Clinical & Translational Oncology最新文献

Background: This study aimed to assess the diagnostic and prognostic potential of adhesion molecules ICAM-1, ICAM-2, and VCAM-1 by analyzing their levels in serum and bronchoalveolar lavage (BAL) samples from patients with lung cancer.

Methods: This prospective, single-center, cross-sectional study was conducted at the chest diseases clinic of Atatürk University Faculty of Medicine from March 2024 to May 2025. Patients diagnosed with malignant or benign lung disease by bronchoscopy, along with a control group of healthy volunteers, were included in the study. Serum samples were collected from all participants, and BAL samples were obtained from the patient groups. ICAM-1, ICAM-2, and VCAM-1 levels were measured by ELISA. Statistical analyses were performed using the SPSS 20.0 software package. Diagnostic accuracy was evaluated with ROC analysis, and 1-year survival was assessed using Kaplan-Meier curves.

Results: In the lung cancer group, ICAM-1, ICAM-2, and VCAM-1 levels in serum and BAL samples were significantly higher compared to the benign and control groups (p < 0.001 for all). BAL ICAM-2 level showed the highest diagnostic performance (AUC: 0.990; sensitivity and specificity: 96.4%). Serum ICAM-2 and ICAM-1 also showed high diagnostic performance. BAL ICAM-1 levels were significantly higher in non-small cell lung cancer (NSCLC) than in small cell lung cancer (SCLC) (p = 0.036). High serum ICAM-1 and BAL ICAM-2 levels were associated with mortality (p = 0.048 and p = 0.015, respectively).

Conclusions: Serum and BAL levels of ICAM-1, ICAM-2, and VCAM-1 show promise as potential diagnostic biomarkers for lung cancer. Among these, BAL ICAM-2 levels are especially notable due to their high diagnostic accuracy and link to survival.

Purpose: Proton therapy (PT) offers dosimetric advantages over conventional X-ray-based radiotherapy (XRT), aiming to reduce toxicity and better spare healthy tissues. The Agency for Health Quality and Assessment of Catalonia (AQuAS), commissioned by the Spanish Ministry of Health, conducted a Health Technology Assessment to evaluate the safety and clinical effectiveness of PT for cancer indications not yet approved for PT in Spain. This article summarizes the main findings regarding PT's safety and clinical performance in adults compared with XRT.

Methods: The assessment was based on a systematic review of primary studies published between 2012 and 2024, following Cochrane methodological standards, PRISMA guidelines, and the GRADE approach. Eligibility criteria were defined using the PICO-DT framework, focusing on adult cancer patients, comparative study designs, and primary outcomes including serious adverse events, mortality, overall survival, and progression-free survival. Risk of bias was evaluated with RoB 2.0 and ROBINS-I depending on study design. Searches covered major biomedical databases.

Results: Of 6958 records screened, 76 were included (five randomized trials and 71 observational studies) across 16 tumour types. Overall, evidence certainty was low or very low, limited by few randomized trials, methodological concerns, and heterogeneity. For some indications, including leptomeningeal metastases, lung cancer, and anal cancer, evidence suggests that PT may be equivalent or superior to XRT, although certainty remains limited.

Conclusions: PT shows variable, cancer-specific results and does not consistently outperform XRT. Some indications appear promising, but substantial evidence gaps persist, emphasizing the need for high-quality comparative studies and systematic clinical data collection.

Background: HER2-overexpressing (3+) breast cancer exhibits distinct clinicopathological characteristics compared to HER2 1+ and 2+ tumors; however, differences in their molecular features remain poorly defined. This study aimed to investigate clinicopathologic and somatic alterations in breast tumors stratified by HER2 status.

Materials and methods: Ninety breast cancer patients were stratified by HER2 expression (1+, 2+, 3+) using immunohistochemistry and confirmed by FISH. For each patient, paired diagnostic biopsies and post-neoadjuvant chemotherapy (NACT) residual tumors were analyzed. Targeted next-generation sequencing (NGS) was performed on 34 paired samples, and shortlisted variants were validated by digital droplet PCR (ddPCR) in 90 cases.

