Japanese journal of clinical oncology最新文献

Objective: In the CLEAR trials, the starting dose of lenvatinib in lenvatinib+pembrolizumab (L + P) was set at 20 mg for renal cell carcinoma (RCC). The incidence of adverse events is not low with L + P compared with other combination immunotherapies. There have been no reports of initiating treatment at 14 mg lenvatinib in (L + P) combination treatment for metastatic RCC (mRCC).

Methods: Patients who initiated L + P for mRCC between January 2022 and 2024 in our institution were included. Clinical data were collected retrospectively. Patients' backgrounds and adverse events were summarized, and the maximum tumor shrinkage rate and treatment progress were analyzed.

Results: Eleven patients were enrolled in this study; median age: 69 years, median body weight: 63.0 kg. Two patients were female. The International Metastatic Renal Cell Database Consortium risk score was favorable in two cases, intermediate in six cases, and poor in three cases. Adverse events led to drug interruption or discontinuation of treatment in four cases, 2 months after initiating L + P. Partial response was achieved in 10 (91%) cases; stable disease was achieved in only 1 case. Almost all patients experienced some type of adverse event (AE). Only one patient discontinued treatment due to AEs.

Conclusions: Although management of AEs was essential, early drug interruption was less frequent in our study compared with the CLEAR trial Japanese cohort. The response of a reduced starting dose of 14 mg lenvatinib for mRCC was almost the same as that in the CLEAR trial.

Background: Despite the dosimetric advantages of intensity-modulated proton therapy (IMPT) in treating patients with nasopharyngeal carcinoma (NPC), it remains unclear whether these advantages confer improved health-related quality of life (HRQoL) compared to state-of-the-art photon-based techniques such as volumetric-modulated arc therapy (VMAT).

Patients and methods: Patients with NPC eligible for definitive radiation therapy (RT) were invited to participate in the longitudinal observational study. Patient-reported outcomes were assessed using the Functional Assessment of Cancer Therapy-Head & Neck Cancer (FACT-HN) questionnaire at multiple time points: before, during, and after treatment. Propensity score matching (PSM) was utilized to align the IMPT group with the VMAT group. Longitudinal changes in HRQoL were then analyzed using generalized estimating equations (GEEs).

Results: From 2008 to 2021, a total of 353 patients were enrolled in the study. After applying PSM at a 1:3 ratio, the final analysis included 213 patients in the VMAT group and 71 patients in the IMPT group. There were no significant differences were noted in the mean changes of FACT-HN scores from baseline between the IMPT and VMAT groups during treatment or throughout the follow-up periods as follows (IMPT vs. VMAT): -13.3 vs -14.4 (during RT), 2.2 vs. 1.0 (3 months post-RT), 5.4 vs. 8.5 (6 months post-RT), 10.8 vs. 10.1 (12 months post-RT), 10.2 vs. 10.5 (24 months post-RT), and 13.2 vs. 11.1 (36 months post-RT). Among all the subscales, only the emotional well-being (EWB) subscale demonstrated a significant difference at 36 months, favoring IMPT with scores of 2.7 versus 1.8 (p = 0.026). No significant differences were detected at other time points or within other subscales of interest.

Conclusions: This study found no clinically significant differences in overall HRQoL, as measured by the FACT-HN questionnaire, between IMPT and VMAT in the treatment of NPC.

Background: Owing to the nonspecific symptoms in early stage and the propensity for secondary obstructive jaundice, cholangiocarcinoma (CCA) is frequently diagnosed at an advanced stage, thereby missing the optimal window for surgical intervention. The aim of this study was to evaluate the efficacy and safety of biliary stenting implantation with 125I seed strand (SI) plus chemotherapy with PD-1inhibitor for patients with CCA and malignant obstructive jaundice (MOJ).

Methods: Between January 2015 and December 2023, 88 patients diagnosed with CCA and MOJ were enrolled for this retrospective study. Then, 36 patients (observation group) received SI plus chemotherapy with PD-1inhibitor, whereas 52 patients (control group) received biliary stenting implantation plus chemotherapy. The response to therapy and adverse effect were compared between both groups. The data of stent patency time, progression-free survival (PFS) and overall survival (OS) obtained through clinical follow-up, were performed using the Kaplan-Meier method and analysed with the log-rank test. Prognostic risk factors were evaluated using Cox regression analysis.

