Japanese journal of clinical oncology最新文献

In patients with non-small cell lung cancer (NSCLC) who present with radiologically undetermined malignant pleural dissemination or incidental surgical diagnosis of the same, surgery is generally not the preferred option; systemic therapy is favoured. However, there is no consensus on incorporating primary site resection into the treatment plan. Retrospective analyses hint at potential benefits of combining systemic therapy with primary site resection, but prospective studies have yet to confirm these findings. Consequently, we have planned a multicentre, open-label, randomized controlled phase III trial to assess the efficacy of adding primary site resection to standard systemic therapy for stage IVA (cT1-2bN0-1M1a) NSCLC patients with radiologically undetermined pleural dissemination. The primary endpoint is overall survival. We aim to enroll 170 patients from 71 institutions over 5 years. This trial is registered at the Japan Registry of Clinical Trials (jRCT) under study number jRCTs031220666.

Background: Trastuzumab emtansine (T-DM1) is a novel therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, combining the targeted action of trastuzumab with the cytotoxic effects of emtansine. Although T-DM1 has demonstrated greater efficacy and safety compared to traditional therapies, concerns about hepatotoxicity and spleen-related complications have arisen.

Methods: We conducted a retrospective study of 64 HER2-positive metastatic breast cancer patients treated with T-DM1 at our institution. Patients underwent computed tomography or magnetic resonance imaging at baseline and during treatment cycles. Spleen volume, portal vein diameter, and laboratory values were compared between baseline and 12 months after T-DM1 treatment.

Results: Median spleen volume significantly increased from 201 cm3 (IQR, 157-275) at baseline to 291 cm3 (IQR, 215-420) after 12 months of T-DM1 treatment (P < 0.001). Spleen enlargement was observed in 87.5% of patients, while no significant alteration was detected in portal vein diameter. The change in spleen volume was positively correlated with changes in serum globulin levels, liver enzymes, and bilirubin levels, but did not impact survival outcomes.

Conclusions: T-DM1 therapy in HER2-positive metastatic breast cancer leads to significant spleen enlargement and systemic biochemical changes. Future studies should focus on elucidating the long-term implications of these findings and optimizing monitoring strategies for spleen-related complications.

Background: Consultation with palliative care specialists can be beneficial in addressing the numerous demands of patients with cancers and their families within communities. In settings lacking palliative care specialists, establishing a new community-based palliative care consultation system necessitates gathering evidence to support its development. This study aimed to identify the specific palliative care consultation needs and the consultation methods requested by Japanese physicians in settings without palliative care specialists.

Methods: A qualitative descriptive study utilizing semi-structured virtual interviews. From August 2023 to October 2023, we conducted interviews with 11 physicians providing cancer treatment in hospitals or clinics in a prefecture within the Kanto region of Japan without palliative care specialists. Participants were asked about the specific palliative care consultation needs they have and the need for consultation methods.

Results: Of the 11 physicians, nine had completed the nationwide basic primary palliative care education program. The survey revealed three themes regarding their consultation needs: 'receiving specialized insight', 'inspiring confidence', and 'improving care capacity', Two themes emerged regarding the need for consultation methods: 'enhancing care collaboration' and 'improving accessibility'.

Conclusions: Physicians require consultation systems to empower them and enhance the community care capacity, in addition to providing specialized knowledge. These systems would include collaboration with specialists through outreach consultations, utilization of information and communications technology, and the establishment of nurse-led consultation teams to improve access to palliative care teams.

In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes.

