Association Between Pathological Complete Response and Tumor Location in Patients with Rectal Cancer After Neoadjuvant Chemoradiotherapy, a Prospective Cohort Study

AUTHORS

Kambiz Novin ORCID 1 , Mastane Saneii 1 , Reyhaneh Noori 1 , * , Mohadeseh Shahin 1 , Maede Berahman 2 , Soodabeh Hoveidamanesh 3

1 Department of Radiotherapy and Oncology, Faculty of Medicine, Haft‑e‑Tir Hospital, Iran University of Medical Sciences, Tehran, Iran

2 Department of Radiotherapy and Oncology, Firoozgar Clinical Research Development Center (FCRDC), Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

3 Burn Research Center, Iran University of Medical Science (IUMS), Tehran, Iran

How to Cite: Novin K, Saneii M , Noori R, Shahin M , Berahman M , et al. Association Between Pathological Complete Response and Tumor Location in Patients with Rectal Cancer After Neoadjuvant Chemoradiotherapy, a Prospective Cohort Study, Int J Cancer Manag. 2021 14(5): e113135. doi: 10.5812/ijcm.113135.

ARTICLE INFORMATION

International Journal of Cancer Management: 14 (5); e113135
Published Online: June 9, 2021
Article Type: Research Article
Received: January 31, 2021
Revised: May 10, 2021
Accepted: May 12, 2021
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Abstract

Background: Colorectal cancers are the third common malignancies after lung and breast neoplasms. Some contributing factors for pathological complete response (pCR) to neoadjuvant therapy of rectal cancer have been defined. Despite various studies in this era, there are few studies on the location of tumors.

Objectives: Regarding the high prevalence of colorectal cancer in Iran and the importance of neoadjuvant chemoradiation for survival and morbidity, this study was carried out to determine the association between pathologic complete response and tumor location in patients with rectal cancer after neoadjuvant chemoradiotherapy.

Methods: In this prospective cohort, 100 cases with rectal adenocarcinoma from 2017 to 2019 were enrolled. Distance between anal verge and tumor was measured by clinical examination, colonoscopy, endo-sonography, and MRI. Tumors were defined as distal (less than 5 cm from the anal verge) and none distal (more than 5 cm from the anal verge). Another subdivision was inferior (0 - 4.99 cm), middle (5 - 9.99 cm), and superior (10 - 15 cm). The pathological response was compared across the groups.

Results: In this study, the pCR was seen in 30%. In univariate analysis body mass index (BMI), grade, N-stage, and distance from anal verge were related to pCR. In cases with BMI over 25 kg/m2 and in tumors with low to medium grade N0/N1, and distance less than 5 cm from the anal verge (low lying tumors) the pCR to neoadjuvant treatment was higher. In multivariate analysis tumor grade, N stage, and distance from anal verge were still related to pCR.

Conclusions: According to the obtained results in this study, there may be some association between rectal tumor location and pathologic complete response.

1. Background

Colorectal cancers are the third common malignancies after lung and breast neoplasms (1). However, there are multiple screening methods to reduce the morbidity and mortality of these cancers (2). Multiple risk factors including environmental and genetic issues have been involved in the pathogenesis of the disease (3). Dietary is one of the important environmental factors and studies have shown that a healthy dietary pattern can reduce the risk of colorectal cancer and colorectal adenoma, on the other hand, the “western” dietary pattern can increase the risks (4). The risk of postoperative recurrence rate is high) ranging from 4 to 27 percent (and preoperative chemotherapy is a useful method to improve the survival and reduce the recurrence (3). The main benefit of preoperative chemoradiation is complete clinical regression and pathological response (5). Pathological complete response (pCR), ranging from 10 to 30 percent, would increase the survival and decrease the recurrence rate (6). The pathological studies among patients with preoperative chemoradiotherapy have shown a significant reduction in the number and size of involved lymph nodes and frequency of lymph node metastasis (7). In this regard, there are different grading systems such as Mandard, Dowrak, Dowrak/Rodel, and tumor regression grading (TRG) (8). The outcome is related to multiple factors such as metastasis, size, lymph node involvement, and the like (9, 10). The standard treatment in locally advanced case is surgery, chemoradiotherapy, and chemotherapy (11). Safety, feasibility, and better resection are factors for preference of neoadjuvant chemoradiotherapy (12). It is usually used in cases with T3 and T4 tumors and sometimes in T1 and T2 tumors with lymphatic involvement (13). The pCR is defined according to both tumor and lymph nodes presenting sensitivity to treatment (14, 15). It is even useful in cases without response to discontinuing the treatment or increasing the intensity to achieve response and improvement in prognosis (16-20). Contributing factors for pCR include CEA level, anal verge distance, peripheral extension, smoking status, lymph node status, grade, size less than 5 cm, and time interval to surgery (21, 22). Despite various studies in this era, there are few studies on the location of tumors (21, 23-36).

