Skip to main content
Download PDF

Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma

World Journal of Surgical Oncology volume 22, Article number: 288 (2024) Cite this article

Abstract

Background

The current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma.

Methods

Patients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety.

Results

Forty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1–28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3–4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034–0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not.

Conclusions

Conversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma.

Background

For advanced unresectable esophageal squamous cell carcinoma, which is inoperable because of preoperative tumor or lymph node invasion of adjacent organs, the current standard treatment protocol is definitive chemoradiotherapy (dCRT) [1, 2]. For locally advanced resectable esophageal squamous cell carcinoma, the advent of neoadjuvant therapy has significantly increased the R0 resection rate and improved long-term outcomes of patients [3,4,5,6]. It is challenging to assess the resectability of borderline resectable esophageal squamous cell carcinoma (BR-ESCC) because of its close relationship with adjacent organs and the inability to determine the extent of tumor invasion through preoperative examinations [7]. However, the optimal treatment strategy for this patient population remains controversial. Patients receiving dCRT might miss the opportunity to undergo radical surgery, even if the tumor shrinks significantly. When chemotherapy or radiotherapy is administered initially, followed by surgery to convert an initially inoperable tumor into a resectable one, it is termed conversion surgery. Although the non-R0 resection rate of BR-ESCC is significantly higher than that of definitively resectable ESCC, patients with BR-ESCC can achieve a survival outcome equal to that of definitively resectable esophageal squamous cell carcinoma when R0 resection is performed [8]. Preoperative induction therapy is key to improving R0 resection rates in patients with BR-ESCC. However, there is no uniformity in the induction therapy protocol, and the surgery conversion rate is poor with traditional induction therapy protocols [9,10,11].

In recent years, the application of immunotherapeutic drugs, such as programmed cell death 1 (PD-1) inhibitors, has revolutionized the field of tumor treatment. It has demonstrated long-term survival benefits in the first-line treatment of advanced or metastatic ESCC [12,13,14,15,16,17]. Meanwhile, the combination of PD-1 inhibitors with neoadjuvant therapy can significantly enhance the pathological complete remission rate, reduce the toxic response during induction therapy, and increase patient tolerability in locally advanced resectable ESCC [18,19,20,21]. In contrast, there are limited studies on the use of immunotherapeutic drugs as induction therapy for BR-ESCC. This study aimed to evaluate the efficacy and safety of surgery following induction immunochemotherapy in patients with BR-ESCC.

Methods

Patients

The study was approved by the Ethics Committee of our institution and conducted in accordance with the 2013 edition of the Declaration of Helsinki (File number:2024ER357-1). The requirement for written informed consent was waived. In this study, we retrospectively analyzed 40 patients with BR-ESCC who underwent induced immunochemotherapy at the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from January 1, 2020 to July 1, 2023. The inclusion criteria were a preoperative pathologically confirmed diagnosis of esophageal squamous cell carcinoma, preoperative evaluation of thoracic segment tumors with suspicious invasion of adjacent organs, clinical stage T4, preoperative treatment with induction chemotherapy combined with immunotherapy, and no previous antitumor therapy. Patients with definite clinical stages of T4b and T1-3 and those with distant metastasis at the initial visit were excluded.

Diagnosis and treatment

We primarily determined the clinical staging through gastroscopy, upper gastrointestinal imaging, contrast-enhanced chest and abdominal CT scans, and bilateral cervical Doppler ultrasound. Ultrasonographic endoscopy and positron emission tomography were performed when necessary. In this study, BR-ESCC was defined as suspected but not definitively diagnosed unresectable adjacent organ invasion (including the aorta, trachea, or vertebral body). Tracheal invasion was suspected when compression or deformation of the tracheal wall was observed, and all patients with suspected tracheal invasion underwent fiberoptic bronchoscopy to exclude definitive endotracheal lesions. The angle between the outermost part of the lesion in contact with the aorta and the line joining the center of the aorta was defined as suspected aortic invasion at an angle of > 60° or < 90° [22, 23]. Clinical and pathological staging was determined according to the American Joint Committee on Cancer 8th edition TNM staging system.

