Impact of weight loss on survival after chemoradiation for locally advanced head and neck Cancer: secondary results of a randomized phase III trial (SAKK 10/94)

As previously described [1], all eligible patients had invasive HNSCC of the oral cavity, oro- or hypopharynx, or larynx. All patients gave informed consent and a total of 224 patients were randomized between July 1994 and July 2000.

Patients were treated with 1.2 Gy RT twice daily with an interfraction interval of at least 6 hours, 5 days per week, up to a median total dose of 74.4 Gy (range, 72 – 76.8 Gy). In patients of the combined arm cisplatin 20 mg/m² was administered with intravenous hydration on 5 consecutive days during weeks 1 and 5 or 6 of RT, 1.5 hours before the afternoon RT session.

The trial was registered at the National Institutes of Health (www.​clinicaltrials.​gov; identifier number: NCT00002654) and was approved by the ethics committees of all participating institutions.

Patient weight was measured 6 months before treatment (patients were asked to recall their weight 6 months before), at treatment start, before the second cycle and at the end of treatment. Weight loss before treatment was defined as the weight loss from 6 months before treatment start until treatment start. Weight loss during treatment was defined as the maximal weight loss from treatment start to the beginning of the second cycle and the end of treatment. Weight loss was categorized to “no weight loss”, “≤5% weight loss”, “>5-10% weight loss” and “>10% weight loss” [6].

The primary endpoint was time to any treatment failure (TTF). Secondary endpoints included time to local or regional treatment failure (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS).

All time-to-event end-points were calculated from the date of randomization and were tested for differences using the log-rank test. Treatment failure was defined as either tumor recurrence at any site, salvage surgery, second primary tumor, or death of any cause which ever occurred first. Locoregional failure was defined as local or nodal progression or recurrence or death as a result of tumor. Diagnosis of distant metastasis and death as a result of tumor were considered as events in the time to distant metastasis analysis. Uni- and multivariable Cox regressions were performed to assess prognostic variables. In addition to treatment arm, the following clinical and pathological variables were considered as covariates in the regression models: gender (female vs. male), performance status (WHO grade 0 vs. grade 1–2), primary tumor site (other sites vs. hypopharynx), tumor classification (cT1-2 vs. cT3-4), nodal classification (cN0-1 vs. cN2-3), age (<50 years vs. ≥50 years), acute or late dysphagia (grade 0–2 vs. grade ≥ 3). Categorical endpoints were compared using Fisher’s exact test. As no adjustment for multiple testing was applied all analyses were exploratory and hypothesis generating. Statistical analyses were performed using SAS version 9.2 (SAS Institute Inc., Cary, NC, USA).