Skip to main content
Download PDF

Preoperative chemoradiotherapy for esophageal or gastroesophageal junction cancer: results from a retrospective study using extended CROSS regimen

Radiation Oncology volume 20, Article number: 71 (2025) Cite this article

Abstract

Background

The standard of care for locally advanced esophageal cancer includes perioperative chemotherapy or neo-adjuvant chemo-radiotherapy (CRT), followed by surgery. At our institution, a modified neo-adjuvant regimen combining elements from CROSS and CALGB 9781 trials was adopted. This study aimed to assess the impact of our modified regimen on oncological outcomes, toxicity profile and pathological complete response rates compared to the CROSS trial.

Methods

This observational study included patients with esophageal cancer who underwent neo-adjuvant CRT followed by tumor resection at a tertiary care university hospital between 2014 and 2018. The modified radiation therapy consisted of 28 fractions of 1.8 Gy (50.4 Gy in total) with weekly carboplatin/paclitaxel. We assessed mortality over time using the median survival time. The impact of pathological complete response and radiation intensity on mortality was assessed in multivariable Cox regression analysis, adjusting for clinically relevant variables, including sex, age, American Society of Anesthesiologists (ASA) physical status classification system score, tumor and nodal stage, and the histological tumor type.

Results

A total of 46 patients were included. Median age was 67 years (IQR 9), 36 patients (78.3%) were male. An ASA score ≥ 3 was reported in 90.7% of the patients. Among the patients, 38 (82.6%) had a clinical tumor stage (cT) of ≥ 3, and 42 (91.3%) showed a positive endo-sonographic nodal stage (uN+). Pathological complete response was found in 7/42 patients (16.7%). Median survival time was 2.7 years (95% CI 1.340–4.084). In multivariable Cox regression analysis, pathological complete response was associated with significantly lower mortality over time (OR 0.152, 95%CI 0.049–0.989, p = 0.048). For larger radiation volumes, a trend towards increased mortality was shown, although not statistically significant (radiation volume/100: OR 1.172, 95%CI 0.987–1.392).

Conclusions

In patients with esophageal cancer undergoing trimodal therapy, the radiation dose escalation to 50.4 Gy was not associated with higher rates of pathological complete response or a survival benefit compared to the results of the CROSS trial. However, multivariable analysis revealed a trend toward increased mortality with larger radiation volumes. Based on these results, using modern radiotherapy techniques such as online adaptive radiotherapy might be more beneficial instead of escalating the radiation dose.

Introduction

Worldwide, esophageal cancer (EC) has been reported as the sixth leading cause of cancer-related mortality [1]. Both the incidence of EC and related mortality are expected to increase in the coming years [2]. Despite advances in oncological treatment, the 5-year overall survival rates for locally advanced EC remain poor [3].

Treatment for non-metastatic EC typically consists of multimodality therapy, including perioperative chemotherapy or neo-adjuvant CRT followed by surgery [2]. Neo-adjuvant therapies have the potential to improve oncological outcomes by downsizing the primary tumor and reducing the incidence of distant metastases [4]. The CROSS trial reported an increased overall survival with neo-adjuvant CRT using 41.4 Gy in 23 fractions with concurrent weekly carboplatin and paclitaxel compared to surgery alone [5]. On the other hand, the CALGB 9781 trial utilized 50.4 Gy in 28 fractions with concurrent cisplatin/5-FU and revealed a long-term survival benefit for this neo-adjuvant treatment regimen compared to surgery alone [6].

At our institution, we have adopted a neo-adjuvant treatment regimen combining elements from these two trials. Patients with esophageal or gastroesophageal junction cancer received CRT with 50.4 Gy over 5.6 weeks and weekly carboplatin/paclitaxel. We avoided using simultaneous integrated boost (SIB) for dose escalation since most studies applying the SIB concept focused on patients with inoperable EC undergoing definitive CRT. The rationale for the increased radiation dose was to account for cases initially selected for a multimodal treatment approach but later deemed inoperable due to associated side effects. The aim of the current study was, therefore, to investigate the radiation toxicity of the modified neo-adjuvant CRT and to compare its effect on clinical outcomes with the results of previous studies, namely the CROSS trial. In other words, we aimed to determine whether the extended CROSS regimen with 50.4 Gy offers comparable toxicity and either equivalent or potentially enhanced clinical efficacy compared to the standard 41.4 Gy in neo-adjuvant setting.

