review of the Cyclooxygenase-2 (COX-2) Expression in Rectal Cancer Patients Treated with Preoperative Radiotherapy or Radiochemotherapy
Abstract
1. Introduction
2. Guidelines for the Colorectal Cancer Treatment
3. Patients and Methods
3.1. Assessment of Methodological Quality
3.2. Outcome Measures
4. Results
Ref. | Study | Year | Country | Study Design | Analyzed Samples | Total Number of Patients | Treatment Strategy | COX-2 Expression Measurement |
---|---|---|---|---|---|---|---|---|
[76] | Pachkoria et al. | 2005 | Sweden | Prospective randomized trial of preoperative radiotherapy | Samples: - distal normal mucosa (n = 28) - adjacent normal mucosa (n = 108) - primary cancer (n = 138) - lymph node metastasis (n = 30) - biopsy (n = 85) | 75 (138—total 75—RTH + surgery 63—surgery alone) | Short-term radiation (radiotherapy 5 × 5 Gy to total dose of 25 Gy) followed by surgery | IHC Western Blott |
[75] | de Heer et al. | 2007 | Netherlands | Retrospective multicenter randomized clinical trial | Archival tumor material | 1038 (924—RTH + surgery 927—surgery alone) | Short-term radiation (radiotherapy 5 × 5 Gy to total dose of 25 Gy) followed by TME surgery | IHC |
[77] | Giralt et al. | 2007 | Spain | Retrospective study | Preirridation diagnostic biopsies | 34 (81—total 34—radiotherapy 47—radiochemotherapy) | Long-term radiation (radiotherapy: conventional fractionation 1.8 Gy/day to a total dose of 45 Gy; additionally, boost to 50.4 Gy in 8 cases) followed by TME surgery | IHC |
[78] | Bouzourene et al. | 2008 | Switzerland | Retrospective multicenter cohort study | Pretherapeutic tumor biopsies (n = 26) and surgical specimens (n = 88) | 104 (88 specimens 26 pretherapeutic biopsies) | Hyperfractionated radiotherapy (HART) followed by surgery (APR or low anterior resection) | IHC |
[79] | Wen et al. | 2020 | Sweden | Randomized clinical trial | Surgical samples | 219 (127—RTH + surgery 92—surgery alone) | Radiotherapy (25 Gy in 5 fractions during a median of 6 days (range, 5–12)) followed by surgery | IHC |
Ref. | Study | Year | Country | Study Design | Analyzed Samples | Total Number of Patients | Treatment Strategy | COX-2 Expression Measurement |
---|---|---|---|---|---|---|---|---|
[80] | Yeoh et al. | 2005 | Australia | Retrospective study | Samples obtained from patiets treated with preoperative radiotherapy | 28 |
| IHC |
[81] | Smith et al. | 2006 | Ireland | Retrospective and prospective study | Pretreatment specimens | 49 |
| IHC |
[77] | Giralt et al. | 2007 | Spain | Retrospective study | Preirridation diagnostic biopsies | 47 (81—total 34—radiotherapy 47—radiochemotherapy) |
| IHC |
[82] | Min et al. | 2008 | Korea | Prospective study | Pretreatment biopsy specimens | 30 |
| IHC |
[83] | Edden et al. | 2010 | USA | Retrospective study | Preatrement and surgical specimens | 152 |
| IHC |
[84] | Peng et al. | 2016 | China | Retrospective study | Pretreatment biopsies | 82 |
| IHC |
[85] | Jafarian et al. | 2016 | Iran | Retrospective cohort study | Pretreatment specimens | 55 |
| |
[86] | Sole et al. | 2016 | Spain | Prospective study | Pretreatment endoscopic biopsy and surgical specimens | 38 |
| IHC |
[87] | Shinto et al. | 2020 | Japan | Retrospective and prospective study | Pretreatment biopsies | 144 (95 in the retrospective study 49 in the prospective study) | In the retrospective study:
In the prospective study:
| IHC |
Ref. | Study | Total Number of Patients | Male | Female | Median Age | Age Range |
---|---|---|---|---|---|---|
[75] | de Heer et al. | 1038 (924—RTH + surgery, 927—surgery alone) | 573 | 324 | 65 | 26–88 |
[78] | Bouzourene et al. | 104 | ND | ND | 63 | 28–85 |
[76] | Pachkoria et al. | 75 | 40 | 23 | 67 | 36–85 |
[81] | Smith et al. | 49 | 31 | 18 | ND | ND |
