Modification and Implementation of NCCN Guidelines™ on Colon Cancer in the Middle East and North Africa Region

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  • a From Ankara University Medical School, Ankara, Turkey; Section of Medical Oncology, King Faisal Specialist and Research Centre, Riyadh, Kingdom of Saudi Arabia; University of Ankara, Department of Surgery, Ankara, Turkey; Tata Memorial Center, Mumbai, India; Hamad Medical Corporation, Al-Amal Hospital, Doha, Qatar; Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan; Hacettepe University Medical School, Ankara, Turkey; and Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Colorectal cancer is less common in the Middle East and South Asia than in western countries, with the rectum the most common primary site, unlike in the United States. A project was planned to address various local issues regarding the management of common cancers, including colorectal cancer, and to adapt the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to the Middle East and North Africa (MENA) region. A survey of oncologists in this geographic area showed that the management practices and issues regarding colorectal cancer are similar to those presented in the NCCN Colorectal Cancer Guidelines. However, 2 major differences exist: most oncologists in the MENA region prefer chest radiograph over CT in pretreatment workup, and almost 50% of them prefer to use cetuximab in the first-line treatment of patients with the wild-type KRAS gene. The committee, comprising 9 oncologists from different countries, proposed 4 modifications to the 2009 version of the NCCN Colorectal Cancer Guidelines for use in the MENA region, relating to 1) short-course preoperative radiotherapy, 2) dose of capecitabine, 3) stereotactic radiotherapy for liver metastasis, and 4) qualification of surgeons performing colorectal surgery. The modification of NCCN Colorectal Cancer Guidelines for use in the MENA region represents a step toward creating a uniform practice in the region based on evidence and local experience.

Colorectal cancer is less common in the Middle East and South Asia region than in the United States (Table 1). However, it is among the 10 most common cancer types in all the countries.1 The age-standardized incidence rate is below 10 per 100,000 in most countries in this region, and ranges between 10 to 40 per 100,000 in a few countries such as Turkey, Qatar, Kuwait, and Israel.1

In a study from Turkey, one third of patients were younger than 50 years, and the rectum was the most common site of occurrence (42.5%), followed by the sigmoid colon (23.2%).2 The epidemiologic features are similar in India.3 However, in a study from Qatar, the descending and sigmoid colon were the most common sites.4

Although the management of colorectal cancer should ideally be based on evidence-based medicine, standardized practices do not exist in other parts of the world. The social, cultural, and economic differences among the countries may be responsible for this lack of standard management. The paucity of local randomized trials from the region adds to the difficulty in following new developments and innovations. However, the need for guidelines that are compatible with evidence-based medicine and social, cultural, and economic realities of the MENA region cannot be denied. The NCCN–MENA project was established to address this need.

Table 1

Colorectal Cancer Age Standardized Rate per 100,000 Population

Table 1
Methods and Results

The colorectal cancer committee comprised 9 members from 6 different countries who collected the data and participated in the deliberations. A survey with 11 questions related to the management of colorectal cancer was prepared and sent to all members to determine the patterns of care and compatibility with the 2009 version of the NCCN Clinical Practice Guidelines in Oncology: Colorectal Cancer (to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org). The survey was distributed to 24 well-known gastrointestinal oncologists in Turkey, and personal opinions were obtained from members in Qatar, United Arab Emirates, and India; Table 2 summarizes the results. Answers from most oncologists in Turkey and committee members from other countries were generally in accordance with the NCCN Guidelines, except those related to questions number 1 and 10. According to the results, 69% did not perform routine chest CT before surgery for all patients with colon cancer. With regard to first-line chemotherapy for metastatic colorectal cancer, 47% of those surveyed preferred to use cetuximab in addition to chemotherapy as first-line treatment in patients with wild-type KRAS tumors.

Committee members met on March 8, 2009, in Istanbul to discuss the survey results and other issues, including proposals for adapting the NCCN guidelines to the MENA region. The proposals accepted by the majority were prepared for presentation at a congress in the United Arab Emirates.

Proposed Modifications
Proposal 1

Short-course preoperative radiotherapy (SCRT) may be an alternative for long-course preoperative radiotherapy (LCRT) or chemoradiotherapy in operable rectal cancer with smaller tumors (< T4).

