DOI: https://doi.org/10.21203/rs.3.rs-2827005/v1
Background
Management of locally advanced rectal cancer is evolving with current emphasis on the addition of chemotherapy to short course radiotherapy regimen. In this study, we primarily aimed to analyse the difference in overall response rates between the experimental regimen of short-course radiotherapy and sequential chemotherapy and standard long-course CTRT in patients of locally advanced rectal cancer.
Methods
33 patients of locally advanced rectal cancer were randomized to a standard long-course CTRT arm and SCRT followed by a sequential chemotherapy arm. Patients in the standard arm received 45Gy in 25 fractions over five weeks with concurrent oral capecitabine while patients in the experimental arm received 25Gy in 5 fractions over 1 week followed by 3 cycles of CAPOX chemotherapy. Clinical and radiological response assessment was conducted after the completion of neoadjuvant treatment, right before surgery.
Results
Radiological tumour regression showed a statistically non-significant trend favouring the experimental arm (rates of complete tumour regression 35.7% versus 23.1%). Pathological tumour regression rates also showed a trend favouring the experimental arm with a pCR rate of 30% versus 20% in the CTRT arm. a higher number of patients in the short-course arm experimental arm experienced grade 3 diarrhoea, whereas acute skin toxicity was seen only in the CTRT arm. Short-course radiotherapy was tolerated with fewer treatment interruptions compared to CTRT.
Conclusions
Short-course radiotherapy followed by three cycles of CAPOX chemotherapy is comparable to long-course CTRT in terms of tumour response. This is a better alternative regimen with fewer treatment interruptions in a resource-limited setting.
Colorectal cancers account for 10% of all new cancer cases worldwide(1). In India, 28260 new cases of rectal cancer were diagnosed in 2020, with a mortality of 16149(2). Although the absolute rates are low, there was a 20% increase in the incidence of CRC in the Indian population from 2004 to 2014(3). The contemporary approach to managing rectal cancer has evolved with greater emphasis on surgical technique, improved preoperative imaging, and integration of neoadjuvant chemotherapy into the radiation schedule. Both short-course preoperative radiotherapy (SCRT) with immediate surgery and long-course chemoradiation (LCCRT) are standard neo-adjuvant strategies, both demonstrating similar efficacy in preventing local recurrence, distant metastasis and improving disease-free survival (DFS). SCRT is highly cost-effective with high compliance rates and hence is gaining popularity worldwide, partly because of the inherent flexibility in timing and the ability to add neo-adjuvant systemic chemotherapy when surgery is delayed.
Short course radiation schedule was introduced by the Swedish rectal cancer trial in the 1990s and showed better survival and local control when added to surgical treatment(4). The Dutch TME trial used the same protocol with an improved surgical total mesorectal excision technique. It showed a further reduction in local recurrence with no survival benefit(5). The five-year local recurrence rates decreased from almost one-third of the cases to about 5% after introducing total mesorectal excision and preoperative short-course radiotherapy. Later in 2004, the German rectal cancer trial established neoadjuvant long-course CTRT as the standard in locally advanced rectal cancer with better local control and toxicity profile(6). Trials that investigated the role of chemotherapy along with long-course radiotherapy showed better local control, pathological complete response rates and tumour downstaging with 5FU-based chemotherapy protocols(7)(8). Prospective studies comparing long-course CTRT and short-course RT demonstrated no significant difference in late oncological outcomes(9). Higher tumour downsizing rates observed in the long-course CTRT arm were not reflected in the survival or sphincter preservation rates(10). Introducing an interval of time (4–8 weeks) between SCRT and surgery resulted in reduced postoperative complications and increased PCR rates(11). Sequential neoadjuvant chemotherapy after SCRT aims to improve tumour downstaging, decrease distant metastasis and increase compliance. Recently published RAPIDO(12) and STELLAR(13) trials have explored the total neoadjuvant approach in the US and the Chinese populations, respectively and shown promising results.