Results: After the 6-month follow-up, the DCR (86.11% vs 67.31%) was statistically different (P = 0.045), while ORR (33.33% vs 23.08%) not (P = 0.288) between both groups. There were no serious interventional treatment-related adverse events and the differences of severe toxicities of chemotherapy between both groups were not statistically significant (P > 0.05). The median stent patency time, PFS and OS were 300 days (95%CI 260-330) vs 215 days (95%CI 194-240), 360 days (95%CI 260-372) vs 230 days (95%CI 200-248) and 420 days (95%CI 330-452) vs 309 days (95%CI 252-340) between both groups, respectively and the differences between both groups were statistically significant (P < 0.05). Staging of CCA and subsequent therapy method were independent risk factors that affected the prognosis for survival.

Conclusions: SI plus chemotherapy with PD-1inhibitor is an effective and safe therapy and shows promising results compared to biliary stenting implantation plus chemotherapy for CCA patients with MOJ.

Background: Small-sized, peripherally located, and radiologically solid-dominant or pure solid nonsmall cell lung cancer (NSCLC) tumors are related to lymph node metastasis at a certain frequency. The aim of this study is to disclose the validity of lymph node dissection on oncological local control during segmentectomy for such tumors.

Methods: We investigated the clinicopathological findings, the distribution of the involved lymph nodes, the patterns of lymph node recurrences, and the prognosis of 1921 patients with radiologically-determined ≤3 cm-sized, solid-dominant or pure solid NSCLC tumors without clinical lymph node involvement following complete resections with lobectomy (n = 1472) or segmentectomy (n = 449) between 2010 and 2020. The median follow-up duration for anonymized cases was 51.8 months.

Results: The median age, solid tumor size, whole tumor size, and maximum of standardized uptake value were 72/69 years, 1.5/1.8 cm, 1.6/2.1 cm, and 2.0/3.5 in patients undergoing segmentectomy/lobectomy, respectively. Hilar lymph node metastases were recognized in 13 (3%) patients who underwent segmentectomy, and in 110 (8%) patients who underwent lobectomy, respectively. No patients experienced a recurrence of hilar lymph node metastasis in either adjacent or nonadjacent areas without distant metastasis after segmentectomy, while three patients experienced recurrence after lobectomy.

Conclusions: Lymph node dissection can be adequately performed during segmentectomy for selected small and peripherally located NSCLC tumors.

Objective: Bladder cancer is a prevalent and costly malignancy characterized by significant heterogeneity in presentation and clinical outcomes. This study aimed to classify the molecular subtypes of bladder cancer using immunohistochemistry (IHC) and to evaluate the prognosis, treatment responsiveness, and clinical utility of IHC-based subtype classification.

Methods: We retrospectively reviewed the data of 84 patients with bladder cancer who underwent radical cystectomy. Immunohistochemistry was performed using the markers CK5/6, CK14, CK20, GATA3, and UPK2. Molecular subtypes were identified through hierarchical clustering, and statistical analyses were conducted to evaluate cancer-specific survival (CSS) and recurrence-free survival (RFS).

Results: Among the 68 patients included in the final analysis, 52 were classified as luminal type and 16 as basal type. The 5-year CSS and RFS were 76.2% and 64.2%, respectively. Among patients who received platinum-based neoadjuvant chemotherapy, those with the luminal subtype showed significantly better RFS than those with the basal subtype (P = 0.016, HR 5.27, 95%CI 1.15-24.1). However, no significant difference in CSS was observed between the luminal and basal subtypes.

Conclusions: Molecular subtypes can be inferred using common immunohistochemical markers, providing a practical approach for personalized treatment strategies. Further prospective studies are needed to validate these findings.

Purpose: Prostate-specific membrane antigen radioligand therapy (PSMA RLT) improves survival in metastatic castration-resistant prostate cancer (mCRPC). However, evidence in Japanese cohorts is limited. We evaluated the safety and efficacy of PSMA RLT in Japanese patients with mCRPC.

Materials and methods: We retrospectively analyzed 82 Japanese patients with mCRPC treated with PSMA RLT between 2018 and 2024 in Australia. PSMA RLT included Lutetium-177, Actinium-225, or Terbium-161 conjugated PSMA ligands, following PSMA Positron Emission Tomography / Computed Tomography confirmation of target expression. Endpoints were prostate-specific antigen (PSA) response (≥50% decline), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TrAEs). Cox proportional hazards regression identified prognostic factors for survival.