Materials and methods

Study design

This is a retrospective single-center study performed at a tertiary care university hospital in Switzerland. The study included patients with EC who underwent neo-adjuvant CRT followed by surgical tumor resection between 2014 and 2018. The competent ethics committee (ID 2018 − 01937) approved the study.

The aim of this study was to (1) investigate the radiation toxicity of the modified preoperative treatment regimen, as well as (2) its effect on the pathological response and overall mortality in comparison to the CROSS trial.

Patient selection and data collection

Patients with histopathologically confirmed resectable adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction (Siewert type 1 and 2) undergoing multimodal therapy were retrospectively included. The homogenous multimodal treatment consisted of neo-adjuvant CRT followed by esophagostomy. We excluded patients with distant metastases, tumors located in the cervical esophagus, or the distal gastroesophageal junction (Siewert type 3), as these cases required different treatment regimens.

We retrieved patient and tumor characteristics, along with treatment modalities, from electronic medical records. We obtained radiotherapy data from the Eclipse treatment planning system.

Staging and oncologic treatment

For initial staging and workup, patients underwent esophagogastroduodenoscopy with biopsy, contrast-enhanced computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS). Following this, a multidisciplinary gastrointestinal tumor board, including medical oncologists, radiation oncologists, pathologists, radiologists, and surgeons, reviewed all cases. A dedicated upper GI surgical team evaluated the eligibility of patients for oncological tumor resection after neo-adjuvant CRT based on clinical examinations and re-staging with EUS and CT.

Our team administered neo-adjuvant CRT using a modified CROSS protocol, which included 28 fractions of 1.8 Gy (totaling 50.4 Gy) and weekly chemotherapy with carboplatin (AUC 2) and paclitaxel (50 mg per square meter of body surface area). For all patients, we used volumetric modulated arc therapy for radiotherapy application. The team defined target delineation for the primary tumor, positive lymph nodes, and elective volumes according to international contouring guidelines [7]. Four to six weeks after completing preoperative treatment, the team performed re-staging using esophagogastroduodenoscopy and PET/CT scans. If no signs of distant metastasis appeared, the patients proceeded to surgical tumor resection.

Radiotherapy parameters

We evaluated radiation-induced toxicity using the following parameters: the whole radiation volume in cubic centimeters (cc), the mean radiation dose to the heart and lungs in Gray, and the lung volumes receiving 10 Gy (V10Gy), 20 Gy (V20Gy), and 30 Gy (V30Gy).

Statistical analysis

Normality of distribution was assessed using histograms, skewness, and the Shapiro-Wilk test. Categorical variables were reported as numbers and percentages, continuous variables as medians and interquartile ranges (IQR).

Survival over time, as well as survival in patients with or without histopathological complete response was plotted using Kaplan-Meier curves. To visualize the effect of the radiation volume on survival over time, the volume was dichotomized at the median. Survival over time was then plotted for patients with a radiation smaller or greater than the median radiation volume.

The effect of the radiation dose and pathological complete response on mortality over time was assessed in univariable and multivariable Cox regression analysis. Variables that were significantly associated with mortality in univariable analysis were further assessed in multivariable analysis. In multivariable analysis, the effect of the radiation dose and pathological complete response and was adjusted for clinically important variables, including sex, age, ASA physical status classification system score, tumor and nodal stage, as well as the histological tumor type. Collinearity between the covariates of the regression model was assessed using the variance inflation factor (VIF). A VIF < 5 was assumed to exclude significant collinearity.

P-values of 0.05 or less were considered statistically significant. Analysis was performed using SPSS Statistics (IBM Corporation, Armonk, NY, USA) and STATA (StataCorp, College Station, TX) software.

Results

Patient characteristics

A total of 46 patients with EC undergoing multimodal therapy were included in the current study. The majority of included patients were male (n = 36, 78.3%) and of older age (median age 67.0 years, IQR 9.0). Median BMI was 25.5 kg/m2 (IQR 4.7) and pretreatment median weight loss 2.0 kg (IQR 7.0). Comorbid conditions were frequent with an ASA score ≥ 3 in 74.4% of the patients (Table 1).