Sequential neoadjuvant chemotherapy after SCRT aims to improve tumour downstaging, decrease distant metastasis and increase compliance. With improved local control, distant metastasis was the major challenge in rectal cancer-18% of diagnosed colorectal cancer patients present with metachronous metastasis(14). With the evolution of neoadjuvant treatment in rectal cancer, overall survival rates were not improved significantly. Poor compliance with chemotherapy in an adjuvant setting can be one of the reasons for this. While introducing chemotherapy in a neoadjuvant setting, further studies are required to explore the optimal regimen, schedule and number of chemotherapy schedules. Our study was driven by the paucity of data in the Indian population comparing the two neoadjuvant radiation therapy protocol with chemotherapy in the management of rectal cancer. In a resource constraint setting like India, especially in centres with long waiting list for radiation therapy, a five-day radiation course has logistic benefits, including short overall treatment time leading to better compliance, cost-effectiveness and convenience. Under the limited time frame of our study, our primary aim was to assess the difference in the clinical and radiological response to sequential SCRT and chemotherapy compared to long-course CTRT in the neo-adjuvant setting.
This study was conducted at the Department of Radiation Oncology, Dr B.R.A. IRCH, in collaboration with the Department of Medical Oncology and Surgical Oncology, AIIMS, New Delhi. Ethical clearance was obtained from the Institute Ethics Committee (IECPG-758/30.01.20). Patients with biopsy-proven adenocarcinoma of the rectum were chosen for the study according to inclusion criteria. All patients were explained the treatment options, and written consent was obtained before the start of therapy.
Previously untreated patients with ECOG ≤ 1, above or 18 years of age with confirmed histopathological diagnosis of rectal cancer were included in the study if they fulfilled at least one of the following criteria on pelvic MRI/CECT (cT3-T4, node-positive, mesorectal fascia involvement, metastatic lateral lymph nodes, extra-mural vascular invasion (EMVI)). Patients were evaluated with complete metastatic workup with CECT of the chest, abdomen and pelvis or a whole-body PET CT and assessed for their tolerance for planned chemotherapy if they have adequate blood counts and normal liver and kidney function. Patients who presented with distant metastasis, relapse/synchronous malignancies, uncontrolled comorbidities, active Crohn’s disease or ulcerative colitis and those who received prior treatment for rectal cancer were excluded. Demographic details (age, gender, performance status, comorbidity), symptoms at presentation, radiological laboratory investigations and treatment parameters were recorded in predesigned proforma.
Patients were randomized to receive either preoperative long-course radiation therapy (Arm A) to a dose of 45Gy in 25 fractions with concurrent Capecitabine chemotherapy followed by TME performed 6–8 weeks later or with short-course radiation (Arm B) to a dose of 25 Gy in 5 fractions in 5 days followed by CAPOX started after 7–10 days for three cycles at three weekly intervals and TME within 2–3 weeks of completion of chemotherapy. Chemotherapy and radiotherapy-related toxic effects were assessed according to Common Terminology Criteria for Adverse Events (V.5.0). Response assessment included clinical evaluation with digital rectal examination and radiological with CEMRI after treatment completion, one week before surgery in both groups of patients. The images were reviewed for the radiological response by comparing the pre-treatment and post-treatment scans. The tumour regression was graded according to the 5-point radiological tumour regression grading adapted from Tayler et al. (15).
Radiotherapy was delivered by 3DCRT in VERSA-HD, ELEKTA. Patients in the standard arm (arm A) received a total dose of 45 Gy in 25 daily fractions over five weeks, treated five days per week at 1.8 Gy per fraction. This dose fractionation regime's biologically effective dose (BED) is 72Gy & 53.1Gy for α/β of 3 and 10, respectively. Patients in the experimental arm (arm B) received 25 Gy in 5 fractions over one week (BED of 66.6Gy & 37.5Gy for α/β of 3 and 10, respectively). RTOG consensus guidelines were used for target volume delineation in both arms(16).
