Untitled Document
 
 
 
 
Untitled Document
Home
Current issue
Past issues
Topic collections
Search
e-journal Editor page

Incidence of Pathological Complete Response after Neoadjuvant Treatment in Current Vajira Hospital Rectal Cancer Practice

อุบัติการณ์การตอบสนองทางพยาธิวิทยาแบบสมบูรณ์ในผู้ป่วยมะเร็งลำไส้ตรงที่ได้รับยาเคมีบำบัดร่วมกับ การฉายรังสีในโรงพยาบาลวชิรพยาบาล

Punnawat Chandrachamnong (ปุณวัฒน์ จันทรจำนง) 1, Kullawat Bhatanaprabhabhan (กุลวัฒน์ พัฒนประภาพันธุ์) 2, Marisa Chongthanakorn (มาริสา จงธนากร) 3, Boonchai Ngamsirimas (บุญชัย งามสิริมาศ) 4




หลักการและวัตถุประสงค์: มะเร็งลำไส้ใหญ่และลำไส้ตรง เป็นมะเร็งที่พบได้มากที่สุดเป็นอันดับสามทั่วโลก  การรักษาที่ได้รับการยอมรับในปัจจุบันในผู้ป่วย locally advanced rectal cancer คือการให้ ยาเคมีบำบัดร่วมกับการฉายรังสี (concurrent chemoradiation therapy; CCRT) ตามด้วยการผ่าตัด total mesorectal excision (TME) ซึ่งผลการตอบสนองต่อ CCRT ในแต่ละงานวิจัยมีความแตกต่างกันอย่างมาก และมีผู้ป่วยประมาณร้อยละ15-30 ที่มีการตอบสนองทางพยาธิวิทยาแบบสมบูรณ์ (pathological complete response; pCR) โดยงานวิจัยนี้จึงมีเป้าหมายที่จะศึกษาเกี่ยวกับอัตราการตอบสนองทางพยาธิวิทยาแบบสมบูรณ์ (pCR rate) และปัจจัยที่มีผลต่อการตอบสนองทางพยาธิแบบสมบูรณ์ ในผู้ป่วยมะเร็งลำไส้ตรงที่ได้รับยาเคมีบำบัด ร่วมกับการฉายรังสีในประเทศไทย

วิธีการศึกษา: เป็นการศึกษาแบบย้อนหลัง (retrospective review of a prospectively collected database) โดยศึกษา ผู้ป่วยที่ได้รับการวินิจฉัยว่าเป็นมะเร็งลำไส้ตรง ระยะที่ 2-3 ที่มี cT3-4, N0 หรือ any cT, cN1-2 เท่านั้น และผู้ป่วยต้องได้รับการรักษาด้วยการให้เคมีบำบัดร่วมกับฉายรังสีก่อนการผ่าตัด (neoadjuvant CCRT)  ในช่วงปี_พ.ศ. 2557-2563

ผลการศึกษา: ผู้ป่วยมะเร็งลำไส้ตรง ระหว่างปีพ.ศ. 2557-2563 ทั้งสิ้น 234 ราย มีผู้ป่วย 101 ราย (ร้อยละ 43.1)ที่ได้รับ neoadjuvant CCRT โดยมีผู้ป่วยชาย 68 ราย (ร้อยละ 67.3) อายุเฉลี่ย 58.5±11.5  ปี ตำแหน่งก้อน ที่พบมาก ที่สุดคือ lower rectum 60 ราย (ร้อยละ 59.4) มีclinical T staging เป็น cT3 76 ราย (ร้อยละ 75.2)และ clinical N staging เป็น cN1-2 54 ราย (ร้อยละ 53.5) มีผู้ป่วยทั้งสิ้น 14 ราย (ร้อยละ 13.9) ที่มีการตอบสนองทางพยาธิวิทยาแบบ pCR เมื่อคำนวณ univariate analysis และ multivariate analysis แล้วพบว่าCEA>2.5, cN1-2 และ การให้ยา capecitabine เป็น radiosensitizing agent มีผลต่อการเกิด pCR โดยมี OR 0.23 P = 0.04 (95%CI 0.59-0.93), OR 0.15 P = 0.02 (95%CI 0.03-0.79) และ OR 9.89 P = 0.01(95%CI 1.62-60.25)

