Systemic control and evaluation of the response to neoadjuvant chemotherapy in resectable thoracic esophageal squamous cell carcinoma with 18F-fluorodeoxyglucose positron emission tomography-positive lymph nodes

Yasuda, Takushi; Yano, Masahiko; Miyata, Hiroshi; Yamasaki, Makoto; Higuchi, Ichiro; Takiguchi, Shuji; Fujiwara, Yoshiyuki; Doki, Yuichiro

doi:10.1007/s00595-014-0956-7

Cited by 6 publications

(10 citation statements)

References 26 publications

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“…Sixty‐eight patients (50.7%) received neoadjuvant chemotherapy (NAC) that consisted of cisplatin, doxorubicin, and 5‐fluorouracil (Table ). The precise regimen is described elsewhere . In the study period, the NAC was given to patients with tumors in any T category (cT1‐4) accompanied with metastasis only to the regional or non‐regional lymph nodes.…”

Section: Methodsmentioning

confidence: 99%

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Immunoregulatory influence of abundant MFG‐E8 expression by esophageal cancer treated with chemotherapy

et al. 2018

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Milk fat globule‐epidermal growth factor factor 8 (MFG‐E8) is secreted from macrophages and is known to induce immunological tolerance mediated by regulatory T cells. However, the roles of the MFG‐E8 that is expressed by cancer cells have not yet been fully examined. Expression of MFG‐E8 was examined using immunohistochemistry in surgical samples from 134 patients with esophageal squamous cell carcinoma. The relationships between MFG‐E8 expression levels and clinicopathological factors, including tumor‐infiltrating lymphocytes, were evaluated. High MFG‐E8 expression was observed in 23.9% of the patients. The patients with tumors highly expressing MFG‐E8 had a significantly higher percentage of neoadjuvant chemotherapy (NAC) history (P < .0001) and shorter relapse‐free survival (P = 0.012) and overall survival (OS; P = .0047). On subgroup analysis, according to NAC history, patients with high MFG‐E8 expression had significantly shorter relapse‐free survival (P = .027) and OS (P = .0039) only when they had been treated with NAC. Furthermore, tumors with high MFG‐E8 expression had a significantly lower ratio of CD8+ T cells/regulatory T cells in tumor‐infiltrating lymphocytes (P = .042) only in the patients treated with NAC, and those with a lower ratio had a shorter OS (P = .026). High MFG‐E8 expression was also found to be an independent prognostic factor in multivariate analysis. The abundant MFG‐E8 expression in esophageal squamous cell carcinoma might have a negative influence on the long‐term survival of patients after chemotherapy by affecting T‐cell regulation in the tumor microenvironment.

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Section: Methodsmentioning

confidence: 99%

“…The precise regimen is described elsewhere. 21 In the study period, the NAC was given to patients with tumors in any T category (cT1-4) accompanied with metastasis only to the regional or non-regional lymph nodes. The NAC was also given to patients with tumors classified as cT2 or more in depth with or without lymph node metastasis.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulatory influence of abundant MFG‐E8 expression by esophageal cancer treated with chemotherapy

et al. 2018

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“…Because clinical diagnosis of LN metastasis in esophageal squamous cell carcinoma is not exact and it is well known that LN metastasis is not often detected in small-sized lymph node (less than 10 mm), discrepancies between preoperative staging and pathologic findings are not uncommon, especially in locoregional LN [11]. Thoracic surgeons do not usually perform invasive evaluation for a locoregional LN when the LN is negative on PET-CT and upfront surgery without neoadjuvant therapy may be performed on patients with LN metastasis [9]. Although neoadjuvant therapy can increase the rate of postoperative complication or length of hospital stay for patients, neoadjuvant therapy followed by complete esophagectomy (R0) is well-established as being superior to upfront esophagectomy when LN metastasis is present.…”

Section: Discussionmentioning

confidence: 99%

“…Neoadjuvant therapy is usually recommended for patients with lymph node (LN) metastases in esophageal cancer [2,4,6]. In esophageal cancer, positron emission tomography computed tomography (PET-CT) is essential to the evaluation of the cancer stage, especially with respect to distant or locoregional LN metastases [7][8][9][10]. A lesion is usually regarded to be malignant or metastatic when the maximum standardized uptake value is ≥2.5 and the size is ≥1 cm on PET-CT and endoscopic ultrasound [11,12].…”

