Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial.

BACKGROUND: In patients with non-small-cell lung cancer (NSCLC), the use of postoperative radiotherapy (PORT) has been controversial since 1998, because of one meta-analysis showing a deleterious effect on survival in patients with pN0 and pN1, but with an unclear effect in patients with pN2 NSCLC. Because many changes have occurred in the management of patients with NSCLC, the role of three-dimensional (3D) conformal PORT warrants further investigation in patients with stage IIIAN2 NSCLC. The aim of this study was to establish whether PORT should be part of their standard treatment. METHODS: Lung ART is an open-label, randomised, phase 3, superiority trial comparing mediastinal PORT to no PORT in patients with NSCLC with complete resection, nodal exploration, and cytologically or histologically proven N2 involvement. Previous neoadjuvant or adjuvant chemotherapy was allowed. Patients aged 18 years or older, with an WHO performance status of 0-2, were recruited from 64 hospitals and cancer centres in five countries (France, UK, Germany, Switzerland, and Belgium). Patients were randomly assigned (1:1) to either the PORT or no PORT (control) groups via a web randomisation system, and minimisation factors were the institution, administration of chemotherapy, number of mediastinal lymph node stations involved, histology, and use of pre-treatment PET scan. Patients received PORT at a dose of 54 Gy in 27 or 30 daily fractions, on five consecutive days a week. Three dimensional conformal radiotherapy was mandatory, and intensity-modulated radiotherapy was permitted in centres with expertise. The primary endpoint was disease-free survival, analysed by intention to treat at 3 years; patients from the PORT group who did not receive radiotherapy and patients from the control group with no follow-up were excluded from the safety analyses. This trial is now closed. This trial is registered with ClinicalTrials.gov number, NCT00410683. FINDINGS: Between Aug 7, 2007, and July 17, 2018, 501 patients, predominantly staged with 18F-fluorodeoxyglucose (18F-FDG) PET (456 [91%]; 232 (92%) in the PORT group and 224 (90%) in the control group), were enrolled and randomly assigned to receive PORT (252 patients) or no PORT (249 patients). At the cutoff date of May 31, 2019, median follow-up was 4·8 years (IQR 2·9-7·0). 3-year disease-free survival was 47% (95% CI 40-54) with PORT versus 44% (37-51) without PORT, and the median disease-free survival was 30·5 months (95% CI 24-49) in the PORT group and 22·8 months (17-37) in the control group (hazard ratio 0·86; 95% CI 0·68-1·08; p=0·18). The most common grade 3-4 adverse events were pneumonitis (13 [5%] of 241 patients in the PORT group vs one [<1%] of 246 in the control group), lymphopenia (nine [4%] vs 0), and fatigue (six [3%] vs one [<1%]). Late-grade 3-4 cardiopulmonary toxicity was reported in 26 patients (11%) in the PORT group versus 12 (5%) in the control group. Two patients died from pneumonitis, partly related to radiotherapy and infection, and one patient died due to chemotherapy toxicity (sepsis) that was deemed to be treatment-related, all of whom were in the PORT group. INTERPRETATION: Lung ART evaluated 3D conformal PORT after complete resection in patients who predominantly had been staged using (18F-FDG PET-CT and received neoadjuvant or adjuvant chemotherapy. 3-year disease-free survival was higher than expected in both groups, but PORT was not associated with an increased disease-free survival compared with no PORT. Conformal PORT cannot be recommended as the standard of care in patients with stage IIIAN2 NSCLC. FUNDING: French National Cancer Institute, Programme Hospitalier de Recherche Clinique from the French Health Ministry, Gustave Roussy, Cancer Research UK, Swiss State Secretary for Education, Research, and Innovation, Swiss Cancer Research Foundation, Swiss Cancer League.

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113-08113 LungTech Phase II Trial Results.

INTRODUCTION: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. METHODS: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. RESULTS: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. CONCLUSIONS: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.