Induction chemotherapy regimens included nedaplatin (80 mg/m2, IV, D1) + docetaxel (70 mg/m2, IV, D2) or nedaplatin (80 mg/m2, IV, D1) + nab-paclitaxel (200 mg/m2, IV, D2), and immunologic agents included Sintilimab (200 mg, IV, D3), Camrelizumab (200 mg, IV, D3), and Tislelizumab (200 mg, IV, D3). Almost all patients completed two cycles of induction chemotherapy combined with immunotherapy. Each cycle was spaced > 3 weeks apart. Tumor resectability was assessed via multidisciplinary consultation after treatment. Patients evaluated as viable for radical resection underwent McKeown esophagectomy combined with second- or third-field lymph node dissection. Patients with unresectable tumors underwent definitive chemoradiotherapy combined with immunotherapy(The typical chemotherapy regimen is nedaplatin plus nab-paclitaxel, with a radiation therapy dose of 60 Gy/30Fx. The immunotherapy drug Camrelizumab is also administered. The number of chemotherapy cycles and the radiation dose are determined based on the specific condition of the patient).

Observation outcomes

The primary study outcome was the R0 resection rate. Secondary outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission rate (pCR), and safety. R0 resection was defined as a resection with negative microscopic margins. PFS was defined as the time from the start of induction therapy to disease progression or death from any cause. OS was defined as the time from the start of induction therapy to death from any cause. pCR was defined as the absence of residual tumor cells in the resected primary tumor and in all sampled regional lymph nodes. The clinical stages were compared before and after induction therapy. Reduced TNM stage was defined as tumor downstaging. Safety was evaluated based on the incidence of surgical complications and the proportion or incidence of treatment-related adverse events, which were graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (version 5.0) [24].

Statistics

The patients were divided into surgical and non-surgical groups. Differences in clinical characteristics between the two groups were compared using the chi-square test, Fisher’s exact test, or Student’s t-test. We analyzed the data using SPSS software (version 27.0). Kaplan–Meier survival analysis curves were used to assess PFS and OS, and a log-rank test was used to compare survival differences between the groups. Kaplan–Meier curves were plotted using the R software (version 4.3.2). In all analyses, statistical tests were two-tailed, and P-values less than 0.05 were considered statistically significant.

Results

Baseline characteristics

A total of 40 patients with BR-ESCC who visited our hospital from January 1, 2020 to July 1, 2023 were included in the analysis. A flowchart of patient screening is shown in Fig. 1. We categorized the patients into surgical and non-surgical groups based on whether they underwent surgery after induction therapy. Of these, 28 (70%) underwent curative resection after induction therapy, 12 (30%) were evaluated as unresectable, one refused to continue treatment, and the remaining 11 received definitive chemoradiotherapy combined with immunotherapy(two individuals refused to continue immunotherapy for unknown reasons). The baseline characteristics are shown in Table 1. The mean age of all patients was 63.2 years (± 8.2). Among them, 77.5% were male. 80% of the tumors were located in the midthoracic region. As this was a retrospective study, the chemotherapy and immunotherapy regimens used were different; however, the statistical tests suggested no significant differences between the two groups.

Fig. 1
figure 1

Flowchart of the study

Full size image
Table 1 Patients characteristics
Full size table

Induction immunochemotherapy

As shown in Table 1, 28 individuals showed a decrease in T stage after induction therapy (70%), whereas the change in N stage after induction therapy was not significant. Coincidentally, there are also 28 individuals (70%) underwent clinical TNM downstaging. Table 2 lists the treatment-related adverse events that occurred during induction therapy in all patients. The highest incidence of grade 3–4 adverse reactions was neutropenia (10%, n = 4), followed by leukopenia (5%, n = 2). The most common grade 1–2 adverse event was anemia (45%, n = 18).

