Background. Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management. Methods. In an IRB approved retrospective protocol, we identified 72 patients with DDCS treated at our institution between 1993 and 2017 and reviewed clinicopathological characteristics, treatment modalities, and outcomes to analyze prognostic factors. Results. Femur (44.4%), pelvis (22.2%), and humerus (12.5%) were most commonly involved sites. Twenty-three patients (31.9%) presented with distant metastasis, and 3 (4.2%) of them also had regional lymph node involvement. The median overall survival (OS) was 13.9 months. On multivariate analysis, pathological fracture, larger tumor size, lymph node involvement, metastasis at diagnosis, extraosseous extension, and undifferentiated pleomorphic sarcoma component correlated with worse OS, whereas surgical resection and chemotherapy were associated with improved OS. For progression-free survival (PFS), pathological fracture and metastasis at diagnosis showed increased risk, while chemotherapy was associated with decreased risk. Among patients who received chemotherapy, doxorubicin and cisplatin were significantly associated with improved PFS but not OS. Among patients without metastasis at diagnosis, 17 (34.7%) developed local recurrence. Thirty-one (63.3%) developed distant metastases at a median interval of 18.1 months. On multivariate analysis, R1/R2 resection was related with local recurrence, while macroscopic dedifferentiated component was associated with distant metastasis. Conclusions. The prognosis of DDCS is poor. Complete resection remains a significant prognostic factor for local control. Chemotherapy with doxorubicin and cisplatin seems to have better PFS. More prognostic, multicenter trials are warranted to further explore the effectiveness of chemotherapy in selected DDCS patients.

Although patients with gallbladder papillary adenocarcinoma (GBPA) appear to have better prognoses than patients with other pathological subtypes of gallbladder carcinoma (GBC), the clinicopathological features and outcomes of GBPA have not been fully explored. This study therefore analyzed the clinicopathological characteristics and outcomes of GBPA.This study included 16 patients with GBPA and 101 with gallbladder adenocarcinoma (GBA) not otherwise specified (NOS), all diagnosed pathologically after surgical resection. Clinicopathological and survival data were retrospectively collected and compared. Fever was significantly more common in GBPA (7/16 vs 10/101; P = 0.000). Serum carbohydrate antigen 19-9 level was increased in 1 of 9 patients with GBPA and 39 of 76 with GBA (P = 0.022). More patients with GBPA underwent curative resection (15/16 vs 54/101; P = 0.009). Pathologically, patients with GBPA were at much earlier tumor (T) (4 in situ, 8 T1; P = 0.000) and Tumor, Node, Metastases (TNM) stages (P = 0.000). The overall 1-, 3-, and 5-year survival rates were significantly higher in patients with GBPA (100%, 76.9%, and 76.9%, respectively), than in patients with GBA (72.2%, 38.8%, and 31.0%, respectively; P = 0.001). Preoperative jaundice (odds ratio 7.69; 95% confidence interval, 1.53-38.76; P = 0.013) was a significant prognostic factor in patients with GBA, but was no longer significant when the patients with GBA and GBPA were pooled together. The clinicopathological features of patients with GBPA differed from those in patients with GBA (not otherwise specified). Pooling of patients may mask prognostic factors in each group.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with KRAS mutations occurring in approximately 40% of cases. These mutations drive tumorigenesis through the constitutive activation of key signaling pathways, such as RAS-RAF-MEK-ERK (MAPK) and PI3K-AKT-mTOR, contributing to therapeutic resistance and poor prognosis. Advances in molecular biology have led to significant breakthroughs, including the development of KRAS G12C inhibitors, such as sotorasib and adagrasib, which have shown promise in clinical trials. However, their efficacy is limited to a small subset of KRAS-mutant CRC, and resistance mechanisms often emerge through compensatory pathway activation. Combination strategies, including KRAS inhibitors with anti-EGFR agents, have been explored in trials like KRYSTAL-1 and CodeBreaK 300. Emerging research highlights the role of the tumor microenvironment in immune evasion and therapeutic resistance, offering opportunities for novel immunotherapy approaches, including KRAS neoantigen vaccines and adoptive T-cell therapy. Despite these advancements, challenges such as intratumoral heterogeneity, limited immune infiltration, and non-G12C KRAS mutations remain significant hurdles. This review provides a comprehensive overview of the molecular mechanisms, current advances and challenges, and future prospects in the management of KRAS-mutant CRC.

Background: Limited data are available regarding the anticancer activity of PARP inhibitors (PARPis) in pancreatic cancer with mutations in HRR genes other than BRCA and PALB2. Methods: We retrospectively reviewed the clinical characteristics and outcomes of 48 patients with advanced pancreatic cancer harboring pathogenic germline and/or somatic HRR mutations who were treated with PARPis. Results: Thirty patients had germline (g)HRR mutations only, twelve had somatic (s)HRR mutations only, and six had concomitant gHRR and sHRR mutations. The objective response rate (ORR) was 22%. The median progression-free survival (mPFS) and overall survival (mOS) were 6.9 and 11.5 months, respectively. Five patients received olaparib in the front-line setting due to borderline performance status. Their ORR was 20%, and their mPFS and mOS were both 11.3 months. The ORR was higher in patients with BRCA or PALB2 mutations (germline or somatic) than in those with non-BRCA/PALB2 mutations. Patients with somatic non-BRCA/PALB2 variants had a shorter mPFS. Patients with concomitant gHRR/sHRR mutations or gHRR mutations alone had a significantly longer mPFS than those with sHRR mutations only. Conclusions: PARP inhibitors may be considered for patients with advanced pancreatic cancer harboring pathogenic alterations of BRCA who cannot tolerate standard chemotherapy. Maintenance PARPis can be considered in selected patients with non-BRCA/non-PALB2 HRR mutations.