Rectal cancer and chemoradiation in Iraq: systematic review and meta-analysis

Rectal cancer is one of the most common malignant tumors of gastrointestinal tract. Combining chemotherapy with radiotherapy has a sound effect on its management.

Objectives

Assessment the patterns of characterizations of rectal cancer. Evaluation of the efficacy, and long-term survival of pre-/ postoperative chemoradiation. Collecting all eligible evidence articles and summarize the results.

Methods

By this systematic review and meta-analysis study, we include data of chemoradiation of rectal cancer articles from 2015 until 2019. The research was carried out at Baghdad Medical City oncology centers. Accordance with the PRISMA guidelines, and the Newcastle-Ottawa Scale used.

Results

Starting with gender distribution as M:F ratio of 0.94:1.06. Regarding the age, recorded mean ± SD of 48.7 ± 14.2 years. Rectosigmoid represented the most common site as 50(49.5%), and adenocarcinoma was common histopathology as 76(75.2%) of patients, with localized stage in 50(49.5%). The moderate differentiation was most grade as 65(64.4%). The distant from anal verge mostly seen was 5-10 cm in 59(58.4%). The pulmonary was commonest site of metastasis in 11(10.9%). Most patients undergo APR operation, which has done in 41(40.6%). Adjuvant chemoradiation received by 40(39.6%) patients, whereas neoadjuvant chemoradiation gave to 25 patients. A total of 2609 articles from 12 databases met our search strategies. The highest Newcastle-Ottawa score (8) demonstrated in three studies, and median score (7) calculated in five studies.

Conclusions

The incidence belonged to 5th and 6th decade of life. Rectosigmoid represented the most common site. Mostly, the 5-10 cm distant of tumor from anal verge was common finding. The pulmonary was most site of metastasis. We concluded the formulation of a novel point that survival benefit found in many pre or postoperative chemoradiation trials in rectal cancer.

Keywords
Rectal cancer; Chemoradiation; Rectosigmoid; TMR; APR

Characterizes		n (%)
Gender	Male	49 (48.5)
Gender	Female	52 (51.5)
Age (years) Mean ± SD = 48.7 ± 14.2	<20	0
	21-30	6 (5.9)
	31-40	13 (12.9)
	41-50	20 (19.8)
	51-60	24 (23.8)
	61-70	25 (24.8)
	>70	13 (12.9)
Family history	Positive	7 (6.9)
Family history	Negative	94 (93.1)
Smoking	Smoker	50 (49.5)
Smoking	Non-smoker	51 (50.5)
Comorbidity	Present	46 (45.5)
Comorbidity	Absent	55 (54.5)
IBD	Present	5 (4.9)
IBD	Absent	96 (95.1)

Characteristic		n (%)
Location	Rectosigmoid	50 (49.5)
	Rectum	42 (41.6)
	Anorectal	9 (8.9)
Histopathology	Adenocarcinoma	76 (75.2)
	Mucinous carcinoma	13 (12.9)
	Signet-ring cell carcinoma	4 (4)
	Undifferentiated carcinoma	7 (6.9)
	Adenosequomous carcinoma	1(1)
Stages	Localized	50 (49.5)
	Regional	19 (18.8)
	Distant metastasis	32 (31.7)
Grades	Well differentiation	20 (19.8)
	Moderate differentiation	65 (64.4)
	Poorly differentiation	14 (13.9)
	Undifferentiation	2 (2)
Distant from anal verge	<5 cm	13 (12.9)
	5-10 cm	59 (58.4)
	>10 cm	29 (28.7)

Characteristic		n (%)
Metastatic patterns	Liver	2 (2)
	Lung	11 (10.9)
	Local recurrence	7 (6.9)
	Bone	3 (3)
	Multiple metastases	10 (9.9)
	No metastases	68 (67.3)

Variables		n (%)
Surgery	APR	41 (40.6)
	LAR + loop ieliostomy	4 (4)
	LAR without ieliostomy	3 (3)
	TME	23 (22.8)
	Local excision	5 (5)
	No surgery	25 (24.8)
Chemoradiation	Neoadjuvant chemotherapy + CRT	12 (11.9)
	Neoadjuvant RT + Adjuvant chemotherapy	4 (4)
	Neoadjuvant CRT	7 (6.9)
	Neoadjuvant CRT + Adjuvant chemotherapy	6 (5.9)
	Adjuvant CRT	40 (39.6)
	Palliative CRT	32 (31.7)

