Publications by authors named "Shiotsu Shinsuke"

In individuals with a history of renal cell carcinoma (RCC), mediastinal lymphadenopathy is frequently attributed to metastatic recurrence. However, secondary malignancies, despite their rarity, should also be considered. During routine follow-up examinations, a 63-year-old male with a history of renal cell carcinoma demonstrated progressive mediastinal lymphadenopathy.

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Background: Clinical trial eligible patients with advanced non-small cell lung cancer (aNSCLC) and low programmed cell death ligand 1 (PD-L1) expression achieve greater benefit from immune checkpoint inhibitor (ICI) combination chemotherapy (ICI-Chemo) compared with Chemo alone. We examined whether patients ineligible for clinical trials may benefit from ICI-Chemo.

Methods: This multicenter retrospective cohort study enrolled patients with aNSCLC, including unresectable Stage III (IIIB/IIIC) and IV disease with a PD-L1 tumor proportion score of 1-49% treated with ICI-Chemo or Chemo as first-line therapy from 2018 to 2023 in Japan.

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Background: Although chemoimmunotherapy is recommended for advanced nonsquamous non-small cell lung cancer (NSCLC) with low programmed cell death ligand 1 (PD-L1) expression, no head-to-head comparisons of immune checkpoint inhibitors (ICIs) have been performed. Therefore, we compared the effect and safety of regimens in these patients to guide evidence-based treatment.

Methods: This retrospective study included patients with advanced nonsquamous NSCLC with a PD-L1 tumor proportion score of 1% to 49% administered ICI combination platinum-based chemotherapy between May 2018 and May 2023 at 19 institutions in Japan.

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This retrospective, multicenter cohort study aimed to determine whether cancer cachexia serves as a biomarker for determining the most effective treatment for patients having non-small-cell lung cancer (NSCLC) with high programmed death ligand 1 (PD-L1) expression treated with immune checkpoint inhibitors (ICIs) alone or combined with chemotherapy (ICI/chemotherapy). We included 411 patients with advanced NSCLC with a PD-L1 tumor proportion score of ≥50%. The patients were treated with pembrolizumab monotherapy or ICI/chemotherapy.

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Article Synopsis
  • The study investigated the role of thyroid transcription factor 1 (TTF-1) as a predictor for treatment response in advanced non-squamous non-small-cell lung cancer (NSCLC) patients undergoing chemotherapy or chemoimmunotherapy with specific levels of PD-L1 expression.
  • Out of 624 patients surveyed, 283 met the criteria, revealing that TTF-1 positivity was associated with significantly longer progression-free survival (PFS) and overall survival (OS) in those receiving chemotherapy, but not in the chemoimmunotherapy group.
  • The findings suggest that TTF-1 expression can help predict treatment effectiveness for chemotherapy, while its impact on chemoimmunotherapy remains unclear in patients with PD-L1 levels between
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Background: Tumor markers such as serum carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1) are utilized for assessing the effectiveness of chemotherapy in non-small cell lung cancer (NSCLC) patients. Yet, it remains uncertain whether these markers can reliably forecast responses to combined chemoimmunotherapy. Our study aimed to examine the significance and effectiveness of these markers in predicting responses among NSCLC patients undergoing combined chemoimmunotherapy.

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The association between depth of response (DpR) and treatment outcomes has been documented across various types of cancer. Immune checkpoint inhibitor (ICI)-based treatment is globally used as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥ 50%. However, in this population, the significance of DpR is not elucidated.

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Introduction: Several studies explored the association between thyroid transcription factor-1 (TTF-1) and the therapeutic efficacy of immunotherapy. However, the effect of TTF-1 on the therapeutic efficacy of programmed death-1 (PD-1) inhibitor/chemoimmunotherapy in patients with non-squamous non-small cell lung cancer (non-Sq NSCLC) with a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or more who are highly susceptible to immunotherapy remains unresolved. Therefore, we evaluated whether TTF-1 has a clinical impact on this population.

