The medical records of patients diagnosed with LARC who were treated with preoperative SIB-VMAT at the Oncology Center at King Faisal Specialist Hospital & Research Centre in Riyadh, Saudi Arabia (KFSH&RC) were retrospectively evaluated. Data retrieved included: demographic data, clinical (c) TN stage, tumor size (cranio-caudal dimension), tumor distance from the anal verge (AV distance), circumferential radial margin (CRM) status on magnetic resonance imaging (MRI) (considered positive if tumor is less than 1 mm away from the mesorectal fascia), pre-operative chemotherapy data, radiation therapy data, surgical data, post-operative morbidity and mortality, pathological TN stage (pTN), Tumor regression grade (TRG), actual number of retrieved lymph nodes, adjuvant chemotherapy data, late toxicity data, site and date of recurrence and status (alive without disease, alive with disease or dead).
All patients diagnosed with rectal cancer underwent: full laboratory work up including tumor markers, full colonoscopy assessment, rigid proctosigmoidoscopy, endorectal ultrasound (ERUS), endoscopic guided biopsy, Computed Topography (CT) chest, abdomen and pelvis and Magnetic resonance imaging (MRI) of the pelvis.
All the patients were evaluated and managed by a multidisciplinary team that included: colorectal surgeons, medical and radiation oncologists, abdominal radiologists, gastrointestinal pathologists, enterostomal therapists and hereditary colorectal tumor registrars.
All the patients included in this study were diagnosed with LARC and satisfied the following inclusion criteria: age ≥ 18 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, pathologically proven adenocarcinoma for rectal lesion up to 15 cm from the anal verge, adequate hematological, renal and hepatic functions, (c) T3, T4 and/or lymph node positive (cN+) by MRI pelvis and/or ERUS, and no evidence of distant metastatic disease.
All patients were planned to receive preoperative CCRT (SIB-VMAT 55 Gy/25 fractions/ 5 weeks’ concomitant with oral daily Capecitabine 825 mg/m2/12h 5 days per week/ 5 weeks. The dose of radiation therapy was reduced to 50 Gy in some patients when our acceptance criteria for (OARs) were not met mostly due to the small bowel. For more details about radiation therapy plans, volumes and acceptance criteria, please review our previous published study (16).
Neoadjuvant chemotherapy for an average of 4 months was used in our center in patients with cT4B and/or upfront unresectable disease to improve tumor surgical resectability. Adjuvant chemotherapy was used for those patients who did not receive neoadjuvant chemotherapy and did not achieve PCR post CCRT with pathologically (pT3, T4) and/or had pathologically node positive disease (pN+). Different regimens were utilized as neoadjuvant or adjuvant chemotherapy (including FOLFOX, CAPEOX and Capecitabine). The type and number of chemotherapy regimens were decided by medical oncologist based on several factors including: age, performance status (PS), co-morbidities, T N stage, in addition to the choice of the patient.
All the patients were followed once weekly during CCRT to assess for acute toxicity. Acute toxicity was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (17). In order to assess response to CCRT and exclude metastasis, a repeated MRI and CT were performed for all patients prior to surgical treatment.
Surgery was performed after an elapsed period of (6–12) weeks post CCRT. The 30 days Postoperative complications rates were evaluated according to the Clavien-Dindo grading system (18).
Tumor regression grade (TRG) was assessed according to the American Joint committee on Cancer (AJCC) staging manual, 8th edition and the College of American Pathologists (CAP) guidelines as modified by Rayan, et al (19). The patients in our study were divided into two groups for comparison (good responders including grade 0,1) and poor responders (grade 2,3).
All patients were kept under regular follow with medical oncology and/or colorectal surgery teams.
Follow up intervals were as follow: every 3–4 months during the first 2 years, every 6 months during the 3rd-5th year and then annualy. Follow up included: history, physical examination, complete laboratory work up with tumor markers, CT chest, abdomen and pelvis. Colonoscopy is usually performed at one and 3 years after the initial colonoscopy and then subsequently every 5 years as long as there are no clear indications to be conducted earlier.
Primary end point for our study was 5-year local recurrence free survival (LRFS). Secondary end points included: 5-year disease free survival (DFS), 5-year overall survival (OS) and late toxicity.
Statistical analysis was conducted utilizing IBM SPSS® Statistics version 26 (IBM® Corp., Armonk, NY, USA). Quantitative variables were described as median and range. Qualitative variables were described as numbers and percentages. Pearson's Chi-square test or Fisher's exact test was used to test the relationship between qualitative variables.
DFS was calculated from the surgery date till the date of documented recurrence, death or last follow up. OS was calculated from the date of diagnosis till the date of death or date of last follow up. Survival analysis was performed utilizing the Kaplan-Meier method, and a comparison between two survival curves was conducted using the log-rank test.
Multivariate analysis was performed using the Cox-proportional hazard regression model with the forward likelihood ratio method for the factors affecting survival on univariate analysis. Hazard ratio (HR) with its 95% confidence interval (CI) was used for risk estimation. All tests were two-tailed. A p-value < 0.05 was considered significant.