Future oncology最新文献

Introduction: Breast cancer, due to its heterogeneous nature and variable response to current systemic treatment, can be a great concern. Deregulation of the DNA Damage Response (DDR) pathway genes due to mutation and expression increases cancer risk, progression, and metastasis. The current study was designed to check the expression deregulation patterns of the selected DDR pathway genes (ATM, CHEK1, and CHEK2) at the protein level.

Material & method: Immunohistochemistry-based expression profiling was conducted in 102 histopathological confirmed breast cancer-diagnosed tissues and their adjacent uninvolved control tissues.

Results: Downregulated expression of the selected DDR pathway (ATM, CHEK1, and CHEK2) proteins was observed in breast tumor tissues compared to control tissues. Downregulated protein expression of the DDR pathway genes (ATM, CHEK1, and CHEK2) correlates with aggressive breast cancer phenotypes and increased tumor burden. The selected proteins showed significant diagnostic potential having strong area under curve values for CHEK2 (0.828, p < 0.0001), CHEK1 (775, p < 0.0001) and ATM (0.725, < 0.0001) proteins.

Conclusions: Kaplan-Meier analysis showed that dysregulated expression of these three proteins leads toward poor survival outcomes, suggesting their role to be used as a better and more effective diagnostic and prognostic marker for early diagnosis and effective treatment of breast cancer patients.

Background/objectives: Thyroid-cancer demands age-linked histology and nodule-architecture - factors rarely studied in papillary-thyroid-carcinoma (PTC). Severe-paucity exists in high-quality data about region-specific surveillance and epidemiology.

Methods: We retrospectively analyzed 208-patient-data for prevalences and associations King Salman Specialist Hospital (2022-2025) for age, sex, first-degree-family-history, smoking, obesity (BMI ≥30 kg m^-2), oral-contraceptive-pill (OCP)-use, hypertension, diabetes, nodule-pattern, and tumor-subtype. Associations tested χ² or Fisher's-exact (α = 0.05); effect size as odds ratios (ORs, 95% CI).

Results: Females dominated (70.2%) aged 30-39-years (52.4%). Histology indicated PTC (87.5%), then follicular (8.2%), medullary (3.4%), and anaplastic (1.0%). Age strongly-associated subtype (χ² = 30.7, p < 0.001): PTC comprised 98.2% tumors <40-years but only 72.5% were ≥50-years, where follicular and medullary-cancers reached 27.5%. A positive family-history indicated medullary-carcinoma (11.4% vs 1.7%; χ² = 8.95, p = 0.030; OR = 7.4). Smoking exclusively in men (9.7% vs 0%; χ² = 14.5, p < 0.001). Intriguingly, the novel-finding multinodularity dominating males (43.5% vs 8.9%; χ² = 33.6, p < 0.001) and women-non-users OCPs (32.7% vs 7.3%; χ² = 21.5, p < 0.001) while OCP-use associated to single-nodules warrants investigation. Obesity, hypertension, and diabetes correlated with occurrence.

Conclusions: Thyroid cancer displays age-, sex- and heredity-associations: non-PTC subtypes rose with age, medullary tumors cluster in families, multinodularity predominanted male, and OCP use associated to single-nodules. These findings support age-stratified diagnostics, targeted RET-proto-oncogene-testing, and consideration of hormonal influences.

Aims: This study aimed to describe first-line venetoclax in the Medicare population and its impacts on treatment patterns, utilization, and costs.

Materials and methods: This retrospective cohort study used Medicare Fee-For-Service data from 1 September 2016, to 31 December 2022. Patients were continuously-enrolled, had incident acute myeloid leukemia (AML) and no confounding diagnoses, and were treated with first-line venetoclax-based regimens. Initiation of second line of therapy was modeled using cumulative incidence functions.

Results: Among 2,765 included patients, median age was 76 years. Median venetoclax dosage was 140.4 mg/day - lower than the 400-600 mg/day recommended by clinical guidelines. Patients were less likely to initiate second-line therapy if they were older or had more comorbidities.Patients had a per-month median of 5.3 outpatient visits, 0.3 emergency department visits, and 0.2 hospitalizations; length of stay was 10 days. Mean monthly healthcare costs were $18,092 (SD=$14,289) per patient, with $12,042 (SD=$12,147) and $6,050 (SD=$7,841) attributable to medical services and drug costs, respectively.

Conclusions: A growing number of patients enrolled in Medicare Fee-For-Service with AML use first-line venetoclax. Older patients and those with comorbidities are less likely to initiate second-line therapy. Costs were lower and length of stay was shorter than described in previous research.

Management of penile squamous cell carcinoma (PSCC) remains challenging, with limited effective treatment options. Preclinical studies have shown that combining a PD-1 inhibitor with a PARP inhibitor may produce synergistic antitumor activity. This phase II trial will evaluate the combination of niraparib (PARP inhibitor) with dostarlimab (PD-1 inhibitor) in patients with recurrent or refractory stage III or IV PSCC. The primary endpoint will be the objective response rate (ORR) assessed using iRECIST. Progression-free survival (PFS), overall survival (OS), and safety will be included as secondary endpoints. A first stage cohort of 15 patients will be enrolled; if the ORR exceeds 13%, enrollment will be expanded to include an additional 10 patients in the second stage. If successful, this combination could represent a novel therapeutic strategy for advanced platinum refractory PSCC.Clinical trial registration: www.clinicaltrials.gov identifier is NCT05526989.