[77] | Giralt et al. | 81 | 54 | 27 | 64.8 | 34–92 |
[83] | Edden et al. | 152 | 77 | 75 | 58.1 | 31–82 |
[80] | Yeoh et al. | 28 | 21 | 7 | ND | ND |
[82] | Min et al. | 30 | 26 | 4 | 48.0 | 31–69 |
[87] | Shinto et al. | 144 | 100 | 44 | 61,8 | ND |
[79] | Wen et al. | 219 (127—RTH+ surgery, 92—surgery alone) | ND | ND | ND | ND |
[84] | Peng et al. | 82 | 57 | 25 | 57 | 15–75 |
[86] | Sole et al. | 38 | 27 | 11 | 62 | 43–77 |
[85] | Jafarian et al. | 55 | 27 | 18 | 52 | 18–87 |
5. Discussion
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Region | Preoperative Therapy Description |
---|---|
Europe | A short-course radiotherapy—1 week of radiation without chemotherapy (5 Gy × 5) followed by surgery the next week (TME < 10 days from the first radiation fraction. |
United States and Canada | A long-course chemoradiotherapy—45–50.4 Gy, 1.8–2 Gy/fraction without or with 5-Fluorouracil (5-FU; bolus injections with leucovorin at 6–10 times during the radiation or continuous infusion or oral capecitabine), followed by radical surgery 6–8 weeks later |
Ref. | Study | TNM Stage | Preoperative Treatment | Type of Resection | Effect of Preoperative Treatment (%) | |||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 | I | II | III | IV | pT1 | pT2 | pT3 | pT4 | pN0 | pN1-2 | M | - | Hartmann | Rectal Amputation/Low Anterior | Abdominoperineal Resection | Unknown | Complete Tumor Regression (pCR) | Partial Regression | Absence of Tumor Regression | Overall Survival—OS | ||
[75] | de Heer et al. | 11 | 265 | 252 | 300 | 61 | RTH | 50 | 579 | 251 | 1 | 82% (at 24 months) | ||||||||||
[78] | Bouzourene et al. | 2 | 21 | 66 | 14 | RTH | 50 | 51 | 2 | 0% | 79% | 20% | Median—53 months | |||||||||
[76] | Pachkoria et al. | RTH | 25 | 38 | No data | |||||||||||||||||
[81] | Smith et al. | 4 | 7 | 26 | 6 | 32 | 16 | CRTH | 39 | 10 | 10% (pCR) + 33% (near pCR) | 22% | 35% | No data | ||||||||
[77] | Giralt et al. | 6 | 62 | 13 | 48 | 27 | CRTH | 48 | 33 | Median—53 months | ||||||||||||
[83] | Edden et al. | CRTH | 103 | 46 | 24.5% (pCR) + 15.1% (near pCR) | 39.40% | 21% | No data | ||||||||||||||
[80] | Yeoh et al. | RTH | No data | |||||||||||||||||||
[82] | Min et al. | CRTH | 1 | 16 | 16,70% | 50% | 26.70% | No data | ||||||||||||||
[87] | Shinto et al. | 35 | 98 | 78 | 66 | CRTH | ||||||||||||||||
[79] | Wen et al. | RTH | ||||||||||||||||||||
[84] | Peng et al. | Neo-CRTH | 28% | |||||||||||||||||||
[86] | Sole et al. | Neo-CRTH | ||||||||||||||||||||
[85] | Jafarian et al. | Neo-CRTH |
Ref. | Study | COX-2 Expression Level | |
---|---|---|---|
[75] | De Heer et al. (2015) | Irradiated Specimens: | |
Absent | 0.4% | ||
Weak | 12.4% | ||
Moderate | 59.2% | ||
Strong | 28% | ||
[78] | Bouzourene et al. (2008) | Non-irradiated specimens: | |
Absent | 50% | ||
Weak | 15.4% | ||
Moderate | 15.4% | ||
Strong | 19.2% | ||
Irradiated specimens: | |||
Absent | 11% | ||
Weak | 44% | ||
Moderate | 28% | ||
Strong | 17% | ||
[76] | Pachkoria et al. (2005) | Non-irradiated specimens: | |
Weak | 22% | ||
Strong | 51% | ||
Irradiated specimens: | |||
Weak | 18% | ||
Strong | 53% | ||
[82] | Min et al. (2008) | ND | |
[81] | Smith et al. (2006) | COX-2 overexpression | Tumor regression grade |
0% | Complete | ||
10% | Moderate | ||
8% | Poor | ||
20% | Absent | ||
[77] | Giralt et al. (2007) | Irradiated specimens: | |
Absent | 48.6% | ||
Present | 51.4% | ||
[83] | Edden et al. (2010) | Pretreatment biopsies: | |
Weak | 32.9% | ||
Moderate | 34.9% | ||
Strong | 32.2% | ||
[80] | Yeoh et al. (2005) | ND | |
[87] | Shinto et al. (2020) | Irradiated specimens: | |
Retrospective cohort: | |||
Low | 21.1% | ||
High | 78.9% | ||
Prospective cohort: | |||
Low | 30.6% | ||
High | 69.4% | ||