Rationale

Preoperative SCRT was found to reduce the local recurrence in rectal cancer when compared with surgery alone.5 In a large randomized trial, the Dutch Colorectal Cancer Group showed a significant reduction of local recurrence risk with SCRT followed by total mesorectal excision (TME) compared with TME alone.6 Significant improvement was observed for rectal lesions 5 cm or smaller and those larger than 5 cm.

Another small randomized study from Bulgaria suggests that although SCRT is less effective than conventional radiotherapy in reducing local tumor recurrences in the lower third of the rectum and for advanced rectal cancer (T4 and N2), it is equally as effective in treating other occurrences.7 A Polish study comparing preoperative SCRT with chemoradiation showed similar survival, local control, and late toxicity for both treatments at 4 years.8 Another review of the 2 randomized trials on 396 patients showed that SCRT may be as effective as conventional radiotherapy/chemoradiation.9 A recent retrospective analysis of clinical outcome in 520 Danish patients with rectal cancer also confirmed the efficacy of SCRT.10 Furthermore, a survival benefit was observed for SCRT in the Swedish Rectal Cancer Trial.11

In conclusion, the evidence favors preoperative SCRT as an alternative to conventional preoperative radiotherapy/chemoradiation in operable rectal cancer.

Proposal 2

Dose of capecitabine may be lower than 1000 mg/m2 twice daily.

Table 2

Questionnaire Related to the Management of Colorectal Cancer and the Results

Table 2
Rationale

Many patients in this region are unable to tolerate recommended higher dosages because of severe hand–foot syndrome or diarrhea (based on personal experience of the committee). This could be related to high folate intake in the diet or issues related to food hygiene. The committee proposed a prospective trial be conducted to find the optimal dose for the patients in the region.

Proposal 3

Stereotactic radiation for liver metastasis could be an alternative.

Rationale

Resection is the standard of care for treating liver metastasis in colorectal cancer. However, more than 80% of patients have unresectable disease. Several studies have shown the efficacy of stereotactic body radiation therapy as an alternative to radiofrequency ablation in treating this condition.1215 A phase I/II study showed that it is also safe and effective for treating grade 1 to 3 metastasis.16

Proposal 4

Operations should be performed by surgeons experienced in colorectal surgery and TME, and the surgeries should occur at centers conducting more than 50 surgeries per year.

Rationale

The surgeon is an independent factor for outcome in colorectal surgery. The outcome was also related to surgical caseload and training/teaching activities.17

Because of the lower incidence of colorectal cancer, a dilution of cases between centers occurs in some countries. Some patients managed by general surgeons are found to lack TME for rectal cancer or adequate lymph node dissection. Although no specific caseload number has been established for surgeons, the committee recommended that colorectal surgery should be performed at centers performing at least 50 operations per year.

Conclusions

This multinational project is the first in the region with the goal of establishing standard management of colorectal cancer. The recommendations are based on evidence in the literature and personal experiences that must be tested in prospective randomized studies. Continuation of this scientific cooperation between NCCN and the MENA countries may improve quality of care for patients with colorectal cancer in the region.

Drs. İçli, Akbulut, Bazarbashi, Kuzu, Rasul, Strong, Syed, and Zorlu have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors. Dr. Mallath has disclosed that he has received research funding from GlaxoSmithKline, Amgen Inc., Merck & Co., Inc., and Pfizer Inc. Dr. Engstrom has disclosed that he is an advisory board member for Novartis Pharmaceuticals Corporation.

References

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    Siegel R, Burock S, Wernecke KD. Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society. BMC Cancer 2009;9:50.

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    Mendez Romero A, Wunderink W, Hussain SM. Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase I-II study. Acta Oncol 2006;45:831837.

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    Kim MS, Kang JK, Cho CK. Three-fraction stereotactic body radiation therapy for isolated liver recurrence from colorectal cancer. Tumori 2009;95:449454.

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    Dawood O, Mahadevan A, Goodman KA. Stereotactic body radiation therapy for liver metastases. Eur J Cancer 2009;45:29472959.

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    Fuss M & Thomas CR Jr. Stereotactic body radiation therapy: an ablative treatment option for primary and secondary liver tumors. Ann Surg Oncol 2004;11:130138.