Result: Among the 90 paired samples, 40 were HER2-high, and 50 were HER2-low/TNBC. HER2-high tumors presented with a larger mean size (3.34 cm vs. 2.29 cm) but lower lymph-node metastasis (40% vs. 60%) compared to HER2-low/TNBC. NGS identified frequent mutations in PIK3CA (24%), TP53 (32%), and ERBB2 (9%). PIK3CA variants His1047Arg and Glu542Lys exhibited significantly higher variant allele frequencies in post-NACT tumors (p < 0.05). HER2-high tumors demonstrated a greater prevalence of ERBB2 mutations (13.5%), whereas in HER2-low patients, such mutations appeared only after neoadjuvant chemotherapy (NACT). Importantly, PIK3CA mutations were correlated with increased lymph-node metastasis (p = 0.04) and poorer survival outcomes, underscoring their prognostic impact.

Conclusion: HER2-high and HER2-low/TNBC breast cancers demonstrate distinct clinicopathologic and molecular profiles. Therapy-associated enrichment of PIK3CA mutations and their association with aggressive behavior underscore their prognostic and therapeutic significance in HER2-positive disease. Further studies are needed to clarify their role in guiding personalized treatment strategies.

Purpose: In many cases, cancer is diagnosed during hospital admission. The rapid development of the cancer can, sometimes, make medical oncologist consider to start chemotherapy treatment (ChT) in an inpatient setting to seek quick symptomatic improvement. However, it remains unclear which patients are going to benefit from this approach. Our purpose is to find prognostic factors that can predict which patients are unlikely to benefit from palliative ChT, helping to avoid unnecessary or harmful treatments and focus care on improving quality of life.

Methods: A retrospective, observational analysis was completed of 209 patients with metastatic or locally advanced and unresectable disease that received ChT in inpatient regimen with palliative intent. Traditional clinical parameters (ECOG-PS, Charlson Comorbidity Index-CCI, G8 score) and other novel one (neutrophil-lymphocyte ratio-NLR) were recovered and evaluated at the start of inpatient treatment. 30 and 90 day survival were selected as efficacy outcomes.

Results: 30 and 90 day mortality rates were 22.5% and 39.2%, respectively, for the inpatients starting treatment. ECOG-PS 0-1 was associated with improved 30 and 90 day survivals in comparison with worse ECOG-PS ≥ 2. On the other hand, CCI and G8 score were not related to statistically significant differences in 30 and 90 day survival. NLR < 5 was associated with better 30 and 90 day survival in inpatients starting ChT.

Conclusion: NLR may be added to ECOG-PS in the choice of inpatients that can benefit from starting treatment during the hospital stay. However, further prospective studies should be carried out to bring light to this matter. The accurate selection of patients is essential to optimize symptoms control and avoid unnecessary treatment toxicity.

Objective: Flow cytometry (FC) is an expensive method that is unaffordable for many patients from underprivileged nations. We aimed to reduce the total budget of the test by optimizing a limited antibody panel, guided by morphological assessment.

Materials and methods: This retrospective observational study included 395 patients referred for flow cytometry at the Rehman Medical Institute in Peshawar. Bone marrow or peripheral blood samples were immunophenotyped using a limited panel of flow markers after morphological and cytochemical assessments. The samples were stained with fluorochrome-labeled monoclonal antibodies and analyzed using a Cytoflex flow cytometer. Data were analyzed using R and R studio by calculating frequency and percentage for descriptive statistics while results are presented in graphs, tables, and charts.

Results: Out of 395 cases, an acute leukemia panel was requested for 225 (56.9%) cases, a lymphoproliferative panel for 80 (20.3%) cases, an absolute CD4 count for 80 (20.3%) cases, and proximal nocturnal hemoglobinuria (PNH) clone screening for 10 (2.5%) cases. Of the 225 acute leukemia cases, 160 (71.1%) were newly diagnosed and 65 (28.9%) were follow-up cases. In the follow-up cases, 21 (32.3%) were in remission, 13 (19.3%) were not in remission, and 31 (48.4%) were in relapse. 98% of cases of acute leukemia and lymphoproliferative disorders and 100% of cases of PNH and absolute CD4 count were conclusively diagnosed using our limited flow panels. Our panel achieved 74-82% average cost reductions and 61-68% reductions in turnaround time (TAT) compared with established reference laboratories in Pakistan.

Conclusions: Optimizing a minimal antibody panel in resource-limited settings enhances flow cytometry-based diagnosis, reduces patient financial burden, enables timely and accurate results, and guides treatment decisions to improve patient outcomes.