2. Objectives

Regarding the high prevalence of colorectal cancer in Iran and the importance of neoadjuvant chemo-radiation for survival and morbidity, this study was carried out to determine the association between pathologic complete response and tumor location in patients with rectal cancer after neoadjuvant chemoradiotherapy.

3. Methods

3.1. Study Design

In this prospective descriptive comparative cohort, 100 cases with rectal adenocarcinoma from 2017 to 2019 were enrolled. Inclusion criteria consisted of stages 2 and 3, being candidates for neoadjuvant chemoradiation, +N/T3-4, no previous chemotherapy or hormone therapy or abdominal and pelvic radiotherapy, maximal age of 75 years, normal renal, hepatic, and hematological function. Exclusion criteria were dissatisfaction, loss to follow-up, simultaneous malignancy, and severe chemoradiotherapy adverse effects (If it causes the interruption in treatment).

All patients underwent radiotherapy at a dose of 45 grays in 28 fractions with capecitabine 825 mg/m2 twice daily and 5 times a week, and underwent surgery between 4 to 6 weeks after the completion of chemoradiation.

The pathologic complete response was defined as the absence of any cancer cells in the sample examined in pathology.

This study was approved by the ethics committee of Iran University of Medical Sciences: IR.IUMS.FMD.REC 1398.235.

3.2. Study Population

In this prospective study, the eligible cases were enrolled and the written informed consent form was received and demographic and clinical data were recorded in the checklist. Distance between anal verge and tumor was measured by clinical examination, colonoscopy, endo-sonography, and MRI. Tumors were defined as distal (less than 5 cm from the anal verge) and none distal (more than 5 cm from anal verge). Another subdivision was inferior (0 - 4.99 cm), middle (5 - 9.99 cm), and superior (10 - 15 cm). The pathological response was compared across the groups.

3.3. Statistical Analysis

Data analysis was done by SPSS software. The student’s t-test was used for numerical variables and the Pearson’s chi-square test was used for categorical factors. To determine the association between pCR and tumor location and calculation of odds ratio (OR), the logistic regression test was done. The P-values less than 0.05 were considered statistically significant.

4. Results

Among 192 studies cases, 100 patients including 24 female subjects were enrolled with a mean age of 55.2 (ranging from 23 to 70 years old). Also, the mean body mass index (BMI) was 23.87 (ranging from 19 to 27 kg/m2). The mean anal verge distance was 7.21 cm (ranging from 2 to 15 cm). Tumors were well, moderate, and poorly differentiated in 29%, 41%, and 30%, respectively.

Table 1 shows the association of 2-group location and variable, Table 2 shows the association of 3-group location and variables.

Table 1. Association of 2-Group Location and Variablesa
Location, cmP-Value
< 5≥ 5
Age0.304
< 509/28 (32.1)19/28 (67.9)
> 5016/72 (22.2)56/72 (77.8)
Family History0.517
No22/86 (25.6)64/86 (74.4)
Yes3/14 (21.40)11/14 (78.6)
Grade0.417
Well-differentiated9/29 (31)20/29 (69)
Moderate differentiated11/41 (26.8)30/41 (73.2)
Poorly and undifferentiated5/30 (16.7)25/30 (83.3)
T stage0.134
T27/18 (38.9)11/18 (61.1)
T316/78 (20.5)62/78 (79.5)
T42/4 (50)2/4 (50)
N stage0.002
N03/20 (15)17/20 (85)
N118/50 (36)32/50 (64)
N22/28 (7.1)26/28 (92.9)
N32/2 (100)0/2 (0)
Stage0.248
II3/20 (15)17/20 (85)
III22/80 (27.5)58/80 (72.5)
Sex0.443
Female7/24 (29.2)17/24 (70.8)
Male18/76 (23.7)58/76 (76.3)

aValues are expressed as No. (%).

