International tumor board weighs personalized options for colon cancer with no measurable disease

A single-patient case report published in Volume 17 of the journal Oncotarget on October 16, 2026 describes how an international molecular tumor board approached one of the most difficult dilemmas in modern oncology: a patient whose scans show no measurable cancer, yet whose blood tests keep detecting molecular traces of the disease. The report, titled “WIN-MTB-2024002 – WIN International Molecular Tumor Board: A 52-year-old female with unmeasurable Stage IIIc colon cancer,” was led by first and corresponding author Dr. Wafik S. El-Deiry, affiliated with the Worldwide Innovative Network (WIN) Consortium and the Legorreta Cancer Center at Brown University. Equal-contributing author Razelle Kurzrock is affiliated with the WIN Consortium and the Medical College of Wisconsin. The case centers on a 52-year-old woman with stage IIIc colon cancer whose disease remained difficult to monitor despite extensive treatment, and it illustrates how comprehensive molecular profiling and international collaboration may help guide treatment decisions when imaging and molecular findings point in different directions.

Colorectal cancer is a leading cause of cancer-related deaths worldwide, and stage IIIc colon cancer represents one of its more challenging forms. This stage involves extensive regional lymph node involvement and carries a substantial risk of recurrence even after surgery and chemotherapy. Monitoring for residual disease in such patients can be particularly frustrating when suspicious lymph nodes are too small to characterize or show limited metabolic activity on conventional imaging. In this diagnostic gray zone, clinicians must decide whether to intensify treatment, maintain current therapy, or simply watch and wait. Molecular profiling can help identify genetic alterations that influence cancer growth and treatment response, while liquid biopsy testing offers an additional layer of information by detecting circulating tumor DNA (ctDNA) released by cancer cells into the bloodstream. This blood-based approach can potentially identify molecular evidence of residual disease even when imaging shows no measurable tumor, but it also raises questions about how such findings should shape clinical decisions.

The patient’s illness began with nonspecific symptoms. In June 2021, she experienced weight loss, paleness and reduced appetite. In February 2022, severe anemia prompted hospitalization and further investigation. Colonoscopy revealed an obstructing mass, and she underwent a right hemicolectomy, the surgical removal of the right portion of the colon. Pathological examination confirmed moderately differentiated adenocarcinoma with mucinous features, classified as stage IIIc disease with the designation pT4bN2bM0. The staging reflects a tumor that had grown through the wall of the bowel and involved nearby structures, along with substantial lymph node spread: ten of the twenty-five lymph nodes examined under the microscope contained cancer. This degree of nodal involvement placed her in a high-risk category where recurrence remains a serious concern even after apparently complete surgical resection and adjuvant therapy.

Following surgery, the patient completed six months of adjuvant FOLFOX chemotherapy, a standard regimen combining fluorouracil, leucovorin and oxaliplatin. Subsequent imaging identified suspicious retroperitoneal and mesenteric lymph nodes, prompting eleven cycles of FOLFIRI combined with bevacizumab, a regimen that pairs irinotecan-based chemotherapy with an antibody targeting blood vessel formation. She later received local radiotherapy targeting suspicious aortocaval lymph nodes in August 2023. Despite this intensive sequence of treatments, determining whether cancer actually remained proved difficult. Biopsies of the suspicious sites came back negative, and PET-CT imaging showed decreasing lymph node activity over time. By January 2024, the previously suspicious areas no longer demonstrated abnormal fluorodeoxyglucose (FDG) uptake, the radioactive glucose signal that PET scans use to detect metabolically active tumor tissue, indicating no metabolically detectable disease in those regions.

Imaging, however, told only part of the story. Repeated Signatera and Guardant360 liquid biopsy tests detected ctDNA in the patient’s blood, while additional blood-based testing identified DNA methylation patterns associated with cancer. These findings raised concern about possible molecular residual disease despite the absence of measurable cancer on imaging, creating genuine uncertainty about whether additional treatment or continued surveillance was the more appropriate course. This discordance between imaging and molecular testing formed the central challenge of the case. Although PET-CT scans and tissue biopsies did not identify measurable active disease at the time of review, the persistent ctDNA positivity suggested the possibility of residual cancer existing below the detection limits of conventional imaging, complicating decisions about whether additional systemic treatment might offer more benefit than careful observation.