Table 2 Treatment-related adverse events during induction therapy
Full size table

Surgical treatment

Table 3 lists the perioperative characteristics of all patients who underwent curative resection (one patient who underwent surgery at another hospital was not included). All the patients were treated using the McKeown procedure. In addition, 23 patients (57.5%) underwent R0 resection. Postoperative pCR was achieved in 11 (27.5%) patients. The number of lymph nodes that were intraoperatively excised was 19.5 (range, 2–54); median operative time was 206.1 min (range, 145.8–395.0 min); median operative bleeding was 100 ml (range, 10–500 ml), and median hospitalization time after surgery was 8 days (range, 7–24). Postoperative pulmonary infection (33.3%, n = 9) was the most common complication. One patient (3.7%) developed a pulmonary infection on postoperative day 7 and died of sudden acute respiratory failure on postoperative day 13. No complications were observed in any other patient.

Table 3 Surgical and pathological results
Full size table

Survival outcomes

The median follow-up time was 23.6 months (95% CI, 19.1–28.2). OS and PFS are shown in Fig. 2, with 1-year OS and PFS rates of 77.7% and 71.8%, respectively. The median survival time was not determined. A total of 10 deaths occurred among all patients, of which six died owing to disease progression, one refused further treatment after one cycle of induction therapy, one developed immune-related pneumonia during postoperative immunization drug maintenance therapy leading to death, one developed severe postoperative pulmonary infection leading to acute respiratory failure, and one died of unknown cause.

Fig. 2
figure 2

Overall survival and progression-free survival

Full size image

Figure 3 shows the survival curves for the different cohorts. The 1-year OS rates were 84.7% and 58.2% in the surgical and nonsurgical groups, respectively. One-year PFS rates were 76.0% and 49.4% in the surgical and nonsurgical groups, respectively. Statistical tests suggested a significant difference in PFS between the surgical and nonsurgical groups (P = 0.008, HR: 0.144 95%CI: 0.034–0.606), whereas the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). After grouping patients according to whether they achieved clinical downstaging, it was observed that patients who achieved clinical downstaging after induction therapy experienced significantly greater benefits in terms of OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not.

Fig. 3
figure 3

Overall survival and progression-free survival. A. Overall survival of surgery and non-surgery groups. B. Progression-free survival of surgery and non-surgery groups. C. Overall survival of downstaging and non-downstaging groups. D. Progression-free survival of downstaging and non-downstaging groups

Full size image

Discussion

The National Comprehensive Cancer Network and Chinese Society of Clinical Oncology recommend preoperative neoadjuvant chemotherapy or chemoradiotherapy for patients with locally advanced resectable esophageal cancer [25, 26]. However, the treatment protocols for BR-ESCC remain inconsistent. Some researchers have applied this treatment regimen to patients with BR-ESCC, which is not feasible in our opinion. Owing to its local mechanism of action, neoadjuvant radiotherapy may cause a certain degree of inflammatory reaction and edema in the treated area. This inflammatory edema may complicate the clinical staging of the tumor difficult, especially for BR-ESCC, making it challenging to determine its resectability in the short term after treatment. Waiting for the edema to completely subside before evaluation may increase the difficulty of surgery owing to radiation-induced fibrosis or even lead to rapid disease progression due to delayed treatment [27]. While neoadjuvant chemotherapy alone usually results in a low postoperative pCR rate, owing to smaller drug doses and shorter treatment cycles, its efficacy may be even more unsatisfactory if it is simply applied to the treatment of borderline resectable esophageal cancer.