Patients randomised to the standard arm received concurrent capecitabine at a dose of 825 mg/m2 twice daily, five days/week, during five weeks of RT. In the Experimental arm, three cycles of 3 weekly CAPOX regimen were given. CAPOX regimen consisted of capecitabine 1000mg/m2 twice daily for days 1–14 combined with oxaliplatin 130mg/m2 once every three weeks. Dose modifications were made according to patient tolerance. Adjuvant chemotherapy was added in both arms to complete six months of peri-operative chemotherapy.
Surgery was performed after 8–10 weeks of completion of radiation treatment in both arms. Response assessment with CE-MRI pelvis was carried out 1–2 weeks before surgery. Surgical treatment was the same in 2 trial groups aiming at sphincter preservation with LAR (low anterior resection) & ultra–LAR in upper and mid-rectal tumours sufficiently away from sphincter complex and inter-sphincteric resection (ISR) in low-lying tumours with good response to neoadjuvant treatment. APR (abdominoperineal resection) was done in other lower rectal cancers, with exenteration reserved for extensive disease post-neo-adjuvant treatment.
A weekly review was done in all patients during treatment—the first assessment after radiotherapy was done at one month to assess treatment-related toxicities. The monthly evaluation was continued till the completion of surgery and adjuvant chemotherapy. Patients were then followed up at three and six months.
We initially planned a feasibility study with 25 patients in each arm. Due to the COVID-19 pandemic and related issues, a total of 33 patients were recruited within the stipulated duration of the study. Statistical analysis was carried out in the SPSS software v 23.0. Statistical differences between the two groups were compared using paired student t and chi-square tests. Parameters for clinical response assessment were compared with the baseline values using the Wilcoxon rank sum (Mann-Whitney) test and the chi-square test. Radiological tumour regression was analysed between 2 groups using the chi-square test. P-value < 0.05 was considered significant.
A total of 33 patients were accrued in the study between February 2020 to July 2021. Patients were randomised into standard and interventional arms with the help of computer-generated block randomisation. Seventeen patients were recruited in the long-course CTRT arm (standard arm-A), and 16 were recruited in the short-course RT followed by the chemotherapy arm. The median age of patients recruited was 44.6 in arm A and 46.3 in arm B. All patients presented with the symptom of per rectal bleeding. All the patient-related characteristics were comparable in both arms (Table 1). Baseline CEMRI was performed in all recruited patients along with a complete metastatic workup, including chest imaging, carcinoembryonic antigen (CEA) levels and routine haematological investigations to ascertain the exact stage of disease and to rule out distant metastasis before treatment. CEA value less than or equal to 5 ng/ml was considered normal. In the colonoscopy, distance from the anal verge and total length of disease was noted if the scope was negotiable. Mesorectal fascia involvement was seen in one-third of all recruited patients and distributed equally between the two arms. A higher proportion of patients in the standard arm had lymph nodal metastasis at presentation compared to the study arm (94% versus 62.5%). The rate of treatment interruption was significantly lower in the SCRT/Chemotherapy arm compared to the long-course CTRT arm (p-value = 0.038). All patients in the SCRT arm completed treatment within one week, whereas four patients in the long-course CTRT arm had treatment interruptions of more than ten days. The rest of the tumour workup and treatment-related details were comparable, as shown in Table 2.