Results: Thirty-one patients (38%) achieved a PSA response. Median PFS and OS were 4 and 20 months, respectively. While no significant difference was observed in >50% PSA decline, >80% decline was significantly higher in chemo-naïve patients (43% vs. 7.4%, P < .001), with longer PFS (8 vs. 3 months, P = .006) and OS (not reached vs. 11 months, P < .001). On multivariable analysis, poorer performance status and prior chemotherapy were independent factors for worse OS. TrAEs of any grade occurred in 49 patients (60%), most commonly fatigue. Grade ≥ 3 TrAEs occurred in 15%, with no treatment-related deaths.

Conclusion: PSMA RLT provided meaningful clinical benefit with favorable tolerability in Japanese patients with mCRPC, especially those without prior chemotherapy. Early integration of PSMA RLT may offer additional therapeutic advantages.

Background: Malignant phyllodes tumors (MPTs) are rare fibroepithelial breast tumors with no standard treatment for metastatic or recurrent cases. Comprehensive genomic profiling (CGP) has been conducted for MPT; however, its association with treatment remains unclear.

Methods: A retrospective study was conducted on patients with advanced or recurrent MPTs treated with chemotherapy between 2013 and 2022 at two hospitals, analyzing clinical data, CGP, treatment outcomes, and survival.

Results: Five patients with metastatic MPTs who had received chemotherapy were identified. The median age was 55 years (range, 50-66), and all patients were female. As first-line treatment, four patients received doxorubicin plus ifosfamide (AI) combination therapy, while one received doxorubicin monotherapy. Among those treated with AI therapy, the best responses were partial response in three patients and stable disease in one. The median progression-free survival (PFS) for patients treated with AI therapy was 5.3 months. Of the five patients two proceeded to second-line therapy, and one patient received up to fourth-line treatment. Next-generation sequencing-based CGP testing was performed in four cases. One patient with an FGFR1-N546K-mutated MPT achieved a relatively long PFS of 6.8 months with pazopanib therapy, a multi-kinase inhibitor targeting FGFR1 among other kinases, as fourth-line therapy.

Conclusion: AI therapy is useful for advanced or recurrent MPTs. The observed clinical benefit of pazopanib in a patient with FGFR1 N546K-mutated MPT suggests that FGFR1 kinase domain mutations may be a relevant factor in responsiveness of FGFR1-targeted therapy. Further data accumulation is warranted.

Background: The super T2-weighted imaging-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign has been identified as a prognostic imaging biomarker for non-contrast-enhancing astrocytoma, isocitrate dehydrogenase (IDH)-mutant, central nervous system World Health Organization grade 2 or 3. However, its relevance to other gliomas remains uncertain. Here, we evaluated the significance of the super T2-FLAIR mismatch sign in non-contrast-enhancing oligodendroglioma, IDH-mutant, and 1p/19q codeleted.

Methods: We retrospectively analyzed oligodendroglioma cases from our institution and The Cancer Genome Atlas (TCGA)/The Cancer Imaging Archive lower-grade glioma (LGG) dataset. The super T2-FLAIR mismatch sign was defined as a markedly low signal, comparable to cerebrospinal fluid, in noncystic lesions, distinct from the conventional T2-FLAIR mismatch sign. We assessed its association with prognosis and diagnostic utility by including 33 non-contrast-enhancing astrocytoma cases from our institution and 30 from TCGA-LGG, calculating the positive predictive value (PPV) and negative predictive value (NPV).

Results: Among 19 non-contrast-enhancing oligodendroglioma cases in our dataset and 16 in TCGA-LGG, the T2-FLAIR mismatch sign was present in 1 and 3 cases, respectively, while the super T2-FLAIR mismatch sign was observed in 3 and 2 cases. The mean follow-up period was 38.8 months (our dataset) and 28.2 months (TCGA-LGG). The super T2-FLAIR mismatch sign was not associated with either progression-free or overall survival in oligodendroglioma. In TCGA-LGG, it had a PPV of 86.7% and an NPV of 45.2% (P = 0.0487) for astrocytoma.

Conclusions: The super T2-FLAIR mismatch sign was primarily observed in astrocytoma but also appeared in non-contrast-enhancing oligodendroglioma. It served as a prognostic biomarker for astrocytoma but not for oligodendroglioma.