For conversion therapy in advanced esophageal squamous cell carcinoma, improving the R0 resection rate is crucial for patient prognosis. In a retrospective study by Suzuki et al. on BR-ESCC, induction therapy using a CF regimen combined with radiotherapy resulted in an R0 resection rate of 81.5% (n = 22) and a conversion success rate of only 54% (n = 27) [10]. In another retrospective single-arm study by Nakajima et al., which included 32 individuals who received DCF regimen induction therapy, the R0 resection rate was 81.5% (n = 22) and the conversion success rate was as high as 84.4% (n = 27) [11]. Induction therapy using the DCF regimen achieved a higher conversion success rate than that of the CF regimen. However, at the same time, their study also reported up to 79.3% grade 3–4 hematologic toxic reactions [11]. The same results were reported by Yokota et al. [28], in which the R0 resection rate (62.5% vs. 35.7%) and 1-year survival rate (90.0% vs. 58.3%) in the DCF group were significantly higher than those in the CF group. Meanwhile, hematologic toxicity in the DCF group was significantly higher than that in the CF group (p = 0.0017). For BR-ESCC, an induction regimen with a higher conversion success rate and less toxicity is urgently needed to improve the survival prognosis of these patients.

Our study investigated the efficacy of induction immunochemotherapy in patients with BR-ESCC, an innovative strategy that combines the direct cytotoxic effects of conventional chemotherapy with the immune-modulating ability of immunotherapy, which enhances both tumor sensitivity to treatment and patient immune response [29]. Chemotherapeutic agents can induce tumor cell death and release tumor-associated antigens that activate the immune system. PD-1/PD-L1 inhibitors have been demonstrated to alleviate tumor suppression of the immune system and enhance T cell-mediated tumor killing [30]. A potential advantage of this combination therapy is that it may exert a synergistic effect through these two mechanisms, thereby improving the surgical conversion rate and survival prognosis of patients with BR-ESCC.

Fan et al. [31] reported that 36 patients with unresectable esophageal squamous cell carcinoma were treated with PD-1 inhibitors in combination with induction chemotherapy; 27 (75%) underwent successful conversion surgery; 22 (81.5%) underwent R0 resection, and the pCR rate was 22.2%. Li et al. [32] similarly used induction immunochemotherapy to treat 27 patients with BR-ESCC, with a conversion rate of 74.1% (n = 20), R0 resection rate of 95% (n = 19), and pCR rate of 25% (n = 5). In our study, the R0 resection rate(R0/surgery) was 85.2% (n = 23); the conversion success rate was 67.5% (n = 27), and pCR rate(pCR/surgery) was 40.7% (n = 11). In contrast, the R0 resection rate(R0/surgery) of conventional chemotherapy was 81.5–92.6%; the conversion success rate was 54-84.4%, and the pCR rate(pCR/surgery) was 14.8–18.5% [9,10,11]. Thus, the efficacy of induction immunochemotherapy was evident.

Regarding safety, the incidence of grade 3–4 adverse events in our study was 10%, which was significantly lower than the 31.9-79.4% in the conventional regimen [9,10,11]. This may be owing to missing data in this retrospective study or the relatively small sample size. However, in two other studies using immune-inducing therapy, the incidence of grade ≥ 3 adverse events was also 14.7–30% [31, 32], which was significantly lower than that of conventional regimens. In locally advanced resectable ESCC, neoadjuvant immunotherapy has demonstrated lower toxicity responses and increased patient compliance [33, 34]. Induction immunotherapy did not increase the incidence of post-operative complications. In our study, nine (33%) patients developed postoperative pulmonary infections, contrasting with 5.0–23.68% in several other studies involving neoadjuvant chemotherapy combined with immunotherapy [18, 34,35,36]. Studies have shown that PD-I/PD-L1 inhibitors can cause lung inflammation by enhancing T cell-mediated immune activation, inducing autoantibody upregulation, and disrupting cytokine homeostasis [37]. Previous reports on the incidence of postoperative pulmonary infections were mainly from phase II clinical trials and did not reflect the real-world incidence. No studies have reported that induction immunotherapy increases the incidence of postoperative pulmonary infections in patients with esophageal cancer. However, in our research, we recommend that patients with positive lymph nodes post-surgery continue adjuvant immunotherapy in combination with chemotherapy. Among them, one patient developed immune-related pneumonia during the maintenance therapy with Camrelizumab after surgery, and ultimately died 10.6 months post-surgery. In conclusion, further phase III clinical trials are needed to confirm whether the addition of immunological agents increases the incidence of postoperative pulmonary infections and the risk of death due to immune-related pneumonia.

