Search

Simple Summary: Tertiary lymphoid structures (TLS) arise in non-lymphoid tissues due to inflammation or cancer and play a key role in adaptive immune responses. In this study, we analyzed the TLS maturity in 78 patients with pathological T4 colorectal cancer (CRC). Mature TLS, identified by organized T (CD3+) and B (CD20+) lymphocytes with Ki-67-positive B cells, have been linked to microsatellite instability and improved cancer-specific and post-recurrence survival. High tumor Ki-67 expression correlated with poorer outcomes. The absence of mature TLS independently predicted poor survival. Tumors with mature TLS showed a higher infiltration of CD3+ T cells, FOXP3+ T cells, and CD86+ immune cells, including M1-like macrophages. Focusing on the Ki-67 expression pattern, the simultaneous evaluation of TLS maturity and tumor proliferation potency is suggested to be a potential prognostic indicator in CRC. Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes and prognostic factors of 127 patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from the initiation of ARSI were assessed. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS varied among patients treated with enzalutamide, abiraterone acetate, apalutamide, and darolutamide (27.0, 20.0, 10.0, and 14.0 months, respectively; p = 0.33). Multivariate analysis indicated that a baseline PSA level of ≥3.67 ng/mL (p = 0.002) was significantly associated with poorer OS prognosis. ARSI demonstrated favorable efficacy in nmCRPC patients, with no significant differences in clinical outcomes among different types of ARSI. High baseline PSA of ARSI was found to have a significantly poor prognosis associated with OS. We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from ARSI initiation were assessed using the Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥ 3.67 ng/mL at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular targeted therapies are very effective as a treatment for postoperative recurrence of non-small cell lung cancer (NCSLC) with driver mutations. On the other hand, the efficacy of local therapies for oligo-recurrence has also been reported. To investigate the optimal treatment strategy for oligo-recurrence in NSCLC patients with driver mutations, we retrospectively evaluated 66 NSCLC patients with driver mutations who were treated with local or molecular targeted therapies as the initial treatment after recurrence. Patients treated with local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival and progression-free survival compared with those treated with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can be curative after recurrence and can delay the start of the administration of molecular targeted therapies. Background: The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Methods: Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. Results: The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701–2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459–1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Conclusions: Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: The Barcelona clinic liver cancer (BCLC) system is used widely for staging hepatocellular carcinomas (HCCs). However, it is questionable that for patients classified as BCLC stage C, control of intrahepatic targets using various treatment procedures is not the main topic of discussion, whereas the importance of intrahepatic tumor control in patients with extrahepatic tumor spread is reviewed. Therefore, this study analyzed the data of 64 consecutive BCLC stage C patients with intrahepatic target nodules who received systemic therapy and evaluated the efficacy of the combined use of systemic sequential therapy, including more than two agents, and locoregional treatment administered after initiation of systemic therapy. We showed that the combined use of systemic sequential therapy of more than two agents and locoregional-treatment improved overall survival in BCLC stage C HCC patients with intrahepatic target nodules who had previously received systemic therapy-based treatment. Background: The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). Methods: Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP). Results: R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively; p = 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio [HR]; 0.053, p = 0.006 and 0.189, p < 0.001, respectively) compared with that for STP (HR; 0.279, p = 0.003). Conclusions: MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Although sarcopenia-related factors, including decreased skeletal muscle index (SMI), have been reported to affect therapeutic efficacy and the occurrence of adverse events in sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC), there is considerably less evidence regarding the relationship between SMI and prognosis in the HCC patients treated with atezolizumab plus bevacizumab (atezo/bev) therapy. Furthermore, there are no reports of muscle strength, including grip strength (GS), which is essential for an accurate