SOCCER Trial Research Articles

A Prospective Real-World Multi-Center Study to Evaluate Progression-Free and Overall Survival of Radiotherapy with Cetuximab and Platinum-Based Chemotherapy with Cetuximab in Locally Recurrent Head and Neck Cancer.

Simple SummaryDespite recent developments in immune checkpoint inhibitors, the treatment of locoregionally recurrent head and neck squamous cell cancer (HNSCC) remains challenging. Prospective data comparing re-irradiation with systemic treatment are not available. The SOCCER trial represents a prospective non-interventional multicenter trial that enrolled patients with locoregionally recurrent HNSCC treated with cetuximab in combination with re-radiotherapy or chemotherapy. A total of 192 patients were analyzed. Radiotherapy combined with cetuximab had superior progression-free and overall survival compared to chemotherapy with cetuximab. This highlights the high efficacy of local re-radiotherapy in combination with cetuximab in patients with locoregionally recurrent HNSCC.Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of ≥60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27–0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33–0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC.

Treatment response lowers tumor symptom burden in recurrent and/or metastatic head and neck cancer

BackgroundHead and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC.MethodsIn this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0–100), which were summarized to the overall VAS score.ResultsFourhundred seventy patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (− 2.13 vs. non-responders + 1.15, p = 0.048), and even more for the best post-baseline assessment (− 7.82 vs. non-responders − 1.97, p = 0.0005). The VAS for pain (− 16.37 vs. non-responders − 8.89, p = 0.001) and swallowing of solid food (− 16.67 vs. non-responders − 5.06, p = 0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05–1.20, p = 0.0009).ConclusionIn unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC.Trial registrationClinicalTrials.gov, NCT00122460. Registered 22 Juli 2005,

Oxygen therapy in patients with ST elevation myocardial infarction based on the culprit vessel: results from the randomized controlled SOCCER trial

BackgroundOxygen (O2) treatment has been a cornerstone in the treatment of patients with myocardial infarction. Recent studies, however, state that supplemental O2 therapy may have no effect or harmful effects in these patients. The aim of this study was thus to evaluate the effect of O2 therapy in patients with ST Elevation Myocardial Infarction (STEMI) based on the culprit vessel; Left Anterior Descending Artery (LAD) or Non-LAD.MethodsThis was a two-center, investigator-initiated, single-blind, parallel-group, randomized controlled trial at the Skåne university hospital, Sweden. A simple computer-generated randomization was used. Patients were either randomized to standard care with O2 therapy (10 l/min) or air until the end of the primary percutaneous coronary intervention. The patients underwent a Cardiac Magnetic Resonance Imaging (CMRI) days 2–6. The main outcome measures were Myocardium at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI) as measured by CMRI, and median high-sensitive troponin T (hs-cTnT).ResultsA total of 229 patients were assessed for eligibility, and 160 of them were randomized to the oxygen or air arm. Because of primarily technical problems with the CMRI, 95 patients were included in the final analyses; 46 in the oxygen arm and 49 in the air arm. There were no significant differences between patients with LAD and Non-LAD as culprit vessel with regard to their allocation (oxygen or air) with regards to MSI, MaR, IS and hs-cTnT.ConclusionThe results indicate that the location of the culprit vessel has probably no effect on the role of supplemental oxygen therapy in STEMI patients.Trial registrationSwedish Medical Products Agency (EudraCT No. 2011–001452-11) and ClinicalTrials.gov Identifier (NCT01423929).

Ischemic QRS prolongation as a biomarker of myocardial injury in STEMI patients.