Section: Introductionmentioning

confidence: 99%

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

Kim

Park

Moon

et al. 2019

European Journal of Surgical Oncology

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Background: Although neoadjuvant therapy followed by esophagectomy is well-established as being superior to upfront esophagectomy when locoregional lymph node (LN) metastasis is present in esophageal cancer, upfront esophagectomy without neoadjuvant therapy may be performed in patients with LN metastasis due to unreliable preoperative evaluations. However, outcomes in this setting remain unclear. The purpose of the present study was to clarify whether upfront esophagectomy without neoadjuvant therapy in patients with unsuspected lymph node metastasis in esophageal cancer is appropriate. Methods: We included 215 squamous cell esophageal cancer patients who met the study criteria. Inclusion criteria included complete (R0) and curative surgery cases, intra-thoracic esophageal cancer, preoperative biopsy-proven squamous cell carcinoma, and cases without LN metastasis (WL, cN0 and pN0) or with unsuspected LN metastasis (UL, cN0 and pN1). Exclusion criteria were palliation or salvage cases, other uncured previous or current primary cancers, complete remission cases, and operative mortalities (defined as patients who died during hospitalization or within one month after surgery). We compared 5-year disease-free survival (DFS) between WL and UL. In addition, we investigated the influence of neoadjuvant therapy in UL. To overcome heterogeneity in baseline characteristics between the groups, a propensity matched-analysis based on propensity scores was then carried out to create a cohort of WL with clinical characteristics similar to those in UL. Results: The incidence of UL among preoperative N0 patients was 25.6% and the incidence of UL cases who did not receive neoadjuvant therapy was 47.2%. All subjects were stratified into either WL (160 patients) or UL (55 patients). Twenty nine of 55 patients in UL received neoadjuvant therapy before esophagectomy and all patients with LN metastasis received adjuvant therapy after esophagectomy. There was no significant difference in DFS between WL and UL (p = 0.242). Furthermore, there were no significant differences in DFS between cases that received and did not receive neoadjuvant therapy (p = 0.769). Conclusions: Upfront surgery without neoadjuvant therapy in UL is appropriate for patients who can tolerate adjuvant therapy.

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“…Because clinical diagnosis of LN metastasis in esophageal squamous cell carcinoma is not exact and it is well known that LN metastasis is not often detected in small-sized lymph node (less than 10 mm), discrepancies between preoperative staging and pathologic findings are not uncommon, especially in locoregional LN [ 11 ]. Thoracic surgeons do not usually perform invasive evaluation for a locoregional LN when the LN is negative on PET-CT and upfront surgery without neoadjuvant therapy may be performed on patients with LN metastasis [ 9 ]. Although neoadjuvant therapy can increase the rate of postoperative complication or length of hospital stay for patients, neoadjuvant therapy followed by complete esophagectomy (R0) is well-established as being superior to upfront esophagectomy when LN metastasis is present.…”

Section: Discussionmentioning

confidence: 99%

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

Park

Kim

Moon

et al. 2018

J Cardiothorac Surg

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BackgroundAlthough neoadjuvant therapy followed by esophagectomy is well-established as being superior to upfront esophagectomy when locoregional lymph node (LN) metastasis is present in esophageal cancer, upfront esophagectomy without neoadjuvant therapy may be performed in patients with LN metastasis due to unreliable preoperative evaluations. However, outcomes in this setting remain unclear. The purpose of the present study was to clarify whether upfront esophagectomy without neoadjuvant therapy in patients with unsuspected lymph node metastasis in esophageal cancer is appropriate.MethodsWe included 215 squamous cell esophageal cancer patients who met the study criteria. Inclusion criteria included complete (R0) and curative surgery cases, intra-thoracic esophageal cancer, preoperative biopsy-proven squamous cell carcinoma, and cases without LN metastasis (WL, cN0 and pN0) or with unsuspected LN metastasis (UL, cN0 and pN1). Exclusion criteria were palliation or salvage cases, other uncured previous or current primary cancers, complete remission cases, and operative mortalities (defined as patients who died during hospitalization or within one month after surgery). We compared 5-year disease- free survival (DFS) between WL and UL. In addition, we investigated the influence of neoadjuvant therapy in UL. To overcome heterogeneity in baseline characteristics between the groups, a propensity matched-analysis based on propensity scores was then carried out to create a cohort of WL with clinical characteristics similar to those in UL.ResultsThe incidence of UL among preoperative N0 patients was 25.6% and the incidence of UL cases who did not receive neoadjuvant therapy was 47.2%. All subjects were stratified into either WL (160 patients) or UL (55 patients). Twenty nine of 55 patients in UL received neoadjuvant therapy before esophagectomy and all patients with LN metastasis received adjuvant therapy after esophagectomy. There was no significant difference in DFS between WL and UL (p = 0.242). Furthermore, there were no significant differences in DFS between cases that received and did not receive neoadjuvant therapy (p = 0.769).ConclusionsUpfront surgery without neoadjuvant therapy in UL is appropriate for patients who can tolerate adjuvant therapy.

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Systemic control and evaluation of the response to neoadjuvant chemotherapy in resectable thoracic esophageal squamous cell carcinoma with 18F-fluorodeoxyglucose positron emission tomography-positive lymph nodes

Abstract: NAC significantly suppressed postoperative recurrence in TESCC PET-N-positive patients, but the survival benefit was unclear. However, post-treatment PET-N-negative patients were likely responders to NAC.

Cited by 6 publications

References 26 publications

Immunoregulatory influence of abundant MFG‐E8 expression by esophageal cancer treated with chemotherapy

Immunoregulatory influence of abundant MFG‐E8 expression by esophageal cancer treated with chemotherapy

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

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