สรุป: อัตราการตอบสนองทางพยาธิวิทยาแบบ pCR  คือ ร้อยละ 13.9 โดยมีปัจจัยที่มีผลต่อ pCR คือ CEA>2.5; OR 0.23, P = 0.04 (95%CI 0.59-0.93), cN1-2 OR 0.15 P = 0.02 (95%CI 0.03-0.79) และการได้รับยา capecitabine เป็น radiosensitizing agent OR 9.89 P = 0.01(95%CI 1.62-60.25)

Background and objective: Colorectal cancer is the third most common cancer worldwide. The current standard treatment for locally advanced rectal cancer is neoadjuvant concurrent chemoradiation therapy (CCRT) followed by total mesorectal excision (TME). The responses to CCRT differ significantly in each study, and approximately 15-30% of patients have pathological complete response(pCR). This research aims to investigate the pCR rate and the factors affecting the pCR after neoadjuvant CCRT in rectal cancer.

Method: A retrospective study of locally advanced rectal cancer, diagnosed with cT3-4, N0 or any cT, cN1-2, who underwent neoadjuvant CCRT during 2014-2020.

Results: A total of 234 rectal cancer patients, there were 101 (43.1%) patients treated with neoadjuvant CCRT, with 68 (67.3%) male patients and a mean age of 58.5 years (+/- 11.5). The most common cancer location was the lower rectum, 60 (59.4%). For clinical staging, 76 patients had cT3 (75.2%) and 54 patients had cN1-2 (53.5%). A total of 14 patients (13.9%) had pCR. When univariate analysis and multivariate analysis were calculated, it was found that CEA> 2.5, cN1-2 and capecitabine as a radiosensitizing agent affected pCR with OR 0.23 P = 0.04 (95% CI 0.59-0.93), OR 0.15 P = 0.02 (95% CI 0.03-0.79) and OR 9.89 P = 0.01 (95% CI 1.62-60.25), respectively.

Conclusion: The pCR rate was 13.9%, with factors affecting pCR were CEA> 2.5, cN1-2 and capecitabine as a radiosensitizing agent.

Introduction

    Colorectal cancer is the third most common cancer worldwide.1 Concurrent chemoradiation therapy (CCRT) followed by total mesorectal excision (TME) is considered as standard treatment in locally advanced rectal cancer (T3-4, N0 or anyT, N 1-2)2-4 which causes tumor downsizing and greatly reduced local recurrence rate.5-8

       The response to CCRT varies widely from study to study and approximately 11-30% of patients achieve pathological complete response(pCR).9-12 According to several studies, it is found that these patients had better treatment outcomes and survival rates13 which led to the new theory of treatment for rectal cancer, “a watch and wait approach”, believing that patients with complete response may not require surgery and gave a therapeutic effect that was comparable to that of surgery.9-12

    Currently, in Thailand, there has not been a precise study of the incidence of pCR. Based on current studies, T staging, N staging, initial CEA, initial Hb level, the interval from complete CCRT to surgery, endoscopic circumferential rate affect pCR rate14-21, which factors such still haven't had a clear conclusion. This research aims to study the pCR rate and factors affecting the pathological complete response in patients with locally advanced rectal cancer who received neoadjuvant CCRT in Thailand.

 

Methods

This research was a retrospective review of a prospectively collected database by studying patients diagnosed with stage 2-3 rectal cancer with cT3-4, N0 or any T, N1-2 who underwent neoadjuvant CCRT followed by TME during 2014-2020. The primary outcome was the incidence of  pCR rate  and the secondary outcomes were the predictive factor for pCR.

Using SPSS version 22 program for data analysis. Continuous data were presented in mean ± SD and Categorical data were presented as a percentage. Binary logistic regression analysis was used to analyze factors associated with pCR for univariate and multivariate analysis. P-value <0.05 was defined for a significant statistical difference.