Table 1: Baseline demographic and clinical characteristics of intention to treat population.
|
Characteristic |
Standard Arm(A) |
Interventional Arm(B) |
p-value |
|
Age |
44.6 ± 13.9 |
46.3 ± 16.5 |
0.738 |
|
Male |
8 (47.1) |
5(31.2) |
0.353 |
|
Female |
9 (52.9) |
11(68.7) |
0.353 |
|
Serum CEA Normal Elevated |
13(76.5) 4(23.5) |
13(81.2) 3(18.7) |
0.737 |
|
Initial imaging MRF positive LN involved Organ infiltration Tumour length |
7(41.2) 16(94.1) 3(17.6) 7(3.5-13) |
4(25) 10(62.5) 2(12.5) 6.2(2.7-10) |
0.325 0.026 0.680 0.169 |
|
Colonoscopy Scope not passed Length Distance from AV |
4(23.5) 8(4-10) 4(0-10) |
2(12.5) 6(3-10) 4(0-10) |
0.412 0.125 0.413 |
|
Initial clinical T stage T3 T4a T4b |
12(70.6) 2(11.8) 3(17.6) |
12(75) 2(12.5) 2(12.5) |
0.919 |
|
Initial clinical N stage N0 N1a N1b N2a N2b |
1(5.9) 1(5.9) 5(29.4) 8(47.0) 2(11.8) |
6(37.5) 3(18.7) 2(12.5) 4(25) 1(6.2) |
0.112 |
|
Initial stage group IIA IIIB IIIC |
1(5.9) 10(58.8) 6(35.3) |
6(37.5) 5(31.2) 5(31.2) |
0.071 |
Table 2: Details of surgery and pathological findings.
|
Characteristic |
Standard Arm(A) |
Interventional Arm(B) |
p-value |
|
Surgery Done Not done |
11(68.7) 5(31.2) |
12(75) 4(25) |
0.694 |
|
Type of surgery LAR APR ISR Exenteration EL only |
6(54.5) 4(36.4) 0(0) 0(0) 1(9.1) |
4(33.3) 4(33.3) 3(25) 1(8.3) 0 |
0.252 |
|
Pathological T stage T0 T1 T2 T3 T4b |
2(20) 0 0 8(80) 0 |
3(27.3) 1(9.1) 2(18.2) 4(36.4) 1(9.1) |
0.240 |
|
Pathological N stage N0 N1a N1b N2b |
7(70) 0 1(10) 2(20) |
9(81.8) 1(9.1) 1(9.1) 0(0) |
0.360 |
|
Pathological stage group 0 I IIA IIC IIIA IIIB IIIC |
2(20) 0(0) 5(50) 0(0) 0(0) 1(10) 2(20) |
3(27.3) 2(18.2) 3(27.3) 1(9.1) 1(9.1) 1(9.1) 0 |
0.353 |
Table 3: Clinical response assessment, radiological and pathological tumour regression rates. TRG, tumour regression grade.
|
Variable |
Standard arm(A) |
Interventional arm(B) |
Difference |
p-value |
|
Distance from AV Baseline Post-treatment |
3.6 ± 1.9 2.9 ± 2.0 |
3.4 ± 1.9 3.25 ± 2.4 |
0.2(-1.2 – 1.5) -0.3(-2.2 – 1.5) |
0.785 0.718 |
|
Decreased anal tone Baseline Post-treatment |
3(17.6%) 2(12.5%) |
2(12.5%) 1(6.7%) |
|
0.680 0.583 |
|
Fixed disease Baseline Post-treatment |
2(11.8%) 4(30.8%) |
2(12.5%) 1(8.3%) |
|
0.948 0.161 |
|
Location Baseline Circumferential Anterior Posterior Lateral Post-treatment Circumferential Anterior Posterior Lateral |
14(82.3%) 1(5.9%) 2(11.8%) 0(0%)
12(93.3%) 0(5.9%) 1(7.7%) 0 |
11(68.5%) 2(12.5%) 1(6.2%) 2(12.5%)
8(66.7%) 2(16.7%) 2(16.7%) 0 |
|
0.392
0.212 |
|
Radiological TRG TRG 1 TRG 2 TRG 3 TRG 4 TRG 5 |
3(23.1%) 2(15.4%) 5(38.5%) 2(15.4%) 1(7.7%) |
5(35.7%) 3(21.4%) 2(14.3%) 2(14.3%) 2(14.3%) |
|
0.683 |
|
Pathological TRG TRG 0 TRG 1 TRG 2 TRG 3 |
2(20%) 2(20%) 2(20%) 4(40%)
|
3(30%) 4(40%) 2(20%) 1(10%) |
|
0.446 |
Table 4: Summary of published studies comparing total neoadjuvant therapy with standard CTRT in locally advanced rectal cancer, compared with current study results.
