|
|
ORIGINAL ARTICLE |
|
Year : 2018 | Volume
: 31
| Issue : 1 | Page : 114-117 |
|
Evaluation of lymphadenectomy in patients receiving neoadjuvant radiotherapy for rectal adenocarcinoma
Alaa A El Sesy1, Mohammed S Ammar1, Ahmed M Elgarhy2
1 General Surgery Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt 2 General Surgery Department, Shebin El-Kom Teaching Hospital, Shebin El-Kom, Egypt
Date of Submission | 29-Sep-2016 |
Date of Acceptance | 23-Nov-2016 |
Date of Web Publication | 14-Jun-2018 |
Correspondence Address: Ahmed M Elgarhy General Surgery Department, Shebin El-Kom Teaching Hospital, Shebin El-Kom Egypt
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/1110-2098.234218
Objective The objective of this study was to evaluate the effect of neoadjuvant radiation on total number and number of positive lymph nodes (LNs) in patients with rectal adenocarcinoma. Background Colorectal cancer is the third most common cancer worldwide. Treatments for colorectal cancer include combinations of surgery, radiation therapy, chemotherapy, and targeted therapy. Neoadjuvant therapy aims to reduce the size or extent of the cancer before radical-treatment intervention, thus making the procedures easier and more likely to succeed. Patients and methods A total of 20 patients with stage 2 and stage 3 cancer were chosen and divided into two groups. The first group included 10 patients who received neoadjuvant therapy before radical surgery for rectal cancer. The second group included 10 patients who underwent radical surgery for rectal cancer without neoadjuvant therapy. For compression number of LNs in both groups before and after course of neoadjuvant and after surgery. Results Neoadjuvant therapy significantly decreased both the number and size of affected LNs in rectal cancer. Conclusion Neoadjuvant therapy was associated with decreased number of affected LNs up to complete clearance. There is a need for more larger randomized trials using preoperative chemoradiotherapy with larger number of patients for better evaluation of response and toxicity in comparison with postoperative chemoradiotherapy.
Keywords: lymph nodes, neoadjuvant, rectal cancer
How to cite this article: El Sesy AA, Ammar MS, Elgarhy AM. Evaluation of lymphadenectomy in patients receiving neoadjuvant radiotherapy for rectal adenocarcinoma. Menoufia Med J 2018;31:114-7 |
How to cite this URL: El Sesy AA, Ammar MS, Elgarhy AM. Evaluation of lymphadenectomy in patients receiving neoadjuvant radiotherapy for rectal adenocarcinoma. Menoufia Med J [serial online] 2018 [cited 2024 Mar 28];31:114-7. Available from: http://www.mmj.eg.net/text.asp?2018/31/1/114/234218 |
Introduction | | |
Colorectal cancer (CRC) is the third most common cancer worldwide, and represents 10% of all cancer-related deaths in North America. In many parts of the western world, CRC is the second leading cause of cancer deaths [1].
Risk factors of colorectal cancer include the following: (i) age, although a person can develop CRC at any age, the risk increases greatly with age; over 90% of CRC cases are diagnosed over the age of 50 years [2]; (ii) lifestyle, a sedentary lifestyle is associated with a higher risk of CRC [3]; studies have also linked obesity, lack of exercise, smoking, and excessive alcohol consumption to a greater risk of CRC [4]; (iii) colorectal polyps or inflammatory bowel diseases, a history of polyps or inflammatory bowel disease, where the bowel is inflamed for many years increases the risk of CRC [5]; (iv) family history, a person's risk doubles if a direct relative has previously had the disease; there is an even greater risk if more than one relative has had CRC [6]; and (v) genetics, individuals with inherited disorders such as familial adenomatous polyposis, where an individual is prone to polyp formation, have a higher risk of developing CRC [7]. CRC is diagnosed by obtaining a biopsy of the colon during a sigmoidoscopy or colonoscopy. This is then followed-up by imaging (computed tomography, MRI, ultrasound) to determine whether the disease has spread [8]. In Europe, the 5-year survival rate for CRC is less than 60%. In the developed world, about a third of people who have the disease die because of it. Survival is directly related to detection and the type of cancer involved, but the overall survival is poor in case of symptomatic cancers, as they are typically quite advanced. Survival rates in early-stage detection are about five times that of late-stage cancers. The most common staging system for CRC is the tumor, node, metastasis (TNM) staging system, which classifies a patient into stages I–IV according to the level of invasion or spread of the tumor to other organs (metastasis). Examination of at least 12 lymph nodes (LNs) is recommended for adequate CRC staging [9].
Treatments for CRC include some combinations of surgery, radiation therapy, chemotherapy, and targeted therapy. Cancers that are confined within the wall of the colon may be curable with surgery, whereas cancers that have spread widely are usually not curable, in which case treatments are focused on improving the quality of life and symptoms. Neoadjuvant therapy is the administration of therapeutic agents before the main treatment. Neoadjuvant therapy aims to reduce the size or extent of the cancer before radical-treatment intervention, thus making procedures easier and more likely to succeed, and reducing the consequences of a more extensive treatment technique that would be required if the tumor does not reduce in size or extent. It is the standard therapy for advanced rectal tumors, which provides better local control of the disease and potentially increases the success rate of sphincter preservation surgery [10]. Neoadjuvant radiation may affect the number of LNs harvested after resection, and may thus influence correct staging of the tumor [11].
