NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the first co-primary endpoint overall survival and superiority for the experimental intervention definitive chemoradiotherapy. A second co-primary endpoint is global health related quality of life (HRQOL) one year after randomisation. A third co-primary endpoint is eating restictions one year after randomisation.
The aim is to compare outcomes after neoadjuvant chemoradiotherapy with subsequent esophagectomy to definitive chemoradiotherapy with surveillance and salvage esophagectomy as needed in patients with resectable locally advanced squamous cell carcinoma (SCC) of the esophagus, with the aim to provide generalisable guidance for future clinical practice.
Histopathologically confirmed SCC of the esophagus in locally advanced stages cT1 N+ or cT2-4a any N, M0, according to current (8th) version of of the AJCC TNM classification.
Technically resectable disease according to the local multidisciplinary team conference (MDT)/tumor board.
Performance status ECOG 0-1.
Adequate organ function.
M1 according to current (8th) version of of the AJCC TNM classification.
cT4b according to current (8th) version of of the AJCC TNM classification.
Primary tumor not resectable without laryngectomy.
Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the eligibility of the patient for multimodality treatment with chemoradiotherapy followed by esophagectomy.
Parallel
Neoadjuvant radiotherapy (arm A)
Radiation1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
Carboplatin, paclitaxel
DrugCarboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy
Esophagectomy
Procedure/SurgeryEsophagectomy performed within 8 weeks after termination of chemoradiotherapy
Neoadjuvant radiotherapy (arm B)
RadiationTwo alternative schemes: 1. 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy. 2. 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
Carboplatin, paclitaxel
DrugCarboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy (5 weeks or 6 weeks, depending on the radiotherapy regimen used).
Cisplatin, paclitaxel
DrugCisplatin 75mg/m2 on the first day of weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion on the first four days of weeks 1 and 5.
Oxaliplatin, calcium folinate, 5-fluorouracil
DrugFOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 on the first days of weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion on the first two days of weeks 1, 3 and 5.
Esophagectomy
Procedure/SurgeryEsophagectomy only in case of residual or recurrent locoregional cancer.
Overall survival
When 398 events have occurred
Global Health-related quality of life (HRQOL)
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, version 3.0 (EORTC QLQ-C30). The two items assessing global health and overall quality of life are responded to in seven categories ranging from 1 (very poor) to 7 (excellent).
Eating restrictions
EORTC QLQ-OG25 instrument. This instrument consists of 25 items covering upper gastric symptoms or problems in four categories ranging from 1 (Not at all) to 4 (Very much).
Health related quality of life of Cancer patients
EORTC HRQOL Questionnaire QLQ-C30 version 3.0, 28 items ranging from 1 (no problems at all) to 4 (very much) and two items assessing global health and overall quality of life are responded to in seven categories ranging from 1 (very poor) to 7 (excellent).
Health related quality of life, oesophageal specific.
EORTC HRQOL gastresophageal-specific questionnaire EORTC QLQ-OG25. 25 items assessing symptoms or problems are responded to in four categories ranging from 1 (no problems) to 4 (very much).
Health related quality of life, general health
The EuroQoL Group's EQ-5D-5L questionnaire consisting of five dimensions ranging from No problems to Extreme problems or Unable to care.
Event-free survival
Time to relapse, initiation of any anti-tumor therapy beyond the study treatments (salvage surgery is considered a study treatment in the dCRT arm), or death, whichever comes first.
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Karolinska University Hospital
Lead sponsor
University of Leipzig
Collaborator
The Swedish Research Council
Collaborator