|
Study |
Eligibility(n) |
Primary outcome |
Treatment regimen |
PCR rates (%) |
Grade 3+ GI toxicity (%) |
Results |
Remarks |
|
PRODIGE 23 |
c T3/T4 (461) |
DFS at 3 years |
Long course CTRT 6 Cycles NACT (FOLFIRINOX) + CTRT |
12 28 |
12 6 |
3-year DFS significantly better with NACT. |
SCRT was not part of the protocol |
|
RAPIDO trial |
High risk MRI features (c T4a or T4b /c N2/ EMVI/ MRF+) (920) |
Disease-related treatment failure |
Long course CTRT SCRT + 6 cycle CAPOX/9 cycle FOLFOX |
14 28 |
9 17 |
Significantly lower disease-related treatment failure in the experimental arm. |
Primarily aimed to reduce distant metastasis, 99% of patients received CAPOX. |
|
Polish II trial |
Fixed T3/ T4(541) |
R0 resection rate |
Long course CTRT SCRT + 3 cycle FOLFOX |
12 16 |
26 14 |
No difference in R0 resection rates, the 3-year OS favoured SCRT/CCT arm, but 8 years OS was not different. |
64% of patients in long course CTRT arm received oxaliplatin |
|
STELLAR trial |
c T3-T4 or N+(599) |
DFS at 3 years |
Long course CTRT SCRT + 4 cycle CAPOX |
11.8 16.6 |
7.5 10.4 |
DFS was similar in the 2 arms. |
Proved non-inferiority of experimental regimen |
|
Present study |
c T3-T4 or MRI risk factors (33) |
Clinical and radiological response assessment after neoadjuvant treatment |
Long course CTRT SCRT + 3 cycle CAPOX |
20 30 |
5.9 31.2 |
Trends toward better response in the experimental arm |
Proved feasibility of regimen in Indian population. |
Primary Outcomes
31 out of 33 patients were available for response assessment. One patient in the interventional arm could not complete treatment due to myocardial infarction after finishing radiation therapy. One patient of long course CTRT arm succumbed to death due to severe diarrhoea and hypovolemic shock, leading to cardiac arrest after one week of radiotherapy completion. After completion of neoadjuvant treatment, five patients had a complete clinical response with no growth palpable in clinical examination. Clinical response assessment was done by assessing the palpability, tone, mobility, location and distance from the anal verge before and after treatment. There was no significant difference in the proportion of non-palpable disease after neoadjuvant therapy between the two arms. The mean distance from the anal verge to the condition in the baseline was 3.6 and 3.4 cm, respectively, in the long-course CTRT and SCRT arms which reduced in response assessment to 2.9 and 3.2 cm. reduced distance to disease from the anal verge can be an indicator of disease progression and involvement of lower rectum. Although the absolute difference in the reduction is more in the long-course CTRT group, it was statistically insignificant. The reduced anal tone is associated with tumour infiltration of anal sphincters and impaired sphincter functioning. The number and percentage of patients with loss of anal tone decreased in both groups post-treatment. However, the magnitude of this change in both groups was not significantly different. 2 patients each presented with a clinically fixed disease in both groups (restricted mobility of the growth on per rectal examination likely due to involvement of adjacent organs or pelvic side wall). At response assessment, four patients had fixed conditions in the long-course arm compared to only one in the SCRT arm. This difference was also not statistically significant (p = 0.162) (Table 3).