Table 2. Association of 3-Group Location and Variablesa
LocationP-Value
< 55 - 1010
Age 0.054
< 5012/28 (42.9)3/28 (10.7)13/28 (46.4)
> 5024/72 (33.7)25/72 (34.7)23/72 (31.9)
Family History0.468
No33/86 (38.4)23/86 (26.7)30/86 (34.9)
Yes3/14 (21.4)5/14 (35.7)6/14 (42.9)
Grade0.172
Well- differentiated11/29 (37.9)8/29 (27.6)10/29 (34.5)
Moderate differentiated17/41 (41.5)14/41 (34.1)10/41 (24.4)
Poorly and undifferentiated8/30 (26.7)6/30 (20)16/30 (53.3)
T0.031
T212/18 (66.7)4/18 (22.2)2/18 (11.1)
T322/78 (28.2)23/78 (29.5)33/78 (42.3)
T42/4 (50)1/4 (25)1/4 (25)
N0.001
N05/20 (25)4/2 (20)11/20 (55)
N126/50 (52)14/50 (28)10/50 (20)
N23/28 (10.7)10/28 (53.7)15/28 (53.6)
N32/2 (100)0/2 (0)0/2 (0)
Stage0.141
II5 (25)4 (20)11 (55)
III31/70 (38.8)24/70 (30)25/70 (31.3)
Sex0.251
Female10/24 (41.7)9/24 (37.5)5/24 (20.8)
Male26/76 (34.2)19/76 (25)31/76 (40.8)

aValues are expressed as No. (%).

Also, 78% were T3 and 70% were N1/N2. Totally 20% were stage 2 and 80% were stage 3 (Table 3). The anal verge distance in two-third of cases was more than 5 cm. The distance by sex is shown in Figure 1.

Table 3. Association of 2-Group Response and Variablesa
ResponseP-Value
ResponseNo Response
Age group0.578
< 5013 (46)15 (54)
> 5029 (40)43 (60)
BMI0.035
< 2536 (48)39(52)
> 256 (24)19 (76)
Family History0.080
No39 (45)47 (55)
Yes3 (21)11 (79)
Grade0.014
Well differentiated15 (51.7)14(48.3)
Moderate differentiated21 (51.2)20 (48.8)
Poorly and undifferentiated6 (20)24 (80)
T0.369
T210 (55.6)8 (44.4)
T331 (39.7)47 (60.3)
T41 (25)3 (75)
N0.000
N016 (80)4 (20)
N120 (40)30 (60)
N25 (18)23 (82)
N31 (50)1 (50)
Stage0.000
II16 (80)4 (20)
III26 (32.5)54 (67.5)
Location0.031
< 515 (60)10 (40)
> 527 (36)48 (64)
Location0.233
0 - 519 (52.8)17 (47.2)
5 - 1011 (39.3)17 (60.7)
> 10 12 (33.3)24 (66.7)
Sex0.324
Female8 (33.3)16 (66.7)0.324
Male34 (44.7)42 (55.3)

Abbreviation: BMI, body mass index.

aValues are expressed as No. (%).

The anal verge distance was less than 5, between and 10, and more than 10 cm in 36%, 28%, and 36%, respectively. Despite 58% of without response cases, there were 30% and 12% with pCR and partial response, respectively.

The groups were well-distributed in terms of age, BMI, family history, grade, and T-stage. However, the rate of patients with advanced nodal involvement was higher in the non-distal group.

The groups were well-distributed in terms of family history, age, and grade. Although, the rate of patients with advanced nodal involvement and advanced T was higher in the non-distal group.

As shown in Table 4, age, grade, stage, N stage, and location were related to pCR.

Table 4. Association of 3-Group Response and Variablesa
ResponseP-Value
Complete ResponsePartial ResponseNo Response
Age group0.038
< 506 (21.4)7 (25)15 (53.6)
> 5024 (33.3)5 (6.9)43 (59.7)
BMI0.065
< 2527 (36)9 (12)39 (52)
> 253 (12)3 (12)19 (76)
Family History0.065
No28 (32)11 (12)47 (54)
Yes2 (14)1 (7)11 (78)
Grade0.006
Well differentiated12 (41)3 (10)14 (48)
Moderate differentiated17 (41)4 (9)20 (48)
Poorly and undifferentiated1 (3)5 (16)24 (80)
T0.574
T28 (44)2 (11)8 (44)
T321 (26)10 (12)47 (60)
T41 (25)0 (0)3 (75)
N0.000
N09 (45)7 (35)4 (20)
N117 (34)3 (6)30 (60)
N23 (10)2 (7)23 (82)
N31 (50)01 (50)
Stage0.000
II9 (45)7 (35)4 (20)
III21(26)5 (6)54 (67)
Location0.000
< 515 (60)0 (0)10 (40)
> 515 (20)12 (16)48 (64)
Location0.001
0-518 (50)1 (2)17 (47)
5-109 (32)2 (7)17 (60)
> 103 (8)9 (25)24 (66)
Sex0.116
Female8 (33)0 (0)16 (66)0.116
Male22 (28)12 (15)42 (55)

aValues are expressed as No. (%).