To understand what might be driving the disease, the team performed comprehensive genomic profiling. The analysis identified mutations involving KRAS, TP53, IDH1 and APC, along with other alterations affecting cellular growth and signaling pathways. Among these alterations, KRAS G12S was associated with abnormal growth signaling, while TP53 mutations affected tumor-suppressor function. APC alterations were linked to dysregulation of the Wnt pathway, an important driver of colorectal cancer, and the uncommon IDH1 R132C mutation provided another potential molecular target for investigation. The tumor was microsatellite stable (MSS) and carried a relatively low tumor mutational burden, both relevant considerations when evaluating potential immunotherapy options. Additional analysis classified the tumor as consensus molecular subtype 4 (CMS4), a molecular category associated with stromal activity and distinct signaling characteristics.

The tumor microenvironment added further nuance to the molecular picture. Examination showed fibrosis, high PD-L1 expression, elevated VEGFR1 and VEGFR3 levels, and substantial natural killer (NK) cell infiltration. These features helped inform the discussion of targeted and immune-based treatment strategies, since each characteristic suggested different potential vulnerabilities. To evaluate the patient’s options in light of this complex profile, the WIN Consortium International Molecular Tumor Board brought together specialists from 18 institutions across 13 countries. The experts reviewed her clinical history, genomic findings, immune microenvironment and imaging results to discuss potential maintenance therapies and treatments in the event of recurrence. One proposed maintenance approach combined regorafenib, sulindac and metformin. Regorafenib targets several kinases involved in tumor growth and blood vessel formation, while sulindac was considered for its potential effects on the Wnt signaling associated with the patient’s APC alterations. Metformin was discussed because of its influence on metabolic pathways, including mTOR-related signaling, though the effectiveness and safety of this specific combination have not been established.

The board also considered fruquintinib, a VEGF receptor inhibitor, combined with sulindac and metformin. Other options included fluorouracil (5-FU) with or without bevacizumab, or a less intensive maintenance strategy involving capecitabine or 5-FU followed by surveillance. If the cancer recurred, the experts discussed expanding the regorafenib-based combination to include trametinib, a MEK inhibitor, and ivosidenib, an IDH1 inhibitor, to address additional molecular vulnerabilities. These combinations remain investigational in this setting, and their safety and effectiveness have not been established; the board also recognized the potential for treatment-related toxicity and the importance of careful monitoring. Immunotherapy was another consideration. Given the tumor’s high PD-L1 expression, the board discussed a combination of regorafenib, ipilimumab and nivolumab, known as RIN, and potential approaches targeting both PD-1 and TGFβ signaling were explored, particularly in relation to the CMS4 subtype. However, the tumor’s microsatellite-stable status complicated these possibilities, because conventional immune checkpoint inhibitors generally provide limited benefit in most MSS colorectal cancers. High PD-L1 expression alone does not establish sensitivity to immunotherapy, and the proposed combinations require further clinical evaluation. Additional possibilities included clinical trials investigating pan-RAF inhibitors and NK cell-directed immunotherapies, as well as TAS-102 combined with bevacizumab, with the experts emphasizing that further molecular testing could help refine treatment selection if recurrence occurred.

The report carries important limitations that temper its conclusions. As a single-patient case report, it cannot establish the effectiveness of the proposed therapies or identify the best approach for patients who have detectable ctDNA but no measurable disease. Notably, the report does not document implementation of a specific molecular tumor board recommendation or any subsequent clinical outcomes, meaning the discussed strategies remain hypothetical for this patient. Further studies will be needed to determine how ctDNA monitoring should influence treatment decisions and whether molecularly guided maintenance strategies improve outcomes in colorectal cancer, and the safety and effectiveness of the proposed combinations will require prospective evaluation. Nevertheless, the case illustrates how international molecular tumor boards can integrate genomic findings, liquid biopsy results, imaging and clinical expertise to explore personalized treatment opportunities. “This case highlights the role of international MTBs in supporting complex therapeutic decision-making when conventional imaging, tissue biopsy, and molecular profiling provide incomplete or partially discordant information,” El-Deiry said in the report. “This case underscores the critical role of molecular profiling in tailoring personalized treatment strategies for advanced CRC, providing novel avenues for managing recurrent disease, even in the absence of measurable disease.”

Subject of Research: Molecular tumor board guidance for stage IIIc colon cancer with molecular residual disease but no measurable imaging findings

Article Title: International tumor board explores personalized treatment strategies for colon cancer without measurable disease

Article References: International tumor board explores personalized treatment strategies for colon cancer without measurable disease. Original publication (Bibliographic details unavailable.)

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Keywords: colon cancer, colorectal cancer, circulating tumor DNA, liquid biopsy, molecular tumor board, precision oncology, molecular profiling, microsatellite stability, immunotherapy, regorafenib, PET-CT imaging, Oncotarget