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Background: Combination therapy with docetaxel (DTX) and ramucirumab (RAM) has been used as a second-line treatment for advanced or recurrent lung cancer. However, there is insufficient evidence regarding the safety of angiogenesis inhibitors in older patients.

Objective: This multicenter retrospective study aimed to investigate the efficacy and safety of second-line treatment regimens in older patients with advanced or recurrent non-small cell lung cancer (NSCLC).

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Introduction: The proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited.

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Article Synopsis
  • Multiple PD-L1 immunohistochemistry assays (22C3, 28-8, SP142) are used to predict responses to immune therapies in advanced NSCLC, but their comparative effectiveness is not fully understood.
  • A study in Japan observed 70 advanced NSCLC patients treated with combined chemoimmunotherapy, assessing PD-L1 expression using all three assays.
  • Results indicated that the 22C3 assay was the most effective in predicting therapeutic response, showing significant differences in progression-free survival compared to the other assays, suggesting it may be key for clinical decision-making.
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Combination therapy with ipilimumab and nivolumab is indicated for many types of cancers; however, several patients experience immune-related adverse events (irAEs). We herein report a case of cytokine release syndrome (CRS) in a 63-year-old woman with stage IV left clear cell renal cell carcinoma. Our patient developed CRS while taking prednisolone, 43 days after the start of ipilimumab and nivolumab administration.

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Article Synopsis
  • Second-line immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) patients with ≤ 49% PD-L1 expression has limited effectiveness, and there is a need to understand predictors of its efficacy after platinum-based chemotherapy.
  • A study involving 54 advanced NSCLC patients in Japan found that those who did not experience disease progression after first-line chemotherapy had significantly better response rates and overall survival when treated with ICI monotherapy compared to those who had disease progression.
  • Maintaining a non-progressive disease status after chemotherapy emerged as a key independent prognostic factor for better outcomes with ICI therapy, along with a trend suggesting that a modified Glasgow Prognostic Score of 0 could correlate with longer survival.
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Recently, novel Kirsten rat sarcoma viral oncogene homolog (KRAS) inhibitors have been clinically developed to treat KRAS G12C-mutated non-small cell lung cancer (NSCLC) patients. However, achieving complete tumor remission is challenging. Therefore, the optimal combined therapeutic intervention with KRAS G12C inhibitors has a potentially crucial role in the clinical outcomes of patients.

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Background: A history of pre-administration of immune checkpoint inhibitors has been reported to be associated with good outcomes of ramucirumab (RAM) plus docetaxel (DOC) combination therapy for advanced non-small-cell lung cancer (NSCLC). However, existing knowledge on the clinical significance of RAM and DOC following combined chemoimmunotherapy is limited. Therefore, we evaluated the efficacy and safety of RAM plus DOC therapy after combined chemoimmunotherapy and attempted to identify the predictors of its outcomes.

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Article Synopsis
  • The study investigates treatment options for patients with non-small cell lung cancer (NSCLC) who have high PD-L1 expression and poor performance status, focusing on the effectiveness of immune checkpoint inhibitors (ICI) combined with chemotherapy versus pembrolizumab monotherapy.
  • Researchers analyzed data from 425 NSCLC patients, categorizing them based on their performance status (good vs. poor), finding that those with good performance had significantly better survival outcomes compared to those with poor performance when treated with ICI therapies.
  • In the poor performance status group, there was no significant difference in progression-free survival or overall survival between the combination therapy and monotherapy, indicating that both treatment options may be equally ineffective for these
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Background: The long overall survival (OS) observed among patients with non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression in chemoimmunotherapy (CIT) groups in previous phase III trials suggests the limited efficacy of CIT among the subgroup with ≤49% PD-L1 expression on tumor cells. Hence, sequential treatment with first-line platinum-based chemotherapy followed by second-line immune checkpoint inhibitor treatment (SEQ) is an option. This study examined whether first-line CIT would provide better outcomes than SEQ in patients with advanced NSCLC with ≤49% PD-L1 expression.