As shown in Table 5, according to multivariate analysis, the anal verge distance was related to treatment response. According to Table 6, in multivariate analysis for 2-group treatment response the BMI, grade, and location were related to response.

Table 5. Association of Anal Verge Distance and Treatment Response
P-ValueExp(B)95% CI for EXP(B)
LowerUpper
Response/ no response
Grade 0.035
Grade (1)0.8310.8820.2792.785
Grade (2)0.0265.0401.21720.867
Location0.0453.1001.0239.388
N stage0.1162.5680.7928.322
BMI group0.2882.0470.5467.669
total stage0.00110.5742.47145.243
Constant0.0000.000
Table 6. Association of Anal Verge Distance and Complete Response
Complete Response
P-ValueOR95% CI for EXP(B)
LowerUpper
Step 1
Grade 0.021
Grade (1)0.8610.9010.2812.888
Grade (2)0.00820.5312.183193.055
Location0.0036.2241.89620.435
N stage0.0264.5291.19817.128
BMI group0.2052.7730.57213.448
Constant0.001.003

In multivariate and univariate analysis with considering the confounding effect of the N stage, in pCR, the anal verge distance was still meaningful.

5. Discussion

In this study, the pCR was seen in 30%. It ranged from 18% to 30% in previous studies (1). In univariate analysis BMI, grade, N-stage, and distance from anal verge were related to pCR. In cases with BMI over 25 kg/m2 and in tumors with low to intermediate grade, N0/N1, and distance less than 5 cm from the anal verge (low lying tumors) the pCR to neoadjuvant treatment was higher. Also, univariate analysis showed that BMI less than 25 kg/m2, low/intermediate grade, N0/N1, stage 2, a distance less than 5 cm from anal verge were related to tumor down-staging. In multivariate analysis tumor grade, N stage, and distance from anal verge were related to pCR. Also, tumor grade, total stage, distance from the anal verge, and N stage (P = 0.092) were related to tumor down-staging.

Various results were obtained in the other studies. In some studies pathologic complete response was more in distal tumor and in some other studies it was lower in distal tumors or there was no difference between pCR to neoadjuvant therapy and location of the tumor. Bitterman et al. (37) assessed 135 cases with T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal tumors with pCR in 26.3%. In multivariate analysis, CEA less than 5 cm, tumor size less than 3 cm, distance from anal verge less than 3 cm, the negative clinical node at diagnosis time, and time interval between surgery and chemoradiation more than 8 weeks were related to pCR. These results are in line with our findings.

In another study by Armstrong et al. (38) 885 cases with rectal tumors at stages 2 and 3 were assessed for contributing factors of pCR to neoadjuvant chemo-radiation. The pCR was seen in 18.2 percent. In multivariate analysis low CEA level, statin use, and less distance of rectal tumor from anal verge were significantly related to higher pCR (38). Das et al. (21) assessed 562 non-metastatic rectal cancer cases under chemo-radiation and surgical therapy and reported pCR in 19 percent and also 20 percent had a near-complete response. The circumferential extent was the only related factor for pCR and response was higher with less than 60 percent involvement. Circumferential extent less than 60 percent and distance from anal verge less than 5 cm were related to tumor down-staging (21).

The studies by Guillem et al. (39), Patel et al. (29), Restivo et al. (28), and Han et al. (32) were done among 109, 827, 260, and 332 cases, respectively and showed that distal rectal tumors had lower pCR (39). Also, the pCR was not related to anal verge distance in some other studies. Some possible causes for the difference in results include retrospective design, selection bias, small sample size, and lack of adjustment for confounding factors such as grade, radiotherapy dose, chemotherapy protocol, stage, aspirin/statin use, radiotherapy length, and time interval between surgery and chemo-radiation termination time, and also genetic/racial differences. Despite the novel improvements in the management of cancers such as the discovery of new molecular targets and subsequently new drugs (40-43), considering the basic topics such as the location of the tumor might provide not only new data for the management of these cancers especially in countries with limited resources but also provide the new concepts for further studies.