Patients with acute coronary occlusion (ACO) may not only have ischemia-related ST-segment changes but also changes in the QRS complex. It has recently been shown in dogs that a greater ischemic QRS prolongation (IQP) during ACO is related to lower collateral flow. This suggests that greater IQP could indicate more severe ischemia and thereby more rapid infarct development. Therefore, the purpose was to evaluate the relationship between IQP and measures of myocardial injury in patients presenting with acute ST-elevation myocardial infarction (STEMI). Seventy-seven patients with first-time STEMI were retrospectively included from the recently published SOCCER trial. All patients underwent a cardiac magnetic resonance (CMR) examination 2-6days after the acute event. Infarct size (IS), myocardium at risk (MaR), and myocardial salvage index (MSI) were assessed and related to IQP. IQP measures assessed were; computer-generated QRS duration, QRS duration at maximum ST deviation, absolute IQP and relative IQP, all derived from a pre-PCI, 12-lead ECG. Median absolute IQP was 10ms (range 0-115ms). There were no statistically significant correlations between measures of IQP and any of the CMR measures of myocardial injury (absolute IQP vs IS, r=0.03, p=0.80; MaR, r=-0.01, p=0.89; MSI, r=-0.05, p=0.68). Unlike previous experimental studies, the IQP was limited in patients presenting at the emergency room with first-time STEMI and no correlation was found between IQP and CMR variables of myocardial injury in these patients. Therefore, IQP does not seem to be a suitable biomarker for triaging patients in this clinical context.

Effect of oxygen therapy on myocardial salvage in ST elevation myocardial infarction: the randomized SOCCER trial.

Recent studies suggest that administration of O2 in patients with acute myocardial infarction may have negative effects. With the use of cardiac MRI (CMR), we evaluated the effects of supplemental O2 in patients with ST elevation myocardial infarction (STEMI) accepted for acute percutaneous coronary intervention (PCI). This study was a randomized-controlled trial conducted at two university hospitals in Sweden. Normoxic STEMI patients were randomized in the ambulance to either supplemental O2 (10 l/min) or room air until the conclusion of the PCI. CMR was performed 2-6 days after the inclusion. The primary endpoint was the myocardial salvage index assessed by CMR. The secondary endpoints included infarct size and myocardium at risk. At inclusion, the O2 (n=46) and air (n=49) patient groups had similar patient characteristics. There were no significant differences in myocardial salvage index [53.9±25.1 vs. 49.3±24.0%; 95% confidence interval (CI): -5.4 to 14.6], myocardium at risk (31.9±10.0% of the left ventricle in the O2 group vs. 30.0±11.8% in the air group; 95% CI: -2.6 to 6.3), or infarct size (15.6±10.4% of the left ventricle vs. 16.0±11.0%; 95% CI: -4.7 to 4.1). In STEMI patients undergoing acute PCI, we found no effect of high-flow oxygen compared with room air on the size of ischemia before PCI, myocardial salvage, or the resulting infarct size. These results support the safety of withholding supplemental oxygen in normoxic STEMI patients.

Effect of oxygen therapy on chest pain in patients with ST elevation myocardial infarction: results from the randomized SOCCER trial

Objective. Oxygen (O2) have been a cornerstone in the treatment of acute myocardial infarction. Studies have been inconclusive regarding the cardiovascular and analgesic effects of oxygen in these patients. In the SOCCER trial, we compared the effects of oxygen treatment versus room air in patients with ST-elevation myocardial infarction (STEMI). There was no difference in myocardial salvage index or infarct size assessed with cardiac magnetic resonance imaging. In the present subanalysis, we wanted to evaluate the effect of O2 on chest pain in patients with STEMI. Design. Normoxic patients with first time STEMI were randomized in the ambulance to standard care with 10 l/min O2 or room air until the end of the percutaneous coronary intervention (PCI). The ambulance personnel noted the patients´ chest pain on a visual analog scale (VAS; 1-10) before randomization and after the transport but before the start of the PCI, and also registered the amount of morphine given. Results. 160 patients were randomized to O2 (n = 85) or room air (n = 75). The O2 group had a higher median VAS at randomization than the air group (7.0 ± 2.3 vs 6.0 ± 2.9; p = .02) and also received a higher median total dose of morphine (5.0 mg ± 4.4 vs 4.0 mg ± 3.7; p = .02). There was no difference between the O2 and air groups in VAS at the start of the PCI (4.0 ± 2.4 vs 3.0 ± 2.5; p = .05) or in the median VAS decrease from randomization to the start of the PCI (−2.0 ± 2.2 vs −1.0 ± 2.9; p = .18). Conclusion. Taken together with previously published data, these results do not support a significant analgesic effect of oxygen in patients with STEMI.European Clinical Trials Database (EudraCT): 2011-001452-11.ClinicalTrials.gov Identifier: NCT01423929