Table 1 Patient and tumor characteristics
Full size table

Tumor characteristics

Tumor characteristics are outlined in Table 1. Thirty-nine patients (84.8%) suffered from adenocarcinoma, while 7 patients (15.2%) had squamous cell carcinoma. A clinical tumor stage (cT) ≥ 3 was found in 38 patients (86.2%). Endosonographically, nodal positive disease (uN+) was detected in 42 patients (91.3%). On histopathological examination, viable tumor cells (ypT1-4) were found in 34 of 42 patients (81.0%). Twenty-one patients (45.7%) had histopathologically confirmed nodal tumor metastasis (ypN1-3). The median number of resected lymph nodes was 30.0 (IQR 14.0). Pathological complete response was found in 7 patients (16.7%).

Radiation

The median radiation volume was 786.5 cc (IQR 423). The median heart and lung dose was 23.0 Gy (IQR 5.0) and 10.0 Gy (IQR 6.0), respectively. The median lung V10 Gy, V20 Gy and V30 Gy were 46.0% (IRQ 33.0), 12.0% (IQR 0.0), and 3.5% (IQR 2.0), respectively.

Survival

Following a standardized follow-up protocol, we scheduled patient visits every 3 months during the first year after therapy, every 6 months in the second year, and annually from the third year onward. Each visit included clinical examination and CT scan. Patients underwent esophagogastroduodenoscopy if they experienced dysphagia, odynophagia, or if imaging modalities indicated a suspicious tumor. Median follow-up was 2.653 years (4.045). Overall survival over time is shown in Fig. 1. Median survival time was 2.712 years (95% CI 1.340–4.084).

Fig. 1
figure 1

Overall survival estimate

Full size image

In univariable analysis, higher radiation volumes were associated with significantly higher mortality over time (OR 1.184, 95% CI 1.070–1.311, p = 0.001), whereas pathological complete response was associated with significantly lower mortality over time (OR 0.221, 95% CI 0.049–0.989, p = 0.048). The mean heart and lung dose, as well as the lung V10 Gy, V20 Gy und V30 Gy were not significantly associated with mortality in univariable analysis.

Multivariable analysis, adjusting for sex and age, together with the ASA score, clinical tumor stage, endosonographic nodal stage, and histological tumor type, revealed histopathological complete response as an independent predictor for lower mortality over time (OR 0.152, 95% CI 0.020–1.155, p = 0.017). For the radiation volume, a trend towards higher mortality in association with higher radiation volumes was visible, although not statistically significant (OR 1.172, 95% CI 0.987–1.392, p = 0.071) (Table 2; Figs. 2 and 3). No significant collinearity was detected between the covariates of the regression analysis. The VIF was smaller than 1.508 for all variables included in regression analysis.

Table 2 Effect of pathological response and radiation on mortality over time
Full size table
Fig. 2
figure 2

Survival estimates for radiation volume

Full size image
Fig. 3
figure 3

Survival estimates for pathological complete response

Full size image

Discussion

The current study investigated a modified neo-adjuvant CRT approach in patients with resectable esophageal cancer, using 28 fractions of 1.8 Gy (50.4 Gy in total) with weekly carboplatin/paclitaxel. The median survival time was 2.7 years. In addition to following our institutional protocols that favor extending fractions over the SIB concept, most studies applying SIB in this context have used higher doses than 50.4 Gy [8]. Moreover, more data exist on using the SIB concept for esophageal SCC as part of definitive CRT [9, 10]. We deliberately avoided applying a boost, as our goal was to compare our results primarily with data from the CROSS trial, which also did not employ the SIB technique. Pathological complete response was found in 16.7% of the patients. Multivariable Cox regression analysis identified pathologic complete response as an independent predictor for lower overall mortality over time.

For the radiation volume, a trend towards higher mortality over time was observed, although not statistically significant. In univariable analysis, higher radiation volumes were associated with significantly higher mortality over time, whereas in multivariable analysis, a trend towards higher mortality was visible (Table 1; Fig. 2). The trend, but not statistically significant association between the radiation volume and mortality in multivariable analysis may be explained by the relatively small sample size. These results must be interpreted with care, as higher radiation volumes are required for larger tumors and pathological lymph nodes. It is therefore important to note that in the current analysis, the effect of radiation volume was adjusted for the tumor and nodal stage. Although in the current study with a small number of cases the radiation volume was not significantly associated with mortality in multivariable analysis, it seems reasonable to keep the radiation volume as limited as possible. Decreasing the size of irradiated volume could not only be beneficial in terms of better survival, but also may reduce radiation toxicity to adjacent organs, namely heart and lungs. According to the literature, radiation-induced toxicity following radiotherapy for esophageal cancer may lead to pulmonary and cardiac complications with a corresponding increase in mortality [11,12,13,14]. Modern radiation techniques that limit the irradiation volume are therefore highly desirable. Online adaptive radiotherapy may be an option for radiotherapy in patients with esophageal cancer. This technique allows for daily re-planning of radiotherapy, offering the potential to reduce radiation exposure to adjacent organs while ensuring better coverage of the target volumes [15]. Our group recently demonstrated the feasibility of online adaptive radiotherapy in patients with locally advanced esophageal adenocarcinoma [16]. However, the current study excludes patients treated with online adaptive therapy, as our clinic only started implementing this technique in 2021.

