Cancer diagnosis & prognosis最新文献

Background/aim: Vascular endothelial growth factor (VEGF) inhibitors, such as bevacizumab (Bev), are key in the pharmacological treatment of advanced hepatocellular carcinoma (HCC) but are associated with a high incidence of adverse events, including hypertension and proteinuria. Strategies to reduce proteinuria through blood pressure control are particularly important. A new angiotensin receptor neprilysin inhibitor (ARNI) (sacubitril/valsartan) was recently approved for the treatment of hypertension. ARNI exerts its antihypertensive effects through vasodilation, sympathomimetic inhibition, and natriuresis by enhancing the action of natriuretic peptides, together with suppression of the renin-angiotensin system by angiotensin II receptor blockers (ARB). Herein, the aim was to investigate the efficacy of ARNI for blood pressure control and proteinuria in advanced hepatocellular carcinoma (HCC) patients during treatment with atezolizumab plus Bev (Atez/Bev).

Patients and methods: We retrospectively identified patients with advanced HCC under Atez/Bev treatment, who experienced inadequate blood pressure control with ARB and were transitioned to ARNI. Data on estimated glomerular filtration rate (eGFR), urinary protein/creatinine ratio (UPCR), and Bev continuation were analyzed.

Results: The mean patient age was 76.6 years, and the liver background was hepatitis B virus (HBV) (n=1), hepatitis C virus (HCV) (n=4), or non-HBV/non-HCV (n=5). eGFR significantly improved from a mean of 52.87 to 59.46 ml/min/1.73 m² (p=0.006); UPCR decreased from 2.31 to 0.79 (p=0.025) after switching to ARNI. Among patients with UPCR ≥2 (n=5), switch from ARB to ARNI improved eGFR from 50.54 to 58.62 ml/min/1.73 m², (p=0.026), while UPCR decreased from a mean of 3.99 to 1.13 (p=0.025), allowing uninterrupted Bev treatment.

Conclusion: ARNI appears to support renal function preservation and proteinuria reduction during Atez/Bev therapy, allowing the continuation of Bev treatment.

Background/aim: Ramucirumab (RAM)-based treatment is often discontinued if proteinuria levels rise to 2+ or higher (≥2+) after treatment initiation. Several risk factors contributing to an increase in ≥2+ proteinuria during RAM-based treatment have been identified. However, the impact of pre-treatment changes on proteinuria fluctuations following RAM-based treatment initiation remains unclear.

Patients and methods: This retrospective study included patients with gastric cancer who received RAM-based therapy following prior treatment with platinum-based chemotherapy at Gifu Prefectural General Medical Center between August 2015 and December 2021. Kaplan-Meier estimates were used to evaluate the incidence of ≥2+ proteinuria after initiating RAM-based treatment, based on the aggravating levels of proteinuria before initiating RAM-based treatment.

Results: This study included 62 cases. The patients were divided into two groups: 14 with ≥2+ proteinuria after initiating RAM-based treatment (severe group) and 48 patients with <1 proteinuria (control group). The severe group had a higher proportion of patients presenting with trace proteinuria, i.e., proteinuria (+/-), at the start of RAM-based treatment. They also exhibited aggravating proteinuria within six months before initiating RAM-based treatment compared to the control group. The number of days until the onset of ≥2+ proteinuria was influenced by several factors, including proteinuria (+/-) at the start of RAM-based treatment, concurrent use of a calcium antagonist and aggravating proteinuria within six months before starting RAM-based treatment.

Conclusion: In addition to previously reported risk factors, aggravating proteinuria within six months before initiating RAM-based treatment appears to influence post-treatment proteinuria outcomes.

Background/aim: Prostate cancer is linked to an elevated risk of osteoporotic fractures, which can lead to significant morbidity and even mortality. The optimal screening methods and frequency, particularly for patients with non-metastatic disease receiving androgen deprivation therapy (ADT), remain contentious. This study aimed to assess the utility of incidental cross-sectional imaging in the diagnosis of osteoporosis.

Patients and methods: We screened patients diagnosed with prostate cancer and followed-up at our tertiary cancer center between July 1, 2006, and December 31, 2023. For eligible patients, three cross-sectional images (computed tomography, alone or with positron-emission tomography) acquired at different times were evaluated to determine the mean attenuation of the L5 vertebral body.

Results: A total of 66 patients were included, with 31 patients (47%) receiving adjuvant ADT. The median follow-up period was 45.2 months. Skeletal events were recorded in 15 patients (26.2%). The mean attenuation of the L5 vertebral body, expressed in Hounsfield units (HU), was measured across three consecutive imaging sessions. The median change in the overall cohort was -4.5, it was -5.7 in patients who received adjuvant ADT, -3.9 in patients with bone metastasis, -2.8 in patients who had skeletal events, and -1.65 in patients who received bone-modifying agents. No significant difference was observed between patient subgroups. Logistic and Bayesian regression analyses showed no relationship between skeletal events and changes in bone density (Bayesian Factor 01: 2.494-2.892, low causality).

