International Journal of Clinical Oncology最新文献

Background: The purpose of this study was to compare the diagnostic performance of radiolabeled prostate-specific membrane antigen-targeted positron emission tomography/computed tomography (PSMA-PET/CT) with ¹⁸F, whole-body magnetic resonance imaging (WB-MRI), including diffusion-weighted imaging (DWI) and a combination of conventional computed tomography and bone scintigraphy (CT/BS) for the detection of recurrent lesions in patients with prostate cancer with rising PSA levels following initial definitive treatment.

Methods: This retrospective study used part of the dataset from a previous phase 2 study conducted between February 2019 and March 2022, which evaluated the detection efficacy of ¹⁸F-FSU-880 PSMA-PET/CT in 72 patients with suspected recurrent prostate cancer after definitive treatment. Of these, 35 patients (age 56-82 years, PSA level 0.24-40.00 ng/ml) who underwent both PSMA-PET/CT and WB-MRI were reviewed by six radiologists. Sensitivity, specificity, and overall accuracy were compared using McNemar's test, and positive predictive value was compared using Fisher's exact test.

Results: Total 132 true-positive prostate cancer lesions were detected in 23 of 35 patients (66%). The sensitivity of PSMA-PET/CT (100%) was significantly higher than those of both WB-MRI (57%) and CT/BS (32%) in the per-patient analysis (p = 0.002 and p < 0.001, respectively). In the per-lesion analysis, the sensitivity of PSMA-PET/CT (88%) was significantly higher than those of WB-MRI (44%) and CT/BS (6%) (p < 0.001 and p < 0.001, respectively).

Conclusions: ¹⁸F-FSU-880 PSMA-PET/CT showed a more favorable diagnostic performance, especially in terms of sensitivity, than WB-MRI and CT/BS in detecting recurrent disease in patients with prostate cancer after definitive treatment.

Background: Comprehensive genomic profiling (CGP) tests were approved, and opportunities to consider tissue-agnostic targeted therapies based on molecular tumor profiling have increased even in the community-based medicine practice. However, low treatment success rates and regional disparities in access to investigational drugs remain significant challenges. This retrospective study aimed to evaluate the drug accessibility rate and prognostic impact of CGP testing for advanced or metastatic solid tumors at Hiroshima Prefectural Hospital, a facility located far from clinical trial sites.

Methods: We analyzed data from 378 patients who underwent CGP testing between June 2019 and June 2024. Patient characteristics, specimen details, molecular tumor board (MTB) assessments of CGP results, and clinical courses were collected. Overall survival (OS) after MTB assessment was evaluated using the Kaplan-Meier method and log-rank test.

Results: The median patient age was 69 (range: 10-92) years. Lung cancer was the most common cancer type, affecting 105 patients (27.8%). CGP testing identified one or more gene mutations in 356 patients (94.2%), of whom 248 (65.6%) harbored druggable genomic alterations, and 37 (9.8%) received genomically matched therapy. Among them, 27 (73%) received approved drugs. The OS advantage observed in patients who received genomically matched therapy was statistically significant. Among patients who did not receive genomically matched therapy, approximately 20% expressed willingness to participate in clinical trials.

Conclusions: These findings demonstrate the clinical utility of CGP testing in local medical facilities; however, the high proportion of approved drugs among genomically matched treatments highlights significant barriers to clinical trial participation.

Background: Although human papillomavirus (HPV) vaccines effectively prevent cervical cancer, the HPV vaccination rates in Japan remain low because of concerns about alleged neurological adverse events. Darja Kanduc proposed a flawed hypothesis that molecular mimicry between HPV and human proteins could induce cross-reactive antibodies, causing autoimmune organ damage, even when only the portions of amino acid (AA)-sequences of the epitopes were identical between HPV and human proteins.

Methods: In this study, we conducted the same computational data analysis as Kanduc, using 22 linear epitopes (9-23 AA-length) of the HPV type 16 L1 protein (HPV16L1) registered in the database.

Results: We found that no human epitopes had identical AA-sequences to any HPV16L1 epitopes, demonstrating that HPV16L1 had no molecular mimicry with linear epitopes that have the potential to induce cross-reactive autoantibodies. On the other hand, we identified various numbers of human protein epitopes whose AA-sequences were partially identical with epitopes of HPV16L1, hepatitis B virus (HBV), and respiratory syncytial virus (RSV). We found that HPV16L1 had a smaller number of such proteins having "partial molecular mimicry" than HBV and RSV.