[79] | Wen et al. (2020) | Non-irradiated specimens: | |
Absent | 67.7% | ||
Present | 32.3% | ||
Irradiated specimens: | |||
Absent | 52.2% | ||
Present | 47.8% | ||
[84] | Peng et al. (2016) | Irradiated specimens: | |
Low | 58.5% | ||
High | 41.5% | ||
[86] | Sole et al. (2016) | ND | |
[85] | Jafarian et al. (2016) | COX-2 expression was observed in 95.6% of cases with various extent and intensities. |
Ref. | Study | COX-2 Expression versus Treatment Effects |
COX-2 Expression versus Tumor Prognosis:
|
---|---|---|---|
[75] | De Heer et al. (2015) | High COX-2 expression is an independent poor prognostic factor for disease-free and overall survival in irradiated rectal cancer patients |
|
[78] | Bouzourene et al. (2008) | (1) Inconclusive data (2) COX-2 is overexpressed in the majority of rectal cancer treated with radiotherapy and it plays a role in local relapse |
|
[76] | Pachkoria et al. (2005) | COX-2 expression is an early event involved in rectal cancer development |
|
[82] | Min et al. (2008) | COX-2 overexpression is a predictor of poor tumor regression |
|
[81] | Smith et al. (2006) | COX-2 overexpression significantly associated with poor response to RCT |
|
[77] | Giralt et al. (2007) | Value of COX-2 as a biomarker is controversial |
|
[83] | Edden et al. (2010) | Evaluation of pretreatment COX-2 expression may predict tumor response to neoadjuvant rectal cancer therapy |
|
[80] | Yeoh et al. (2005) |
| |
[87] | Shinto et al. (2020) | The expression of COX-2 was significant predictor of tumour response to preoperative RCT. However, expression levels of COX-2 showed no statistical significance. |
|
[79] | Wen et al. (2020) | The expression of COX-2 had diagnostic value for rectal cancer patients preoperatively (the expression in biopsy sample was higher than that in surgical samples including distance normal mucosa (histologically free from tumor cells), p < 0.05) |
|
[84] | Peng et al. (2016) | Low expression of COX-2 was associated with achieving the highest pCR rate, which was significantly higher than those with high expression of COX-2. |
|
[86] | Sole et al. (2016) | No significant differences in COX-2 expression level. |
|
[85] | Jafarian et al. (2016) | The mean COX-2 immunoreactivity extent in pre-RCT samples was significantly higher in cases with post-RCT biopsies showing >50% necrosis than those with <50% necrosis (p < 0.01) |
|
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Berbecka, M.; Forma, A.; Baj, J.; Furtak-Niczyporuk, M.; Maciejewski, R.; Sitarz, R. A Systematic Review of the Cyclooxygenase-2 (COX-2) Expression in Rectal Cancer Patients Treated with Preoperative Radiotherapy or Radiochemotherapy. J. Clin. Med. 2021, 10, 4443. https://doi.org/10.3390/jcm10194443
Berbecka M, Forma A, Baj J, Furtak-Niczyporuk M, Maciejewski R, Sitarz R. A Systematic Review of the Cyclooxygenase-2 (COX-2) Expression in Rectal Cancer Patients Treated with Preoperative Radiotherapy or Radiochemotherapy. Journal of Clinical Medicine. 2021; 10(19):4443. https://doi.org/10.3390/jcm10194443
Chicago/Turabian StyleBerbecka, Monika, Alicja Forma, Jacek Baj, Marzena Furtak-Niczyporuk, Ryszard Maciejewski, and Robert Sitarz. 2021. "A Systematic Review of the Cyclooxygenase-2 (COX-2) Expression in Rectal Cancer Patients Treated with Preoperative Radiotherapy or Radiochemotherapy" Journal of Clinical Medicine 10, no. 19: 4443. https://doi.org/10.3390/jcm10194443
APA StyleBerbecka, M., Forma, A., Baj, J., Furtak-Niczyporuk, M., Maciejewski, R., & Sitarz, R. (2021). A Systematic Review of the Cyclooxygenase-2 (COX-2) Expression in Rectal Cancer Patients Treated with Preoperative Radiotherapy or Radiochemotherapy. Journal of Clinical Medicine, 10(19), 4443. https://doi.org/10.3390/jcm10194443