The Comparative Effect of Definitive Chemoradiotherapy and Neoadjuvant Chemoradiotherapy Plus Surgery on One-Year Survival Rate of Esophageal Cancer Patients

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Dis Diagn. Vol 11, No 4, 2022 148 http://ddj.hums.ac.ir http is one of the major treatments for esophageal cancer, the survival rate of patients treated with this method alone is reported to be poor (9). The five-year survival rate of patients, treated only by surgery, scarcely exceeds 20%, whereas some studies have shown that surgery, along with neoadjuvant chemoradiotherapy (NCRT) has better therapeutic outcomes (10). Performing NCRT prior to surgery may decrease the incidence of metastases, improve resectability, and control this systemic disease (11,12). Radiotherapy causes the palliation of symptoms in 70% of cases, but the survival rate and the local control of the disease in patients treated with radiotherapy alone are extremely poor (one-year survival rate of 30% and twoyear survival of 3%) (13). In some cases, the combination of radiotherapy and surgery improves the survival rate of esophageal cancer patients (14). Considering the role of chemotherapy in reducing the systematic spread of the disease to other organs and the radiosensitizer effect, chemotherapy is added to therapies based on radiotherapy and surgery (15,16). Some studies indicated that the overall survival rate of esophageal cancer patients was superior in the neoadjuvant chemoradiotherapy plus surgery (NCRT + S) group than in the definitive chemoradiotherapy (DCRT) group (17,18). On the other hand, the findings of some studies demonstrated that the survival of esophageal cancer patients was not significantly different in the NCRT + S treatment group compared with the CRT treatment group (18,19). Esophageal cancer is one of the most prevalent cancers in Zanjan province based on the epidemiologic study conducted in this province in 2019 (20). Moreover, the results of previous studies on effective treatment methods are somehow contradictory. Accordingly, it seemed necessary to conduct a study in this regard. Thus, this study aimed to compare the efficacy of DCRT to NCRT + S based on the one-year survival rate of esophageal cancer patients.

Patient Characteristics
In this cross-sectional descriptive study, 43 patients were eligible who had esophageal cancer based on computed tomography and/or pathologic reports and referred to the Radiotherapy Oncology Department of Vali-e-Asr Teaching Hospital in Zanjan province from February 2018 to October 2019. The inclusion criteria were patients older than 18 years and those who received DCRT or NCRT + S. The chemotherapy regime included 5fu and cisplatin or paclitaxel and carboplatin weakly. The therapeutic radiation dose of all patients was the same and equal to 50.4 Gy. Patients with incomplete medical records, metastatic diseases, and cervical esophageal cancer were excluded from the study.

Data Collection
The medical records of the patients were studied and the specifics of patients were extracted from the files. The obtained data were related to age, gender, treatment method (DCRT or NCRT + S), histology (SCC or ADC), location of the tumor (upper third [upper thoracic esophagus]), middle third [middle thoracic esophagus]), and lower third of the esophagus (lower thoracis), and the exact date of the treatment course ending.

Follow-up
Considering that the primary outcome of this survey was to assess the one-year survival rate of esophageal cancer patients, the survival status of patients was completed by contacting the patients or their families precisely one year after the treatment.

Ethical Considerations
Keeping privacy and not disclosing confidential information of patients was necessary. The procedure of this study was completely explained to the family members of the patients, and their permission was received for inquiring whether the patients have survived for one year.

Statistical Analysis
Data were analyzed by SPSS, version 16 (SPSS Inc. Chicago, USA), and the acquired data were categorized using tables and charts. The independent t test and chisquare test were used to compare the independent and categorical variables, respectively. The overall survival was estimated via the Kaplan-Meier method with the log-rank test. A P value of less than 0.05 was considered significant for all performed tests.