 

Results

          There were 234 cases of rectal cancer between 2014 and 2020. One hundred and one patients (43.1%) were treated with neoadjuvant CCRT prior to surgery. There were 68 (67.3%) male patients with a mean age of 58.5 years (± 11.5). The most common tumor location was lower rectum (59.4%). The clinical stage was cT3 in 76 cases (75.2%) and cN1-2 in 54 cases_(53.5%). Most of the cases (80.2%) received total radiation dose of 50 Gy with dose per fraction 2 Gy/Fr (85.1%). Ninety-three patients (92.1%) received 5FU where 8 patients (7.9%) received capecitabine as the radiosensitizing agent. (Table1)

Eight patients (7.9%) received total neoadjuvant therapy, 5 in 8 patients (62.5%) with induction chemotherapy, 2 in 8 patients (25%) with consolidation chemotherapy, and 1 in 8 patients (12.5%) with induction plus consolidation chemotherapy. All patients received FOLFOX as a chemotherapy regimen, 2 cycles in 2 patients, 4_cycles in 2 patients, 6_cycles in 2 patients, and 8_cycles in 2 patients. (Table1)

Table 1  Patient characteristic

Patient characteristics

Number (%)

N=101

Sex

     Male                 

68 (67.3)

     Female

33 (32.7)

Age (mean ± SD)

58.5 ± 11.5

BMI (mean ± SD)

23.1 ± 4.8

Underlying

55 (54.5)

     Diabetes mellitus    

18 (17.8)

     Hypertension

32 (31.7)

     Dyslipidemia

17 (16.8)

     Ischemic heart disease

4 (3.9)

     Chronic kidney disease

5(4.9)

     HIV

2 (1.9)

     Other

27 (26.7)

CEA (mean)

14.6

Hb (mean)

12.1

Tumor site

     Upper rectum

11(10.9)

     Mid rectum

30 (29.7)

     Lower rectum

60 (59.4)

Distant from AV (mean ± SD)

6.2 ±3.5

cT staging

     cT3

76 (75.2)

     cT4

25 (24.8)

cN staging

     cN0

47 (46.5)

     cN1-2

54 (53.5)

Total radiation dose

     50Gy

81 (80.2)

     50.4Gy

13 (12.9)

     > 50.4Gy

7 (6.9)

Dose per fraction

     1.8 Gy/Fr

15 (14.9)

     2 Gy/Fr

86 (85.1)

Radiosensitizing agent

     5FU

93 (92.1)

     Capecitabine

8 (7.9)

Total neoadjuvant therapy(TNT)

8 (7.9)

     Induction chemotherapy

5 (62.5)

     Consolidation chemotherapy

2 (25)

     Induction + consolidation

1 (12.5)

TNT regimen

     FOLFOX4

8 (100)

TNT cycle (mean)

5 cycle

Interval to surgery (wk) (mean± S/D)

10.2 ± 4.6

 

Mean interval after CCRT to surgery was 10.7 weeks (4-32 weeks).  Most of the cases (62.4%) underwent laparoscopic surgery. There were 47 (46.5%) patients undergoing Low Anterior Resection (LAR), 23 (22.8%) patients with Intersphincteric Resection(ISR)/Coloanal Anastomosis(CAA) and there were 31 patients (30.7%) undergoing Abdominoperineal Resection(APR), in which only 3 patients (2.9%) did not have a protective ostomy. A total of 40 patients (39.6%), had a loop transverse colostomy before CCRT. (Table 2)

Table 2  Operative technique

Patient characteristics

Number (%)

N=101

Approach

     Open

38 (37.6)

     Laparoscopy

63 (62.4)

Procedure

     LAR

47 (46.5)

     ISR/CAA

23 (22.8)

     APR

31 (30.7)

Stomal formation

98 (97.0)

Type of stoma

     Loop transverse colostomy

49 (48.5)

     Loop ileostomy

18 (17.8)

     End colostomy

31 (30.7)

Stoma formation before CCRT

40 (39.6)

 