Patients and Methods | | |
This study included 20 patients who presented with rectal adenocarcinoma to the outpatient clinic of both Menoufia University Hospitals and Shebin El-Kom Teaching Hospital. All patients in the present study required resection of their tumors with intent to cure. The study was prospectively conducted during the period from 2014 to 2015, and all the procedures were performed on elective basis. Patients were divided into two groups: group 1 received neoadjuvant radiotherapy (NRT), and group 2 did not receive NRT. Written informed consent was obtained from all patients to be included in this study. All patients were evaluated with regard to complete clinical assessment (personal and clinical examination), colonoscopy, and biopsy. Laboratory investigations (complete blood picture, kidney profile, liver profile, carcinoembryonic antigen test, and carbohydrate antigen 19-9 test), radiological investigations (MRI, transrectal ultrasound, computed tomography), and preoperative adjuvant radiochemotherapy consisting of a total of 5040 Gy delivered (as at least 6-MV photons) in 28 fractions of 180 Gy, five times weekly for 5 weeks to the pelvis with individually shaped portals and the use of a three-field or four-field box technique, were carried out. During the first and fifth weeks of RT, 5-fluorouracil was administered as a 120-h continuous infusion at a dose of 1000 mg/m 2/day. Evaluation of radiochemotherapy effects was performed 3–5 weeks after the end of therapy, regarding downstaging of the tumor using clinical rectal examination (Mason's classification) and MRI. Operative resection was performed for resectable tumors, either by total mesorectal excision or by abdominoperineal therapy 5 weeks after the end of therapy.
Statistical analysis
Data were collected in tables and then analyzed using X2-tests. P values of less than 0.05 were considered significant.
Results | | |
This prospective study included 20 patients, who underwent radical surgery for rectal cancer. They were divided into two groups: the first group (group 1) included 10 patients who received NRT before surgery, and the second group (group 2) included 10 patients who underwent radical surgery for rectal cancer without preoperative radiotherapy (RT). The total number of LNs in both groups before NRT was less than four in two patients in group 1 and three patients in group 2, from 4 to 11 in five patients in group 1 and four patients in group 2, and more than 12 in three patients each in both groups [Table 1]. | Table 1: Number of lymph nodes in both groups before neoadjuvant radiotherapy, as detected by MRI
Click here to view |
The status of LNs in both groups before NRT was as follows: no patient in both groups was N0; three patients in group 1 and four patients in group 2 were N1, and seven patients in group 1 and six patients in group 2 were N2 [Table 2]. | Table 2: Status of lymph nodes in both groups before neoadjuvant radiotherapy, as detected by MRI
Click here to view |
The total number of LNs in both groups after NRT was less than four in eight patients in group 1 and three patients in group 2, from 4 to 11 in two patients in group 1 and four patients in group 2, and more than 12 in no patient in group 1 and three patients in group 2 with a significant P value [Table 3]. | Table 3: Number of lymph nodes in both groups after neoadjuvant radiotherapy, detected by MRI
Click here to view |
The status of LNs in both groups after NRT was as follows: three patients in group 1 and no patient in group 2 were N0, five patients in group 1 and four patients in group 2 were N1, and two patients in group 1 and six patients in group 2 were N2 with insignificant P value [Table 4]. | Table 4: Lymph node status in both groups after neoadjuvant radiotherapy, as detected by MRI
Click here to view |
The total number of LNs in both groups after surgery was 12 in eight patients in group 1 and three patients in group 2, more than 12 in two patients in group 1 and seven patients in group 2 with significant P value [Table 5]. | Table 5: Number of lymph nodes in each group according to pathological specimen
Click here to view |
The status of LNs in both groups after surgery was as follows: seven patients in group 1 and no in group 2 were N0, two patients in group 1 and three patients in group 2 were N1, one patient in group 1 and seven patients in group 2 were N2, with significant P value [Table 6]. | Table 6: Effect of neoadjuvant radiotherapy on lymph node status (whether positive or negative after surgery)
Click here to view |
Discussion | | |
The mainstay of treatment for carcinoma of the rectum is radical surgery, with or without sphincter preservation. The beneficial effect of preoperative pelvic irradiation as an adjuvant treatment has been confirmed in several studies [12]. Pahlman and Glimelius [13] showed the superiority of preoperative RT over postoperative therapy. Many studies have reported that combining conventional-dose preoperative RT with 5-fluorouracil is safe, tolerable, and increases surgical downstaging [14]. Group 1 patients were subjected to preoperative RT with a daily fraction of 1.8 Gy to a total dose of 45–50 Gy over 5–5.5 weeks concomitantly with chemotherapy; leucoverin 20 mg/m 2 was administered as a 30-min intravenous infusion followed by 5-flourouracil 370 mg/m 2 as 1-h infusions on days 1–5 and repeated on days 29–34 through the course of RT. With MRI 20% of patient had criteria suggestive 11 LNs affected and about 80% of patient with criteria suggestive more than 11 LNs affected. In our study, we found 70% patient with negative LNs and 30% with positive LN in rectal cancer. Mignanelli et al. [15] showed that the risk of LN positivity decreases to almost 5% when primary tumor regression is complete. Adequate lymphadenectomy has shown to allow accurate pathological staging and better prediction of prognosis [16]. Neoadjuvant therapies may decrease the size of irradiated benign LNs by 1–2 mm [17]. The reduction in LN size may decrease the likelihood of smaller LNs to be detected in the surgical specimen and lead to a lower number of examined LNs. Also, the decrease in examined LNs may have a direct tumoricidal effect, and thus correlates with the lower LN yield in patients who receive NRT [18]. Other studies have demonstrated a correlation between NRT and reduction of examined LNs retrieved in radical rectal cancer resections [19]. Among these, three retrospective, single-institution studies showed a reduction of 3–7 LNs when patients received NRT. Two multicenter studies reported a lower number of examined LNs (6–10) with NRT compared with other multicenter and population-based studies [20].