Recommendations for Post-Operative RadioTherapy After Complete Resection of Thymoma-a French DELPHI Consensus Initiative.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement. RESULTS: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years. CONCLUSION: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

Stereotactic radiotherapy for brain metastases: predictive factors of radionecrosis.

PURPOSE: Stereotactic radiotherapy (SRT) is a highly effective approach and represents the current standard of treatment for patients with limited number of brain metastasis (BM). SRT is generally well tolerated but can sometimes lead to radionecrosis (RN). The aim of this study was to identify predictive factors of radionecrosis related to SRT for brain metastasis. METHODS: This retrospective observational cohort study included patients who underwent SRT in the Institut Sainte Catherine between January 1st, 2017 and December 31st, 2020 for the treatment of brain metastasis from any cancer. Individual data and particularly signs of radionecrosis (clinical, imaging, anatomopathological) were collected from electronic medical records. Radionecrosis was defined as the occurrence on MRI of contrast-enhancing necrotic lesions, surrounded by edema, occurring at least 6 months after SRT and localized within fields of irradiation. RESULTS: 123 patients were included; median age was 66 years. 17 patients (11.8%) developed radionecrosis after a median follow up of 418.5 days [63;1498]. Predictive factors of radionecrosis in multivariate analysis were age under 66 years with a sensitivity of 77% and a specificity of 56%. No other factor as the presence of comorbidities, the number of irradiated metastases, the PTV volume or the volume of irradiated healthy brain were predictive of radionecrosis. CONCLUSION: Age at treatment initiation and tumor location seems to be correlated with radionecrosis in patients with brain metastasis treated with SRT. These elements could be useful to adapted radiation therapy.

Contribution of respiratory gating techniques for optimization of breast cancer radiotherapy.

A comparative, nonrandomized, multicenter, and prospective analysis were performed between April 2004 and June 2008 in 20 French centers in order to compare clinical aspects of respiratory-gated conformal radiotherapy (RGRT) during breast cancer irradiation versus conventional conformal radiotherapy. The final results based on 233 evaluable patients at 48 months confirm the feasibility and good reproducibility of the RGRT systems. The main results demonstrated a marked reduction of dosimetric parameters predictive of lungs and cardiac toxicities in the RGRT group; especially the dose delivered to the heart during irradiation of the left breast; mostly observed with deep inspiration breath-hold techniques.

Innovation, value and reimbursement in radiation and complex surgical oncology: Time to rethink.

BACKGROUND AND PURPOSE: Complex surgery and radiotherapy are the central pillars of loco-regional oncology treatment. This paper describes the reimbursement schemes used in radiation and complex surgical oncology, reports on literature and policy reviews. MATERIAL AND METHODS: A systematic review of the literature of the reimbursement models has been carried out separately for radiotherapy and complex cancer surgery based on PRISMA guidelines. Using searches of PubMed and grey literature, we identified articles from scientific journals and reports published since 2000 on provider payment or reimbursement systems currently used in radiation oncology and complex cancer surgery, also including policy models. RESULTS: Most European health systems reimburse radiotherapy using a budget-based, fee-for-service or fraction-based system; while few reimburse services according to an episode-based model. Also, the reimbursement models for cancer surgery are mostly restricted to differences embedded in the DRG system and adjustments applied to the fees, based on the complexity of each surgical procedure. There is an enormous variability in reimbursement across countries, resulting in different incentives and different amounts paid for the same therapeutic strategy. CONCLUSION: A reimbursement policy, based on the episode of care as the basic payment unit, is advocated for. Innovation should be tackled in a two-tier approach: one defining the common criteria for reimbursement of proven evidence-based interventions; another for financing emerging innovation with uncertain definitive value. Relevant clinical and economic data, also collected real-life, should support reimbursement systems that mirror the actual cost of evidence-based practice.

Innovation, value and reimbursement in radiation and complex surgical oncology: Time to rethink.