The CROSS trial compared preoperative CRT with 41.4 Gy in 23 fractions and weekly carboplatin/paclitaxel, followed by surgery, to surgery alone in patients with esophageal or junctional cancer [5]. In the NA treatment group, the rate of pathologic complete response was 29% and the median 5-year overall survival 4.1 years. Thus, both the rate of pathologic complete response and median overall survival were lower in the current study compared to the CROSS trial. However, when comparing these results, the different patient and tumor characteristics in the current study and the CROSS trial must be taken into account. Patients in the NA treatment arm of the CROSS trial were younger (median 60 vs. 67 years) and suffered less frequently from adenocarcinoma (75% vs. 86%). Furthermore, no patients with a clinical tumor stage four (cT4) were included in the NA treatment arm, whereas in the current study, a cT4 stage was detected in 6.5% of the patients. Regarding the histologic subtype, radio-sensitivity and the complete response rate to neo-adjuvant CRT has been reported to be lower in adenocarcinoma than squamous cell carcinoma of the esophagus [17, 18]. Considering the higher age, more advanced tumor stage, and higher rate of adenocarcinoma in the current study compared to the CROSS trial, the difference in pathologic complete response and median overall survival time may have been less pronounced, if these patients and tumor characteristic had been balanced in the two cohorts. Recently, Van Laarhoven et al. reported real-world outcomes of the CROSS regimen in neo-adjuvant setting for EC [19]. They reported the median OS of 33.7 months with a 3-year OS rate of 48.1%. Furthermore, 20.5% of patients in real-world analysis achieved pCR; this aligns closely to our data with pCR rate of 17%.

In the current study, the radiation dose escalation to 50.4 Gy did not lead to better outcomes compared to the current standard of care for neo-adjuvant CRT, i.e. the CROSS regimen. In a post-hoc analysis of data from the CROSS trial it has been shown, that only 5% of recurrences occurred within the radiation field [20]. A retrospective cohort study including patients with esophageal cancer undergoing neo-adjuvant CRT followed by esophagectomy revealed that recurrent disease most frequently occurred distantly with dismal prognosis. Post-recurrence survival was superior for patients with loco-regional compared to distant and combined locoregional and distant recurrence [21]. These results support the use of preoperative CRT to reduce the risk of loco-regional treatment failure. However, increasing the radiation dose beyond 41.4 Gy may have a minimal effect on loco-regional recurrence.

Multivariable analysis revealed pathologic complete response as an independent predictor for lower mortality over time (Table 2; Fig. 3). This is in line with the findings of previous studies that reported significantly higher rates of overall and disease-free survival, as well as lower recurrence rates in patients with pathologic complete response after NA therapy and surgical tumor resection [22,23,24].

Aside from the usual restrictions of a retrospective analysis, the current study has a number of limitations. First, radiation therapy was performed at the same tertiary care university hospital in all patients included. However, surgical tumor resection and the oncologic follow-up were also performed in other hospitals. Thus, a more extensive data collection regarding long-term outcomes was not feasible in the scope of this retrospective study. Furthermore, the treatment at other institutions has led to missing data for some variables, as outlined in Table 1. Second, different surgical techniques for oncologic tumor resection may have been applied but were not accounted for in multivariable analysis. Third, the number of covariates in the regression models was relatively high compared to the number of patients included, which may have led to overfitting of the model. Fourth, the number of patients included in the current analysis is relatively small, limiting generalizability of the results.