diagnosis of sarcopenia. This is the first study to show the relationship between sarcopenia, diagnosed by decreased GS and SMI, and clinical outcomes in atezo/bev therapy, with novel evidence having a strong impact. The presence of sarcopenia is significantly associated with shorter overall survival with the occurrence of adverse events and decreased liver function. Monitoring of both GS and SMI is useful for assessing the general condition and predicting prognosis in HCC patients treated with atezo/bev therapy. Although there have been advances in the prevention and diagnosis of hepatocellular carcinoma (HCC) in recent years, many HCC patients are still diagnosed with advanced stage. Systemic therapy is indicated for unresectable HCC (uHCC) with major vascular invasion and/or extrahepatic metastases, and the atezolizumab plus bevacizumab (atezo/bev) combination is currently recommended as first-line treatment for uHCC. Recently, sarcopenia-related factors, including decreased skeletal muscle index (SMI), have been reportedly associated with prognosis in uHCC patients treated with sorafenib or lenvatinib. There are few reports on muscle strength assessments, including grip strength (GS), despite their importance in accurate sarcopenia diagnosis, and furthermore, there is no evidence regarding atezo/bev therapy. In this study, we investigated whether sarcopenia affects the clinical outcome of atezo/bev therapy. This study included 64 uHCC patients on atezo/bev therapy and assessed their GS and SMI, and SMI was measured using bioelectrical impedance analysis (BIA). We diagnosed sarcopenia based on GS and BIA-SMI and compared the clinical outcomes in the sarcopenia and non-sarcopenia groups. Of these patients, 28 had sarcopenia, and 36 had non-sarcopenia. Adverse events (AEs) frequently occurred, and the albumin-bilirubin score significantly decreased after atezo/bev therapy in the sarcopenia group than in the non-sarcopenia group. The median progression-free survival was 4.7 (0.4–26.4) and 10.6 (1.1–24.5) months in the sarcopenia and non-sarcopenia groups, respectively. The median overall survival (OS) was 12.6 (1.4–27.7) months in the sarcopenia group and was not reached in the non-sarcopenia group, indicating a significant difference in the Kaplan-Meier survival curves for both groups (p < 0.01). In multivariate analysis, sarcopenia was significantly associated with OS. In conclusion, sarcopenia was significantly associated with poor clinical outcomes based on the occurrence of AEs and decreased liver function in uHCC patients on atezo/bev therapy. GS and SMI are important parameters for accurately diagnosing sarcopenia. [ABSTRACT FROM AUTHOR]

Simple Summary: Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. Eight cases (6.9%) were diagnosed as tumor mutation burden-high and/or microsatellite instability-high. The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Six patients (5.2%) underwent gene-matched therapy based on results of CGP tests. The median overall survival (OS) was significantly longer in the HRD (+) group. In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search. Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program since 2018, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. We evaluated the results of CGP tests, treatments based on CGP tests, and survival time. Eight cases (6.9%) were diagnosed as tumor mutation burden-high (TMB-H) and/or microsatellite instability-high (MSI-H). The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Four patients (3.5%) having TMB-H and/or MSI-H were treated with pembrolizumab, and only two patients (1.7%) participated in the clinical trials. Patient characteristics were not significantly different between patients with and without HRD-related gene mutations. The median OS was significantly longer in the HRD (+) group than in the HRD (−) group (749 days vs. 519 days, p = 0.047). In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment strategies have changed dramatically in recent years with the development of a variety of agents for metastatic hormone-naïve prostate cancer. There is a need to identify prognostic factors for the appropriate choice of treatment for patients with hormone-naïve prostate cancer in Japanese men. Among the prostate cancer patients receiving treatment at our institution from 2000 to 2019, 198 patients with bone or visceral metastases at the initial diagnosis were included in the study. We retrospectively examined these factors of the overall survival, and identified Gleason pattern 5 content, bone scan index ≥ 1.5, and lactate dehydrogenase evels ≥ 300 IU/L as prognostic factors. Using these three factors, we developed a new prognostic model for overall survival that can more objectively predict the prognosis of patients simply and objectively. Background: Treatment strategies have changed dramatically in recent years with the development of a variety of agents for metastatic hormone-naïve prostate cancer (mHNPC). There is a need to identify prognostic factors for the appropriate choice of treatment