Publications by authors named "Haruhiro Saito"

Background: Concurrent chemoradiotherapy is the standard therapy for locally advanced non-small cell lung cancer (NSCLC). However, there is little evidence supporting its use in older adults. Low-dose daily carboplatin combined with thoracic radiotherapy is considered a standard regimen for this population.

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Introduction: The primary analysis (median follow-up 34.9 mo across all arms) of the phase 3 POSEIDON study revealed a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR and ALK wild-type metastatic NSCLC (mNSCLC). D+CT had a trend for OS improvement versus CT that did not reach statistical significance.

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Neutrophil extracellular traps (NETs) released from neutrophils are related to cancer progression. However, the relationship between the therapeutic effects of immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-PD-L1 antibodies and plasma NET concentration in patients with non-small cell lung cancer (NSCLC) is poorly understood. In this study, concentrations of citrullinated histone H3 (CitH3), a surrogate marker of NETs, in plasma before/after treatment were examined in patients with advanced or recurrent NSCLC undergoing ICI treatment (n = 185).

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Objectives: This exploratory integrated analysis of the randomized Phase III IMpower130 and IMpower132 trials evaluated the efficacy and safety of atezolizumab plus platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC) who were aged ≥75 years or had renal dysfunction.

Materials And Methods: Chemotherapy-naïve patients with stage IV non-squamous NSCLC received atezolizumab-containing therapy or platinum-doublet chemotherapy in IMpower130 and IMpower132. This integrated analysis assessed efficacy (including overall survival [OS], progression-free survival [PFS], and objective response rates) and safety in the integrated population and in patients ≥75 years old.

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Background: Atezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II-IIIA non-small cell lung cancer with 1% or more programmed death ligand-1 (PD-L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non-small cell lung cancer. Therefore, our study aimed to compare two PD-L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab.

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Purpose: Genetic mutation detection has become an important step in nonsmall-cell lung cancer (NSCLC) treatment because of the increasing number of drugs that target genomic rearrangements. A multiplex test that can detect multiple gene mutations prior to treatment is thus necessary. Currently, either next-generation sequencing (NGS)-based or polymerase chain reaction (PCR)-based tests are used.

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Clinical roles of plasma IL-6 levels have been reported in patients with various cancers, including non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (ICIs). However, the roles of other IL-6 signaling components, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130), in the plasma have not been elucidated. Blood was collected from 106 patients with NSCLC before initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody).

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Article Synopsis
  • The study assesses combination immunotherapy with nivolumab and ipilimumab for stage IV or recurrent non-small cell lung cancer in Japanese patients, revealing potential survival benefits compared to chemotherapy.
  • In an analysis of 353 patients over an average follow-up of 7.1 months, safety was monitored with 32.1% of those treated experiencing serious adverse events, mainly in the first month.
  • The results indicate a median progression-free survival of approximately 6.0 months for patients receiving immunotherapy with chemotherapy and 5.8 months without, providing important clinical insights for similar patient populations.
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Background: The terminology for lung cancer diagnosis in small biopsies was adopted in the 2015 World Health Organization classification. If non-small cell lung cancer (NSCLC) has no clear adenocarcinoma (AD) or squamous cell carcinoma morphology, the tumor is further classified based on mucin or immunohistochemical staining as NSCLC favor AD (NFAD), NSCLC favor squamous cell carcinoma, or NSCLC not otherwise specified. Since this new term was defined, the difference between AD and NFAD has not yet been fully explored.

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  • - The study investigates the effectiveness and safety of combining bevacizumab with chemotherapy and atezolizumab in advanced non-small cell lung cancer (NSCLC) patients, building on the existing standard treatment protocols.
  • - Conducted as a phase 3 randomized clinical trial at 37 hospitals in Japan, it enrolled patients with advanced nonsquamous NSCLC between January 2019 and August 2020, focusing on those without genetic driver alterations or who had prior treatment with tyrosine kinase inhibitors.
  • - The primary outcome measured was progression-free survival (PFS), assessed by independent reviewers, with a total of 412 patients enrolled in two treatment groups: one receiving the standard regimen and the other receiving the combination with bev
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Background: Impact of RNA-binding motif protein 10 (RBM10) and programmed death-ligand 1 (PD-L1) on the postoperative prognosis of patients with epidermal growth factor receptor gene mutation (-Mt) lung adenocarcinoma with pathological lymph node metastasis is still unclear.

Methods: Patients who underwent curative surgery for pN1-N2 -Mt lung adenocarcinoma (n=129) harboring the exon 19 deletion mutation (Ex19) (n=66) or exon 21 L858R mutation (Ex21) (n=63) between January 2010 and December 2020 were included in this retrospective study. The prognoses of patients with low/high cytoplasmic RBM10 expression and PD-L1 negativity/positivity based on immunohistochemistry (IHC) of resected specimens were compared using the log-rank test.