5.1. Conclusions

The findings of the current study showed that there may be some association between rectal tumor location and pathologic complete response. The main limitations of our study were retrospective design, loss to follow-up cases, lack of clinical staging by a single radiologist, and lack of re-assessment of slides by a single pathologist (inter-observer bias), no access to data about the distance between chemo-radiation and surgery, and also small sample size. Further studies with a larger sample population and alleviation of these limitations are encouraged to attain more definite results.

Footnotes

References

  • 1.

    Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98(7):1521-30. doi: 10.1002/cncr.11660. [PubMed: 14508841].

  • 2.

    Beddy D, Hyland JM, Winter DC, Lim C, White A, Moriarty M, et al. A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2008;15(12):3471-7. doi: 10.1245/s10434-008-0149-y. [PubMed: 18846402].

  • 3.

    Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer. 2002;94(4):1121-30. [PubMed: 11920483].

  • 4.

    Bahrami A, Houshyari M, Jafari S, Rafiei P, Mazandaranian M, Hekmatdoost A, et al. Dietary patterns and the risk of colorectal cancer and adenoma: a case control study in Iran. Gastroenterol Hepatol Bed Bench. 2019;12(3):217-25. [PubMed: 31528305]. [PubMed Central: PMC6668762].

  • 5.

    Capirci C, Valentini V, Cionini L, De Paoli A, Rodel C, Glynne-Jones R, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys. 2008;72(1):99-107. doi: 10.1016/j.ijrobp.2007.12.019. [PubMed: 18407433].

  • 6.

    Kang SB, Park JW, Jeong SY, Nam BH, Choi HS, Kim DW, et al. Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial. Lancet Oncol. 2010;11(7):637-45. doi: 10.1016/S1470-2045(10)70131-5. [PubMed: 20610322].

  • 7.

    Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680-6. doi: 10.1002/1097-0142(19940601)73:11<2680::aid-cncr2820731105>3.0.co;2-c. [PubMed: 8194005].

  • 8.

    Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23(34):8688-96. doi: 10.1200/JCO.2005.02.1329. [PubMed: 16246976].

  • 9.

    Roudbari M, Abbasi Asl M, Barfei F, Gohari MR, Khodabakhshi R. Survival analysis of colorectal cancer patients and its prognostic factors using cox regression. Razi J Med Sci. 2015;22(130):21-8.

  • 10.

    Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343-51. doi: 10.1056/NEJMoa032709. [PubMed: 15175436].

  • 11.

    O'Neil BH, Tepper JE. Current options for the management of rectal cancer. Curr Treat Options Oncol. 2007;8(5):331-8. doi: 10.1007/s11864-007-0048-7. [PubMed: 18181024].

  • 12.

    Onaitis MW, Noone RB, Fields R, Hurwitz H, Morse M, Jowell P, et al. Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival. Ann Surg Oncol. 2001;8(10):801-6. doi: 10.1007/s10434-001-0801-2. [PubMed: 11776494].

  • 13.

    Guillem JG, Diaz-Gonzalez JA, Minsky BD, Valentini V, Jeong SY, Rodriguez-Bigas MA, et al. cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol. 2008;26(3):368-73. doi: 10.1200/JCO.2007.13.5434. [PubMed: 18202411].

  • 14.

    Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. [PubMed: 20692872].

  • 15.

    Zorcolo L, Rosman AS, Restivo A, Pisano M, Nigri GR, Fancellu A, et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol. 2012;19(9):2822-32. doi: 10.1245/s10434-011-2209-y. [PubMed: 22434243].

  • 16.

    Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol. 2016;17(2):174-83. doi: 10.1016/S1470-2045(15)00467-2. [PubMed: 26705854].

  • 17.

    Yasuda K, Nirei T, Sunami E, Nagawa H, Kitayama J. Density of CD4(+) and CD8(+) T lymphocytes in biopsy samples can be a predictor of pathological response to chemoradiotherapy (CRT) for rectal cancer. Radiat Oncol. 2011;6:49. doi: 10.1186/1748-717X-6-49. [PubMed: 21575175]. [PubMed Central: PMC3120676].

  • 18.

