Retrospective analysis of neoadjuvant chemotherapy followed by surgery versus definitive chemoradiotherapy with proton beam for locally advanced esophageal squamous cell carcinoma

Ogawa, Kōichi; Ishikawa, Hitoshi; Hisakura, Katsuji; Hiroshima, Yuichi; Moriwaki, Toshikazu; Yamada, Takeshi; Yamamoto, Yoshiyuki; Akashi, Yoshimasa; Owada, Yohei; Ohara, Yusuke; Enomoto, Tsuyoshi; Furuya, Kinji; Doi, Motomichi; Shimomura, Osamu; Takahashi, Kazuhiro; Hashimoto, Shinji; Sakurai, Hideyuki; Oda, Tatsuya

doi:10.1007/s10147-021-01981-1

Cited by 4 publications

(8 citation statements)

References 25 publications

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“…A total of 45 studies met the inclusion criteria and were included in the meta-analysis Figure 1. describes the selection process and the reasons for excluding studies.…”

Section: Resultsmentioning

confidence: 99%

“…describes the selection process and the reasons for excluding studies. Among the included studies, 31 studies included dosimetric comparison (eTable 1 in Supplement 1), 17 studies assessed proton vs photon therapy (Table 1), and 10 studies were single-group studies of proton therapy (Table 2). Three studies used propensity score–matched analysis to control for confounding factors, and results from those analyses were used for data synthesis.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 45 studies met the inclusion criteria and were included in the meta-analysis. 4 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 Figure 1 describes the selection process and the reasons for excluding studies. Among the included studies, 31 studies 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , ...…”

Section: Resultsmentioning

confidence: 99%

“…Pooled analysis found that that the 1-year OS was 89% (95% CI, 84%-93%; I 2 = 69.3%), 2-year OS was 71% (95% CI, 63%-78%; I 2 = 75.5%), 3-year OS was 63% (95% CI, 53%-73%; I 2 = 81.9%), and 5-year OS was 56% (95% CI, 46%-67%; I 2 = 82%). In analyses of PFS for proton therapy, we found 6 studies 16,25,28,31,35,40 that reported 1-year PFS, 5 studies, 25,28,31,35,40 that reported 2-year PFS, 4 studies 25,28,35,40 that reported 3-year PFS, and 4 studies 25,28,35,40 that reported 5-year PFS. Pooled analysis found that the 1-year PFS was 65% (95% CI, 53%-77%; I 2 = 83.3%), 2-year PFS was 56% (95% CI, 48%-64%; I 2 = 52.1%), 3-year PFS was 48% (95% CI, 40%-56%; I 2 = 45%), and 5-year PFS was 42% (95% CI, 34%-51%; I 2 = 54.2%).…”

Section: Efficacy and Safety Of Proton Therapymentioning

confidence: 96%

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Efficacy and Safety in Proton Therapy and Photon Therapy for Patients With Esophageal Cancer

Zhou

Zhang

et al. 2023

JAMA Netw Open

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ImportanceRadiotherapy plays an important role in the treatment of esophageal cancer. Proton therapy has unique physical properties and higher relative biological effectiveness. However, whether proton therapy has greater benefit than photon therapy is still unclear.ObjectiveTo evaluate whether proton was associated with better efficacy and safety outcomes, including dosimetric, prognosis, and toxic effects outcomes, compared with photon therapy and to evaluate the efficacy and safety of proton therapy singly.Data SourcesA systematic search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and China National Knowledge Infrastructure databases was conducted for articles published through November 25, 2021, and updated to March 25, 2023.Study SelectionFor the comparison of proton and photon therapy, studies including dosimetric, prognosis, and associated toxic effects outcomes were included. The separate evaluation of proton therapy evaluated the same metrics.Data Extraction and SynthesisData on study design, individual characteristics, and outcomes were extracted. If I2 was greater than 50%, the random-effects model was selected. This meta-analysis is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.Main Outcomes and MeasuresThe main outcomes were organs at risk (OARs) dosimetric outcomes, prognosis (overall survival [OS], progression-free survival [PFS], and objective response rate [ORR]), and radiation-related toxic effects.ResultsA total of 45 studies were included in the meta-analysis. For dosimetric analysis, proton therapy was associated with significantly reduced OARs dose. Meta-analysis showed that photon therapy was associated with poor OS (hazard ratio [HR], 1.31; 95% CI, 1.07-1.61; I2 = 11%), but no difference in PFS was observed. Subgroup analysis showed worse OS (HR, 1.42; 95% CI, 1.14-1.78; I2 = 34%) and PFS (HR, 1.48; 95% CI, 1.06-2.08; I2 = 7%) in the radical therapy group with photon therapy. The pathological complete response rate was similar between groups. Proton therapy was associated with significantly decreased grade 2 or higher radiation pneumonitis and pericardial effusion, and grade 4 or higher lymphocytopenia. Single-rate analysis of proton therapy found 89% OS and 65% PFS at 1 year, 71% OS and 56% PFS at 2 years, 63% OS and 48% PFS at 3 years, and 56% OS and 42% PFS at 5 years. The incidence of grade 2 or higher radiation esophagitis was 50%, grade 2 or higher radiation pneumonitis was 2%, grade 2 or higher pleural effusion was 4%, grade 2 or higher pericardial effusion was 3%, grade 3 or higher radiation esophagitis was 8%, and grade 4 or higher lymphocytopenia was 17%.Conclusions and RelevanceIn this meta-analysis, proton therapy was associated with reduced OARs doses and toxic effects and improved prognosis compared with photon therapy for esophageal cancer, but caution is warranted. In the future, these findings should be further validated in randomized clinical trials.