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Objectives: In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs).

Patients And Methods: Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy.

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  • The KEYNOTE-407 trial established pembrolizumab plus platinum-based chemotherapy as the standard treatment for advanced squamous non-small-cell lung cancer (NSCLC), and this study will evaluate the drug ubenimex when combined with this regimen.
  • Conducted as a phase II clinical trial, patients will receive ubenimex along with pembrolizumab, nab-paclitaxel, and carboplatin, with a focus on establishing safety and efficacy through systematic dose escalation.
  • This trial represents the first investigation of ubenimex in this combination treatment, and its findings could inform future therapeutic approaches for patients with advanced squamous NSCLC.
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  • The phase III IMPACT study evaluated the effectiveness of adjuvant gefitinib compared to cisplatin plus vinorelbine (cis/vin) for patients with completely resected EGFR-mutated non-small cell lung cancer (NSCLC).
  • Although the study didn't meet its main goal of improving disease-free survival (DFS), researchers focused on identifying molecular predictors of gefitinib's effectiveness among 202 patients analyzed for cancer-related gene mutations.
  • Key findings revealed that NOTCH1 co-mutations indicated a poorer overall survival in the gefitinib group, while CREBBP co-mutations suggested better outcomes in terms of DFS and overall survival for the cis/vin group.
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  • Segmentectomy is a less invasive surgical option compared to lobectomy for patients with non-small cell lung cancer (NSCLC), but the reasons behind this reduced invasiveness are not well understood.
  • The study analyzed data from 315 patients who had either segmentectomy or lobectomy, measuring changes in psoas muscle mass over postoperative periods using CT scans.
  • Results showed that the lobectomy group experienced significantly greater muscle mass loss compared to the segmentectomy group, with muscle mass remaining stable in the segmentectomy group throughout the observation period.
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  • - The JIPANG study is a phase III trial comparing the effectiveness of pemetrexed plus cisplatin (PemP) to vinorelbine plus cisplatin (NP) in treating stage II-IIIA nonsquamous non-small-cell lung cancer.
  • - The trial included 804 patients, with results showing that the median recurrence-free survival (RFS) was 37.5 months for NP and 43.4 months for PemP, revealing no significant difference.
  • - After a median follow-up of 77.3 months, overall survival (OS) rates were comparable between the two treatments, indicating that PemP has similar efficacy to NP in long-term outcomes for these patients.
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  • Squamous cell carcinoma is less common in EGFR mutation-positive non-small cell lung cancers and responds poorly to early EGFR tyrosine kinase inhibitors compared to adenocarcinomas.
  • A study highlighted a 57-year-old male with stage IIIC squamous cell lung cancer who had both an exon19 deletion and a T790M mutation identified through genetic testing.
  • The patient was treated with osimertinib after other treatments failed, achieving a partial response that lasted over 20 months, suggesting that accurate genetic testing can help predict the effectiveness of EGFR-TKIs.
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Background: The PACIFIC trial findings drastically changed the c-stage III non-small cell lung cancer (NSCLC) treatment strategy. However, it remains uncertain whether surgery is no longer needed for treatment. We aimed to evaluate the efficacy of surgery and explore the prognostic factors of better outcomes in surgery-treated patients than in PACIFIC regimen-treated patients.

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  • Immune checkpoint inhibitors (ICIs) have improved survival for patients with non-small-cell lung cancer (NSCLC), but their effectiveness can vary; hence, a new machine learning tool called the Cytokine-based ICI Response Index (CIRI) was developed to enhance prediction of patient responses based on blood cytokine profiles.
  • The study involved 222 NSCLC patients, analyzing the levels of 93 cytokines before and after treatment, and utilized ensemble learning methods to identify key cytokines that could forecast overall survival (OS) for those undergoing ICI therapy.
  • The CIRI models identified specific cytokines that correlated with worse OS, achieving accurate prediction rates in independent cohorts; further advancements incorporating additional clinical data improved prediction capabilities,
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Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved the prognosis of non-small cell lung cancer (NSCLC). However, only a limited proportion of patients can benefit from this therapy, and clinically useful predictive biomarkers remain to be elucidated.

Methods: Blood was collected from 189 patients with NSCLC before and six weeks after the initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody).

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Article Synopsis
  • * Initially treated with alectinib, the patient experienced disease progression within five months but showed significant improvement after switching to pembrolizumab, an ICI.
  • * The results suggest that ICIs can be effective for treating MSI-high NSCLC, even when anaplastic lymphoma kinase (ALK) rearrangements are present, as evidenced by the patient's tumor shrinkage over a year without adverse effects.
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Purpose: The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non-small-cell lung cancer (mNSCLC).

Methods: Patients (n = 1,013) with / wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT.

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