Development and Validation of a Predictive Model of Therapeutic Effect in Patients with Esophageal Squamous Cell Carcinoma Who Received Neoadjuvant Treatment: A Nationwide Retrospective Study in Japan

Okamura, Akihiko; Watanabe, Masayuki; Okui, Jun; Matsuda, Satoru; Takemura, Ryo; Kawakubo, Hirofumi; Takeuchi, Hiroya; Muto, Manabu; Kakeji, Yoshihiro; Kitagawa, Yuko; Doki, Yuichiro

doi:10.1245/s10434-022-12960-9

Cited by 9 publications

(7 citation statements)

References 43 publications

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“…However, not all patients with early or locally advanced tumors can bene t from NACT. Some patients are unable to undergo surgery due to disease progression during treatment [30]. For example, clinical research revealed that Neoadjuvant chemotherapy might exacerbate postoperative complications, which led to a negative prognostic impact [31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

The genomic signature of resistance to platinum-containing neoadjuvant therapy based on single-cell data

Sui

Jin

et al. 2023

Preprint

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Background Neoadjuvant chemotherapy (NACT) becomes the first-line option for advanced tumors, while patients who are not sensitive to it may not benefit. Therefore, it is important to screen patients suitable for NACT. Methods Single-cell data of lung adenocarcinoma (LUAD) and esophageal squamous carcinoma (ESCC) before and after cisplatin-containing (CDDP) NACT and cisplatin IC50 data of tumor cell lines were analyzed to establish a CDDP neoadjuvant chemotherapy score (NCS). Differential analysis, GO, KEGG, GSVA and logistic regression models were performed by R. Survival analysis were applied to public databases. siRNA knockdown in A549, PC9, TE1 cell lines, qRT-PCR, western-blot, cck8 and EdU experiments were used for further verification in vitro. Results 485 genes were expressed differentially in tumor cells before and after neoadjuvant treatment for LUAD and ESCC. After combining the CDDP-associated genes, 12 genes, CAV2, PHLDA1, DUSP23, VDAC3, DSG2, SPINT2, SPATS2L, IGFBP3, CD9, ALCAM, PRSS23, PERP, were obtained and formed the NCS score. The higher the score, the more sensitive the patients were to CDDP-NACT. The NCS divided LUAD and ESCC into two groups. Based on differentially expressed genes, a model was constructed to predict the high and low NCS. CAV2, PHLDA1, ALCAM, CD9, IGBP3 and VDAC3 were significantly associated with prognosis. Finally, we demonstrated that the knockdown of CAV2, PHLDA1 and VDAC3 in A549, PC9 and TE1 significantly increased the sensitivity to cisplatin. Conclusions NCS scores and related predictive models for CDDP-NACT were developed and validated to assist in selecting patients who might benefit from it.

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Section: Discussionmentioning

confidence: 99%

The genomic signature of resistance to platinum-containing neoadjuvant therapy based on single-cell data

Sui

Jin

et al. 2023

Preprint

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“…The authors concluded that the validated model developed in this study predicts the therapeutic effect in patients with esophageal SCC who received neoadjuvant treatment. They emphasize that the model might contribute to individualized treatment 7 The authors need to be commended for a fine study that demonstrates the possibility of predicting the response to neoadjuvant chemo and/or chemoradiotherapy in a large cohort of patients with esophageal squamous cell carcinoma (ESCC).…”

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confidence: 99%

“…It is noteworthy to mention that the presented model considers the clinical and hematological variables, preoperative information, and neoadjuvant treatment strategies, data that can be obtained preoperatively. 7 Only a few nomograms for predicting therapeutic effect of NAC and/or NACRT, or pCR are currently available in patients with esophageal cancer. In addition, most of them are focused on esophageal adenocarcinoma.…”

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confidence: 99%

“…[9][10][11][12] In this scenario, Okamura's manuscript included data from more than 4000 patients from several Japanese centers, highlighting the possible clinical usefulness of this nomogram, and the authors should pursue an external validation with independent cohorts. 7 Some studies that evaluated the NACRT response have utilized response evaluation criteria in solid tumors (RECIST) using preoperative imaging evaluation effect. Others have used pathologic criteria, such as the Ryan score to evaluate the treatment effect.…”