Radiological tumour regression grade was compared between the two treatment groups. Four out of the 31 patients developed distant metastasis, two patients to the liver and one each to the lung and sacral bone. Out of these, three patients were in the standard arm, while 1 with liver metastasis was in the experimental arm. Tumour regression grading (TRG) was not performed in the patients who developed metastatic disease. Hence, 27 patients were analysed. Complete tumour regression was seen in 8 patients – 3 in arm A and 5 in arm B. The rates of complete radiological response were higher in the SCRT group (35.7% versus 23.1%) though it was not statistically significant. Most patients in the long-course CTRT group presented with moderate tumour regression (TRG 3 – in 38.5%).
Out of the 23 patients who underwent surgery, pathological tumour regression grading was available for 20 patients. 5 patients had a pathological complete response – 2 in the standard arm and 3 in the interventional arm (Table 3). Complete and near complete tumour regression (TRG 0& 1 combined) was observed in 70% of patients in the SCRT arm compared to 40% in the long-course CTRT arm.
The most commonly observed acute toxicity was acute bowel toxicity characterised by diarrhoea and pain abdomen in both groups. 4 out of 17 patients in the standard arm and 9 out of 16 patients in the interventional arm experienced at least grade 2 bowel toxicities (p-value = 0.085). A higher proportion of patients in the experimental arm presented with grade 3 bowel toxicities requiring inpatient care (5 patients). Apart from the one death caused by bowel toxicities, no grade 3 or more bowel complaints were seen in patients receiving standard chemoradiotherapy. All acute toxicities subsided within one month of completion of treatment. Acute grade 2 or more skin toxicities were observed in the long course CTRT arm only (p value = 0.136). One patient had grade 3 dermatitis requiring inpatient care. The most common haematological toxicity was anaemia. 2 patients in long course CTRT arm and one patient in short course CTRT arm presented with grade 2anaemia. No grade 3 or more haematological toxicities were observed. Commonly observed chronic toxicity was rectovaginal fistula seen in 3 out of 15 patients in the SCRT arm. No postoperative complications were observed in the long-course CTRT arm. Two patients in the SCRT arm presented with postoperative complications, one with urinary retention and bleeding from the stoma, both managed conservatively.
Neoadjuvant treatment is the standard of care in rectal cancer. Long-course chemoradiotherapy and short-course radiotherapy have separately evolved to be effective neoadjuvant treatment approaches. Head-on comparisons between these schedules also showed similar oncologic outcomes. However, tumour downstaging was better in the chemoradiotherapy arm. Immediate surgery within ten days of radiotherapy in patients receiving a short course of radiotherapy might have contributed to this. Recent studies have incorporated chemotherapy into the short course radiation schedule and shown promising results. These studies had different chemotherapy protocols aiming at different endpoints. In our study, we introduced three cycles of CAPOX chemotherapy before surgery in the experimental arm, primarily aiming to improve tumour downstaging. Several other studies with similar neoadjuvant protocols and objectives including the POLISH II trial(18), RAPIDO(12) trial and STELLAR tr l also followed three cycles of FOLFOX, 6 cycles of CAPOX and 4 cycles of CAPOX in the neoadjuvant setting. The salient features of similar studies are compared with our study in Table 4.