Conclusion: While computed tomography imaging can detect bone loss in this patient population, it does not appear to be of sufficient utility to predict skeletal events. This highlights the need for exploring new imaging techniques and their integration with nomograms, which are crucial research areas for improving the management of osteoporosis in patients with prostate cancer.

Background/aim: The clinical significance of human epidermal growth factor receptor 2 (HER2)-low expression in triple-negative breast cancer (TNBC) remains unclear. Although the emergence of antibody-drug conjugates has drawn attention to HER2-low tumors, whether HER2-low represents a biologically distinct subtype within TNBC is still under investigation.

Patients and methods: We retrospectively analyzed 261 patients with TNBC who underwent neoadjuvant chemotherapy followed by curative surgery at four institutions between 2008 and 2018. Clinicopathological features, chemotherapy effect, and patient outcomes were compared between HER2-low and HER2-null groups.

Results: No significant differences were observed in pathological complete response rates or survival outcomes between the HER2-low and HER2-null groups. However, compared to HER2-low tumors, HER2-null tumors showed a significantly higher Ki67 labeling index (p=0.004), a trend toward higher pathological complete response rates, and a tendency for worse distant metastasis-free survival (p=0.401).

Conclusion: Although the HER2-low and HER2-null tumor groups among TNBC showed no significant differences in response to neoadjuvant chemotherapy or patient outcomes, the higher proliferative activity and differing outcome trends in HER2-null tumors suggest possible biological differences.

Background/aim: Dedifferentiated liposarcoma (DDLS) is a rare but aggressive subtype of liposarcoma that arises in soft tissues. In orbital liposarcoma, malignant transformation from well-differentiated to DDLS typically takes at least a year. We herein report a case of a young female with an aggressive DDLS, that developed from an orbital lipoma within one year.

Case report: A 25-year-old woman presented with left upper eyelid swelling. MRI revealed abnormal adipose tissue in the medial orbit. The excised tissue was diagnosed as an orbital lipoma. The eyelid swelling recurred three months later, and the orbital tumor enlarged. An additional resection was performed, which again revealed a lipoma without malignant features. Three months later, the swelling worsened, and tumor resection confirmed well differentiated liposarcoma with a Ki-67 labeling index of 10%. Two months later, CT imaging depicted calcified lesions within the tumor. The patient subsequently underwent orbital exenteration followed by proton beam radiation. Histopathological examination of the exenterated tissue revealed DDLS with extensive osseous components. The Ki-67 labeling index exceeded 50%.

Conclusion: Ocular oncologists should pay attention to the possibility of rapid malignant transformation in DDLS in primary orbital liposarcoma.

Background/aim: The National Comprehensive Cancer Network (NCCN) Guidelines for cutaneous melanoma (CM) recommend avoiding sentinel lymph node biopsy (SLNB) when the positivity risk is <5%, considering SLNB when the risk is 5-10%, or offering SLNB when the risk is >10%. Most patients undergoing SLNB have a negative result, showing that reliance upon the American Joint Committee on Cancer (AJCC) T-stage alone results in most patients undergoing an unnecessary, negative, unreliable, invasive procedure.

Materials and methods: Two gene expression profile (GEP) tests, the CP-GEP and the 31-GEP, have been developed to identify patients at low risk of SLN positivity who may consider avoiding SLNB. We analyzed the accuracy of the CP-GEP and 31-GEP in identifying patients with <5% risk of SLN positivity across the five validation studies of the CP-GEP and four validation studies of the 31-GEP in T1-T2 tumors.

Results: Patients considered low risk by the CP-GEP had an SLN positivity rate of 6.2%, higher than the risk threshold of 5% used by the NCCN to guide SLNB decisions. In contrast, patients considered low risk by the 31-GEP or i31-SLNB had a 2.8% SLN positivity rate, a substantial improvement over AJCC-staging guidance.

Conclusion: Overall, the CP-GEP did not perform as well as AJCC, while the 31-GEP performed better than AJCC.

Background/aim: Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary tumor-predisposition syndrome and a genetic bone disease. The case report describes tumor-associated mandibular changes, their therapy and follow-up over several decades. The aim of the presentation is to highlight the tumorous and hamartomatous components of the facial skeleton and to examine the stability of surgical measures over the long term.

Case report: A 13-year-old male patient had developed an extensive diffuse plexiform neurofibroma of the left cheek and neck region. Radiological examination showed a mandibular defect, which enlarged over time. Surgical treatment consisted of a corrective procedure for the asymmetrical bony chin and augmentation osteoplasty of mandibular defect. The transplant was an integral part of a functionally stable bone for decades.