for patients with mHNPC, and we retrospectively examined these factors. Methods: Patients with mHNPC treated at our institution from 2000 to 2019 were included in this study. Overall survival (OS) was estimated retrospectively using the Kaplan–Meier method, and factors associated with OS were identified using univariate and multivariate analyses. A prognostic model was then developed based on the factors identified. Follow-up was terminated on 24 October 2021. Results: The median follow-up duration was 44.2 months, whereas the median OS was 85.2 months, with 88 patients succumbing to their disease. Multivariate analysis identified Gleason pattern (GP) 5 content, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) levels ≥ 300 IU/L as prognostic factors associated with OS. We also developed a prognostic model that classified patients with mHNPC as low risk with no factor, intermediate risk with one factor, and high risk with two or three factors. Conclusions: Three prognostic factors for OS were identified in patients with mHNPC, namely GP5 inclusion, BSI ≥ 1.5, and LDH ≥ 300. Using these three factors, we developed a new prognostic model for OS that can more objectively predict patient prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to evaluate treatment patterns and real-world clinical outcomes since immunotherapy was introduced in Japan as the initial (first-line) therapy for treating patients with lung cancer, the leading cause of cancer-related deaths in Japan. For 1182 patients with advanced non-small-cell lung cancer, the survival rate at two years after starting first-line therapy was 40% with platinum doublet chemotherapy, 58% with immunotherapy, and 31% with nonplatinum regimens. The results of this large study enabled us to describe the characteristics of a real-world patient population, together with the treatment patterns for advanced non-small-cell lung cancer and clinical outcomes from real-world settings, where most patients receive treatment. Most first-line therapies were administered in accordance with contemporaneous national treatment guidelines, and the study findings indicate improvement in real-world clinical outcomes for patients with advanced non-small-cell lung cancer since the introduction of first-line immunotherapy. The aims of this study were to describe systemic treatment patterns and clinical outcomes for unresectable advanced/metastatic non-small-cell lung cancer (NSCLC) by first-line regimen type in real-world clinical settings in Japan after the introduction of first-line immune checkpoint inhibitor (ICI) monotherapy in 2017. Using retrospective chart review at 23 study sites, we identified patients ≥20 years old initiating first-line systemic therapy from 1 July 2017 to 20 December 2018, for unresectable stage IIIB/C or IV NSCLC; the data cutoff was 30 September 2019. Eligible patients had recorded programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) and no known actionable EGFR/ALK/ROS1/BRAF genomic alteration. Kaplan-Meier method was used to determine time-to-event endpoints. Of 1208 patients, 647 patients (54%) received platinum doublet, 463 (38%) received ICI monotherapy, and 98 (8%) received nonplatinum cytotoxic regimen as first-line therapy. PD-L1 TPS was ≥50%, 1–49% and <1% for 44%, 30%, and 25% of patients, respectively. Most patients with PD-L1 TPS ≥50% received ICI monotherapy (453/529; 86%). Excluding 26 patients with ECOG performance status of 3–4 from outcome analyses, the median patient follow-up was 11.3 months. With first-line platinum doublet, ICI monotherapy, and nonplatinum cytotoxic regimens, median overall survival (OS) was 16.3 months (95% CI, 14.0–20.1 months), not reached, and 14.4 months (95% CI, 10.3–21.2 months), respectively; 24-month OS was 40%, 58%, and 31%, respectively. Differences in OS relative to historical cohort data reported in Japan are consistent with improvement over time in real-world clinical outcomes for advanced NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Pembrolizumab improves overall survival (OS) in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas objective response was observed in a modest number of patients (<25%) for this treatment, implying the distinct survival outcomes for those patients. Thus, the optimal risk stratification to predict survival outcomes at the initiation of pembrolizumab treatment would be helpful for physicians. In the present study, we examined a risk model developed using two clinical factors, including the number of metastatic sites and neutrophil–lymphocyte ratio (NLR), for predicting OS at the initiation of pembrolizumab treatment. This risk stratification seemed to be well-balanced (26.5%, 44.3%, and 29.2% in the favorable-risk, intermediate-risk, and poor-risk groups, respectively), and Kaplan–Meier curves illustrated clear discrimination of OS among the risk groups. Since the model proposed in the present study can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice. Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice. [ABSTRACT FROM AUTHOR]