Effects of oxygen therapy on wall‐motion score index in patients with ST elevation myocardial infarction—the randomized SOCCER trial

Although oxygen (O2 ) is routinely used in patients with acute myocardial infarction (AMI), it may have negative effects. In this substudy of the SOCCER trial, we aimed to evaluate the effects of O2 -treatment on myocardial function in patients with ST elevation myocardial infarction (STEMI). Normoxic (≥94%) STEMI patients were randomized in the ambulance to either supplemental O2 or room air until the end of the percutaneous coronary intervention (PCI). The patients underwent echocardiography on day 2-3 after the PCI and once again after 6months. The study endpoints were wall-motion score index (WMSI) and left ventricular ejection fraction (LVEF). Forty-six patients in the O2 group and 41 in the air group were included in the analysis. The index echocardiography showed no significant differences between the groups in WMSI (1.32±0.27 for O2 group vs 1.28±0.28 for air group) or LVEF (47.0±8.5% vs 49.2±8.1%). Nor were there differences at 6months in WMSI (1.16±0.25 vs 1.14±0.24) or LVEF (53.5±5.8% vs 53.5±6.9%). The present findings indicate no harm or benefit of supplemental O2 on myocardial function in STEMI patients. Our results support that it is safe to withhold supplemental O2 in normoxic STEMI patients.

994P - Cetuximab in combination with platinum-based chemotherapy or radiotherapy in recurent and/or metastatic SCCHN in a non-selected patient cohort (interim analysis of the phase IV SOCCER trial)

994P - Cetuximab in combination with platinum-based chemotherapy or radiotherapy in recurent and/or metastatic SCCHN in a non-selected patient cohort (interim analysis of the phase IV SOCCER trial)

External validation of two prediction models of complete secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer

ObjectiveThe purpose of this study was to validate the performance of two prediction models, the AGO score and the Tian model, of complete secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer. The predictive value of both models for survival controlled for the outcome of SCS was analyzed and known predictive factors for complete SCS were tested. MethodsA population-based database with 408 patients, who underwent SCS between 2000 and 2013 in 38 Dutch hospitals, was used. The validation cohorts for the AGO score and the model of Tian contained 273 (66.9%) and 257 (63.0%) patients, respectively. ResultsThe AGO score and Tian model showed a positive predictive value for complete SCS of 82.0% and 80.3% respectively, and a false negative rate of 68.5% and 55.6% respectively. A positive AGO score had no significant association with overall survival (HR 0.73; 95% CI 0.51–1.06) whereas the low risk score of the Tian model did (HR 0.62; 95% CI 0.41–0.93). A good performance status (OR 0.60; 95% CI 0.33–1.10) and the absence of ascites (OR 0.18; 95% CI 0.08–0.41) were prognostic factors for complete SCS. ConclusionsBoth the AGO score and the model of Tian showed a high positive predictive value for complete SCS but also relatively high false negative rates. However, before the two prediction models can be applied in daily clinical practice the usefulness of SCS itself has to be proven first by the three ongoing randomized controlled trials: DESKTOP III trial, the GOG 213 trial and the Dutch SOCceR trial.

Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study

BackgroundImprovement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence.Methods/DesignMulticentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat.DiscussionWhere the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We present a recently started multicentre randomized controlled trial that will investigate the role of secondary cytoreductive surgery followed by chemotherapy will improve progression free survival in selected patients with first recurrence of platinum-sensitive epithelial ovarian cancer.Trial registrationNetherlands Trial Register number: NTR3337.