Conclusion

In conclusion, in patients with resectable esophageal cancer undergoing trimodal therapy, radiation therapy dose escalation (50.4 Gy in total) was not associated with a higher rate of pathological complete response or a survival benefit compared to the results of the CROSS trial. However, multivariable analysis revealed a trend towards increased mortality in association with higher radiation volumes. Based on these results, utilizing modern radiotherapy techniques, such as online adaptive radiotherapy that accounts for anatomical and tumoral changes, may be more advantageous than merely escalating the radiation dose.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

EC:

Esophageal Cancer

CRT:

Chemo-Radiotherapy

CT:

Computer Tomography

PET:

Positron Emission Tomography

EUS:

Endoscopic UltraSound

Gy:

Gray

AC:

Adenocarcinoma

SCC:

Squamous Cell Carcinoma

SIB:

Simultaneous Integrated Boost

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

    Article  PubMed  Google Scholar 

  2. Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J et al. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology [Internet]. 2022;163(3):649–658.e2. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1053/j.gastro.2022.05.054

  3. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12–49.

    Article  PubMed  Google Scholar 

  4. Lewis S, Lukovic J. Neoadjuvant Therapy in Esophageal Cancer. Thorac Surg Clin [Internet]. 2022;32(4):447–56. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.thorsurg.2022.06.003

  5. van Hagen P, Hulshof MCCM, van Lanschot JJB, Steyerberg EW, Henegouwen MI, van Wijnhoven B. Preoperative chemoradiotherapy for esophageal or junctional Cancer. N Engl J Med. 2012;366(22):2074–84.

    Article  PubMed  Google Scholar 

  6. Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R et al. J OURNAL OF C LINICAL O NCOLOGY Phase III Trial of Trimodality Therapy With Cisplatin, Fluorouracil, Radiotherapy, and Surgery Compared With Surgery Alone for Esophageal Cancer: CALGB 9781. 2016;26(7).

  7. Wu AJ, Bosch WR, Chang DT, Hong TS, Jabbour SK, Kleinberg LR et al. Expert consensus contouring guidelines for intensity modulated radiation therapy in esophageal and. Gastroesophageal Junction Cancer. 2015;92(4).

  8. Zeng M, Fernando NA, Taral P, Knapp M, Zhu XQ, Chen XL, et al. Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma. World J Gastrointest Oncol. 2016;8(5):474–80.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Welsh JW, Seyedin SN, Allen PK, Hofstetter WL, Ajani JA, Chang JY et al. Local Control and Toxicity of a Simultaneous Integrated Boost for Dose Escalation in Locally Advanced Esophageal Cancer: Interim Results from a Prospective Phase I/II Trial. J Thorac Oncol [Internet]. 2017;12(2):375–82. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.jtho.2016.10.013

  10. Ristau J, Thiel M, Katayama S, Schlampp I, Lang K, Häfner MF et al. Simultaneous integrated boost concepts in definitive radiation therapy for esophageal cancer: outcomes and toxicity. Radiat Oncol [Internet]. 2021;16(1):1–9. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-021-01749-x

  11. Frandsen J, Boothe D, Gaffney DK, Wilson BD, Lloyd S. Increased risk of death due to heart disease after radiotherapy for esophageal cancer. 2015;6(5):516–23.

  12. Kowalchuk RO, Spears GM, Morris LK, Owen D, Yoon HH, Jethwa K, et al. Risk stratification of postoperative cardiopulmonary toxicity after trimodality therapy for esophageal cancer. Front Oncol. 2023;13(February):1–8.

    Google Scholar 

  13. Witt JS, Jagodinsky JC, Liu Y, Yadav P, Kuczmarska-haas A, Yu M et al. Cardiac toxicity in operable esophageal Cancer patients treated with or without chemoradiation. 2019;42(8):662–7.

  14. Xu C, Guo L, Liao Z, Wang Y, Liu X, Zhao S et al. Heart and lung doses are independent predictors of overall survival in esophageal cancer after chemoradiotherapy. Clin Transl Radiat Oncol [Internet]. 2019;17:17–23. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ctro.2019.04.016

  15. Lim-reinders S, Keller BM, Al-ward S, Sahgal A, Kim A. Online Adaptive Radiation Therapy. Radiat Oncol Biol [Internet]. 2017;99(4):994–1003. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ijrobp.2017.04.023

  16. Bachmann N, Schmidhalter D, Corminboeuf F, Berger MD, Borbély Y, Ermiş E et al. Cone beam computed Tomography-Based online adaptive radiation therapy of esophageal cancer: first clinical experience and dosimetric benefits. Adv Radiat Oncol. 2025;10(1).