Systemic therapy has now become mainstream for the treatment of hepatocellular carcinoma (HCC) and is also changing from molecular-targeted therapy, such as with sorafenib and lenvatinib, to immunotherapy, such as with the atezolizumab plus bevacizumab and durvalumab plus tremelimumab combination regimens. Molecular-targeted therapy is selected as the first-line treatment when immunotherapy is not indicated or as second- or later-line treatment when immunotherapy is ineffective. It is necessary to select the appropriate treatment taking into consideration the expected treatment efficacy and adverse events, as well as the hepatic reserve. Currently, newer agents and combination regimens as first-line/second-line treatment for advanced-stage HCC, combined therapy with transarterial chemoembolization for intermediate-stage HCC, and perioperative adjuvant therapy for curative treatment for early-stage HCC are being developed. Therefore, systemic therapy is now indicated for any stage of the disease. While local therapies were previously used as the main treatment strategy for HCC, systemic therapy in combination with local therapies is being actively attempted at present. Systemic therapy is currently the main focus of development of novel treatments for HCC.

Objective: To evaluate the real-world clinical usage and effectiveness of apalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).

Methods: We retrospectively reviewed the data of 186 men who received apalutamide across 17 institutions. The primary outcomes were the clinical usage of apalutamide for nmCRPC: prior usage of other androgen receptor signaling inhibitors (ARSIs), prior radical treatment, and the distribution of the prostate-specific antigen (PSA) doubling time (PSA-DT) at the initial administration of apalutamide. The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events (AEs).

Results: We identified 75 patients with nmCRPC. A total of 31 (41.3%) patients received prior treatment with other ARSIs. A total of 42 men (56%) did not receive any prior radical treatment. The PSA-DT was <3.0, 3.0-5.9, 6.0-10, and > 10 months in 34.7%, 40%, 14.7%, and 10.6% of the patients, respectively. Patients receiving prior treatment with other ARSIs showed a significantly lower PSA response (PSA 50% decline, 88.4% vs. 18.8%; PSA 90% decline, 60.5% vs. 6.2%, P < .001, respectively) and significantly shorter progression-free survival (median: 37 months vs. 4 months; log-rank P < .001) than those without prior ARSI treatment, although cancer status did not differ between the groups. Skin-AEs were observed in 42.7%.

Conclusions: This real-world study revealed that apalutamide was used for the treatment after other ARSIs in >40% of patients with nmCRPC and showed limited efficacy in this context, although the effectiveness of apalutamide without prior other ARSI treatment was comparable with that reported in clinical trial results.

Background: Chondrosarcoma (CS) is a rare malignant bone tumor exhibiting diverse histological features and clinical behaviors. This study aimed to investigate the epidemiological characteristics, clinical features, prognostic factors, and subtype-specific differences of CS in Japan using National Cancer Registry data.

Methods: We analyzed data from CS cases diagnosed between 2016 and 2019, calculating age-adjusted incidence, estimating overall survival, and identifying prognostic factors through multivariate analysis.

Results: The study identified 1015 CS cases with an age-adjusted incidence of 0.159 per 100 000 population and a mean overall survival of 1205.2 days. Multivariate analysis revealed that female sex, younger age (15-39 years), histological subtypes other than dedifferentiated CS, localized disease, and surgical treatment were associated with better prognoses. Conversely, male sex, older age (≥75 years), dedifferentiated subtype, advanced stage, and non-surgical treatment were linked to a higher risk of death. Significant differences in sex distribution, age at diagnosis, tumor location, disease stage, and tumor differentiation were observed among CS subtypes.

Conclusion: This comprehensive analysis provides valuable insights into CS epidemiology, prognostic factors, and subtype-specific characteristics in Japan. The identification of high-risk groups emphasizes the need for improved therapeutic strategies and supportive care. The observed heterogeneity among CS subtypes underscores the importance of individualized management approaches in treating this complex malignancy.

Background: In the Fourth Basic Plan to Promote Cancer Control Programs, the number of medical practices using claims data from the National Database (NDB) is measured as a clinical indicator. This study aimed to clarify the characteristics of patients who received care as an indicator of medical practices using more manageable claims data.