BACKGROUND AND PURPOSE: Complex surgery and radiotherapy are the central pillars of loco-regional oncology treatment. This paper describes the reimbursement schemes used in radiation and complex surgical oncology, reports on literature and policy reviews. MATERIAL AND METHODS: A systematic review of the literature of the reimbursement models has been carried out separately for radiotherapy and complex cancer surgery based on PRISMA guidelines. Using searches of PubMed and grey literature, we identified articles from scientific journals and reports published since 2000 on provider payment or reimbursement systems currently used in radiation oncology and complex cancer surgery, also including policy models. RESULTS: Most European health systems reimburse radiotherapy using a budget-based, fee-for-service or fraction-based system; while few reimburse services according to an episode-based model. Also, the reimbursement models for cancer surgery are mostly restricted to differences embedded in the DRG system and adjustments applied to the fees, based on the complexity of each surgical procedure. There is an enormous variability in reimbursement across countries, resulting in different incentives and different amounts paid for the same therapeutic strategy. CONCLUSION: A reimbursement policy, based on the episode of care as the basic payment unit, is advocated for. Innovation should be tackled in a two-tier approach: one defining the common criteria for reimbursement of proven evidence-based interventions; another for financing emerging innovation with uncertain definitive value. Relevant clinical and economic data, also collected real-life, should support reimbursement systems that mirror the actual cost of evidence-based practice.

Safety of G-CSF with concurrent chemo-radiotherapy in limited-stage small cell lung cancer - Secondary analysis of the randomised phase 3 CONVERT trial.

OBJECTIVES: The use of granulocyte colony-stimulating factors (G-CSF) during concurrent chemo-radiotherapy (cCTRT) for small cell lung cancer is not recommended by the American Society of Clinical Oncology due to safety concerns. This secondary analysis explored the safety and the role of prophylactic G-CSF (proG-CSF) in the delivery of cCTRT. MATERIAL AND METHODS: Secondary analysis of 487 patients treated as per protocol on the phase 3 CONVERT trial which randomized patients between once-daily RT or twice-daily. RESULTS: 180 of 487 eligible patients (37 %) received proG-CSF, 60 (33 %) as primary prophylaxis and 120 (67 %) as secondary prophylaxis following myelotoxic events. The regimen incidence of febrile neutropenia (FN) was 22 %. Its incidence in the proG-CSF group reduced significantly when proG-CSF was administered (22 % vs 10 %; OR 0.4; 95 %CI 0.2-0.7; p = 0.002). The rate of blood transfusion was higher in the proG-CSF group (51 % vs 31 %; OR 2.4; 95 %CI 1.6-3.5; p < 0.001). The incidence of severe thrombocytopenia was also higher is this group (28 % vs 15 %; OR 2.2; 95 %CI 1.4-3.5; p = 0.001). But this was significantly higher in those on secondary vs primary prophylaxis (34 % vs 15 %; OR 2.9; 95 %CI 1.3-7.4 p = 0.009) No differences observed in RT-related toxicity, treatment-related mortality or any survival outcomes. The optimal dose intensity (85 % or higher) of cisplatin was achieved in more patients within the proG-CSF group (75 % vs 67 %; OR 1.5; 95 %CI 0.9-2.3; p = 0.056). CONCLUSION: There was no evidence that G-CSF directly caused myelotoxicity, instead most patients started G-CSF due to higher myelotoxicity risk. G-CSF maintained the planned dose intensity and there was no detrimental effect on survival. G-CSF may be considered as a supportive measure in this setting.

Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study.