Our study assessed tumour response with clinical and radiological parameters after the delivery of assigned treatment. This is justified by the evolving wait-and-watch strategy in rectal cancer, where we might require well-defined response assessment protocols. The pathological response assessment conducted as a secondary endpoint showed a good correlation with radiological assessment findings (Table 3). Studies with similar protocols have mainly focused on outcomes like radical surgery rates and reduction in distant metastasis as assessed by survival rates. We hypothesised response rates to be surrogates of long-term oncological outcomes and the experimental protocol to be equally efficacious as the standard arm. The experimental arm was well tolerated; fifteen of sixteen recruited patients started chemotherapy within three weeks of radiotherapy completion and received three cycles of chemotherapy. Although not statistically significant, the radiological and pathological tumour regression grading favoured the experimental arm. However, the clinical examination could have been more reliable in assessing response as it is difficult to differentiate between residual disease and post-radiotherapy changes. Higher rates of grade three diarrhoea in this arm may be reduced by more conformal planning techniques like intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). Treatment interruption was only seen in the long-course CTRT arm. This might be due to the long duration of treatment. After completing neoadjuvant therapy, a larger number of patients presented with distant metastasis in the long-course CTRT arm. The probable reason for this might be systemic chemotherapy treating occult metastasis, as suggested by RAPIDO(12) and PRODIGE 23(19) trials. Both these trials introduced chemotherapy into the neoadjuvant setting to improve compliance and reduce distant metastasis. The RAPIDO trial had a design similar to our study but delivered all CAPOX chemotherapy in the neoadjuvant setting. PRODIGE 23 introduced neoadjuvant FOLFIRINOX before long-course chemoradiotherapy. The rate of distant metastasis at 3 years was reduced by 6.8% and 8% respectively in the RAPIDO and PRODIGE 23 trials.
Our study was conducted in the developing part of the world, where resources are limited, and patient compliance to prolonged treatment is poor. Adopting western data to this population is difficult due to different comorbidity and toxicity profiles. In this population, short-course radiotherapy followed by three cycles of CAPOX chemotherapy before surgery is a safe and better alternative due to a shorter treatment period. We proved the feasibility of this regimen and noticed a probability of better oncological outcomes compared to the current standard of care. However, further studies are required in this population, addressing long-term oncological outcomes and toxicities with a larger sample size. The strength of this study is a homogenous protocol of neoadjuvant treatment and surgery followed by adjuvant chemotherapy. No significant deviations from the protocol occurred during the study. Also, we used preoperative MRI for accurate clinical staging in all patients. The major limitation of the study is the sample size. Similar studies around the globe are conducted in larger patient populations. However, due to the time constraints of a postgraduate thesis, we planned a feasibility study with a smaller sample size. The COVID-19 pandemic decreased patient inflow and caused treatment interruptions in ongoing patients, resulting in less than-planned recruitment within the speculated period. The current sample size was achieved despite these logistic issues.
In locally advanced rectal cancer, short-course radiotherapy and sequential chemotherapy is comparable to long-course CTRT in the neoadjuvant setting. We compared clinical and radiological response rates between standard long-course CTRT and SCRT with sequential CAPOX chemotherapy. The results of this study show that the trends in tumour downstaging favour short-course radiotherapy and sequential chemotherapy, even if statistical significance was not reached. We observed higher rates of acute bowel toxicities in the SCRT and chemotherapy arms. Studies with large sample sizes are required to prove the superiority of short-course radiotherapy and sequential chemotherapy to long-course CTRT. In resource-limited settings, short-course radiotherapy and chemotherapy is preferred as it is less expensive and convenient, especially in centres with a long waiting list and improve compliance.
AUTHOR CONTRIBUTION STATEMENT
Dr Sushmita Pathy(SP): Conception and design of the work, Data collection, Data analysis and interpretation, Drafting the article, Critical revision of the article, Final approval of version to be published
Dr Adila Amariyil(AA): Patient recruitment and Treatment, Data collection, Data analysis and interpretation, Drafting the article
Dr Atul Sharma(AS): Critical revision of the article, Final approval of the version to be published
Dr Sunil Kumar(SK): Critical revision of the article, Final approval of the version to be published
Dr Raja Pramanik(RP): Critical revision of the article, Final approval of the version to be published
Dr Sandeep Bhoriwal(SB): Critical revision of the article, Final approval of the version to be published
Dr R M Pandey(RM): Data analysis, Critical revision of the article, Final approval of the version to be published
Conflict of interest: None
Funding: The research received no funds, grants or other supports