This study had certain limitations. First, this was a single-center retrospective study with a small sample size, and the results are required to be validated by large-scale prospective studies. Second, although there was a significant difference in PFS between the surgical and non-surgical groups in our study, and the results were also consistent with conventional chemotherapy regimens [9, 10, 38]. However, the survival follow-up time was short, and a longer follow-up period is needed to determine whether the high conversion rate, high pathological remission rate, and low toxicity of immunotherapy can be converted into long-term survival advantages.

Conclusions

Conversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for patients with BR-ESCC.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

PD-1:

Programmed cell death 1

BR-ESCC:

Borderline resectable esophageal squamous cell carcinoma

pCR:

Pathological complete remission

OS:

Overall survival

PFS:

Progression-free survival

CT:

Computed Tomography

DCF:

Docetaxel, Cisplatin, and 5-fluorouracil

CF:

Cisplatin and 5-fluorouracil

CI:

Confidence Interval

References

  1. NCCN guideline:esophgeal cancer.

  2. Obermannová R, Alsina M, Cervantes A, Leong T, Lordick F, Nilsson M, et al. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:992–1004.

    Article  PubMed  Google Scholar 

  3. Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-Fluorouracil Versus Preoperative Chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012;19:68–74.

    Article  PubMed  Google Scholar 

  4. Van Hagen P, Hulshof MCCM, Van Lanschot JJB, Steyerberg EW, Henegouwen MIVB, Wijnhoven BPL, et al. Preoperative chemoradiotherapy for esophageal or junctional Cancer. N Engl J Med. 2012;366:2074–84.

    Article  PubMed  Google Scholar 

  5. Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. Long-term efficacy of Neoadjuvant Chemoradiotherapy Plus surgery for the treatment of locally advanced esophageal squamous cell carcinoma. JAMA Surg. 2021;156:721–9.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kato K, Ito Y, Daiko H, Ozawa S, Ogata T, Hara H, et al. A randomized controlled phase III trial comparing two chemotherapy regimen and chemoradiotherapy regimen as neoadjuvant treatment for locally advanced esophageal cancer, JCOG1109 NExT study. JCO. 2022;40:238–238.

    Article  Google Scholar 

  7. Yokota T, Yasuda T, Kato H, Nozaki I, Sato H, Miyata Y, et al. Concordance of clinical diagnosis of T classification among physicians for locally advanced unresectable thoracic esophageal cancer. Int J Clin Oncol. 2018;23:73–80.

    Article  PubMed  Google Scholar 

  8. Hirohata R, Hamai Y, Hihara J, Emi M, Kurokawa T, Yoshikawa T, et al. Evaluation of Neoadjuvant Chemoradiotherapy followed by surgery for Borderline Resectable esophageal squamous cell carcinoma. World J Surg. 2022;46:1934–43.

    Article  PubMed  Google Scholar 

  9. Wang Z, Hu M, Hu Y, Li Q, Wu J, Fong WP, et al. Paclitaxel plus cisplatin and 5-fluorouracil induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma: a phase II clinical trial. Esophagus. 2022;19:120–8.

    Article  PubMed  Google Scholar 

  10. Suzuki T, Okamura A, Watanabe M, Mine S, Imamura Y, Asari T, et al. Neoadjuvant Chemoradiotherapy with Cisplatin Plus Fluorouracil for Borderline Resectable esophageal squamous cell carcinoma. Ann Surg Oncol. 2020;27:1510–7.

    Article  PubMed  Google Scholar 

  11. Nakajima M, Muroi H, Kikuchi M, Kubo T, Inoue N, Ihara K, et al. Therapeutic strategy aiming at R0 resection for borderline-resectable esophageal squamous cell carcinoma using induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. Gen Thorac Cardiovasc Surg. 2023;71:584–90.