Conclusions: Our current in silico analysis provided no evidence that HPV vaccinations could induce cross-reactive autoantibodies. The flawed molecular mimicry data should not be used as a scientific basis for alleged HPV vaccine-induced adverse events.

Despite advances in adjuvant therapy for colorectal cancer, tumor relapses, often driven by minimal residual disease, remain a formidable clinical challenge. The cancer stem cell hypothesis provides a key framework for understanding this problem, positing that a small, therapy-resistant subpopulation of cells drives recurrence. To elucidate the role of these cells, we developed LGR5-specific monoclonal antibodies and a high-sensitivity immunofluorescence method to visualize the stem cell marker LGR5 in clinical tumors. Furthermore, we established a unique colorectal cancer cell line, PLR123, which maintains robust stem cell properties, and developed an in vitro model to study tumor recurrence. Through analyses including single-cell RNA sequencing and small molecule screening, we identified the RNA Polymerase I inhibitor BMH-21 as a compound that effectively suppresses recurrence both in vitro and in vivo. This article comprehensively reviews our series of studies on understanding the mechanisms of cancer stem cell-driven resistance and offers insights supporting the development of novel therapies aimed at preventing tumor relapses.

Objective: To evaluate the real-world safety and efficacy of immune checkpoint inhibitors (ICIs) in Japanese patients with persistent, recurrent, or metastatic cervical cancer.

Methods: In this multicenter observational study at four Japanese institutions, 100 patients with recurrent, persistent, or advanced cervical cancer received pembrolizumab or cemiplimab. Primary endpoints were objective response rate (ORR) and the incidence of immune-mediated adverse events (imAEs) and grade 3-5 AEs. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Logistic and Cox regression were used to explore prognostic factors.

Results: Eighteen patients (18%) achieved complete response and 44 (44%) partial response, yielding an ORR of 62.0% and a disease control rate of 77.0%. Median PFS and OS were 10.4 and 22.0 months, respectively. ORR was 74.0% in the first-line setting and 29.6% in the second-line setting. Among patients who met KEYNOTE-826 eligibility criteria, ORR was 82.9% and median PFS 16.1 months. Cemiplimab, which was mainly used as off-label retreatment in frail or previously ICI-exposed patients, showed limited activity (ORR 5.6%). ImAEs occurred in 45.0% of patients, with grade 3-5 events in 19.0% and six treatment-related deaths. Poor performance status and recurrent disease were associated with lower response and shorter PFS, whereas PD-L1 tumor proportion score ≥ 50% and grade 3-5 imAEs were associated with longer PFS.

Conclusion: In this real-world cohort, ICIs, particularly pembrolizumab, demonstrated substantial antitumor activity with acceptable toxicity in Japanese patients with advanced cervical cancer, especially when used as first-line therapy and in patients fulfilling KEYNOTE-826 eligibility criteria.

Background: Immune checkpoint inhibitors (ICIs) are now the standard first-line treatment for metastatic renal cell carcinoma (mRCC), yet many risk factors identified during the tyrosine kinase inhibitor era remain unvalidated in current practice. This study aimed to evaluate the prognostic value of body composition, nutritional, and inflammatory indices in the era of ICI-based first-line therapy.

Methods: We retrospectively analyzed 136 mRCC patients who received systemic therapy. Body composition indices (skeletal muscle index [SMI], visceral adipose tissue index [VATI], subcutaneous adipose tissue index [SATI]), nutritional markers (prognostic nutritional index [PNI], geriatric nutritional risk index [GNRI]), and inflammatory markers (Glasgow Prognostic Score [GPS], systemic inflammatory index [SII], and other indices) were assessed for their association with overall survival (OS). We also compared their prognostic impact on patients treated with non-ICI-based and ICI-based regimens as first-line therapy.

Results: Low VATI (HR 1.64, P = 0.030), and low SATI (HR 2.22, P < 0.001) were associated with shorter survival. PNI (HR 1.70, P < 0.001) and GNRI (HR 1.57, P < 0.001) showed strong prognostic value, as did GPS (HR 2.43, P < 0.001) and SII (HR 2.11, P < 0.001) in the overall cohort. In the ICI-based regimen group, PNI, GNRI, and SATI demonstrated higher prognostic performance (C-indices 0.736, 0.730, and 0.690, respectively), with PNI and SATI providing clear OS stratification.

Conclusion: Several indices reflecting body composition, nutritional status, and systemic inflammation remain valuable prognostic markers in patients with mRCC receiving ICI-based first-line therapy.