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    Rusthoven KE, Kavanagh BD, Cardenes H. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 2009;27:15721578.

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    Renzulli P, Laffer UT. Learning curve: the surgeon as a prognostic factor in colorectal cancer surgery. Recent Results Cancer Res 2005;165:86104.

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    • Export Citation

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Correspondence: Fikri İçli, MD, Department of Medical Oncology, Ankara University School of Medicine, Cebeci Hastanesi, Dikimevi, Ankara 06590, Turkey. E-mail: Fikri.icli@medicine.ankara.edu.tr
  • 1.

    Barchana M, Ibrahim AS, Mikhail N. MOS Epidemiology Group Special report: cancer incidence in Mediterranean populations. Mediterranean Oncology Society Web site. Available at: http://www.mosepi.org. Accessed March 31, 2010.

    • Search Google Scholar
    • Export Citation
  • 2.

    Eser SY. Cancer incidence in Turkey. In: Tuncer M, ed. Cancer Control in Turkey. Ankara, Turkey: The Ministry of Health of Turkey; 2007:1744.

    • Search Google Scholar
    • Export Citation
  • 3.

    Mohandas KM, Desai DC. Epidemiology of digestive tract cancers in India. Indian J Gastroenterol 1999:18:118121.

  • 4.

    Rasul KI, Awidi AS, Mubarak AA, Al-Homsi UM. Study of colorectal cancer in Qatar. Saudi Med J 2001;22:705707.

  • 5.

    Goldberg PA, Nicholls RJ, Porter NH. Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure. Eur J Cancer 1994:30A:16021606.

    • Search Google Scholar
    • Export Citation
  • 6.

    Kapıteijn E, Marijnen CA, Nagtegaal ID. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638646.

    • Search Google Scholar
    • Export Citation
  • 7.

    Klenova A, Georgiev R, Kurtev P, Kurteva G. Short versus conventional preoperative radiotherapy of rectal cancer: indications. J BUON 2007;12:227232.

    • Search Google Scholar
    • Export Citation
  • 8.

    Bujko K, Nowacki MP, Nasierowska-Guttmejer A. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 2006;93:12151223.

    • Search Google Scholar
    • Export Citation
  • 9.

    Sajid MS, Siddiqui MR, Kianifard B, Baig MK. Short-course versus long-course neoadjuvant radiotherapy for lower rectal cancer: a systematic review. Ir J Med Sci 2010; in press.

    • Search Google Scholar
    • Export Citation
  • 10.

    Jensen LH, Altaf R, Harling H. Clinical outcome in 520 consecutive Danish rectal cancer patients treated with short course preoperative radiotherapy. Eur J Surg Oncol 2009;36:237243.

    • Search Google Scholar
    • Export Citation
  • 11.

    Siegel R, Burock S, Wernecke KD. Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society. BMC Cancer 2009;9:50.

    • Search Google Scholar
    • Export Citation
  • 12.

    Mendez Romero A, Wunderink W, Hussain SM. Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase I-II study. Acta Oncol 2006;45:831837.

    • Search Google Scholar
    • Export Citation
  • 13.

    Kim MS, Kang JK, Cho CK. Three-fraction stereotactic body radiation therapy for isolated liver recurrence from colorectal cancer. Tumori 2009;95:449454.

    • Search Google Scholar
    • Export Citation
  • 14.

    Dawood O, Mahadevan A, Goodman KA. Stereotactic body radiation therapy for liver metastases. Eur J Cancer 2009;45:29472959.

  • 15.

    Fuss M & Thomas CR Jr. Stereotactic body radiation therapy: an ablative treatment option for primary and secondary liver tumors. Ann Surg Oncol 2004;11:130138.

    • Search Google Scholar
    • Export Citation
  • 16.

    Rusthoven KE, Kavanagh BD, Cardenes H. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 2009;27:15721578.

    • Search Google Scholar
    • Export Citation
  • 17.

    Renzulli P, Laffer UT. Learning curve: the surgeon as a prognostic factor in colorectal cancer surgery. Recent Results Cancer Res 2005;165:86104.

    • Search Google Scholar
    • Export Citation
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