An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report

Mutations in KRAS (codon 12/13), NRAS, BRAFV600E, and amplification of ERBB2 and MET account for 70–80% of anti-epidermal growth factor receptor (EGFR) monoclonal antibody primary resistance. However, the list of anti-EGFR monoclonal antibody primary resistance biomarkers is still incomplete. Herein, we report a case of wild-type RAS/BRAF metastatic colorectal cancer (CRC) with resistance to anti-EGFR monoclonal antibody and chemotherapy. Initially, mutation detection in postoperative tumor tissue by using amplification-refractory mutation system polymerase chain reaction indicated wild-type RAS/BRAF without point mutations, insertion deletions, or fusion mutations. Therefore, we recommended combined therapy of cetuximab and FOLFIRI after failure of platinum-based adjuvant chemotherapy, but the disease continued to progress. Next generation sequencing analysis of the postoperative tumor tissue revealed that KRAS copy number was increased and detected SMAD4, RNF43, and PREX2 mutations. This is the first case of advanced CRC with increased copy numbers of KRAS resistant to cetuximab and chemotherapy, which results in poor patient survival, and other mutated genes may be associated with the outcomes. Our findings indicate KRAS copy number alterations should also be examined, especially with anti-EGFR monoclonal antibody therapy in CRC, since it may be related with the primary resistance to these drugs.

Deep-Learning-Based Natural Language Processing of Serial Free-Text Radiological Reports for Predicting Rectal Cancer Patient Survival

Most electronic medical records, such as free-text radiological reports, are unstructured; however, the methodological approaches to analyzing these accumulating unstructured records are limited. This article proposes a deep-transfer-learning-based natural language processing model that analyzes serial magnetic resonance imaging reports of rectal cancer patients and predicts their overall survival. To evaluate the model, a retrospective cohort study of 4,338 rectal cancer patients was conducted. The experimental results revealed that the proposed model utilizing pre-trained clinical linguistic knowledge could predict the overall survival of patients without any structured information and was superior to the carcinoembryonic antigen in predicting survival. The deep-transfer-learning model using free-text radiological reports can predict the survival of patients with rectal cancer, thereby increasing the utility of unstructured medical big data.

Evaluation and Predictive Factors of Complete Response in Rectal Cancer after Neoadjuvant Chemoradiation Therapy

The response to neoadjuvant chemoradiation therapy is an important prognostic factor for locally advanced rectal cancer. Although the majority of the patients after neoadjuvant therapy are referred to following surgery, the clinical data show that complete clinical or pathological response is found in a significant proportion of the patients. Diagnostic accuracy of confirming the complete response has a crucial role in further management of a rectal cancer patient. As the rate of clinical complete response, unfortunately, is not always consistent with pathological complete response, accurate diagnostic parameters and predictive markers of tumor response may help to guide more personalized treatment strategies and identify potential candidates for nonoperative management more safely. The management of complete response demands interdisciplinary collaboration including oncologists, radiotherapists, radiologists, pathologists, endoscopists and surgeons, because the absence of a multidisciplinary approach may compromise the oncological outcome. Prediction and improvement of rectal cancer response to neoadjuvant therapy is still an active and challenging field of further research. This literature review is summarizing the main, currently known clinical information about the complete response that could be useful in case if encountering such condition in rectal cancer patients after neoadjuvant chemoradiation therapy, using as a source PubMed publications from 2010–2021 matching the search terms “rectal cancer”, “neoadjuvant therapy” and “response”.

Late Recurrence in a Rectal Cancer Patient Who Underwent Preoperative Chemoradiotherapy Followed by Local Excision: A Case Report

Some patients who have undergone preoperative chemoradiotherapy (CRT) following surgery have been diagnosed with late recurrence more than 5 years after treatment, raising questions about the possible benefit extending surveillance beyond the recommended 5 years. In 2011, a 71-year-old male patient was diagnosed with T3N+ low-lying rectal cancer located 3 cm from the anal verge before undergoing long-course preoperative CRT. After CRT, the patient was reexamined and diagnosed with ycT1–2N0 lesion, so local excision (LE) was performed. The patient underwent intensive surveillance for up to 5 years, and no evidence of recurrence was found. At 74 months after surgery, the patient was hospitalized for a hematochezia, and local recurrence at the excision site and peritoneal seeding nodules were identified. Considering the late recurrence in this patient, it might be necessary to long-term follow-up beyond 5 years in patients with preoperative CRT followed by LE.