Background: Nasopharyngeal carcinoma (NPC) is increasingly diagnosed in elderly populations. However, prognostic tools that incorporate both tumor biology and host vulnerability remain limited.

Methods: In this retrospective cohort study, a total of 185 elderly patients (aged ≥65 years) with histologically confirmed NPC treated with concurrent chemoradiotherapy (CCRT) between March 2020 and June 2023 were evaluated. This study assessed the independent and combined prognostic value of the pan-immune-inflammation value (PIV) and frailty index for overall survival (OS) and progression-free survival (PFS).

Results: Both high PIV and frailty independently predicted shorter OS and PFS (p < 0.001). Combined classification into four subgroups yielded clear prognostic separation: Low PIV + Non-frail patients achieved the best 3-year OS (88.5%) and PFS (82.1%), whereas High PIV + Frail patients had the poorest outcomes (3-year OS 38.6%, PFS 30.4%). The combined model improved the C-index for OS prediction from 0.68 to 0.79 and the AUC for PFS from 0.70 to 0.81 compared with the baseline clinical models. Prognostic value remained robust in stage- and ECOG-stratified analyses with no significant interaction effects.

Conclusion: The combination of PIV and frailty provides a highly discriminative prognostic tool in elderly NPC patients undergoing CCRT.

Aim: This study evaluated the long-term safety and effectiveness of ruxolitinib in Japanese patients with polycythemia vera in clinical practice.

Patients and methods: This multicenter, single-arm, non-interventional, prospective, observational study assessed patients receiving ruxolitinib after approval.

Results: Of 550 patients (median age: 71 years, mean disease duration: 5.43 years, median treatment duration: 1091 days), 51.27% reported adverse drug reactions (ADRs) and 12.18% had serious ADRs, with anemia being the most common ADR. The highest incidence of ADRs (40%) was observed from treatment initiation to Day 182, with no tendency for increased incidence thereafter. ADRs of special interest included myelosuppression (27.64%), hepatic impairment (13.45%), infections (9.27%), hemorrhagic events (5.64%), cardiac failure (1.27%), malignancy (1.09%), interstitial lung disease (0.36%), and tuberculosis (0.18%). Baseline hepatic impairment did not increase the incidence of ADRs, but numerical incidence was higher in patients with baseline renal impairment, with similar events being observed in patients with or without renal impairment. At 36 months, spleen response and symptom improvement were observed in 31.43% and 61.14% of patients, respectively. Reductions in hematocrit, white blood cell count, and platelet count were observed throughout the treatment duration.

Conclusion: Ruxolitinib demonstrated sustained effectiveness with no new safety concerns in the real-world setting.

Aims: To define anterior peritoneal reflection (APR) as a more reasonable boundary for upper rectal cancer (URC) and assess the effect of neoadjuvant chemoradiotherapy (CRT) on locally advanced rectal cancer (LARC) above the APR.

Materials & methods: MRI identified patients with LARC above the APR, excluding T4b cases. Patients were grouped by CRT status, and differences in their treatments and outcomes were compared. Propensity score matching was applied to adjust for baseline differences.

Results: Of 1869 patients, 1702 (91.1%) had visible APR, with median heights of 7.5 cm for females and 8.6 cm for males. From 2011 to 2018, 479 patients with LARC above the APR were included. No significant differences were found between CRT and non-CRT groups in disease-free survival (DFS) (76.9% vs. 79.5%, P = 0.629), local recurrence-free survival (LRFS) (93.6% vs. 90.4%, P = 0.353) and overall survival (OS) (88.5% vs. 87.8%, P = 0.722). Cox regression showed CRT was not an independent influencing factor for DFS or OS.

Conclusions: It was feasible to accurately identify APR using MRI and distinguish upper and lower rectal cancer. CRT might not be essential for LARC patients above the APR after excluding T4b cases, which can avoid unnecessary treatment.

Purpose: Mathematical comparisons of lung adenocarcinoma (LUAD) with epidermal growth factor receptor (EGFR) mutations of L858R and 19DEL.

Methods: A total of 1,980 surgically resected LUAD cases were analyzed, comprising 1,195 ground glass opacity LUAD (GGO-LUAD) and 785 pure solid lung adenocarcinomas (pSD-LUAD). LUAD cases were grouped based on EGFR mutation status. Correlations between tumor size (x) and frequency ratio (y) were analyzed using exponential equations.

Results: Multivariate logistic regression analysis showed that the 19DEL mutation was more frequently observed in younger individuals (OR: 1.60, 95% CI: 1.29-1.99, p < 0.0001) and high-grade tumors (OR: 1.46, 95% CI: 1.01-2.11, p = 0.004). Equations were fitted as follows: y = e^{-0.046 + 0.48} × (x ≤ 2.5 cm, p = 0.0016) (1), y = e^{-2.09 + 0.37} × (x ≤ 4 cm, p < 0.0001) (2), y = e^{-1.65 + 0.38} × (x ≤ 4 cm, p = 0.0001) (3).

Conclusion: pGGO-LUAD with L858R EGFR mutations grew more rapidly than those with 19DEL mutations, but the solidification rate of L858R-mutated GGO-LUAD was lower compared to 19DEL-mutated GGO-LUAD.