    Mohiuddin M, Hayne M, Regine WF, Hanna N, Hagihara PF, McGrath P, et al. Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers. Int J Radiat Oncol Biol Phys. 2000;48(4):1075-80. doi: 10.1016/s0360-3016(00)00732-x. [PubMed: 11072165].

  • 19.

    Theodoropoulos G, Wise WE, Padmanabhan A, Kerner BA, Taylor CW, Aguilar PS, et al. T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum. 2002;45(7):895-903. doi: 10.1007/s10350-004-6325-7. [PubMed: 12130878].

  • 20.

    Polli LV, Pinho M. Analysis of neutrophil–lymphocyte ratio as a prognostic element in the response to neoadjuvant therapy in rectal cancer. J Coloproctol. 2021;35(1):3-7. doi: 10.1016/j.jcol.2015.01.003.

  • 21.

    Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109(9):1750-5. doi: 10.1002/cncr.22625. [PubMed: 17387743].

  • 22.

    Bozkaya Y, Özdemir NY, Erdem GU, Güner EK, Ürün Y, Demirci NS, et al. Clinical predictive factors associated with pathologic complete response in locally advanced rectal cancer. J Oncol Sci. 2018;4(1):5-10. doi: 10.1016/j.jons.2017.12.004.

  • 23.

    Kleiman A, Al-Khamis A, Farsi A, Kezouh A, Vuong T, Gordon PH, et al. Normalization of CEA Levels Post-Neoadjuvant Therapy is a Strong Predictor of Pathologic Complete Response in Rectal Cancer. J Gastrointest Surg. 2015;19(6):1106-12. doi: 10.1007/s11605-015-2814-3. [PubMed: 25859755].

  • 24.

    Garland ML, Vather R, Bunkley N, Pearse M, Bissett IP. Clinical tumour size and nodal status predict pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Int J Colorectal Dis. 2014;29(3):301-7. doi: 10.1007/s00384-013-1821-7. [PubMed: 24420737].

  • 25.

    Wallin U, Rothenberger D, Lowry A, Luepker R, Mellgren A. CEA - a predictor for pathologic complete response after neoadjuvant therapy for rectal cancer. Dis Colon Rectum. 2013;56(7):859-68. doi: 10.1097/DCR.0b013e31828e5a72. [PubMed: 23739192].

  • 26.

    Huh JW, Kim HR, Kim YJ. Clinical prediction of pathological complete response after preoperative chemoradiotherapy for rectal cancer. Dis Colon Rectum. 2013;56(6):698-703. doi: 10.1097/DCR.0b013e3182837e5b. [PubMed: 23652742].

  • 27.

    Moureau-Zabotto L, Farnault B, de Chaisemartin C, Esterni B, Lelong B, Viret F, et al. Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2011;80(2):483-91. doi: 10.1016/j.ijrobp.2010.02.025. [PubMed: 21093174].

  • 28.

    Restivo A, Zorcolo L, Cocco IM, Manunza R, Margiani C, Marongiu L, et al. Elevated CEA levels and low distance of the tumor from the anal verge are predictors of incomplete response to chemoradiation in patients with rectal cancer. Ann Surg Oncol. 2013;20(3):864-71. doi: 10.1245/s10434-012-2669-8. [PubMed: 23010737].

  • 29.

    Patel SV, Roxburgh CS, Vakiani E, Shia J, Smith JJ, Temple LK, et al. Distance to the anal verge is associated with pathologic complete response to neoadjuvant therapy in locally advanced rectal cancer. J Surg Oncol. 2016;114(5):637-41. doi: 10.1002/jso.24358. [PubMed: 27641934]. [PubMed Central: PMC5516624].

  • 30.

    Zhang C, Ye F, Liu Y, Ouyang H, Zhao X, Zhang H. Morphologic predictors of pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Oncotarget. 2018;9(4):4862-74. doi: 10.18632/oncotarget.23419. [PubMed: 29435147]. [PubMed Central: PMC5797018].

  • 31.

    Choi E, Kim JH, Kim OB, Kim MY, Oh YK, Baek SG. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: a single center experience. Radiat Oncol J. 2016;34(2):106-12. doi: 10.3857/roj.2015.01585. [PubMed: 27306776]. [PubMed Central: PMC4938349].

  • 32.

    Han YD, Kim WR, Park SW, Cho MS, Hur H, Min BS, et al. Predictors of pathologic complete response in rectal cancer patients undergoing total mesorectal excision after preoperative chemoradiation. Medicine (Baltimore). 2015;94(45). e1971. doi: 10.1097/MD.0000000000001971. [PubMed: 26559272]. [PubMed Central: PMC4912266].

