Discussion
esophageal cancer, leukocytopenia, tumor, 0113, oesophageal cancer, neutropenia, mg/mAtsushi Ohtsu,1999, ESCC, esophageal carcinoma
LEUKOCYTOPENIA, LATE EFFECTS, TUMOR, RECURRENCE, METASTASIS, OESOPHAGEAL CANCER, NEUTROPENIA, ADVERSE EFFECTS, ADVERSE EVENT, ADENOCARCINOMA, SQUAMOUS CELL CARCINOMA, ARREST, ESOPHAGEAL CARCINOMA
For clinicians, esophageal carcinoma remains a challenging condition, with a poor prognosis and low survival rate. For fit patients with resectable esophageal carcinoma, the 5-year survival rate was only 25% after surgery [Nevertheless, at the initial diagnosis, approximately half of the patients are no longer eligible for surgery [
Studies on definitive radiotherapy with or without chemotherapy for oesophageal cancer patientsProspectiveRandomized(RTOG 85 − 01)T1-3N0-1M0RT + CT (PF)(61)CDDP 75 mg/m1 g/mMinskyBD, 1996 [MinskyBD, 1999 [Prospective(INT 0122)T1-4N0-1M0CT (PF) →RT + CT (PF)(38)Neoadjuvant segment:CDDP 100 mg/mCombined segment: CDDP 75 mg/mAtsushi Ohtsu,1999 [RT + CT (PF)(54)CDDP 40 mg/m5-FU 400 mg/md1-d5, d8-d12, Q5WMinskyBD, 2002 [Prospective(INT 0123)(RTOG 94 − 05)T1-4N0-1M0RT + CT (PF)(109)CDDP 75 mg/m1 g/mRT + CT (PF)(109)CDDP 75 mg/m1 g/mIshida K,2004 [RT + CT (PF)(60)CDDP 70 mg/m700 mg/mAjani JA,2008 [Prospectiverandomized(RTOG 0113)CT(TPF) →RT + CT (TF)(37)CT(TP) →RT + CT (TP)(35)Li QQ,2010 [RT + CT (DP)(59)CDDP 80 mg/mDocetaxel 60 mg/mKato K,2011 [Prospective(JCOG 9906)RT + CT (PF)(74)CDDP 40 mg/m5-FU 400 mg/md1-d5, d8-d12, Q5WProspective(KROSG0101/JROSG021)CDDP 70 mg/m700 mg/mRT + CT (PF)(45)Zhao T,2012 [RT + CT (PF)(45)CDDP 75 mg/m250 mg/mRT + CT (DP)(45)CDDP 75 mg/mDocetaxel 75 mg/mConroy T,2014 [Prospective(PRODIGE5/ACCORD17)RT + CT(FOLFOX)(134)RT + CT (PF)(133)CDDP 75 mg/m1 g/mZhang P,2016 [RT + CT (PF)(156)CDDP 60 mg/m300 g/mRT + CT (DP)(161)CDDP 80 mg/mDocetaxel 60 mg/mOR CDDP 25 mg/mDashan Ai,2022 [Prospective(ESO-Shanghai2)RT + CT (TP)(107)RT + CT (TF)(107)RT + CT (TC)(107)RT + CT (DP)(45)CDDP 80 mg/mDocetaxel 60 mg/mRT + CT (PF)(41)CDDP 80 mg/m1000 g/mNotreachedAbbreviations: Ad = adenocarcinoma; CT = chemotherapy; DP = docetaxel + cisplatin, MST = median survival time; ORR = overall response rate; OS = overall survival; PF = cisplatin + 5-FU; QW = every week; Q3W = every three weeks; Q4W = every four weeks; Q5W = every five weeks; RT = radiotherapy; Sq = squamous cell carcinoma; TP = paclitaxel + cisplatin; TF = paclitaxel + fluorouracil; TC = paclitaxel + carboplatin; TPF = fluorouracil + cisplatin + paclitaxel; FOLFOX = oxaliplatin + leucovorin + fluorouracil.To improve the efficacy, some studies have aimed to improve survival by optimizing the radiation dose [Along with the emergence of other drugs, several active drugs have been used in various clinical studies to obtain a better response. Phase II trial RTOG 0113, which compared non-fluorouracil-based therapy (cisplatin plus paclitaxel) and fluorouracil-based therapy (fluorouracil plus paclitaxel), reported that the median survival time were 14.9 months in the cisplatin group and 28.7 months in the fluorouracil group, respectively [34]. In PRODIGE5/ACCORD17, results showed that definitive chemoradiotherapy with FOLFOX (fluorouracil plus leucovorin and oxaliplatin) did not improve PFS compared to chemoradiotherapy with cisplatin and fluorouracil in patients with unresectable EC [Docetaxel, a new generation of anti-EC drugs, enhances the radiation response by inducing apoptosis and mitotic arrest in murine tumor cells [At the same time, due to the time of data analysis in this article, more than half of the participants had both local recurrence and distant metastasis, coupled with the fact that a consensus salvage treatment strategy for patients with ESCC who recur after definitive chemoradiotherapy or radiotherapy has not been established. In this study, we made a summarized list of the patients who received different salvage treatments after relapse. Notably, because local progression is more common, the salvage treatments and survival of some patients with local residual or local recurrent are summarized in Table 
Salvage therapy for esophageal cancer recurrence after definitive concurrent chemoradiotherapyMakazu,2014 [Yano,2008 [Takeuchi,2013 [Hatogai,2016 [Matsutani,2017 [Yoo C,2012 [Chen Y,2014 [Zhou ZG,2015 [Jie Li,2020 [MST (months)RT:14NRT:7(P = 0.016).Abbreviations: sEMR = salvage Endoscopic mucosal resection; OS = overall survival; sESD = salvage endoscopic submucosal dissection; CR = complete response; sPDT = salvage photodynamic therapy; sAPC = salvage Argon plasma coagulation; MST = median survival time; RT = radiotherapy; NRT = non-radiotherapy; BED = biological effective doseIn summary, we were unable to confirm that the docetaxel plus cisplatin regimen performed better in OS than the fluorouracil plus cisplatin regimen in definitive CCRT for patients with ESCC. Based on these findings, our recommendation is to remain the standard role of the fluorouracil plus cisplatin regimen for definitive CCRT in patients with locally advanced ESCC. What’s more, comparing the adverse event (AE) profiles of the two regimens, it was found that the docetaxel plus cisplatin regimen resulted in severe leukocytopenia and neutropenia, and that the treatment had to be interrupted or terminated. As for late adverse effects, there was no significant difference between two groups. One possible reason is the difficulty in collecting late effects data.In view of the biological characteristics of ESCC, chemotherapy has entered a bottleneck stage; however, it still plays an irreplaceable role in CCRT. Recent studies have indicated that, in combination with immunotherapy, chemoradiotherapy has shown immunomodulatory effects that may result in synergistic treatment responses. Some ongoing studies have explored the combination of chemoradiotherapy regimens with immunotherapies in EC, such as KEYNOTE-975 (study of pembrolizumab in combination with chemoradiotherapy in EC), ESOCORT-CRT (study of camrelizumab (SHR-1210) in combination with concurrent chemoradiotherapy in EC), and Rational-311 (study of Tislelizumab [BGB-A317] versus placebo in combination with chemoradiotherapy in EC), and we expect to hear good news from these studies in the near future.