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“…A total of 45 studies met the inclusion criteria and were included in the meta-analysis Figure 1. describes the selection process and the reasons for excluding studies.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Efficacy and Safety Of Proton Therapymentioning

confidence: 96%

See 2 more Smart Citations

Efficacy and Safety in Proton Therapy and Photon Therapy for Patients With Esophageal Cancer

Zhou

Zhang

et al. 2023

JAMA Netw Open

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“…Previous studies have indicated that chemoradiotherapy should be selected as the initial larynx-preserving treatment and that surgery should be a treatment of choice for patients with non-complete response after chemoradiotherapy for cervical EC ( 18 , 30 ). Although the CROSS trial and NEOCRTEC5010 trial suggested that chemoradiotherapy followed by surgery showed significantly better survival compared to surgery alone for locally advanced ESCC ( 11 , 14 ), the superiority of trimodality therapy over definitive chemoradiotherapy is controversial, especially for patients with clinical complete response to chemoradiotherapy ( 31 ) and patients with proton beam radiotherapy ( 32 ). Interestingly, a retrospective study indicated that patients with upper EC had a significantly higher rate of complete response to chemoradiotherapy compared to patients with middle EC ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Patterns of care and prognostic evaluation for stage I–III upper esophageal squamous cell carcinoma: a population-based study

Chen

Zha

et al. 2022

Ann Transl Med

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Background: There is no strong evidence regarding the optimal treatment and specific prognosis prediction model for upper esophageal squamous cell carcinoma (UESCC). This study aimed to investigate the real-world treatment patterns and develop models to predict overall survival (OS) and esophageal cancerspecific survival (ECSS) in patients with stage I-III UESCC. Methods: Patients with T1-4N0-3M0 UESCC in the Surveillance, Epidemiology, and End Results (SEER) database were identified from 2010 to 2017, and randomized to a training cohort and a validation cohort. The effect of treatment patterns on survival were comprehensively analyzed. Nomograms were developed by incorporating independent prognostic factors analyzed by Cox regression in the training cohort and evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) in two cohorts.Results: A total of 677 patients were identified, including 452 in the training cohort and 225 in the validation cohort. Among all populations, 71.9% (487) received chemoradiotherapy without surgery, and chemoradiotherapy or/and surgery showed better survival than other treatments. However, surgery was rarely carried out for patients with stage II-III. T stage, N stage, surgery, chemotherapy, and radiotherapy were independent risks for both OS and ECSS, while age was also an independent risk for OS. The C-indexes for nomograms to predict OS (0.71 and 0.72) and ECSS (0.70 and 0.73) were greater than 7th AJCC staging system to predict OS (0.61 and 0.64) and ECSS (0.64 and 0.64) in both the training cohort and the validation cohort. Time-dependent ROC curves and DCA also suggested that nomograms performed consistently better than 7th AJCC staging system. The calibration curves demonstrated good consistency in predicting survival.Conclusions: Chemoradiotherapy was a major treatment with preferable survival for patients with stage I-III UESCC. We have firstly developed and validated prognostic nomograms in patients with stage I-III UESCC, which would play a supplementary role in the current staging system.

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As time goes by–developments in surgery for esophageal cancer in the new millennium

et al. 2022

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Summary Background In the last two decades, both treatment options and epidemiological features of cancer have changed. We studied the influence of related parameters on the outcome of patients undergoing resection for esophageal carcinoma. Methods We analyzed 499 consecutive patients who underwent esophagectomy for carcinoma since January 2000, comparing 2000–2010 with 2011–2021 and examining changes over time. Results The percentage of men (87.9 vs. 86.9%; p = 0.74) in the two groups was unchanged, whereas mean age increased significantly from 60.8 to 65.2 years (p = 0.000). There was a trend towards an increase of adenocarcinoma (gamma = 0.120, ASE = 0.055). Despite significantly increasing use of induction chemoradiotherapy (p = 0.000) from 7.14% in 2000 to 68.9% in 2021 the distribution of pT, pN stage, grading and the rate of positive lateral resection margins remained unchanged. When comparing the two periods, the overall 30-day mortality was 4.4 vs. 4.2% (p = 0.56), recurrence-free survival was 36.9 vs. 38% at 60 months and 33.9 vs. 36.4% at 120 months (p = 0.93). Tumor-associated survival was 41.1 vs. 45% at 60 months and 35.5 vs. 38.7% at 120 months (p = 0.78). None of the survival rates differed significantly. A multivariable analysis of year of surgery, age, sex, histological subtype, grading, pT, pN, lateral resection margin, and induction therapy showed that only higher pT (p = 0.01), positive pN (p = 0.000), positive lateral margin (p = 0.003), squamous cell carcinoma (p = 0.04) and higher grading (p = 0.026) had a statistically significant, independent, negative influence on prognosis. Conclusion Optimized noninvasive and invasive therapeutic modalities have produced only marginal improvement in the prognosis of esophageal cancer within the last two decades.

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Retrospective analysis of neoadjuvant chemotherapy followed by surgery versus definitive chemoradiotherapy with proton beam for locally advanced esophageal squamous cell carcinoma

Cited by 4 publications

References 25 publications

Efficacy and Safety in Proton Therapy and Photon Therapy for Patients With Esophageal Cancer

Efficacy and Safety in Proton Therapy and Photon Therapy for Patients With Esophageal Cancer

Patterns of care and prognostic evaluation for stage I–III upper esophageal squamous cell carcinoma: a population-based study

As time goes by–developments in surgery for esophageal cancer in the new millennium

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