Publications by authors named "Harry Yoon"

Purpose: To evaluate the safety and efficacy of pencil beam scanning (PBS) proton radiation therapy (RT) in trimodality therapy for esophageal cancer.

Methods And Materials: This prospective pilot study was planned to accrue 30 patients with locally advanced esophageal or gastroesophageal junction carcinoma medically suitable for chemoradiation therapy (CRT) followed by esophagectomy. PBS proton RT consisted of 25 fractions, 50 Gy to tumor + 1 cm and 45 Gy to a 3.

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Immune checkpoint inhibitors are rapidly transforming the care of patients with esophagogastric cancer. Particularly, anti-PD-1 therapy has demonstrated promising efficacy in metastatic and resectable disease. In this review, the authors discuss landmark clinical trials, highlight challenges and opportunities in this field, and propose potential directions for future work.

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Background: Rivoceranib is an oral, selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. ANGEL (NCT03042611) was a global, randomized, double-blinded, placebo-controlled, phase 3 study evaluating rivoceranib as 3rd-line or ≥4th-line therapy in patients with advanced/metastatic gastric or gastroesophageal junction (GEJ) cancer.

Methods: Patients had failed ≥2 lines of chemotherapy and were randomized 2:1 to rivoceranib 700 mg once daily or placebo with best supportive care.

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Article Synopsis
  • * Conducted globally with participants aged 18 and older, the research was a randomized, double-blind phase 3 trial, comparing the tislelizumab treatment group to a control group receiving a placebo alongside chemotherapy.
  • * The primary goal of the trial was to assess overall survival in patients receiving tislelizumab and chemotherapy versus those receiving the placebo and chemotherapy, with continued treatment until disease progression or intolerable side effects emerged.
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Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation.

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Background: Distinguishing pseudo-progression from true progression on immunotherapy remains a clinical challenge. Clinical tools to aid in this task are currently lacking. DNA mismatch repair (MMR) status is a known predictive marker for anti-programmed death (PD)-1 therapy, but its role in helping to address this situation is not well-defined.

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Purpose/objective: Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes.

Materials/methods: Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy.

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Article Synopsis
  • Targeting focal adhesion kinase (FAK) with the drug defactinib, combined with gemcitabine and pembrolizumab, shows promise in treating pancreatic ductal adenocarcinoma (PDAC) in a multi-center phase I study.* -
  • The study involved two phases: one to determine the optimal dosage and another to treat patients with either refractory or stable PDAC, where an 80% disease control rate was observed among those with refractory disease.* -
  • Preliminary results indicate the treatment combination is well-tolerated and shows potential efficacy, suggesting future studies may benefit from using stronger chemotherapy agents alongside it.*
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Importance: Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.

Objective: To systematically examine the predictive value of tissue-based PD-L1 status compared with that of other variables for ICI benefit in aGEC to assess its stability.

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Exploratory analysis of a phase III trial in esophageal cancer found that the patients who most contributed to an overall survival benefit from PD-1 blockade were not responders, but non-responders. The analysis has limitations but may have implications for investigating the optimal timing of immunotherapy relative to other treatments. See related article by Okada et al.

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Purpose: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma.

Patients And Methods: Patients with GEJ adenocarcinoma (cT1-3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)].

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Immune checkpoint inhibitors (ICIs), as a novel class of anticancer therapy, can be more efficacious and less toxic than chemotherapy, but their clinical success is confined to certain tumor types. Elucidating their targets, mechanisms and scope of action, and potential synergism with chemotherapy and/or targeted therapies are critical to widen their clinical indications. Treatment response to an ICI targeting programmed death-1 (anti-PD-1) is sought to be understood here by conducting a preplanned correlative analysis of a phase II clinical trial in patients with small bowel adenocarcinoma (SBA).

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Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage.

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Background: Fluoropyrimidine with platinum-based chemotherapy has become the standard of care for advanced gastric and gastroesophageal (GEJ) cancer. Trials in colon cancer show that induction chemotherapy followed by maintenance chemotherapy is an efficacious strategy to maximize clinical response while minimizing toxicity. The current retrospective study aims to evaluate the efficacy and tolerability of maintenance versus continuous treatment in advanced GEJ malignancy.

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Objective: Based on the current evidence, review the efficacy and safety profile of pembrolizumab, along with its shortcomings, in an effort to define future research directions.

Background: The survival outcome of esophageal cancer (EC) is poor, especially in patients with advanced stage. Palliative surgery, chemotherapy, radiotherapy and chemoradiotherapy have limited efficacy in prolonging the survival time.

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Esophagogastric cancer (EGC) is a heterogeneous group of malignancies that collectively represent the 2nd leading cause of cancer deaths worldwide. While surgery in combination with chemotherapy and/or radiation therapy represents the primary curative treatment for early stage disease, survival outcomes for the majority of patients with later-stage disease remain poor. Cytotoxic chemotherapy with platinum doublets such as 5-FU/leucovorin/oxaliplatin is the mainstay of treatment with incremental benefits provided by targeted therapy (trastuzumab, trastuzumab deruxtecan, ramucirumab) and immunotherapy (pembrolizumab, nivolumab).

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Article Synopsis
  • The study aimed to evaluate the effectiveness of induction chemotherapy before trimodality therapy in patients with esophageal or gastroesophageal junction adenocarcinoma, building on previous findings that suggested potential survival benefits.
  • In a phase 2 trial involving 28 centers, patients were randomly assigned to receive either induction chemotherapy (Arm A) or none (Arm B) followed by standard treatment, with pathologic complete response (pathCR) as the primary measure of success.
  • Results indicated that while the primary endpoint (pathCR) was not improved, patients receiving induction chemotherapy had significantly longer overall survival and disease-free survival, especially those with well/moderately differentiated tumors, prompting further investigation in future trials.
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Importance: Immunotherapy has been associated with improved outcomes among patients who have received previous treatment for microsatellite instability-high (MSI-H) tumors.

Objective: To evaluate the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received.

Design, Setting, And Participants: This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062.

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Through our involvement in KEYNOTE-059, we unexpectedly observed durable responses in two patients with metastatic gastroesophageal adenocarcinoma (mGEA) who received ramucirumab (anti-VEGFR-2)/paclitaxel after immune checkpoint inhibition (ICI). To assess the reproducibility of this observation, we piloted an approach to administer ramucirumab/paclitaxel after ICI in more patients, and explored changes in the immune microenvironment. Nineteen consecutive patients with mGEA received ICI followed by ramucirumab/paclitaxel.

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Background: High tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not.

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