Newcastle-Ottawa scale
Study ID	Is the definition adequate?	Is it representative?	Selection adequate	Definition of meta-analysis adequate	Study for the most important factor	Study for Important Additional factors	Ascertainment adequate	Same method of ascertainment	Non-response rate adequate	Total score /9
Ellis 2019	yes	yes	yes	yes	yes	yes	unclear	yes	yes	8
Chapman 2019	yes	yes	unclear	yes	yes	yes	yes	unclear	yes	7
Quezada-Diaz 2019	yes	yes	unclear	yes	yes	yes	yes	yes	no	7
Spiegel 2018	yes	yes	yes	yes	yes	no	yes	yes	yes	8
Mancini 2017	yes	yes	yes	no	yes	yes	yes	yes	yes	8
Franke 2017	yes	yes	yes	no	yes	yes	yes	yes	unclear	7
Dossa 2017	yes	yes	yes	yes	yes	yes	unclear	yes	unclear	7
Kimberly 2017	yes	yes	yes	no	no	yes	yes	yes	unclear	6
Rodel 2016	yes	yes	yes	yes	yes	yes	unclear	yes	unclear	7

Study	Type	n of patients	Chemoradiation	Follow up period	Outcome	Conclusions	N-O score
Ellis et al., 2019¹1 Iraqi Cancer Registry. Ministry Of Health, Iraqi Cancer Board, Baghdad, Iraq; 2011 https://moh.gov.iq/upload/upfile/ar/273.pdf https://moh.gov.iq/upload/upfile/ar/273....	Comparison SEER-Medicare	482	Adjuvant/neoadjuvant plus surgery	24 month	2.5%/3.4% complete response	Treated with CRT-only were less likely to receive surveillance than those treated with conventional treatment	8
Chapman et al., 2019²2 Iraqi Cancer Registry. Annual Report. Iraqi Cancer Registry Board, Ministry Of Health and Environment. Baghdad, Iraq; 2015.	Retrospective cohort study	388	Neoadjuvant, and TMR	9 years	pCR rate of 25% and overall recurrence rate of 14.9%	Short course radiation with neoadjuvant multi-agent chemotherapy is at least as effective as long-course CRT	7
Quezada-Diaz et al., 2019³3 Bray F, Ferlay J, Soerjomataram I, et al. Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca Cancer J Clin. 2018;68:394-424.	Retrospective review	176	Adjuvant, neoadjuvant, and surgery	6 years	-	The trimodality treatment does not seem to impair bowel function	7
Spiegel et al., 2018⁴4 NCCN. Clinical Practice Guidelines in Oncology. Rectal Cancer Version.2; 2019 www.nccn.org. www.nccn.org...	Veterans Health Administration analysis	649	Adjuvant, neoadjuvant, and TMR	66 months	Improve both OS and DFS	There was no improvement in OS or DFS with the addition of a multi-agent over single-agent chemotherapy	8
Mancini et al., 2017⁵5 Alberts SR, Grothy A. In: Casciato DA, Territo MC, editors. Manual of Clinical Oncology: Colorectal cancer. 7th ed. USA: Lippincott Williams & Wilkins, a Wolters Kluwer business; 2012. p. 239–58.	Multiple correspondence analysis	174	Neoadjuvant plus surgery	10 years	13.2% complete response	Neoadjuvant CRT and radical surgery enrich the prognostic profile of patients	8
Franke et al., 2017⁶6 Collette L, Bosset JF, den Dulk M, et al. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol. 2007;25:4379-86.	Systematic review	-	Neoadjuvant plus surgery	5 years	Reduced local recurrence rates	Outline the pragmatic opportunities for future investigation into questions of efficacy, safety, and ultimate improvements	7
Dossa et al., 2017⁷7 Mohiuddin M, Willett CG, et al. In: Halperin EC, Perez CA, Brady LW, editors. Principles and practice of radiation oncology: Colon and Rectum, 2015, 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2015. p. 1366–82.	Systematic review and meta-analysis	867	Neoadjuvant plus watch-and-wait	12-68 months	-	Most patients treated by watch-and-wait avoid radical surgery and of those who have regrowth almost all have salvage therapy	7
Kimberly et al., 2017⁸8 Bosset JF, Calais G, Mineur L, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184-90.	Phase II randomized trial	93	Adjuvant and neoadjuvant plus surgery	4 years	All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention.	TRIAL seems to be a well-tolerated alternative to the current standard treatment sequence.	6
Rodel et al., 2016⁹9 Sauer R, Liersch T, Merkel S, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30:1926-33.	Meta-analysis	-	Preoperative/postoperative plus TMR	-	Encouraging pCR rates but increased surgical complications	The benefit role of induction and consolidation chemotherapy before or after CRT. The minimal or omitted surgery following complete response to CRT The omission of radiotherapy for selected patients with response to neoadjuvant chemotherapy.	7

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[1] *Corresponding author. E-mail: ahmedsalihdr2008@yahoo.com (A.S. Alshewered).