    Article  PubMed  Google Scholar 

  12. Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, et al. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ. 2022;377:e068714.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sun J-M, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398:759–71.

    Article  CAS  PubMed  Google Scholar 

  14. Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, et al. Nivolumab Combination Therapy in Advanced Esophageal squamous-cell carcinoma. N Engl J Med. 2022;386:449–62.

    Article  CAS  PubMed  Google Scholar 

  15. Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, et al. Effect of Camrelizumab vs Placebo added to Chemotherapy on Survival and Progression-Free Survival in patients with Advanced or metastatic esophageal squamous cell carcinoma: the ESCORT-1st Randomized Clinical Trial. JAMA. 2021;326:916–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Three-year follow-up of ATTRACTION-3. A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy. | Journal of Clinical Oncology [Internet]. [cited 2024 Jan 8]. https://doiorg.publicaciones.saludcastillayleon.es/10.1200/JCO.2021.39.3_suppl.204

  17. Shah MA, Kojima T, Hochhauser D, Enzinger P, Raimbourg J, Hollebecque A, et al. Efficacy and safety of Pembrolizumab for heavily pretreated patients with Advanced, metastatic adenocarcinoma or squamous cell carcinoma of the Esophagus: the phase 2 KEYNOTE-180 study. JAMA Oncol. 2019;5:546–50.

    Article  PubMed  Google Scholar 

  18. Zhang Z, Ye J, Li H, Gu D, Du M, Ai D, et al. Neoadjuvant sintilimab and chemotherapy in patients with resectable esophageal squamous cell carcinoma: a prospective, single-arm, phase 2 trial. Front Immunol. 2022;13:1031171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yang W, Xing X, Yeung S-CJ, Wang S, Chen W, Bao Y, et al. Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma. J Immunother Cancer. 2022;10:e003497.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yan X, Duan H, Ni Y, Zhou Y, Wang X, Qi H, et al. Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: a prospective, single-arm, phase II study (TD-NICE). Int J Surg. 2022;103:106680.

    Article  PubMed  Google Scholar 

  21. Xing W, Zhao L, Zheng Y, Liu B, Liu X, Li T et al. The Sequence of Chemotherapy and Toripalimab Might Influence the Efficacy of Neoadjuvant Chemoimmunotherapy in Locally Advanced Esophageal Squamous Cell Cancer—A Phase II Study. Frontiers in Immunology [Internet]. 2021 [cited 2023 Dec 8];12. https://www.frontiersin.org/articles/https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fimmu.2021.772450

  22. Picus D, Balfe DM, Koehler RE, Roper CL, Owen JW. Computed tomography in the staging of esophageal carcinoma. Radiology. 1983;146:433–8.

    Article  CAS  PubMed  Google Scholar 

  23. Thompson WM, Halvorsen RA, Foster WL, Williford ME, Postlethwait RW, Korobkin M. Computed tomography for staging esophageal and gastroesophageal cancer: reevaluation. AJR Am J Roentgenol. 1983;141:951–8.

    Article  CAS  PubMed  Google Scholar 

  24. Common Terminology Criteria for Adverse Events (CTCAE). | Protocol Development | CTEP [Internet]. [cited 2024 Jan 9]. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50

  25. Chinese National Cancer Center, Chinese Association of Thoracic Surgeons. Chinese Society for thoracic and Cardiovascular surgery, Chinese Society for diseases of the Esophagus. [Chinese guidelines on Perioperative Management of Resectable Esophageal Cancer (2023 edition)]. Zhonghua Yi Xue Za Zhi. 2023;103:2552–70.

    Google Scholar 

  26. Ajani JA, Barthel JS, Bentrem DJ, D’Amico TA, Das P, Denlinger CS, et al. Esophageal and Esophagogastric Junction cancers. J Natl Compr Canc Netw. 2011;9:830–87.