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References | | |
1. | Gellad F, Provenzale D. Colorectal cancer: national and international perspective on the burden of disease and public health impact. Gastroenterology 2010; 138:2177–2190. |
2. | Huxley R, Ansary A, Clifton P, Czernichow S, Parr L, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer2009; 125:171–180. |
3. | Boyle T, Keegel T, Bull F, Heyworth J, Fritschi L. Physical activity and risks of proximal and distal colon cancers: a systematic review and meta-analysis. J Natl Cancer Inst 2012; 104:1548–1561. |
4. | Renehan G, Tyson M, Egger M, Heller F, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371:569–578. |
5. | Jess T, Simonsen J, Jorgensen T, Pedersen V, Nielsen M, Frisch M. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology 2012; 143:375.e1–381.e1. |
6. | Morris J, Penegar S, Whitehouse E, Quirke P, Finan P, Bishop T, et al. A retrospective observational study of the relationship between family history and survival from colorectal cancer. Br J Cancer 2013; 108:1502–1507. |
7. | Imperiale F, Ransohoff F. Risk for colorectal cancer in persons with a family history of adenomatous polyps: a systematic review. Ann Intern Med 2012; 156:703–709. |
8. | Schoen R, Pinsky P, Weissfeld J, Yokochi L, Church T, Laiyemo A, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 2012; 366:2345–2357. |
9. | Shia J, Wang H, Nash G. Lymph node staging in colorectal cancer revisiting the benchmark of at least 12 lymph nodes in R0 resection. J Am Coll Surg 2012; 214:348–355. |
10. | Habr-Gama A, Perez R, Proscurshim I, Rawet V, Pereira D, Sousa A, et al. Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvantchemo-radiation therapy: what does it mean? Dis Colon Rectum 2008; 51:277–283. |
11. | Kim W, Kim K, Min S, Lee Y, Sohn K, Cho CH, et al. The prognostic impact of the number of lymph nodes retrieved after neoadjuvant chemoradiotherapy with mesorectal excision for rectal cancer. J Surg Oncol 2009; 100:1–44. |
12. | Dahl O, Horn A, Morlid I. Low dose preoperative radiation postpones recurrence in operable rectal cancer. Cancer 1990; 66:2286–2294. |
13. | Pahlman L, Glimedlius B. Pre or postoperative radiotherapy in rectal or rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 1990; 211:187–195. |
14. | Bosset F, Collette L, Calais G. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006; 355:1114–1123. |
15. | Mignanelli D, de Campos-Lobato F, Stocchi L, Lavery C, Dietz W. Down-staging after chemoradiotherapy for locally advanced rectal cancer: is there more (tumor) than meets the eye? Dis Colon Rectum 2010; 53:251256. |
16. | Roh S, Colangelo H, O'Connell J. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 2009; 27:5124–5130. |
17. | Koh M, Chau I, Tait D, Wotherspoon A, Cunningham D, Brown G. Evaluating meso-rectal lymph nodes in rectal cancer before and after neoadjuvant chemo-radiation using thin-section T2-weighted magnetic resonance imaging. Int J Radiat Oncol Biol Phys 2008; 71:456–461. |
18. | Wright C, Law H, Berry S, Smith J. Clinically important aspects of lymph node assessment in colon cancer. J Surg Oncol 2009; 99:248–255. |
19. | Norwood G, Sutton J, West K, Sharpe P, Hemingway D, Kelly J. Lymph node retrieval in colorectal cancer resection specimens: national standards are achievable, and low numbers are associated with reduced survival. Colorectal Dis 2010; 12:304–309. |
20. | Mekenkamp L, Krieken J, Marijnen C, Velde C, Nagtegaal I. Lymph node retrieval in rectal cancer is dependent on many factors: the role of the tumor, the patient, the surgeon, the radiotherapist, and the pathologist. Am J Surg Pathol 2009; 33:1547–1553. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
|