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Background: Durvalumab consolidation after chemoradiotherapy (CRT) is a standard treatment for locally advanced non-small cell lung cancer (NSCLC). However, studies on immunological and nutritional markers to predict progression-free survival (PFS) and overall survival (OS) are inadequate. Systemic inflammation causes cancer cachexia and negatively affects immunotherapy efficacy, which also reflects survival outcomes.

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Background: Osimertinib monotherapy is a common treatment for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC); however, standard treatment strategies for acquired resistance to this drug have not been established. In addition, the clinical significance of first-generation (1G) or second-generation (2G) EGFR-tyrosine kinase inhibitors (TKI) in patients with EGFR-mutant NSCLC and osimertinib resistance has not yet been fully evaluated.

Objective: We aimed to conduct a prospective multicenter observational study to evaluate the efficacy and safety of 1G and 2G EGFR-TKIs after the development of osimertinib resistance.

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Importance: Immune checkpoint inhibitor (ICI) monotherapy with pembrolizumab and ICI plus chemotherapy have been approved as first-line treatments for non-small cell lung cancer (NSCLC) for patients with a programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) of 50% or more, but the choice between these 2 therapeutic options is unclear.

Objective: To clarify the association of a history of concurrent medication use with treatment outcomes for ICIs with or without chemotherapy in patients with NSCLC with a high PD-L1 TPS and to determine whether these clinical histories are biomarkers for appropriate treatment selection.

Design, Setting, And Participants: This retrospective, multicenter cohort study at 13 hospitals in Japan included patients with advanced NSCLC with a PD-L1 TPS of 50% or more who had received pembrolizumab ICI monotherapy or ICI plus chemotherapy as the initial treatment between March 2017 and December 2020.

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Background: Programmed death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy is used as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), regardless of age.

Objective: We examined the role of the Geriatric 8 (G8) screening tool for evaluating treatment outcomes in patients with ES-SCLC treated with PD-L1 inhibitor plus platinum-etoposide chemotherapy as first-line therapy.

Patients And Methods: Between September 2019 and October 2021, we prospectively evaluated patients with ES-SCLC treated with immunochemotherapy at ten institutions in Japan.

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Article Synopsis
  • * The results indicated that patients who experienced greater tumor shrinkage at the first treatment evaluation had significantly longer progression-free survival (PFS) and overall survival compared to those who did not.
  • * The study identified a 57% tumor shrinkage as a key metric for predicting treatment responders, suggesting that ETS is a valuable indicator of clinical outcomes for patients receiving this specific chemotherapy regimen.
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Introduction: Lung adenocarcinoma with negative TTF-1 expression is believed to be a poor prognostic factor for certain systemic treatments. Nevertheless, the impact of TTF-1 expression on combined chemoimmunotherapy remains unclear. We aimed to investigate the relationship between tumor TTF-1 expression and the efficacy of combined chemoimmunotherapy in patients with advanced lung adenocarcinoma.

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Chemoimmunotherapy improved overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC) in two phase III trials. They set the age-stratified subgroup analyses at 65 years; however, over half of the patients with lung cancer were newly diagnosed at ≥75 years in Japan. Therefore, treatment efficacy and safety in elderly patients ≥ 75 years with ES-SCLC should be evaluated through real-world Japanese evidence.

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Article Synopsis
  • Patients with advanced non-small cell lung cancer and EGFR mutations received either immunochemotherapy (ABCP) or standard chemotherapy after failing initial TKI treatment in this study conducted in Japan.
  • Analysis of 57 patients revealed similar median progression-free survival (PFS) and overall survival (OS) between the two treatment groups, with no significant differences except in PD-L1-negative patients where ABCP performed worse.
  • The study suggests that the use of immunochemotherapy should be evaluated cautiously, particularly for those who are PD-L1-negative.
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