Results
Forty-three patients with esophageal cancer who referred to the Vali-e-Asr Hospital from February 2018 to October 2019 were recruited in this study. Overall, 39.5% of the studied population were males (n = 17) and 60.5% of them were females (n = 26). Patients were in the age range of 38-91 years. The mean age of the male and female patients was 67.17 ± 11.51 and 68.8 ± 12.55 years, respectively (P = 0.669). The anatomical location of the lesion was recorded lower third in 39 cases (90.7%), the middle third in three cases (7%), and upper third in one case (2.3%). Histologically, there were 35 (81.4%) and 8 (18.6%) cases of the SCC type and ADC esophageal cancer, respectively. In general, 25 (58.1%) and 18 (41.9 %) patients were treated by DCRT and NCRT + S, respectively. The mean age of the esophageal cancer patients receiving DCRT and NCRT + S was 69.92 ± 11.62 and 65.72 ± 12.5 years, respectively. The demographics of the patients are provided in Table 1. Figure 1 represents a summary of the survival status of The survival in the two treatment groups was compared using the Kaplan-Meier method accompanied by the logrank test, in which no significant difference was observed in the one-year survival rate (P = 0.395, Figure 2). The oneyear survival rate was 68 % and 66.67 % in the DCRT and NCRT + S groups, respectively. Further, no significant correlation was observed between the one-year survival rate of the patients and the histologic subtype (P = 0.741). Twenty-nine patients (13 males and 16 females) were alive one year after the end of their treatment course. The oneyear survival rate in males and females represented no significant difference (P = 0.307, Table 2). The mean age of the patients with a one-year survival rate and those who died before one year was 67.1 ± 11.98 and 70.35 ± 12.30 years, respectively. No significant relevance was found between the one-year survival rate and the age of the patients (P = 0.413). Similarly, there was no statistically significant relationship between the location of the tumor and the one-year survival of patients (P = 0.686).

Discussion
Esophageal cancer is one of the most fatal cancers in the world that is extremely difficult to treat effectively (10,21). Various factors can affect the survival rate of patients, including the choice of the therapeutic method (17). Considering the comparatively high surgical mortality (10) and morbidity (9, 10), researchers have investigated combination therapy. In this regard, multimodality therapy can result in better treatment by enhancing locoregional control and impeding systemic disease (21).
In this study, we compared the one-year survival rate between DCRT and NCRT + S. Overall, 25 (58.1%)      (19) observed no significant difference in the overall survival (two-year and five-year survival, respectively) between DCRT and NCRT + S and concluded that adding surgery to chemoradiotherapy was not advantageous. In a study conducted in the Radiotherapy-Oncology Department of Razi Teaching Hospital in Guilan province, the survival of esophageal patients was examined based on treatment methods. In this study, 68% and 32% of patients received CRT and surgery followed by CRT (S-CRT), respectively. The overall survival in patients treated with CRT and S-CRT was 11.5 and 13 months, respectively, and there was no significant difference in this regard (23).
In a retrospective study by Neuhof et al, the survival of esophageal patients was 8, 9, and 20 months in RT (Radiotherapy), CRT, and NCRT + S, respectively (24). Preoperative therapy followed by surgery is the most accepted treatment method in patients with locally advanced esophageal cancer (2). Moreover, the reason for using CRT before surgery includes the removal of micrometastases and the betterment of tumor resectability (25). In medically unfit patients for surgery, DCRT should be given with a curative purpose (2). In a randomized controlled trial, the result of a comparison between NCRT + S and surgery alone demonstrated a significant increase in the five-year overall survival in the NCRT + S group. The overall survival was 81% at one-year interval for the NCRT + S group compared with 70% for the surgery group (26). Naik et al supported the addition of surgery to chemoradiotherapy for patients with locally advanced esophageal cancer (2).
Mirinezhad et al enrolled 331 esophageal cancer patients and evaluated four treatment methods (S + RT, CRT, RT, and NCRT + S). They reported that the five-year survival was significantly better in the NCRT + S group compared to the CRT group (35% and 11%, respectively, P < 0.001), and the survival rate was not associated with the histological subtype (27), which is consistent with the result of our study. The findings of a survey by Semrau et al (28) are consistent with those of the current study, indicating that gender and histological subtypes are not effective factors in the survival rate. Regarding survival, the advantages of the collaboration of chemotherapy, radiotherapy, and surgery are unclear in multimodality therapy. In different studies, the radiation dose of radiotherapy, the type, and the dose of chemotherapy drugs are dissimilar (5fu and cisplatin or paclitaxel and carboplatin). Utilizing different radiotherapy protocols and chemotherapy drugs with varied doses alters the result of research. One cause for the breakdown of surgical treatment is the fact that most esophageal cancer patients are diagnosed at advanced stages of the malignancy (10); more specifically, almost 50% of esophageal cancer patients have distant metastases at the time of the initial diagnosis (29); furthermore, surgery may not be positively effective on survival because of surgical complications (10).
Among the limitations that the authors faced in this study were the relatively small number of patients available to enter the study, as well as access to the patients or their relatives to follow up on the survival status because some patients in this study moved after the end of the treatment and/or had changed their contact information.

Conclusion
In general, the efficacy of DCRT and NCRT + S on the one-year survival rate of esophageal cancer patients was evaluated, and no significant difference was observed in this regard. However, the results of previous studies are contradictory, and the choice of a competent treatment method is controversial. Accordingly, it is recommended that further investigations be conducted with a more appropriate treatment plan accompanied by a prolonged follow-up on a prospective larger population of patients with the same chemotherapy regimen.