Plasma-based tumor mutational profiling is arising as a reliable approach to detect primary and therapy-induced resistance mutations required for accurate treatment decision making. Here, we compared the FDA-approved Cobas® EGFR Mutation Test v2 with the UltraSEEK™ Lung Panel on the MassARRAY® System on detection of EGFR mutations, accompanied with preanalytical sample assessment using the novel Liquid IQ® Panel. 137 cancer patient-derived cell-free plasma samples were analyzed with the Cobas® and UltraSEEK™ tests. Liquid IQ® analysis was initially validated (n = 84) and used to determine ccfDNA input for all samples. Subsequently, Liquid IQ® results were applied to harmonize ccfDNA input for the Cobas® and UltraSEEK™ tests for 63 NSCLC patients. The overall concordance between the Cobas® and UltraSEEK™ tests was 86%. The Cobas® test detected more EGFR exon19 deletions and L858R mutations, while the UltraSEEK™ test detected more T790M mutations. A 100% concordance in both the clinical (n = 137) and harmonized (n = 63) cohorts was observed when >10 ng of ccfDNA was used as determined by the Liquid IQ® Panel. The Cobas® and UltraSEEK™ tests showed similar sensitivity in EGFR mutation detection, particularly when ccfDNA input was sufficient. It is recommended to preanalytically determine the ccfDNA concentration accurately to ensure sufficient input for reliable interpretation and treatment decision making.

Compliance and Outcome of Elderly Patients Treated in the Concurrent Once-Daily Versus Twice-Daily Radiotherapy (CONVERT) Trial.

INTRODUCTION: There is a lack of data on the efficacy and safety of concurrent chemoradiotherapy in elderly, limited-stage, patients with SCLC. METHODS: We compared outcomes of patients 70 years of age or older versus younger patients within the Concurrent Once-daily Versus twice-daily RadioTherapy (CONVERT) trial. Patients were randomized to receive 45 Gy/30 twice-daily fractions/19 days or 66 Gy/33 once-daily fractions/45 days concurrently with platinum-based chemotherapy. Overall survival and progression-free survival were evaluated using Kaplan-Meier methodology and Cox proportional hazards regression. RESULTS: Of 547 patients randomized between April 2008 and November 2013, 57 did not receive protocol treatment and were excluded. Of the 490 patients included, 67 (14%) were 70 years of age or older (median age: 73 years; range: 70-82). Fewer older patients received the optimal number of radiotherapy fractions (73% versus 85%; p = 0.03); however, chemotherapy compliance was similar in both groups (p = 0.24). Neutropenia grade 3/4 occurred more frequently in the elderly (84% versus 70%; p = 0.02) but rates of neutropenic sepsis (4% versus 7%; p = 0.07) and death (3% versus 1.4%; p = 0.67) were similar in both groups. With a median follow-up of 46 months; median survival in the elderly versus younger groups was 29 (95% confidence interval [CI]: 21-39) versus 30 months (95% CI: 26-35), respectively; (hazard ratio: 1.15, 95% CI: 0.84-1.59; p = 0.38). Median time to progression in the elderly versus younger groups was 18 months (95% CI: 13-31) versus 16 months (95% CI: 14-19), respectively (hazard ratio: 1.04, 95% CI: 0.76-1.41; p = 0.81). CONCLUSIONS: Concurrent chemoradiotherapy with modern radiotherapy techniques should be a treatment option for fit, older patients.

Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response.

