Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer-related mortality, and it is expected to play an even bigger part in cancer burden in the years to come. Despite concerted efforts from scientists and physicians, patients have experienced little improvement in survival over the past decades, possibly because of the non-specific nature of the tested treatment modalities. Recently, the discovery of potentially targetable molecular alterations has paved the way for the personalized treatment of PDAC. Indeed, the central piece in the molecular framework of PDAC is starting to be unveiled. KRAS mutations are seen in 90% of PDACs, and multiple studies have demonstrated their pivotal role in pancreatic carcinogenesis. Recent investigations have shed light on the differences in prognosis as well as therapeutic implications of the different KRAS mutations and disentangled the relationship between KRAS and effectors of downstream and parallel signaling pathways. Additionally, the recognition of other mechanisms involving KRAS-mediated pathogenesis, such as KRAS dosing and allelic imbalance, has contributed to broadening the current knowledge regarding this molecular alteration. Finally, KRAS G12C inhibitors have been recently tested in patients with pancreatic cancer with relative success, and inhibitors of KRAS harboring other mutations are under clinical development. These drugs currently represent a true hope for a meaningful leap forward in this dreadful disease.

Liver metastasis and resistance to immunotherapy in microsatellite stable colorectal cancer. A literature review Marcelo Porfirio Sunagua Aruquipa1a, Mauro

The association of age at the onset of CRC and the prevalence of a KRAS G12C mutation is unclear. A retrospective, multicenter study evaluating metastatic CRC patients from January 2019 to July 2023, treated at the Oncoclinicas units and tested for tissue based KRAS/NRAS and BRAF mutations in a centralized genomics lab. A mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness. The chi-square test was used to examine the association between clinical and molecular variables, with p value < 0.05 being statistically significant. A total of 858 cases were included. The median age was 63.7 years (range 22–95) and 17.4% were less than 50 years old at the diagnosis of metastatic CRC. Male patients represented 50.3% of the population. The sidedness distribution was as follows: left side 59.2%, right side 36.8% and not specified 4%. The prevalence of the KRAS mutation was 49.4% and the NRAS mutation was 3.9%. Among KRAS mutated tumors, the most common variants were G12V (27.6%) and G12D (23.5%), while KRAS G12C was less frequent (6.4%), which represented 3.1% of the overall population. The BRAF mutant cases were 7.3% and most commonly V600E. Only five (<1%) non-V600E mutations were detected. MSI-high or dMMR was present in 14 cases (1.6%). In the age-stratified analysis, left-sidedness (p < 0.001) and a KRAS G12C mutation (p = 0.046) were associated with a younger age (<50 years). In the sidedness-stratified analysis, a BRAF mutation (p = 0.001) and MSI-high/dMMR status (p = 0.009) were more common in right-sided tumors. Our data suggest that KRAS G12C mutations are more frequent in early-onset metastatic CRC. To the best of our knowledge, this is the largest cohort in the Latin American population with metastatic CRC reporting RAS, BRAF and MSI/MMR status.

Introduction: Desmoid Tumors (DT) are rare neoplasms with higher incidence in younger women. Methods: Retrospective, single-center analysis of patients with DT. Variables were age, sex, biopsy, treatment and recurrence. The disease-free survival (DFS) was calculated with the Kaplan-Meier method. Results: 242 patients were evaluated, mean age was 34 years, 70.7% women, 44.4% originated in the trunk/abdomen and 54.5% had size > 5cm. Surgery was performed in 70.2%, 31% with negative margin and only 57% with previous biopsy. Recurrence rate was 38% and 1,2,5-year DFS was 75.3%, 64.2%, 57.8%, respectively. Size (p = 0.018) and tumor location in the dorsum (p = 0.001), extremities (p = 0.003) and pelvis (p = 0.003) were related to higher relapse rate. Conclusion: our data reinforces the need to gather data from real world practice and the importance of awareness of DT and medical education about DT behavior and best approach due to the high rates of surgery and elevated number of patients treated without biopsy. Level of Evidence III; Retrospective Comparative Study.

Background: In Brazil, 75% of the population is covered by public health insurance (PubHIn), and the rest pay for private insurance (PrivHIn). The impact of the type of health insurance on clinical presentation of Brazilian patients diagnosed with soft tissue sarcoma (STS) is unknown. We aim to describe the clinical characteristics at diagnosis of patients with STS, stratifying them by type of health insurance, and to evaluate the symptom-diagnosis and -treatment intervals. Methods: Observational, retrospective cohort, single-center study conducted in a Brazilian cancer center that admits both private and public patients. Medical records of individuals with 18 years old or more diagnosed with selected types of STS who started treatment in our center between January 2011 and December 2019 were reviewed. Kaplan–Meier method and log-rank test were used for survival analyses. Chi-square and Mann Whitney test were used for univariate analysis. Significance was defined as a p-value <0.05. Results: 225 patients were included: 25.3% (n=57) with PubHIn and 74.7% (n=168) with PrivHIn. Median tumor size in PrivHIn was 7 cm (0.9–45 cm) versus 10.3 cm (0.8–30.5 cm) in PubHIn (p=0.0001). Metastases were present in 8.9% of patients with PrivHIn (n=15) and in 26.3% (n=15) of those with PubHIn (p=0.002). Median symptom-diagnosis interval was 195 days in the PubHIn group and 163 days in the PrivHIn group (p=0.74). For the whole series, median age at diagnosis was 51 years (18–85 yo). Lower limbs were the most frequent location of tumors (53.8%), and 86% had histological grade 2/3. Conclusions: Patients with STS covered by PubHIn presented larger tumors and more metastatic disease at diagnosis, suggesting that there may be disparities in health care delivery and limited access to health resources. A better understanding of the barriers in the journey of patients with STS could improve outcomes.

Background: The association of age at onset of CRC and prevalence of KRAS G12C mutation is unclear; Methods: Retrospective multicenter study evaluating metastatic CRC patients from January 2019 to July 2023 treated at Oncoclinicas units, tested for tissue-based KRAS/NRAS and BRAF mutations in a centralized genomics lab. Mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness. Chi-square test was used to examine the association between clinical and molecular variables, with p value <0.05 being statistically significant; Results: A total of 858 cases were included. The median age was 63.7 years (range 22-95) and 17.4% were less than 50 years old at diagnosis of metastatic CRC. Male patients represented 50.3% of the population. Sidedness distribution was left-side 59.2%, right-side 36.8% and not specified 4%. Prevalence of KRAS mutation was 49.4% and NRAS mutation 3.9%. Among KRAS mutated tumors, the most common variants were G12V (27.6%) and G12D (23.5%), while KRAS G12C was less frequent (6.4%), which represented 3.1% of the overall population. BRAF mutant cases were 7.3%, most commonly V600E. Only 5 (<1%) non-V600E mutations were detected. MSI-high or dMMR was present in 14 cases (1.6%). In the age-stratified analysis, left-sidedness (p<0.001) and KRAS G12C mutation (p=0.046) were associated with younger age (<50 years). In the sidedness-stratified analysis, BRAF mutation (p=0.001) and MSI-high/dMMR status (p=0.009), were more common in right-sided tumors; Conclusions: Our data suggest that KRAS G12C mutations are more frequent in early-onset metastatic CRC. To the best of our knowledge, this is the largest cohort in the Latin American population with mCRC reporting RAS, BRAF and MSI/dMMR status.