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confidence: 99%

“…6,12 Okamura et al have utilized the Japanese Classification of Esophageal Cancer, which is somewhat similar to the Western classification. 7 Nomograms incorporating clinical data; dynamic hematological indicators, before and after treatment; image analysis from baseline and post therapy, such as conventional parameters derived from computed tomography (CT) or integrated positron emission tomography to estimate treatment response; or radiomics; together with future integration of molecular markers in the nomogram will hopefully improve its clinical utility for assessing patient risk and the ability to predict treatment response after NACRT or immunotherapy. [13][14][15][16] DISCLOSURE I do not have any conflicts of interest.…”

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confidence: 99%

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Nomogram for Predicting Pathologic Response Following Neoadjuvant Chemotherapy or Chemoradiotherapy in Patients with Esophageal Cancer

Ribeiro

2023

Ann Surg Oncol

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Esophageal squamous cell carcinoma (SCC) is an aggressive disease, and the majority of patients are diagnosed with an advanced disease stage at the time of initial presentation. For this reason, multimodality therapeutic approaches remain a crucial strategy for esophageal cancer patients in obtaining better prognosis. 1,2 Neoadjuvant treatment with chemotherapy and/or chemoradiotherapy is recommended to reduce the neoplastic burden, reduce the recurrence rate, and increase survival after esophageal resection. 1,2 Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) are both considered effective. 2 Previous studies have demonstrated that addition of NACRT to surgery results in an increase in the R0 resection rate and improved survival, with acceptable perioperative morbidities. 3 Additionally, in patients who respond remarkably to neoadjuvant treatment, an organ preservation approach might be implemented. Patients with complete clinical response, that is, tumor disappearance, may have a better prognosis when compared with patients with partial or no response to neoadjuvant treatment. 4,5 Therefore, it is essential to restage these patients accurately after completion of NACRT, and to provide more information for subsequent treatment. In this way, unraveling the clinical-pathological factors that predict the response to chemotherapy and/or radiotherapy becomes relevant and much sought after.

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Outcome research on esophagectomy analyzed using nationwide databases in Japan: evidences generated from real-world data

Kakeji,

Yamamoto,

Watanabe

et al. 2024

Esophagus

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Esophagectomy for esophageal cancer is a highly invasive gastrointestinal surgical procedure. The National Clinical Database (NCD) of Japan, initiated in 2011, has compiled real-world data on esophagectomy, one of nine major gastroenterological surgeries. This review examines outcomes after esophagectomy analyzed using the Japanese big databases. Certification systems by the Japanese Society of Gastroenterological Surgery (JSGS) and the Japan Esophageal Society (JES) have shown that institutional certification has a greater impact on short-term surgical outcomes than surgeon certification. Minimally invasive esophagectomy has emerged as a viable alternative to open esophagectomy, although careful patient selection is crucial, especially for elderly patients with advanced tumors. The NCD has significantly contributed to the assessment and enhancement of surgical quality and short-term outcomes, while studies based on Comprehensive Registry of Esophageal Cancer in Japan (CRECJ) have provided data on patient characteristics, treatments, and long-term outcomes. The JES has conducted various questionnaire-based retrospective clinical reviews in collaboration with authorized institutions certified by JES. The Diagnosis Procedure Combination (DPC) database provides administrative claims data including itemized prices for surgical, pharmaceutical, laboratory, and other inpatient services. Analyzing these nationwide databases can offer precise insights into surgical quality for esophageal cancer, potentially leading to improved treatment outcomes.

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Development and Validation of a Predictive Model of Therapeutic Effect in Patients with Esophageal Squamous Cell Carcinoma Who Received Neoadjuvant Treatment: A Nationwide Retrospective Study in Japan

Cited by 9 publications

References 43 publications

The genomic signature of resistance to platinum-containing neoadjuvant therapy based on single-cell data

The genomic signature of resistance to platinum-containing neoadjuvant therapy based on single-cell data

Nomogram for Predicting Pathologic Response Following Neoadjuvant Chemotherapy or Chemoradiotherapy in Patients with Esophageal Cancer

Outcome research on esophagectomy analyzed using nationwide databases in Japan: evidences generated from real-world data

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