Methods: We used the claims data collected by the DeSC Healthcare, Inc., and included patients diagnosed with cancer between 2017 and 2022 in this study. We compared age and cancer type distributions between the study population and population estimates, as well as cancer-specific medical practices with the NDB open data. We also described the number of medical practices, patients, and the percentage of patients receiving care by age and region. The percentage of female patients who underwent treatment was also calculated.

Results: A total of 1 251 850 patients was included. The distribution of cancer types was similar to the estimated prevalence, and the number of medical practices resembled the NDB open data; however, the age distribution was skewed. The highest median number of medical procedures per patient was six for specialized palliative care, whereas the others were one medical procedure per patient. The percentage of patients receiving care according to age was classified into three groups: increased with age, decreased with age, and peaked in their 40s. The percentage of patients receiving care varied by region depending on the type of medical practice. Of the patients who received care for lymphedema, 93.8% were female.

Conclusion: The background information of cancer patients who received designated care may help interpret the total number of medical practices used as clinical indicators in cancer control programs.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis; however, advancements in cancer genome profiling using next-generation sequencing have provided new perspectives. KRAS mutations are the most frequently observed genomic alterations in patients with PDAC. However, until recently, it was not considered a viable therapeutic target. Although KRAS G12C mutations for which targeted therapies are already available are infrequent in PDAC, treatments targeting KRAS G12D and pan-KRAS are still under development. Similarly, new treatment methods for KRAS, such as chimeric antigen receptor T-cell therapy, have been developed. Several other potential therapeutic targets have been identified for KRAS wild-type PDAC. For instance, immune checkpoint inhibitors have demonstrated efficacy in PDAC treatment with microsatellite instability-high/deficient mismatch repair and tumor mutation burden-high profiles. However, for other PDAC cases with low immunogenicity, combination therapies that enhance the effectiveness of immune checkpoint inhibitors are being considered. Additionally, homologous recombination repair deficiencies, including BRCA1/2 mutations, are prevalent in PDAC and serve as important biomarkers for therapies involving poly (adenosine diphosphate-ribose) polymerase inhibitors and platinum-based therapies. Currently, olaparib is available for maintenance therapy of BRCA1/2 mutation-positive PDAC. Further therapeutic developments are ongoing for genetic abnormalities involving BRAF V600E and the fusion genes RET, NTRK, NRG, ALK, FGFR2, and ROS1. Overcoming advanced PDAC remains a formidable challenge; however, this review outlines the latest therapeutic strategies that are expected to lead to significant advancements.

Objective: To validate multiple prognostic models in metastatic renal cell carcinoma patients who received second-line axitinib following first-line nivolumab plus ipilimumab therapy.

Methods: Five prognostic models (ACL, albumin, C-reactive protein, and lactate dehydrogenase; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; MSKCC, Memorial Sloan Kettering Cancer Center; ATP, axitinib treatment prediction; JMRC, Japanese metastatic renal cancer) to predict overall survival (OS) were validated and compared using data from 86 metastatic renal cell carcinoma patients who received second-line axitinib therapy following first-line nivolumab plus ipilimumab therapy at 34 hospitals affiliated with the Japan Urologic Oncology Group.

Results: The Karnofsky performance status, time from initial diagnosis to first-line therapy, and hemoglobin, platelet, albumin, and C-reactive protein levels correlated with OS in univariate Cox regression analyses. Among these factors, only albumin had a significant impact on OS in the multivariate analysis. The integrated area under the curve (AUC) of the ACL, IMDC, MSKCC, ATP, and JMRC models were 0.78, 0.76, 0.76, 0.69, and 0.70, respectively. The ACL model showed a higher value than the others in the time-dependent AUC.

Conclusions: The accuracy of the five prognostic models (ACL, IMDC, MSKCC, ATP, and JMRC) created in the pre-immuno-oncology (IO) treatment cohort was maintained in the second-line axitinib group after nivolumab plus ipilimumab therapy. The ACL model demonstrated moderate accuracy in predicting OS with the fewest number of clinical variables.