Background: Testicular cancer achieves very high cure rates, and current management aims to preserve these outcomes while minimizing treatment-related toxicity. This study aims to describe long-term outcomes of a risk-adapted program for clinical stage I (CSI) testicular germ-cell tumors (TGCT) and to evaluate histopathologic predictors of relapse.

Methods: Single-center retrospective cohort (1994-2023) of CSI TGCT. Endpoints were relapse, progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Associations were tested using Cox and Fisher's exact test; model performance was assessed by discrimination with Harrell's C-index and 5-year calibration.

Results: We retrospectively analyzed 277 selected patients with TGCT, of whom 169 (61%) had CSI disease (seminoma = 104; NSGCT = 65; median age 32 years). Initial management was surveillance in 52.1% and adjuvant chemotherapy in 46.2% (carboplatin in seminoma, BEP in NSGCT). After a median follow-up of 87 months, 17 relapses occurred (10.1%). Adjuvant chemotherapy significantly reduced relapse risk (HR 0.20; p = 0.012). Ten-year OS and CSS were 94.4% and 99.3%, respectively. In surveillance-managed seminoma (n = 54), rete testis invasion independently predicted relapse (HR 9.54, 95% CI 1.29-70.3; p = 0.027), while the Boorman's classification distinguished intermediate- from low-risk patients (31.8% vs 6.5%; p = 0.04). In NSGCT under surveillance, relapse occurred in a single patient with lymphovascular invasion (1/3, 33.3%) and in 4/31 (12.9%) without; none relapsed after adjuvant BEP.

Conclusions: Risk-adapted management provides excellent long-term survival in CSI TGCT. Selective adjuvant therapy effectively prevents relapse, while histopathologic risk stratification supports individualized, deescalated strategies.

Background: Breast cancer patients, particularly those with stage IV disease, on immunosuppressive therapy, or with comorbidities, may have an impaired immune response to vaccination. This raises concerns about their vulnerability to severe COVID-19. This study evaluated the effectiveness of COVID-19 vaccination in preventing severe disease in breast cancer patients.

Methods: We conducted a retrospective cohort study of 2,470 patients with invasive breast cancer from our institutional database (January 2020 to January 2024). COVID-19 cases were confirmed by RT-PCR or lateral-flow test. Patients were considered vaccinated if they had received at least one dose within the previous 12 months. Severe COVID-19 was defined as hospitalization for more than 24 h or death from the disease. We analyzed outcomes using a binomial logistic regression model adjusted for potential confounders (age > 85, comorbidities, BMI > 35, stage IV cancer, chemotherapy, and care home residence). Vaccine efficacy (VE) was calculated as 100 × (1 - adjusted odds ratio).

Results: Seventy-eight patients developed severe COVID-19, including 20 fatalities. Vaccinated patients had significantly lower odds of severe disease (adjusted odds ratio: 0.027; VE: 97.3%). Comorbidities and care home residence were also associated with increased risk. In a sub-analysis of cases after vaccine availability (N = 2,437), the adjusted odds ratio was 0.073 (VE: 92.7%), with comorbidities remaining the only significant non-vaccine risk factor. Vaccination uptake in the cohort was high (91.5%).

Conclusions: COVID-19 vaccination was highly effective at preventing severe disease in breast cancer patients, including those receiving active cancer treatment. The vaccine's efficacy was comparable to, or even higher than, that observed in the general population, suggesting that breast cancer and its treatment do not substantially impair the protective immune response.

Objectives: To evaluate how the implementation of intensity-modulated/image-guided RT (IMRT/IGRT) with intraprostatic seeds can impact the risk of late gastrointestinal (LGI) and genitourinary (LGU) toxicity in prostate cancer (PCa) patients treated with dose-escalation RT.

Materials /methods: Retrospective analysis of a prospective cohort of 1,010 men treated within a risk-adapted, intensification program with a minimum follow-up (FU) of 5 years. The median radiation dose to prostate was 79.5 Gy (IQR: 75.0, 80.3). Short-term ADT (STADT, n = 165) and long-term ADT (LTADT, n = 385) were administered to intermediate- and high-risk patients, respectively. Late toxicities were assessed using the EORTC/RTOG criteria. Kaplan-Meier analysis: to calculate the cumulative incidence of late toxicities; Cox proportional regression model: to estimate hazard ratios (HRs).

