. 2024 Jul 26;24:901. doi: 10.1186/s12885-024-12529-7

Table 2.

Study calendars

ARM A—Experimental

Evaluations during treatment – (LCRT THEN mFOLFIRINOX)

Study Week (± 14 days)^a

Pre

10^k

32–38^f

History and physical^b

Height

Adverse Event Assessment

Colorectal surgeon eval

Med Onc^g

Rad Onc

DRE(digital rectal exam)

Sigmoidoscopy/Proctosigmoidoscopy^c

Biopsy^h

MRI Rectum

CT CAPⁱ

CBC & diff^j

CMP & CEA

Pregnancy Test^d

ARM B—Control

Evaluations during treatment – (LCRT THEN FOLFOX OR LCRT THEN CAPOX)

Study Week (± 14 days)^a

Pre

10^k

32–38^f

History and physical^b

Height

Adverse Event Assessment

Colorectal surgeon eval

Med Onc^g

Rad Onc

DRE (digital rectal exam)

Sigmoidoscopy/Proctosigmoidoscopy^c

Biopsy^h

MRI Rectum

CT CAPⁱ

CBC & diff^j

CMP & CEA

Pregnancy Test^d

^aTiming can vary based on institutional standards (for example, if a center waits longer than 14 days between starting chemotherapy after completion of LCRT this is not a protocol violation) as some centers wait 4–6 weeks after LCRT completion to start systemic chemotherapy. As such, exact week number from registration may vary and as such can be adjusted to reflect timing of start of chemotherapy

^bWeight, Pulse, BP. Performance Status will only be required at pre, week 10 and weeks 32–38

^cThe flexible sigmoidoscopy/proctosigmoidoscopy serves as a key feature for the baseline and final response of the primary tumor to the treatments assigned. The flexible sigmoidoscopy/proctosigmoidoscopy SHOULD NOT/MAY NOT be completed by the referring gastroenterologist BUT SHOULD BE/MUST BE completed by the evaluating/treating surgeon for baseline evaluation and during treatment assessments to maintain continuity of the response assessment (as this is critical for the primary endpoint of clinical complete response)

Baseline characteristics that should be captured include distance from the anal verge, photos, and the percent circumference of the lumen involved by the tumor. If the surgeon evaluating the patient at baseline WAS THE PHYSICIAN WHO completed the colonoscopy that was diagnostic then this would be sufficient for the initial baseline endoscopic evaluation as long the baseline characteristics of the tumor were captured including distance from the anal verge, photos and baseline characteristics of the tumor (as above). Given the importance for the primary endpoint it is critical for a surgeon to be involved who is willing to evaluate the primary tumor for the endpoint throughout the duration of the trial. The surgeon involved should be affiliated with an NCTN hospital or hospital system. It is permissible for the evaluating surgeon to be at a separate institution from the treating medical and radiation oncology teams as long as there is continuity in the management and seamless sharing of relevant clinical data between the teams (assuming all teams are part of NCTN or NCTN-affiliated hospitals and the arrangement is convenient for the patient). Further, the evaluating surgeon must have access to the protocol, all relevant documents and the tumor response forms to participate

^dFor women of childbearing potential (see Sect. 3.2.3 in study protocol/supplementary material). Must be done ≤ 7 days prior to registration

^eTime of evaluation dependent on duration of neoadjuvant chemotherapy FOLFOX (16 weeks) or CAPOX (15 weeks)

^f8–12 weeks (± 4 weeks) after completion of all neoadjuvant therapy

^gPatients will be seen and evaluated during neoadjuvant chemoradiation and chemotherapy with necessary laboratory evaluations per institutional guidelines. For neoadjuvant chemotherapy, recommendation is to be evaluated by medical oncology during (Arm 1) and (Arm 2) chemotherapy every two weeks (every three weeks for patients getting CAPOX) or as needed per institutional guidelines. In patients not seen and evaluated by medical oncology every cycle, adverse events must still be collected and reported every cycle by relevant research staff

^hBiopsy to confirm pathological diagnosis of rectal adenocarcinoma is REQUIRED

ⁱCT of the Chest, Abdomen and Pelvis. Prefer with intravenous contrast, but per institutional standards based on patient’s labs and medical condition

^jCBC & diff, CMP performed at baseline and with each cycle of chemotherapy or per institutional standards

^kAssessment by surgeon, medical and radiation oncology occurs in a multidisciplinary fashion to ensure the patient has tolerated LCRT well and does not have to occur exactly at week 10; SHOULD BE PLANNED and completed prior to initiation of chemotherapy and is meant to ensure appropriate transition to the medical oncology team as they begin systemic chemotherapy. If the patient cannot tolerate a DRE and flexible sigmoidoscopy prior to chemotherapy initiation, the study team should document this; however, the patient must undergo an exam by all groups (surgery, medical oncology and radiation oncology) along with the scheduled laboratory tests as scheduled prior to chemotherapy initiation