Conclusion: Head and neck diffuse plexiform neurofibroma can be associated with craniofacial bone malformations. Distinction between deformity-related bone changes from an infiltrating and destructive tumor can be difficult, especially in cases of rapidly progressive local bone loss. Presumably, both tumor-associated functional lesions of the masticatory muscles and tumor-related effects on the bone influence the shape of the affected bone. Diagnosis of tumor-associated bone lesions can be challenging in NF1. Reconstructive bone surgery of the jaw provides options for functional and esthetic improvement of the affected individual. However, long-term follow-up checks are advisable to assess treatment results. An exact assessment of the tumor type and long-term monitoring of the findings are the basis of a viable surgical therapy.

Background/aim: This study analyzed prognostic factors in patients with lung adenocarcinoma and bone metastases who tested positive for epidermal growth factor receptor (EGFR) mutations.

Patients and methods: We retrospectively reviewed the records of 117 patients with lung adenocarcinoma and bone metastases who were followed up at a single institution for 0.2 months to 66 months. Of these 117 patients, 45 were EGFR mutation-positive and further analysis was performed for these patients. Median survival times and five-year survival rates were investigated according to performance status (PS), oligometastatic status, radiotherapy and EGFR-tyrosine kinase inhibitor (TKI) administration.

Results: The five-year survival rate of EGFR mutation-positive patients was 9.2%, and median survival time was 22.7 months; their mean age was 69.5 years. Many EGFR mutation-positive patients had a PS of 2, and the median survival time showed significant differences according to PS (0/1/2 vs. 3/4) and oligometastatic status.

Conclusion: Although there was no difference in the mean survival time between patients receiving or not receiving bone radiotherapy, the treatment effectively reduced pain and prevented paralysis. As a first-line treatment in EGFR mutation-positive patients, first- or second-generation TKIs followed by third-generation TKIs showed favorable outcomes.

Background/aim: In the CheckMate 214 trial, approximately 40% of patients with advanced renal cell carcinoma (aRCC) treated with nivolumab plus ipilimumab (NIVO + IPI) achieved long-term survival and a durable response to treatment. However, about 20% of patients experienced early disease progression (EDP). This retrospective study aimed to identify predictive factors for EDP among patients with aRCC treated with NIVO + IPI.

Patients and methods: We retrospectively analyzed clinical information from patients with aRCC, 19 patients in the EDP group and 40 patients in the control disease group, all of whom were treated with NIVO + IPI at Kurume University Hospital between September 2018 and February 2024.

Results: The EDP group exhibited significantly worse progression-free survival and overall survival compared to the control disease group. Multivariate analyses revealed that a performance states (PS) ≥2 (p=0.0312) and the presence of bone metastases (p=0.0374) were independent predictors of EDP.

Conclusion: Treatment with NIVO + IPI in patients with aRCC who have a poor PS or bone metastases may be linked to a high risk of EDP.

Background/aim: Transmembrane protease, serine 2 (TMPRSS2), and E1A-associated protein (p300) are important factors in prostate cancer (PCa) pathogenesis, playing significant roles in androgen receptor (AR) signaling and tumor progression. Despite their established role in PCa biology, their immunohistochemical alterations across different Gleason patterns and histological grades remain unclear. This experimental study aimed to assess TMPRSS2 and p300 expression in non-malignant and cancerous prostate tissues, correlating their localization and intensity with Gleason scores and tumor aggressiveness.

Materials and methods: A total of 58 paraffin-embedded prostate adenocarcinoma (PRAD) tissue sections from male patients who underwent radical prostatectomy, including low- and high-grade tumors and high-grade prostatic intraepithelial neoplasia (HGPIN), were analyzed. Immunohistochemistry (IHC) for TMPRSS2 and p300 was performed. Two independent pathologists conducted H-score assessments with complete interobserver concordance, evaluating staining intensity, localization, and expression patterns, correlating findings with Gleason scores and cancer stage.

Results: TMPRSS2 and p300 exhibited variable expression levels across all tissue samples. While TMPRSS2 expression increased in aggressive tumors, its staining intensity did not change significantly across different Gleason grades. p300 over-expression was significantly associated with aggressive tumors, particularly Gleason pattern 5 (p=0.011). High-grade tumors [Gleason ≥7(4+3)] demonstrated higher p300 expression compared to low-grade tumors [Gleason ≤7(3+4)], with minimal staining observed in Gleason score 6.

Conclusion: Expression patterns of TMPRSS2 and p300 correlate with PCa aggressiveness. These findings support the growing evidence suggesting their potential role as prognostic markers and therapeutic targets. The implementation of well-designed studies on a larger scale is of utmost importance, to draw safer conclusions.