INTRODUCTION: Optimal preoperative treatment of stage IIB (Pancoast)/III non-small cell lung cancer (NSCLC) remains undetermined and a subject of controversy. The goal of our study is to confirm feasibility and pathological response rates after induction chemoradiation (CRT) in our community-based treatment center. PATIENTS AND METHODS: Patients were selected according to functional and resectability criteria. Induction treatment comprised 3D conformal 4500 cGy radiotherapy delivered to the primary tumor and pathologic hilar and/or mediastinal lymph nodes on CT scan with an extra-margin of 1-1.5 cm. Concurrent chemotherapy regimen was cisplatinum 20mg/m2 d1-d5 and etoposide 50mg/m2 d1-d5, d1-5 d29-33. Within 3-4 weeks after CRT completion, operability was re-assessed accordingly. Surgery was performed 4-6 weeks after CRT completion in patients (pts) deemed resectable. Inoperable pts were referred for a 20-25 Gy boost +/-1 extra-cycle of cisplatinum+etoposide. RESULTS: From 1996 to 2005, 107 pts were initially selected for treatment and received induction chemoradiation (stage IIB-Pancoast 18, IIIA 58 and IIIB 31, squamous cell carcinoma 48%, adenocarcinoma 44%, large-cell undifferentiated carcinoma 14%). After preoperative evaluation, 72 pts (67%) had a thoracotomy (pneumonectomy 21, lobectomy 45, bilobectomy 5) and all but one (unresectable tumor) had a macroscopic complete resection. During the 3-month postoperative time, five patients (6.9%) died, four after pneumonectomy (right 3, left 1). The analysis of tumoral samples showed a pathological complete response rate or microscopic residual foci of 39.5%. Median follow-up time was 22.3 months (survivors: 36.8 months), 2-year and 3-year overall survival rates were 55% and 40%, respectively (median=26.7 months) for all the intention-to-treat population (n=107), 62% and 51% (median=36.5 months) for 71 resected pts, 41% and 16% for 36 non-resected pts (median=19.1 months). On multivariate analysis, surgical resection and tumoral necrosis >50% (or pathological complete response) were the most pertinent predictive factors of the risk of death (hazard ratio=0.50 and 0.48, p=0.006 and 0.038, respectively). CONCLUSION: Surgery was feasible after induction chemoradiation, particularly lobectomy in PS 0-1, stage IIB (Pancoast)/III NSCLC pts but pneumonectomy carries a high risk of postoperative death (particularly, right pneumonectomy). Pathological response to induction chemoradiation was complete in 39.5% of patients and was a significant predictive factor of overall survival.

Impact of a comprehensive geriatric assessment to manage elderly patients with locally advanced non-small-cell lung cancers: An open phase II study using concurrent cisplatin-oral vinorelbine and radiotherapy (GFPC 08-06).

INTRODUCTION: Few data have been published on the optimal management of elderly patients with locally advanced non-small-cell lung cancers (La-NSCLC). This prospective, multicenter, phase II study was undertaken to evaluate the ability of a comprehensive geriatric assessment (CGA) to select the elderly La-NSCLC patients who potentially may benefit from concurrent radio-chemotherapy. METHODS: The main inclusion criteria were: La-NSCLC, >70 years old, at least one measurable target, ECOG performance status (PS) 0/1 and normal CGA. Weekly cisplatin (30 mg/m2) and oral vinorelbine (30 mg/m2) were combined with standard thoracic radiotherapy (66 Gy, 33 fractions) for 6.5 weeks. The primary evaluation criterion was <15% clinically relevant grade >2 toxicity. Secondary criteria were response rates, overall survival (OS) and progression-free survival (PFS). RESULTS: Among the 49 patients screened, 40 were included: 87.5% men, median age: 75.1 (70-84) years, 67.5% with PS 0, 52.5% squamous cell carcinomas. The full concurrent regimen was administrated in 77.5% of the cases (chemotherapy: 85%, radiotherapy: 90%); 22.5% of the patients experienced toxicity grade >2 (with three treatment-imputed deaths), 15% when restricted to clinically relevant >2 grade toxicities. One (2.6%) patient achieved a complete response, 53.8% had partial responses and 35.9% stable disease. Median PFS was 15 (95%CI: 8,7-35,2) months, OS 21.8 (95%CI: 16-NR) months and 1-, 2- and 4-year survival rates were 77.5%, 45% and 34.8%. CONCLUSION: CGA was able to select fit elderly patients with La-NSCLCs eligible for concurrent chemoradiotherapy with a satisfactory risk/benefit ratio.

Randomized Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in Lung Cancer Patients.