Clinical Reality and Treatment for Local Recurrence of Rectal Cancer: A Single-Center Retrospective Study

Background and Objectives: Despite advances in treatment, local recurrence remains a great concern in patients with rectal cancer. The aim of this study was to investigate the incidence and risk factors of local recurrence of rectal cancer in our single center over a 7-year-period. Materials and Methods: Patients with stage I-III rectal cancer were treated with curative intent. The necessity for radiotherapy and chemotherapy was determined before surgery and/or postoperative histopathological results. Results: Of 365 rectal cancer patients, 76 (20.8%) developed recurrent disease. In total, 27 (7.4%) patients presented with a local tumor recurrence (isolated in 40.7% of cases). Radiotherapy was performed in 296 (81.1%) patients. The most often used schema was 5 × 5 Gy followed by immediate surgery (n = 214, 58.6%). Local recurrence occurred less frequently in patients treated with 5 × 5 Gy radiotherapy followed by surgery (n = 9, 4%). Surgical procedures of relapses were performed in 12 patients, six of whom were operated with radical intent. Only two (7.4%) patients lived more than 5 years after local recurrence treatment. The incidence of local recurrence was associated with primary tumor distal location and worse prognosis. The median overall survival of patients after local recurrence treatment was 19 months. Conclusions: Individualized rectal cancer patient selection and systematic treatment algorithms should be used clinical practice to minimize likelihood of relapse. 5 × 5 Gy radiotherapy followed by immediate surgery allows good local control in resectable cT2N+/cT3N0 patients. Radical resection of isolated local recurrence offers the best chances of cure.

High Expression of VSTM2L Induced Resistance to Chemoradiotherapy in Rectal Cancer through Downstream IL-4 Signaling

Background. Preoperative chemoradiotherapy (pCRT) is a common and essential therapeutic strategy for patients with locally advanced rectal cancer (LARC), but poor tumor response and therapeutic resistance to chemoradiotherapy have appeared usually among persons and affected those patients’ survival prognosis. The resistance to chemoradiotherapy in rectal cancer is difficult to predict. This study was aimed at evaluating the role of V-set and transmembrane domain containing 2 like protein (VSTM2L) in resistance to chemoradiotherapy in rectal cancer. Methods. Analysis of the GEO profiling datasets of rectal cancer patients receiving pCRT disclosed that VSTM2L as a candidate gene was significantly upregulated in nonresponders of rectal cancer with pCRT. The mRNA and protein expression of VSTM2L was detected by quantitate real-time PCR, western blotting, and immunohistochemistry in six rectal cancer biopsy tissues before pCRT. Furthermore, the rectal cancer patient-derived organoids were cultured to evaluate the association of VSTM2L expression and tumor response to CRT. Overexpression of VSTM2L in cancer cells treated with CRT was analyzed for the function of cell proliferation and viability, clone formation, DNA damage repair, and apoptosis ability. The GSEA and RNA-sequence analysis were used to find the downstream mechanism of VSTM2L overexpression in cells treated with CRT. Results. The mRNA levels of VSTM2L were significantly downregulated in normal rectal tissues compared to tumor tissues and were upregulated in nonresponders of rectal cancer patients receiving pCRT and positively correlated with poor survival prognosis from GEO datasets. High expression of VSTM2L was significantly associated with tumor regression after pCRT ( P = 0.030 ). Moreover, high expression of VSTM2L reduced γ-H2AX expression in rectal cancer patient-derived organoids treated with CRT. The overexpression of VSTM2L in colorectal cancer cells induced resistance to CRT via promoting cell proliferation and inhibiting apoptosis. The molecular mechanism revealed that the overexpression of VSTM2L induced resistance to CRT through downstream IL-4 signaling affecting the progress of cell proliferation and apoptosis. Conclusion. The high expression of VSTM2L induced resistance to CRT, and adverse survival outcomes served as a prognostic factor in patients with rectal cancer receiving pCRT, suggesting that VSTM2L high expression may be a potential resistant predictable biomarker for LARC patients receiving pCRT.

Can multidisciplinary approach win the battle against metastatic rectal cancer?

Introduction. Colorectal cancer is the third most common cancer and one of the leading causes of cancer-related deaths in men and women worldwide. The contemporary multidisciplinary approach has decreased rates of local recurrence and improved outcomes in metastatic colorectal cancer. We present a case of a primarily metastatic rectal cancer patient who underwent multidisciplinary planned treatment and showed complete response with now three years disease-free survival. Case outline. A 61-year-old female was diagnosed with a T4N2M1a rectal adenocarcinoma at the age of 58. She underwent six cycles of systemic chemotherapy capecitabine-oxaliplatin plus bevacizumab with partial response confirmed by diagnostic imaging procedures. According to multidisciplinary board decision, preoperative radiotherapy treatment was administered with concomitant Capecitabine-based chemotherapy. A 50.4 Gy total dose was delivered with 1.8 Gy fraction dose. After concomitant chemoradiotherapy treatment, two more cycles of systemic chemotherapy Capecitabine-Oxaliplatin plus Bevacizumab were administered. One month after completion of systemic chemotherapy, primary rectal cancer was operated with a complete response on histopathologic specimens. Six weeks following previous surgery, metastasectomy of lung deposits was performed; histopathology confirmed metastatic adenocarcinoma of colorectal origin. Three more cycles of postoperative chemotherapy capecitabine-oxaliplatin plus bevacizumab were administered. Conclusion. On regular follow-up, no evidence of disease was shown, with disease-free survival of three years. The treatment improved the patient?s quality of life.