A total of 14 patients (13.9%) had a pathological complete response (pCR) (Table 3). The results of the univariate among pCR patients are demonstrated in Table 4. The Result from the univariate analyses indicates that CEA> 2.5; OR 0.27 p = 0.03, cN1-2. ; OR 0.11, p = 0.006 and capecitabine as radiosensitizing agent; OR 8.3 p = 0.007 had a significantly associate with pCR. And when using the above data to study multivariate analysis, it was found that CEA> 2.5, cN1 / 2 and capecitabine as a radiosensitizing agent were significantly associate with pCR with OR 0.23 p = 0.04 (95% CI 0.59-0.93), OR 0.15 p = 0.02 (95% CI 0.03. -0.79) and OR 9.89 p = 0.01 (95% CI 1.62-60.25), respectively. (Table 5)

Table 3 Pathological outcome

Patient characteristics

Number (%)

N=101

pCR

14 (13.9)

yT staging

     T0

16 (15.8)

     T1

6 (5.9)

     T2

23 (22.8)

     T3

48 (47.5)

     T4

7.9

yN staging

     N0

65 (64.3)

     N1

21 (20.7)

     N2

15 (14.8)

Staging

     Stage 0

14 (13.9)

     Stage 1

22 (21.8)

     Stage 2

29 (28.7)

     Stage 3

36 (35.6)

Tumor grading

     Well differentiate

16(15.8)

     Moderately differentiate

72 (71.3)

     Poor differentiate

11 (10.9)

     Mucinous

2 (1.9)

LVI

17 (16.8)

PNI

13 (12.9)

Tumor deposit

4 (3.9)

Lymph node harvested (mean ± SD)

10.7 ± 6.1

     < 12 nodes

64 (63.4)

     ≥ 12 nodes

37 (36.6)

 

Table 4  Univariate analysis of predictors for pCR using logistic regression models.

Variable

Total cases

pCR cases  (%)

OR

P value

Sex

   Female

33

5 (15.2)

1

   Male

68

9 (13.2)

0.85

0.79

Age

   <60yr

53

8 (15.1)

1

   ≥60yr

48

6 (12.5)

0.8

0.7

Obesity

   No

67

11 (16.4)

1

   Yes

34

3 (8.8)

0.49

0.3

Underlying disease

   No

46

9 (19.6)

1

   Yes

55

5 (9.1)

0.41

0.13

CEA level

   ≤ 2.5

26

7(26.9)

1

   > 2.5

75

7(9.3)

0.27

0.03

Hb level

   >10 

88

13(14.8)

1

   ≤10

13

1 (7.7)

0.48

0.49

Distant from AV

   > 5cm  

48

4 (8.3)

1

   ≤ 5cm

53

10(18.9)

2.55

0.13

cT stage

   cT3

76

13 (17.1)

1

   cT4

25

1 (4)

0.2

0.13

cN stage

   cN0

47

12 (25.5)

1

   cN1-2

54

2 (3.7)

0.11

0.006

Tumor grading

   Well/Moderately differentiate

88

13(14.1)

1

   Poor/Mucinous differentiate

13

1(7.7)

0.48

0.49

Total radiation dosage (Gy)

   ≤ 50.4 Gy

94 (93.1)

13 (13.8)

1

   > 50.4 Gy

7 (6.9)

1 (14.3)

1.03

0.97

Interval to surgery

   ≤12 wk

83

10 (12.0)

1

   >12 wk

18

4 (22.2)

2.08

0.26

Radiosensitizing agent

   5FU

93

10 (10.8)

1

   Capecitabine

8

4 (50.0)

8.3

0.007

Total neoadjuvant therapy

  No

93

13 (14)

1

  Yes

8

1 (12.5)

1.13

0.9

 

Table 5  Multivariate analysis of predictors for pCR using logistic regression models.

Variable

OR

P value

95% CI

CEA > 2.5

0.23

0.04

0.59-0.93

cN1-2

0.15

0.02

0.03-0.79

Capecitabine as radiosensitizing agent

9.89

0.01

1.62-60.25

 

Discussion

According to the previous studies, the pCR rate was approximately 11-30%9-12 and was also found to have a significant effect on the better oncological outcome.13 In this study, the incidence of pathological complete response was 13.9%. The factors affecting pCR were CEA> 2.5, cN1-2 and capecitabine as a radiosensitizing agent. Currently, the factors affecting pCR are widely studied and there is still much debate. Tan Y et al.22 found that CEA> 5 was associated with pCR rate OR 0.83 P = 0.01 (95% CI 0.71-0.97), which was found in the same way as our study where CEA> 2.5 affected pCR rate. In addition, clinical T4, N2 was found to affect pCR rate, but there was no correlation between clinical T staging and pCR in this study, which may be due to the preoperative staging limitations of the research. Since CT scans are used for pre-treatment evaluation in the research institutes, a small number of patients use MRI to assess the clinical T staging , so the clinical T staging assessment may not be accurate for seperating T3a, b, c, d, and the limitations to evaluate threatened CRM and EMVI.

