Diagnosis and Risk Assessment of Locally Advanced Rectal Cancer Using Co-registered Ultrasound and Photoacoustic Imaging

The investigators hypothesize that a co-registered photoacoustic ultrasound endorectal device can significantly reduce unnecessary surgeries in rectal cancer patients with complete clinical response while maintaining high sensitivity in identifying those with residual cancer. The proposed new imaging technique combined with deep-learning algorithms will provide a real-time imaging tool to assist surgeons in predicting the neoadjuvant treatment response of rectal cancer patients. Such a tool will offer sensitive vascular and %sO2 contrast for identifying complete responses, thereby assisting surgeons in significantly improving sensitivity and specificity in surgery recommendations. The study will 1) rigorously validate the technique in a group of locally advanced rectal cancer (LARC) patients who will undergo surgical resection or "wait and watch" surveillance of their rectum based on the standard of care (SOC), and 2) explore the technique's potential in assessing a sub-group of LARC patients through the course of neoadjuvant treatment and in post-treatment surveillance. Successful completion of the project will result in a new imaging tool that can significantly improve the SOC by reducing unnecessary surgery without compromising cancer-related outcomes and thereby lowering morbidity and health care cost.

In this trial, the investigators will recruit patients with rectal cancer who have completed neoadjuvant therapy and will undergo surgery or nonoperative management. Approximately 86 patients will be recruited. The first group of 30 patients (group #1) will be used to train/validate identification algorithm. The second group of 56 patients (group #2) will be used as the testing cohort to train the reader team comprised of 3 surgeons and 1 radiologist. Eligible patients will include those with rectal cancer who received neoadjuvant therapy and were deemed to either have incomplete or indeterminant or clinical response based on standard endoscopy and axial imaging with magnetic resonance. PAM/US will be performed before their surgery or at the time of patients' follow up imaging.

In the investigation of group #2 patients, the study surgeon will review each patient's record and decide on surgery (clinical non-responders, non-cCR) for two types of patients of 1) those deemed non-cCR based on SOC at the treatment completion; 2) those deemed cCR at the treatment completion and are under "watch and wait" surveillance .

After initial training using group #1 data, the study surgeon will grade the tumor bed based on MRI and other clinical information as non-cCR or cCR at the time of SOC imaging after treatment completion. PAM/US imaging will be performed at the same time as the patients' SOC imaging. The study surgeon will grade the tumor bed as either PAM/US non-cCR or PAM/US cCR after PAM/US imaging.

For patients with surgery, the pathological outcomes of the patients will be assessed based on the Modified Ryan Scheme for Tumor Regression Score. Score 0, No viable cancer cells (pCR); Score 1, Single cells or rare small groups of cancer cells (near pCR); Score 2, Residual cancer with evident tumor regression, but more than single cells or rare small groups of cancer cells; Score 3, Extensive residual cancer with no evident tumor regression. Scores 2 and 3 are considered as non-pCRs. For patients without surgery, cCR without of any concerns of recurrence at the end of 2 year follow-up window will be considered as responder. The radiologist reader will also independently grade each case based on MRI.