Results: Median FU was 116 months (IQR: 88-133). The median RT dose for IMRT/IGRT was 80.0 Gy (IQR 79.1, 81.2) and 78.0 Gy (IQR 73.1, 79.6), (p = 0.001) for those treated with 3DCRT. The 10-year Kaplan-Meier grade ≥ 2 LGI and LGU toxicities were 10% (95% confidence interval [CI] 8-12) and 16% (95% CI 14-18), respectively. The multivariate analysis (MVA) showed that the use of IMRT/IGRT with intraprostatic seeds was a significant protective factor for grade ≥ 2 LGI toxicity (HR: 0.66, 95%CI: 0.46-0.95, p = 0.021), despite the higher radiation dose in the IMRT/IGRT group. However, its impact on decreasing grade ≥ 2 LGU toxicity did not achieve statistically significance (13% vs 18%; p = 0.053, HR 0.88). A prior transurethral resection of the prostate (TURP) (HR 1.98, 95% CI: 1.30-2.59, p = 0.002) and the presence of acute grade ≥ 2 GU complications (HR:1.76, 95% CI: 1.20-2.9, p = 0.003) were associated with a higher incidence of grade ≥ 2 LGU toxicity, while LTADT was significantly associated with a lower risk of GU complications (HR:0.66, 95% CI: 0.46-0.95, p = 0.021).

Conclusion: The study confirms that IMRT/IGRT with intraprostatic fiducial markers significantly reduces grade ≥ 2 late GI toxicity, and appears to prevent an increase in GU toxicity rates despite dose escalation.

Purpose: Anticoagulation/ antiplatelet treatment could potentially reduce the metastatic process, however, consistent evidence is lacking. Here we explored an in vivo model of experimental metastasis of murine B16 melanoma to observe tumor cell extravasation under therapy with aspirin or enoxaparin.

Methods: Three treatment groups by 5 C57BL/6 female mice were injected with B16/F10 cells in the retro orbital sinus. After two weeks necropsy was performed.

Results: In the group treated with enoxaparin, a marked reduction in the number of metastatic foci in the lungs, with 6-193 metastases and 0.04-2.3% affected lung area were observed. The control group had 561-1000 metastatic lesions and 13-21% affected area. In the aspirin-treated group, there was a reduction in the number of metastatic lesions (386 - 640) and area (6.4-19%).

Conclusions: Both aspirin and enoxaparin treatment affect the progression of metastases in mice, with enoxaparin being the most effective.

Introduction: Adenocarcinoma of the esophageal junction and stomach (AEG/S) remains one of the deadliest cancers worldwide. New treatment options are urgently needed. A new target could be trophoblast cell surface protein 2 (TROP2), which is expressed in a variety of solid tumors and can be targeted, e.g., by sacituzumab govitecan, which has shown promising results in triple-negative breast cancer. This study investigates the expression of TROP2 in patients with AEG/S and correlates its expression with clinical and histopathological endpoints.

Methods: TROP2 expression was assessed in a cohort of 250 patients who underwent primary surgery for AEG/S. Immunohistochemistry was performed on tissue microarrays constructed from primary tumors and lymph node metastases to quantify TROP2 expression intensity. Clinical variables, including overall survival and patient demographics, as well as tumor-specific characteristics such as stage and grade, were correlated with TROP2 expression to evaluate its potential prognostic relevance in AEG/S.

Results: TROP2 was expressed in 86% of primary tumors and 81.3% of lymph node metastases. The intensity of TROP2 expression (low vs. medium vs. high) was correlated negatively with overall survival (p < 0.05, 70.9 months vs. 54.2 months vs. 39.5 months), lymphatic invasion (p = 0.05, V = 0.138), and higher grading (p = 0.037, V = 0.143). The intensity of TROP2 expression in lymph node metastases and primary tumors correlated significantly (p < 0.001, ρ = 0.444). There was a non-significant increase in positive lymphonodal status (p = 0.093, V = 0.138) in patients with higher TROP2 expression.

Conclusion: In Caucasian AEG/S patients, TROP2 is expressed in the majority of cases. TROP2 expression intensity itself has an impact on survival, which could be explained by a more aggressive phenotype, which leads to lymphatic invasion and lymph node metastasis.