        Total neoadjuvant treatment (TNT) is currently in widespread study and interest. Current data support that TNT, whether induction or consolidation chemotherapy increases the incidence of pCR. 23-28 Garcia-Aguilar et al. was administered post-CCRT consolidation chemotherapy in rectal cancer patients23. The study groups were divided into 2, 4, 6 mFOLFOX6 cycles. It was found that the pCR rate was up to 38% in the 6 cycle group compared with 18% of the control group. However, in our study, TNT did not affect the incidence of pCR, possibly because the number of our TNT patients was only 7.9%; therefore may cause the study results to be inaccurate because such treatments are not yet widely available in Thailand.

        For interval to surgery, it is debated whether or not it affects pCR. Kalady et al.29 found that interval> 8 weeks had a more significant effect on pCR rate, but The GRECCAR-6 trial4, which compared interval to surgery between 7 and 11 weeks, showed no difference in pCR rates (15% vs 17.4%, p = 0.59) This study is consistent with our research showing that interval to surgery did not affect pCR rate.   

This research has limitation, retrospective study with relatively few participants. It mays have a discrepancy with the secondary outcome, which is the factor that affects pCR itself. In the future, multi-center study in Thailand could result in a more significant number of patients enrolled and making it possible to get more significant information.

 

Conclusion

          The pCR rate of the study was 13.9%, with factors affecting pCR were CEA> 2.5, cN1-2, and capecitabine as the radiosensitizing agent.

 

References

1.    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69-90.

2.    Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 1999; 17(8): 2396.

3.    Du D, Su Z, Wang D, Liu W, Wei Z. Optimal Interval to Surgery After Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Systematic Review and Meta-analysis. Clin Colorectal Cancer 2018; 17(1): 13-24.

4.    Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, et al. Effect of interval (7 or 11 weeks) between neoadjuvant radiochemotherapy and surgery on complete pathologic response in rectal cancer: A multicenter, randomized, controlled trial (GRECCAR-6). J Clin Oncol 2016; 34(31): 3773-80.

5.    Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336(14):980-7.

6.    Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345(9): 638-46.

7.    Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351(17): 1731-40.

8.    O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol 2014; 32(18): 1927-34.

9.    Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr., Silva e Sousa AH Jr., et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 2004; 240(4): 711-7; discussion 7-8.

10. Dattani M, Heald RJ, Goussous G, Broadhurst J, São Julião GP, Habr-Gama A, et al. Oncological and survival outcomes in watch and wait patients with a clinical complete response after neoadjuvant chemoradiotherapy for rectal cancer: A systematic review and pooled analysis. Ann Surg 2018; 268(6): 955-67.

11. Habr-Gama A, Sabbaga J, Gama-Rodrigues J, São Julião GP, Proscurshim I, Bailão Aguilar P, et al. Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon Rectum 2013; 56(10): 1109-17.

12. Appelt AL, Pløen J, Harling H, Jensen FS, Jensen LH, Jørgensen JC, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol 2015; 16(8): 919-27.

13. Lu Z, Cheng P, Yang F, Zheng Z, Wang X. Long-term outcomes in patients with ypT0 rectal cancer after neoadjuvant chemoradiotherapy and curative resection. Chin J Cancer Res 2018; 30(2): 272-81.

