Chemoradiation With and Without Surgery in Patients With Locally Advanced Squamous Cell Carcinoma of the Esophagus

Ståhl, Michael; Stuschke, Martin; Lehmann, Nils; Meyer, Hans‐Joachim; Walz, Martin K.; Seeber, S.; Klump, Bodo; Budach, Wilfried; Teichmann, R.; Schmitt, Marcus M; Schmitt, G; Franke, C.; Wilke, H.

doi:10.1200/jco.2005.00.034

Cited by 1,160 publications

(949 citation statements)

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“…The median OS of 18.5 months and 3-year OS of 31.5 months compare favorably with the median OS of 12.5 months reported in the RTOG-085 study [12,21]. The activity observed compares well also with the median OS of 17.7 months reported by Bedenne et al [6] and the 16.4 months reported by Stahl et al [37]. In our study, 87% of the patients had stage III and 8% stage IVa disease; 17% had a T4 lesion.…”

Section: Discussionsupporting

confidence: 83%

“…In the RTOG-085 study, nodal involvement was reported in only 13% of patients and there were no patients with T4 or M1a disease. Stahl et al [37] study excluded patients with M1a disease and 18% of them did not have evidence of nodal metastases; Bedenne et al [6] excluded patients with T4 and M1a lesions, and 59% were without evidence of nodal metastases.…”

Section: Discussionmentioning

confidence: 99%

“…BrieXy, oxaliplatin was administered as a 2-h infusion on days 1,8,15,29,37,43,50, 57 at a dose of 60 mg/m 2 , as previously established in our single-center phase I study, on rectal cancer [4], and was followed by leucovorin 20 mg/m 2 over 10Ј and a continuous infusion of Xuorouracil 200 mg/ m 2 per day over days 1-22 and 29-64. Patients received the planned treatment with no dose reduction if they had a neutrophil count¸1,500 l ¡1 and a platelet count¸100,000 l ¡1 ; otherwise chemotherapy was delayed until complete toxicity recovery. Treatment modiWcations were speciWed for hematological, gastrointestinal and neurological toxicity using the NCI Common Toxicity Criteria version 2.0.…”

Section: Chemotherapymentioning

confidence: 99%

“…Fifty-seven patients started the concurrent phase of the treatment: 49 (83%) of them received the whole radiotherapy dose. Unplanned interruptions of more than 2 days occurred in 14 patients as a result of toxicity; 8 patients discontinued radiotherapy due to esophagitis and diarrhea after a median of 40 Gy (range [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Table 2 lists the whole incidence of toxicity during chemo-radiotherapy.…”

Section: Chemo-radiotherapymentioning

confidence: 99%

“…To date, randomized trials on squamous cell carcinoma, have not demonstrated any beneWt on survival. The signiWcant postoperative mortality might have aVected the possible therapeutic beneWt; however, surgical resection had a substantial improvement in local control and decreased the need for stent placement [6,37].…”

Section: Introductionmentioning

confidence: 99%

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Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Chiarion-Sileni

Innocente

Cavina³

et al. 2008

Cancer Chemother Pharmacol

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Purpose The aim of this study was to evaluate the activity and safety of oxaliplatin/5-Xuorouracil-based chemo-radiotherapy in patients with not radically resectable locally advanced esophageal cancer. Methods Fifty-nine patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m 2 ), and leucovorin (20 mg/m 2 on days 1, 8,15,29,36,43,50,57) followed by continuous infusion Xuorouracil (200 mg/m 2 per day on days 1-22 and 29-64) with radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to 64). When feasible, surgery was scheduled 6-8 weeks after chemoradiotherapy completion. The primary endpoint was 1-year progression-free survival. Results Forty (68%) patients completed treatment without modiWcations. An objective clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33 patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic complete responses (pCR) and 3 near pCR.At a median follow-up of 39.7 months for the surviving patients, the median progression-free and overall survivals were 11 months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression-free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%). Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and 8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe neurotoxicity (3% G3) was infrequent. Conclusions Concurrent oxaliplatin, leucovorin, Xuorouracil and radiotherapy followed or not by esophagectomy has a tolerable toxicity and promising activity in locally advanced esophageal cancer.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Chemotherapymentioning

confidence: 99%

Section: Chemo-radiotherapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Chiarion-Sileni

Innocente

Cavina³

et al. 2008

Cancer Chemother Pharmacol

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Underuse of Esophagectomy as Treatment for Resectable Esophageal Cancer

Paulson

Ra²,

Armstrong³

et al. 2008

Arch Surg

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Main Outcome Measures: The rate of surgical intervention was compared across varying patient characteristics, including age, race, comorbidity score, sex, tumor stage, and socioeconomic region. Survival was compared between patients who received surgery and those who did not using Kaplan-Meier curves, the logrank test, and Cox proportional hazards regression. Statistical analysis was performed using the 2 test and multiple logistic regression. Results: The overall rate of surgical intervention in this cohort was 34.1%. In all, 36.8% of white patients underwent surgical treatment of their disease, whereas only 19.2% of nonwhite patients did. Patients residing in areas with high poverty rates were 27% less likely to have surgery. Older age and higher comorbidity scores were also associated with lower rates of surgery. Patients who received surgical treatment for their disease experienced significantly longer survival than did patients who did not undergo surgical resection. Conclusions: There seems to be significant underuse of esophagectomy as treatment for potentially resectable stage I, II, and III esophageal cancers across all patient groups. In nonwhite and low socioeconomic patient cohorts, the underuse is even more pronounced.

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Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer

et al. 2019

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IMPORTANCEEffective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high.OBJECTIVE To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer. DESIGN, SETTING, AND PARTICIPANTSA phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019.INTERVENTIONS Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil.MAIN OUTCOMES AND MEASURES Toxic effects, local (in-field) control, and overall survival rates.RESULTS All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost.CONCLUSIONS AND RELEVANCE These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study.

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Chemoradiation With and Without Surgery in Patients With Locally Advanced Squamous Cell Carcinoma of the Esophagus

Cited by 1,160 publications

References 18 publications

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Underuse of Esophagectomy as Treatment for Resectable Esophageal Cancer

Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer

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