BACKGROUND Accurate imaging-based response assessment is essential for proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC). This study aimed to evaluate the diagnostic performance of MRI, endorectal ultrasound (ERUS) and 18F-FAPI PET/MRI for identifying pathological complete response (pCR) after neoadjuvant short-course radiotherapy (SCRT) followed by chemoimmunotherapy. METHODS This single-center retrospective study included 143 patients. Diagnostic performance was assessed using sensitivity, specificity, and accuracy with 95% confidence intervals. Cohen's κ assessed agreement between imaging-defined complete response (iCR) and pCR. Paired comparisons used Cochran's Q and Holm-adjusted exact McNemar tests. RESULTS The pCR rate was 51.0%. MRI (n = 118), ERUS (n = 81), and PET/MRI (n = 25) achieved sensitivity, specificity, and accuracy of 4.76%, 98.18%, and 48.31%; 30.95%, 87.18%, and 58.02%; and 60.0%, 100.0%, and 84.0%, respectively. PET/MRI-assessed imaging complete response showed substantial agreement with pCR (κ = 0.643). CONCLUSION Neoadjuvant SCRT followed by chemoimmunotherapy achieved high pCR rates in pMMR LARC. Conventional MRI and ERUS showed limited sensitivity despite relatively high specificity. 18F-FAPI PET/MRI showed potential diagnostic utility in a small subgroup, but its moderate sensitivity and limited sample size warrant further validation. These findings highlight the limitations of imaging alone and the need for comprehensive response assessment.
What is this summary about?This summary describes an article published in the Journal of Clinical Oncology in December 2025. The article reports the results of a clinical trial called HER2CLIMB-05, which evaluated how well the addition of tucatinib to standard maintenance therapy (trastuzumab and pertuzumab) stops cancer from getting worse in people with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer.This study included people with HER2+ metastatic breast cancer whose cancer did not get worse after 4 to 8 treatments of first-line chemotherapy combined with trastuzumab and pertuzumab. These individuals were then randomly assigned to receive either tucatinib or placebo in combination with standard maintenance therapy. To evaluate how well the treatments worked, individuals were monitored for cancer worsening by measuring tumor sites on a regular basis. Overall, the researchers wanted to know how long individuals lived without their cancer getting worse and what side effects could happen when receiving the tucatinib combination.What were the results?The HER2CLIMB-05 study showed that people with HER2+ metastatic breast cancer treated with tucatinib plus standard maintenance therapy lived longer without their cancer worsening than people treated with placebo plus standard maintenance therapy. The length of time people lived without their cancer worsening was 24.9 months among those who received the tucatinib combination, and 16.3 months among those who received the placebo combination.The most frequently reported side effects that occurred among the people receiving the tucatinib combination included diarrhea (73%), nausea (33%), elevated levels of liver enzymes (26%–28%), joint pain (21%), and fatigue (21%). These side effects were mostly manageable with supportive care (e.g., taking an anti-diarrhea medication) and/or lowering or holding the dose of the treatment.What do the results mean?The results of the HER2CLIMB-05 study suggest that adding tucatinib to standard maintenance therapy significantly prolongs the length of time that people with HER2+ metastatic breast cancer live without their cancer worsening following first-line therapy with chemotherapy and trastuzumab and pertuzumab.Clinical trial number: NCT05132582.
CLINICAL TRIAL REGISTRATION NCT07144280 (https://clinicaltrials.gov/study/NCT07144280).