  1. Letaief F, Nasri M, Ayadi M, Meddeb K, Mokrani A, Yahyaoui Y, et al. Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma: a single center experience. Cancer Biol Med 2017; 14(3): 327-34.
  2. Peng J, Lin J, Qiu M, Wu X, Lu Z, Chen G, et al. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer. Clinics (Sao Paulo) 2016; 71(8): 449-54.
  3. Ryan JE, Warrier SK, Lynch AC, Heriot AG. Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review. Colorectal Dis 2015; 17(10): 849-61.
  4. Hartley A, Ho KF, McConkey C, Geh JI. Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol 2005; 78(934): 934-8.
  5. Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg 2012; 99(7): 918-28.
  6. Huang Y, Lee D, Young C. Predictors for complete pathological response for stage II and III rectal cancer following neoadjuvant therapy - A systematic review and meta-analysis. Am J Surg 2020; 220(2): 300-8.
  7. Burbach JP, den Harder AM, Intven M, van Vulpen M, Verkooijen HM, Reerink O. Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: a systematic review and meta-analysis. Radiother Oncol 2014; 113(1): 1-9.
  8. Song JH, Park YH, Seo SH, Lee A, Kim KH, An MS, et al. Difference in tumor area as a predictor of a pathological complete response for patients with locally advanced rectal cancer. Ann Coloproctol 2017; 33(6): 219-26.

22. Tan Y, Fu D, Li D, Kong X, Jiang K, Chen L, et al. Predictors and risk factors of pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer: A population-based analysis. Front Oncol 2019; 9: 497.

23. Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol 2015; 16(8): 957-66.

24. Marco MR, Zhou L, Patil S, Marcet JE, Varma MG, Oommen S, et al. Consolidation mFOLFOX6 chemotherapy after chemoradiotherapy improves survival in patients with locally advanced rectal cancer: Final results of a multicenter phase II trial. Dis Colon Rectum 2018; 61(10): 1146-55.

25. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22(1): 29-42.

26. Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C, et al. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†. Ann Oncol 2015; 26(8): 1722-8.

27. Petrelli F, Trevisan F, Cabiddu M, Sgroi G, Bruschieri L, Rausa E, et al. Total neoadjuvant therapy in rectal cancer: A systematic review and meta-analysis of treatment outcomes. Ann Surg 2020; 271(3): 440-8.

28. Zhu S, Brodin NP, English K, Ohri N, Chuy JW, Rajdev LN, et al. Comparing outcomes following total neoadjuvant therapy and following neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer. E Clinical Medicine 2019; 16: 23-9.

29. Kalady MF, de Campos-Lobato LF, Stocchi L, Geisler DP, Dietz D, Lavery IC, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg 2009; 250(4): 582-9.

 

Untitled Document
Article Location

Untitled Document
Article Option
       Abstract
       Fulltext
       PDF File
Untitled Document
 
ทำหน้าที่ ดึง Collection ที่เกี่ยวข้อง แสดง บทความ ตามที่ีมีใน collection ที่มีใน list Untitled Document
Another articles
in this topic collection

 
Current concept in management of cholangiocarcinoma (โรคมะเร็งท่อน้ำดี (Cholangiocarcinoma))
 
Comparative Study Between the Conventional Endoscopic Cholecystectomy of Paient with Gall Stone using the Operative Assistants and Endoscopic Cholecystectomy using the new Innovated Adjustable Telescopic Holder (การศึกษาเปรียบเทียบการผ่าตัดนิ่วในถุงน้ำดีกล้องวิดิทัศน์ด้วยการใช้เครื่องมือช่วยจับถือกล้องวิดิทัศน์ (Adustable Telescopic Holder) ที่ประดิษฐ์ขึ้นเองกับการใช้ผู้ช่วยผ่าตัดถือกล้องวิดิทัศน์)
 
Laparoscopic Cholecystectomy (การผ่าตัดถุงน้ำดีทางกล้องวิดีทัศน์)
 
<More>
Untitled Document
 
This article is under
this collection.

Surgery
 
 
 
 
Srinagarind Medical Journal,Faculty of Medicine, Khon Kaen University. Copy Right © All Rights Reserved.
 
 
 
 

 


Warning: Unknown: Your script possibly relies on a session side-effect which existed until PHP 4.2.3. Please be advised that the session extension does not consider global variables as a source of data, unless register_globals is enabled. You can disable this functionality and this warning by setting session.bug_compat_42 or session.bug_compat_warn to off, respectively in Unknown on line 0