Annals of Surgical Oncology最新文献

Background: The prognostic significance of epidermal growth factor receptor (EGFR) mutations in stage I invasive lung adenocarcinoma (LUAD) remains debated. Improving the lung cancer staging system requires further investigation into actionable mutations and their association with survival outcomes.

Patients and methods: A total of 410 patients with stage I invasive LUAD were analyzed for their driver mutations. Survival analysis of EGFR mutations, exon 19 deletion, L858R in exon 21, and minor genotypes were stratified by clinicopathologic characteristics. Kaplan-Meier and log-rank tests were used to determine prognostic significance. Univariate and multivariate Cox proportional hazard regression models assessed variables' impact on recurrence-free survival (RFS). Patients with further-profiled samples were divided into training and validation datasets by computer-generated random numbers. Multiple machine learning algorithms were applied to construct genomic prediction models, with C index evaluated for each.

Results: EGFR mutations occurred in 210 patients (51.2%). In stage I invasive LUAD, EGFR mutations strongly correlated with poor RFS (P = 0.022), especially in never smoker (P < 0.001), female (P = 0.024), part-solid (P = 0.002), and stage IA subgroups (P = 0.020). The most frequently co-mutated gene was TP53. Moreover, patients with EGFR/TP53 co-mutations, regardless of mutant types, exhibited worse prognosis. A mutational prognostic model based on the random survival forest (RSF) algorithm achieved the highest mean C index (C index: 0.87 in training cohort versus 0.74 in validation cohort), and demonstrated strong RFS estimation performance [area under the curve (AUC):1-year, 0.87, versus 3-year, 0.92, versus 5-year, 0.92].

Conclusions: EGFR mutations are robust biomarkers for RFS estimation in stage I invasive LUAD. Combining EGFR mutations with other actionable mutations enhances individualized RFS estimation.

Background: Colorectal liver metastasis (CLM) is classified into technical and oncologic categories, with recommended treatments for each resectability category. However, the classification of recurrent CLM has not been established to date.

Methods: This study evaluated patients with CLM who underwent initial liver resection between 2006 and 2020 and subsequently experienced liver recurrence. Long-term outcomes and prognostic factors associated with recurrent CLM were investigated.

Results: From 949 patients who underwent an initial liver resection, the analysis included 392 patients with liver recurrence. Repeat liver resection was associated with a significantly longer prognosis than non-resection (5-year overall survival [OS] from initial liver resection: 66.3 % vs 27.2 %, p < 0.0001). Multivariable analysis indicated the following independent prognostic factors: four or more recurrent tumors (p = 0.015), tumor 5 cm or larger in size (p = 0.004), and presence of extrahepatic diseases (p = 0.003). The patients were stratified into resectable, borderline resectable, and unresectable recurrent CLM groups based on these criteria. The prognosis varied significantly across the groups, with 5-year OS rates of 67.3 % for resectable recurrent CLM, 30.8 % for borderline resectable recurrent CLM, and 2.6 % for unresectable recurrent CLM (p < 0.0001). Patients with borderline resectable recurrent CLM who did not receive adjuvant chemotherapy after initial liver resection had a positive prognostic impact of preoperative chemotherapy (p = 0.049).

Conclusion: The significant independent predictors of recurrent CLM prognosis were four or more tumors, tumor size of 5 cm or larger, and the presence of extrahepatic diseases at recurrence. It is critical to onsider the current condition and tumor resectability at the time of recurrence, and tailored treatments could further improve recurrent CLM outcomes.

Background: Sentinel lymph node biopsy (SLNB) for head and neck melanomas involves complex challenges due to intricate lymphatic networks and delicate anatomic structures. The Merlin Assay (CP-GEP), merging clinicopathologic data with gene expression profiling, offers a non-invasive method to identify patients who have a low risk for nodal metastasis, potentially sparing these low-risk patients from surgical procedures.

Methods: This study evaluated 250 clinically node-negative patients with stage I, II, or III melanoma from the Mayo Clinic and University Hospitals Cleveland Medical Center who had tumors in the head and neck region diagnosed between 2004 and 2021. All the patients underwent SLNB. The Merlin Assay, using the CP-GEP model, combines patient age at diagnosis, Breslow thickness, and gene expression of eight specific genes from the primary tumor to predict the risk of nodal metastasis.

Results: The SLNB positivity rate was 14% overall, and CP-GEP predicted a possible 40.8% reduction in SLNB procedures with a negative predictive value (NPV) of 98%. For 215 SLNB-negative patients (5-year recurrence-free survival [RFS] of 76.9%, distant metastasis-free survival [DMFS] of 84.3%, and melanoma-specific survival [MSS] of 90.6%), CP-GEP improved risk stratification by identifying 100 patients as low risk with 5-year RFS of 86.1%, DMFS of 92.7%, and MSS of 95.3%. Among 167 T1-T2 patients, the SLNB positivity rate was 8.4%, and CP-GEP achieved an SLNB reduction rate of 56.3% with an NPV of 98.9%.