Background: The use of web-based monitoring for lung cancer patients is growing in interest because of promising recent results suggesting improvement in cancer and resource utilization outcomes. It remains an open question whether the overall survival (OS) in these patients could be improved by using a web-mediated follow-up rather than classical scheduled follow-up and imaging. Methods: Advanced-stage lung cancer patients without evidence of disease progression after or during initial treatment were randomly assigned in a multicenter phase III trial to compare a web-mediated follow-up algorithm (experimental arm), based on weekly self-scored patient symptoms, with routine follow-up with CT scans scheduled every three to six months according to the disease stage (control arm). In the experimental arm, an alert email was automatically sent to the oncologist when self-scored symptoms matched predefined criteria. The primary outcome was OS. Results: From June 2014 to January 2016, 133 patients were enrolled and 121 were retained in the intent-to-treat analysis; 12 deemed ineligible after random assignment were not subsequently followed. Most of the patients (95.1%) had stage III or IV disease. The median follow-up was nine months. The median OS was 19.0 months (95% confidence interval [CI] = 12.5 to noncalculable) in the experimental and 12.0 months (95% CI = 8.6 to 16.4) in the control arm (one-sided P = .001) (hazard ratio = 0.32, 95% CI = 0.15 to 0.67, one-sided P = .002). The performance status at first detected relapse was 0 to 1 for 75.9% of the patients in the experimental arm and for 32.5% of those in the control arm (two-sided P < .001). Optimal treatment was initiated in 72.4% of the patients in the experimental arm and in 32.5% of those in the control arm (two-sided P < .001). Conclusions: A web-mediated follow-up algorithm based on self-reported symptoms improved OS due to early relapse detection and better performance status at relapse.

Quality of life in long-term survivors of oropharynx carcinoma.

PURPOSE: To collect data on the health-related quality of life (QOL) of long-term survivors and to determine to what extent QOL might be an appropriate end point in the comparison of treatment options in oropharyngeal carcinoma. METHODS AND MATERIALS: All patients treated between 1992 and 1998, in two French comprehensive cancer centers, by brachytherapy (BT) +/- external beam radiotherapy (EBRT) or surgery plus RT, or exclusive EBRT for T1-T3 (International Union Against Cancer staging system) oropharynx squamous cell carcinoma, were included. QOL was measured once in disease-free patients at least 2 years after treatment initiation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module were self-administered by all participating patients. Sociodemographic data were collected using a questionnaire specifically designed for the study. The association between the QOL scores of the various treatment-, disease-, and patient-related variables was performed through bivariate analysis and then by multivariate analysis. The mean QOL scores of the EORTC QLQ-C30 questionnaire were compared with the mean scores in the general population. RESULTS: Of the 159 eligible patients, 113 agreed to participate (97 men and 16 women, median age 61 years, range 41-83). The initial treatment was EBRT plus BT in 49 patients, surgery plus RT in 27, and EBRT alone in 37. The median follow-up time was 62 months (range 24-110). Compared with the general population, the three scores indicating the most impaired QOL were emotional and social functioning and fatigue. The clinical significance of global QOL impairment was borderline. The physical functioning, role functioning, and pain scores did not significantly differ from those of the general population. In multivariate analysis, the initial treatment had no significant influence on any dimension of QOL, except global QOL and emotional functioning. Surprisingly, surgery plus RT, as the initial treatment, favorably influenced the emotional functioning score and EBRT plus BT negatively influenced the global QOL score. None of these treatment modalities influenced any symptom scales. Patient selection was, at least partially, responsible for these paradoxical results. CONCLUSION: The results of this study bring original and useful data about the QOL of long-term survivors of oropharynx carcinoma. In these patients, the QOL was significantly impaired, particularly in its psychosocial dimensions. The level of symptoms and functioning (except global QOL and emotional) was similar whatever the initial treatment. These results suggest the importance of coping processes. In a trial comparing treatment options from a long-term perspective, survival remains the most relevant end point, and a QOL evaluation should be a secondary end point. More prospective studies on QOL in head-and-neck cancer patients are needed to determine new strategies for rehabilitation management.