    Article  PubMed  Google Scholar 

  27. Han D, Li B, Zhao Q, Sun H, Dong J, Hao S, et al. The key clinical questions of Neoadjuvant Chemoradiotherapy for Resectable Esophageal Cancer—A Review. Front Oncol. 2022;12:890688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yokota T, Hatooka S, Ura T, Abe T, Takahari D, Shitara K, et al. Docetaxel plus 5-Fluorouracil and cisplatin (DCF) induction chemotherapy for locally Advanced Borderline-resectable T4 esophageal Cancer. Anticancer Res. 2011;31:3535–41.

    CAS  PubMed  Google Scholar 

  29. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27:450–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nagata Y, Yamamoto S, Kato K. Immune checkpoint inhibitors in esophageal cancer: clinical development and perspectives. Hum Vaccines Immunotherapeutics. 2022;18:2143177.

    Article  Google Scholar 

  31. Fan M, Dai L, Yan W, Yang Y, Lin Y, Chen K. Efficacy of programmed cell death protein 1 inhibitor in resection transformation treatment of esophageal cancer. Thorac Cancer. 2021;12:2182–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chao L, Liu J, Chen Y, Fan Y, Guo S, Zhang S. Benefits of camrelizumab plus carboplatin and albumin paclitaxel as induction therapy for locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma. Thorac Cancer. 2024;15:622-9

  33. Yin G-Q, Li Z-L, Li D. The Safety and Efficacy of Neoadjuvant Camrelizumab Plus Chemotherapy in patients with locally advanced esophageal squamous cell carcinoma: a retrospective study. Cancer Manag Res. 2022;14:2133–41.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wu Z, Zheng Q, Chen H, Xiang J, Hu H, Li H, et al. Efficacy and safety of neoadjuvant chemotherapy and immunotherapy in locally resectable advanced esophageal squamous cell carcinoma. J Thorac Dis. 2021;13:3518–28.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Liu J, Yang Y, Liu Z, Fu X, Cai X, Li H et al. Original research: Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. Journal for Immunotherapy of Cancer [Internet]. 2022 [cited 2024 Jan 5];10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961177/

  36. Chen X, Xu X, Wang D, Liu J, Sun J, Lu M, et al. Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial. J Immunother Cancer. 2023;11:e005830.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ghanbar MI, Suresh K. Pulmonary toxicity of immune checkpoint immunotherapy. J Clin Invest. 2024;134:e170503.

  38. Shiraishi O. ASO author reflections: comparison of aggressive planned salvage surgery versus neoadjuvant chemoradiotherapy plus surgery for Borderline Resectable T4 squamous cell carcinoma. Ann Surg Oncol. 2021;28:6376–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Editage (www.editage.cn) for English language editing.

Funding

This study was funded by Nanchong City University Science and Technology Strategic Cooperation Special Fund (Grant No. 22SXQT0095) and the scientific research foundation for advanced talents, Affiliated hospital of North Sichuan Medical College (Grant No. 2023GC006).

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

    Chengcheng Zhang, Binwen Xu, Tao Luo, Yue Zhang, Liwen Zhang, Guidong Shi & Maoyong Fu

Authors
  1. Chengcheng Zhang
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Binwen Xu
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Tao Luo
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Yue Zhang
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Liwen Zhang
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Guidong Shi
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Maoyong Fu
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

MF completed the study design, CZ completed the statistical analysis and was a major contributor in writing the manuscript. TL and BX were involved in data collection, YZ and LZ were involved in clinical care and patient management. GS helped with the revision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maoyong Fu.

Ethics declarations

Ethics approval and consent to participate

The study was reviewed and approved by The Ethics Committee of Affiliated Hospital of North Sichuan Medical College. According to national legislation and institutional requirements, written informed consent was not required for participation in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, C., Xu, B., Luo, T. et al. Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma. World J Surg Onc 22, 288 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12957-024-03570-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12957-024-03570-8

Keywords

World Journal of Surgical Oncology

ISSN: 1477-7819

Contact us