Conclusions: The Merlin Assay effectively categorizes head and neck melanoma patients by risk, enabling more accurate clinical decision-making regarding SLNB and follow-up evaluation, especially for early-stage melanoma patients.

Background: Recent advancements in therapeutics for BRCA-associated breast cancer have changed indications for germline genetic testing. This study investigated whether Medicaid plans cover National Comprehensive Cancer Network (NCCN)-concordant and/or American Society for Clinical Oncology/Society for Surgical Oncology (ASCO/SSO)-concordant BRCA germline testing for patients with breast cancer.

Patients and methods: Publicly available, complete, and original state Medicaid plans for all 50 states were reviewed to determine coverage criteria for BRCA genetic testing for patients with breast cancer and clinical cancer geneticist consultation. States were categorized into discrete categories on the basis of the policy language.

Results: Only 58% (n = 29) of state Medicaid plans explicitly or implicitly cover NCCN-concordant BRCA testing. Of the remaining 21 states, 85% reference out-of-date NCCN criteria, suggesting delayed uptake of new guidelines. Only one state (Colorado) covers ASCO/SSO guideline-concordant BRCA testing for newly diagnosed breast cancer. Nearly all state Medicaid plans (98%, n = 49) cover clinical cancer genetics consultation.

Discussion: Significant variation in Medicaid coverage for BRCA germline mutation testing may inadvertently exclude socially and economically marginalized populations from the emerging standard of care. Policy language should consider explicit mention of coverage in accordance with NCCN guidelines.

Background: Black patients with colon cancer (CC) exhibit more aggressive tumor biology and higher treatment resistance than white patients, even after adjusting for clinical and demographic factors. We investigated stage-specific transcriptional differences in tumor profiles of Black and white patients with CC.

Patients and methods: Patients with CC from The Cancer Genome Atlas Colon Adenocarcinoma database were categorized by disease stage and propensity-score matched between Black and white patients. Differential gene expression and pathway enrichment analyses were performed for each stage. Logistic regression and quadratic discriminant analysis (QDA) models were developed using consistently differentially expressed genes.

Results: Of 247 patients, 128 had localized (22% Black), 81 had regional (74% Black), and 38 had distant disease (29% Black). Differential expression analysis revealed differences in 312 genes for localized, 105 for regional, and 199 for distant stages between Black and white patients. Pathway enrichment analysis showed downregulation of the IL-17 pathway in Black patients with localized disease. In total, five genes exhibited race-specific transcriptional differences across all stages: RAMACL, POLR2J3, POLR2J2, MUC16, and PRSS21. Logistic regression and QDA model performance indicated that these genes represent racial differences [area under the receiver operating characteristic curve (AUC): 0.863 and 0.880].

Conclusions: Significant transcriptional differences exist in CC between Black and white patients changing dynamically across disease stages, and involving genes with broad functions. Key findings include IL-17 pathway downregulation in Black patients with localized disease and a five-gene signature consistent across all stages. These findings may explain aspects of racial disparities in CC, emphasizing the need for race-specific research and treatment strategies.

Background: Pancreatic acinar cell carcinoma (pACC) is a rare neoplasm of the exocrine pancreas. There is a dearth of information about tumor characteristics and patient outcomes. This study describes the clinical characteristics, genetic alterations, and survival outcomes of resected pACC.

Patients and methods: Consecutive patients undergoing pancreatectomy for pathologically confirmed pACC from 1999 to 2022 across three high-volume pancreas surgery centers were analyzed. Patient demographics, tumor characteristics, treatment data, and genetic sequencing were obtained through retrospective abstraction.

Results: A total of 61 patients with resected pACC were identified. Median overall survival (OS) was 73 months and median recurrence free survival was 22 months. Nine patients underwent resection for oligometastatic disease; median OS was not reached after a median follow-up of 31 months from date of metastasectomy. Adjuvant chemotherapy was administered in 67% of patients with FOLFOX/FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, ± irinotecan) the most common regimen (58%). Sequencing data were obtained in 47 (77%) patients. A mutation in at least one of three core genes associated with the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, or PALB2) occurred in 26% (n = 12) with BRCA2 the most frequently identified. A mutation in any other "non-core" gene associated with DNA damage repair or the HRR pathway was identified in 45% (n = 21) with a high tumor mutational burden of > 10 mutations per megabase in 13%.

Conclusions: Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options.