  17. Tougeron D, Richer JP, Silvain C. Management of esophageal adenocarcinoma. J Visc Surg [Internet]. 2011;148(3):e161–70. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.jviscsurg.2011.05.008

  18. Cools-Lartigue J, Ferri L. Should Multidisciplinary Treatment Differ for Esophageal Adenocarcinoma Versus Esophageal Squamous Cell Cancer? Ann Surg Oncol [Internet]. 2019;26(4):1014–27. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1245/s10434-019-07162-9

  19. van Laarhoven H, Verhoeven R, van Berge Henegouwen M, Mohammad NH, van Hillegersberg R, Slingerland M et al. Real-world outcomes of the CROSS regimen in patients with resectable esophageal or gastro-esophageal junction adenocarcinoma: a nationwide cohort study in the Netherlands. eClinicalMedicine [Internet]. 2025;80:103067. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.eclinm.2024.103067

  20. Oppedijk V, Van Der Gaast A, Van Lanschot JJB, Van Hagen P, Van Os R, Van Rij CM, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014;32(5):385–91.

    Article  PubMed  Google Scholar 

  21. Schuring N, Stam WT, Plat VD, Kalff MC, Hulshof MCCM, van Laarhoven HWM et al. Patterns of recurrent disease after neoadjuvant chemoradiotherapy and esophageal cancer surgery with curative intent in a tertiary referral center. Eur J Surg Oncol [Internet]. 2023;49(10):106947. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ejso.2023.05.022

  22. Blum Murphy M, Xiao L, Patel VR, Maru DM, Correa AM, Amlashi G. Pathological complete response in patients with esophageal cancer after the trimodality approach: the association with baseline variables and survival—The university of Texas MD Anderson Cancer center experience. Cancer. 2017;123(21):4106–13.

    Article  PubMed  Google Scholar 

  23. Hipp J, Kuvendjiska J, Hillebrecht HC, Herrmann S, Timme-Bronsert S, Fichtner-Feigl S et al. Oncological recurrence following pathological complete response after neoadjuvant treatment in patients with esophageal cancer — a retrospective cohort study. Langenbeck’s Arch Surg [Internet]. 2023;408(1):1–10. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00423-023-03100-2

  24. Soror T, Kho G, Zhao K, Le, Ismail M, Badakhshi H. Impact of pathological complete response following neoadjuvant chemoradiotherapy in esophageal cancer. J Thorac Dis. 2018;10(7):4069–76.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Tobias Haltmeier & Yves Borbely

  2. Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Jennifer Brazerol, Elena Riggenbach, Anna Stenger-Weisser, Burim Sermaxhaj & Hossein Hemmatazad

  3. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Jennifer Brazerol & Martin D. Berger

  4. Department of Radiation Oncology , Kantonsspital Luzern, Lucerne , Switzerland

    Anna Stenger-Weisser

  5. Department of Radiation Oncology , Stadtspital Zürich, Zurich , Switzerland

    Burim Sermaxhaj

Authors
  1. Tobias Haltmeier
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Jennifer Brazerol
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Yves Borbely
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Elena Riggenbach
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Anna Stenger-Weisser
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Burim Sermaxhaj
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Martin D. Berger
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Hossein Hemmatazad
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

T. H.: literature review, study design, data management, statistical analysis, data interpretation, drafting of articleJ. B.: literature review, data collection, data management, drafting of articleY. B.: Critical revision of articleE. R.: Data collection (A) S.: Data collectionB. S.: Data Collection M. (B): Study design, supervision, critical revision of articleH. H.: literature review, study design, data management, drafting of article, supervision.

Corresponding author

Correspondence to Hossein Hemmatazad.

Ethics declarations

Ethics approval and consent to participate

Ethical committee in canton Bern has reviewed and approved this study protocol (approval number: 2018 − 01937). We obtained the written informed consent from all participants in this study.

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.

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

Haltmeier, T., Brazerol, J., Borbely, Y. et al. Preoperative chemoradiotherapy for esophageal or gastroesophageal junction cancer: results from a retrospective study using extended CROSS regimen. Radiat Oncol 20, 71 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-025-02637-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-025-02637-4

Keywords

Radiation Oncology

ISSN: 1748-717X

Contact us