  • 33.

    Stanley K, Tait D, Chau I, Brown G. MRI Predictive Factors for Tumor Response in Rectal Cancer Following Neoadjuvant Chemoradiation Therapy-Implications for Induction Chemotherapy? Int J Radiat Oncol Biol Phys. 2013;87(3):505-11. doi: 10.1016/j.ijrobp.2013.06.2052.

  • 34.

    Ward WH, Sigurdson ER, Esposito AC, Ruth KJ, Manstein SM, Sorenson EC, et al. Pathologic response following treatment for locally advanced rectal cancer: Does location matter? J Surg Res. 2018;224:215-21. doi: 10.1016/j.jss.2017.11.072. [PubMed: 29506843]. [PubMed Central: PMC7811804].

  • 35.

    Peng H, Wang C, Xiao W, Lin X, You K, Dong J, et al. Analysis of Clinical characteristics to predict pathologic complete response for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. J Cancer. 2018;9(15):2687-92. doi: 10.7150/jca.25493. [PubMed: 30087709]. [PubMed Central: PMC6072814].

  • 36.

    Jalilian M, Davis S, Mohebbi M, Sugamaran B, Porter IW, Bell S, et al. Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome. J Gastrointest Oncol. 2016;7(4):603-8. doi: 10.21037/jgo.2016.05.03. [PubMed: 27563451]. [PubMed Central: PMC4963368].

  • 37.

    Bitterman DS, Resende Salgado L, Moore HG, Sanfilippo NJ, Gu P, Hatzaras I, et al. Predictors of Complete Response and Disease Recurrence Following Chemoradiation for Rectal Cancer. Front Oncol. 2015;5:286. doi: 10.3389/fonc.2015.00286. [PubMed: 26734570]. [PubMed Central: PMC4686647].

  • 38.

    Armstrong D, Raissouni S, Price Hiller J, Mercer J, Powell E, MacLean A, et al. Predictors of Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer: A Multicenter Study. Clin Colorectal Cancer. 2015;14(4):291-5. doi: 10.1016/j.clcc.2015.06.001. [PubMed: 26433487].

  • 39.

    Guillem JG, Chessin DB, Shia J, Suriawinata A, Riedel E, Moore HG, et al. A prospective pathologic analysis using whole-mount sections of rectal cancer following preoperative combined modality therapy: implications for sphincter preservation. Ann Surg. 2007;245(1):88-93. doi: 10.1097/01.sla.0000232540.82364.43. [PubMed: 17197970]. [PubMed Central: PMC1867929].

  • 40.

    Javadinia SA, Shahidsales S, Fanipakdel A, Joudi-Mashhad M, Mehramiz M, Talebian S, et al. Therapeutic potential of targeting the Wnt/beta-catenin pathway in the treatment of pancreatic cancer. J Cell Biochem. 2018. doi: 10.1002/jcb.27835. [PubMed: 30368889].

  • 41.

    Fanipakdel A, Seilanian Toussi M, Rezazadeh F, Mohamadian Roshan N, Javadinia SA. Overexpression of cancer-testis antigen melanoma-associated antigen A1 in lung cancer: A novel biomarker for prognosis, and a possible target for immunotherapy. J Cell Physiol. 2019;234(7):12080-6. doi: 10.1002/jcp.27884. [PubMed: 30569450].

  • 42.

    Sedighi Pashaki A, Mohammadian K, Afshar S, Gholami MH, Moradi A, Javadinia SA, et al. A Randomized, Controlled, Parallel-Group, Trial on the Effects of Melatonin on Fatigue Associated with Breast Cancer and Its Adjuvant Treatments. Integr Cancer Ther. 2021;20:1534735420988340. doi: 10.1177/1534735420988343. [PubMed: 33543655]. [PubMed Central: PMC7868453].

  • 43.

    Javadinia SA, Shahidsales S, Fanipakdel A, Mostafapour A, Joudi-Mashhad M, Ferns GA, et al. The Esophageal Cancer and the PI3K/AKT/mTOR Signaling Regulatory microRNAs: a Novel Marker for Prognosis, and a Possible Target for Immunotherapy. Curr Pharm Des. 2018;24(39):4646-51. doi: 10.2174/1381612825666190110143258. [PubMed: 30636576].

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