Background: While simple hysterectomy is the standard treatment for adenocarcinoma in situ (AIS) and stage IA1 cervical cancer, minimally invasive surgery has been increasingly adopted. However, evidence on the safety and efficacy of total laparoscopic hysterectomy (TLH) for these conditions remains limited. We compared the safety and efficacy of TLH and total abdominal hysterectomy (TAH) in patients undergoing simple hysterectomy following diagnostic conization.

Methods: We conducted a multicenter retrospective study of 196 patients with cervical intraepithelial neoplasia grade 3 (CIN3), AIS, or stage IA1 cervical cancer who underwent simple hysterectomy following diagnostic conization. Patients were divided into TLH and TAH groups, and intraoperative and postoperative complications and oncologic outcomes were compared.

Results: Operative time was significantly longer in the TLH group, whereas intraoperative blood loss was lower and postoperative hospital stay shorter. No significant difference was noted in severe complication rates, although their patterns varied between groups. Recurrence occurred in one patient (0.5%), a case of CIN3 at the vaginal cuff in the stage IA1 TAH group. No recurrences were observed in patients with AIS or stage IA1 disease in the TLH group.

Conclusions: TLH following diagnostic conization for AIS or stage IA1 cervical cancer demonstrated oncologic efficacy comparable to TAH, with a favorable safety profile. TLH may be a reasonable treatment option for carefully selected patients.

Background: Pulmonary metastasectomy (PM) is a treatment for lung metastases of bone and soft tissue sarcomas. However, the criteria for repeat PM after a second pulmonary recurrence remain unclear. We evaluated prognostic significance of the second disease-free interval (DFI-2; from initial PM to second pulmonary recurrence) and defined the criteria for repeat PM.

Methods: We retrospectively reviewed 60 patients who underwent PM for bone or soft tissue sarcomas (2000-2024), among whom 31 experienced a second pulmonary recurrence. Overall survival (OS) was analyzed using the Kaplan-Meier method and log-rank test. Cox proportional hazards models were used to identify independent prognostic factors. OS was compared between patients with DFI-2 < 6 and ≥ 6 months. The DFI-2 cut-off was determined to maximize Harrell's concordance index for OS.

Results: The median patient age, metastasis number, and metastasis size were 55 years, two, and 1.4 cm. The 5-year OS rate was 41.3%. Multivariable analysis identified DFI-1 < 12 months, ≥ 3 metastases, and incomplete resection as independent adverse factors. Among the 31 patients who developed second pulmonary recurrence, 16 underwent repeat PM, achieving the 5-year OS of 39.5%. Patients with DFI-2 ≥ 6 months had significantly better OS (median, 56.6 vs. 14.4 months, p < 0.001) and were more likely to undergo repeat PM (73.3% vs. 31.3%). All patients with DFI-2 < 6 months who underwent repeat PM experienced recurrence within 6 months.

Conclusions: DFI-2 ≥ 6 months predicts a favorable prognosis and may be a practical criterion for selecting candidates for repeat PM in bone and soft tissue sarcomas.

Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk of lung cancer, with cumulative incidence rates of 3.3% and 15.4% at 1 and 5 years of follow-up, respectively. The prognosis for patients with lung cancer and IPF is worse than that for patients with IPF alone, primarily due to the progression of lung cancer and complications arising after treatment. Epidemiological and molecular studies indicate that IPF and lung cancer share several pathogenic mechanisms, including genetic and epigenetic alterations. Germline mutations may contribute to both conditions by disrupting the balance between oncogenes and tumor suppressor genes, thereby driving carcinogenesis in fibrotic lungs. Epigenetic dysregulation, such as DNA methylation changes, histone modifications, and deregulation of noncoding RNAs, serves as a common link between these diseases by activating key signaling pathways, including Wnt/β-catenin and PI3K/Akt. These pathways promote alveolar type II cell hyperproliferation and metaplasia, both of which are critical processes in disease progression. In addition, mesenchymal transitions represent a shared pathological feature of lung fibrosis and tumorigenesis. In this review, we summarize the current molecular insights into lung carcinogenesis in lung cancer with IPF. Furthermore, we present findings from our recent comprehensive genetic analysis, which identifies distinct gene profiles indicative of unique carcinogenic mechanisms in lung cancer with IPF. These insights may contribute to improved risk assessment, early detection strategies, and the development of targeted therapies for lung cancer patients with IPF.