Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD: This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS: From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION: Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.

[Intensity modulated radiotherapy for head and neck cancers: ethics and patients selection]. / Radiothérapie conformationnelle avec modulation d'intensité dans les cancers de la sphère ORL : éthique et sélection des patients.

PURPOSE: Intensity modulated radiotherapy (IMRT) allows a better coverage of the target volume and a better saving of organs at risk with a decrease of toxicity in head and neck cancers. It requires more human labor and materials compared to conformational radiotherapy. If they are insufficient, a selection of the patients receiving IMRT may be necessary, raising an ethical problem. MATERIAL AND METHODS: We collected the motives guiding the choice of the technique of radiotherapy for head and neck cancers during a month of physicists' shortage. RESULTS: Nineteen patients received IMRT and eight conformational radiotherapy. Conformational irradiation was chosen in palliative and postsurgery treatments, to reduce delay, in laryngeal tumors and re-irradiation. IMRT was preferred for complex target volumes and the localizations at risk of important xerostomia following conformational radiotherapy. These choices were confronted with the bioethics criteria of Beauchamp and Childress. The beneficence justified the use of IMRT or conformational radiotherapy depending on the circumstances. The non-maleficence attempted to decrease the toxicity with IMRT. Justice was questioned by the selection. The autonomy of patients was not totally respected in the choice. CONCLUSION: To help in the choice of the patients receiving an IMRT in a crisis situation, we proposed a hierarchical organization of selection criteria: complex volumes close to critical organs at risk, localization with high risk of xerostomia, long life expectancy and postoperative delay constraints.

Combined transoral and suprahyoid approach for oropharyngeal cancers: an alternative to mandibulotomy.

UNLABELLED: Surgical treatment of oropharyngeal tumours usually requires mandibular osteotomy. Using this technique allows a better exposure and an easier excision, but this approach often generates complications. Since 1995, we used a less aggressive surgical technique, with a suprahyoid pharyngotomy when the oral approach was not sufficient, thus sparing the mandible. OBJECTIVE: The purpose of this study is to evaluate this technical evolution, ensuring that mandibular preservation doesn't affect quality of exeresis, local control and survival, while allowing a lower complication rate. MATERIAL AND METHODS: All patients who have had a surgical treatment for an oropharyngeal carcinoma between 1995 and 2001 in our center were included in this study. RESULTS: Mandibular sparing was used for 55 patients; 19 patients underwent mandibulotomy. The surgical procedure's quality was classified as clear, close, or insufficient margins. All adjuvant treatments were noted, functional and carcinologic results were evaluated. No significant differences are found for exeresis quality and local control. There are less complications (p = 0.045) and less surgical revisions (p = 0.023) in the preservation group. Survival and functional results are better in the preservation group, but without significant difference. For oropharyngeal tumours, survival is dependent on tumoural aggressivity, on general condition and co-morbidity and on the development of a second tumour. Results in local control rate (83.7% at 1 year) are satisfying compared to literature. CONCLUSION: Mandibular preservation is an efficient and safe procedure, even for T3/T4 tumours. Most of oropharyngeal tumours can be removed without mandibulotomy. The suprahyoid approach provides a good exposure when oral approach is insufficient, thus avoiding mandibulotomy and its complications.

Management of patients with head and neck tumours presenting at diagnosis with a synchronous second cancer at another anatomic site.

AIMS: To understand management strategies and outcomes of patients diagnosed with a head and neck tumour and a synchronous second cancer developed at another anatomic site. MATERIALS AND METHODS: Retrospective analysis of all patients diagnosed with a head and neck carcinoma and a synchronous cancer and engaged in curative-intent treatments. To evaluate therapeutic strategies, each patient's treatment process was divided into sequential therapeutic modalities and corresponding targets (head and neck and/or synchronous tumour) were identified. Patient outcome was analysed with an intent-to-treat approach. RESULTS: Forty-three patients were entered into the study (mean age=57.4 years). Synchronous tumours concerned the lung (57.8%), oesophagus (31.1%) or other sites (11.1%). Treatments were complex, including one to four consecutive modalities, with a mean duration of 4.6 months. When both tumours were advanced, treatments were frequently initiated with dual-spectrum chemotherapy (66.7%). In other situations, a locoregional treatment was often (81.1%) proposed immediately. When both tumours were in early stages, this initial locoregional treatment could be extended to target both tumours together (30.0%). For patients whose tumours differed in severity, this locoregional treatment targeted only one tumour (85%); priority was given to the most advanced one (76.5%). Nine patients had definitive treatment interruption. Associated risk factors were a low body mass index (P=0.03) and advanced-stage tumours (P=0.01). Thirty-one patients died (72.1%) with a median time to death of 7.7 months. The median follow-up for survivors was 46.2 months. Three-year overall survival was 33.9%. Low body mass index (P=0.001), advanced-stage synchronous tumours (P=0.03) and oesophageal primaries (P=0.03) altered the overall survival. Three-year locoregional and metastatic progression-free survival was 40.8 and 62.5%, respectively. Low body mass index (P=0.01) and advanced-stage synchronous tumours (P=0.01) increased the risk of disease failure. CONCLUSIONS: Head and neck tumours diagnosed with a synchronous cancer are a complex challenge. Despite a severe prognosis, patients who are not underweight, presenting with lower-stage tumours (especially the synchronous tumour) and without oesophageal involvement could most benefit from aggressive treatments.

[Radiotherapy after prostatectomy: experiences in Luxembourg from 2005 to 2006]. / Radiothérapie après prostatectomie: expérience au Luxembourg de 2005 a 2006.

Radical prostatectomy is a therapeutic option for the treatment of localized prostate cancer (T1 and T2). The prognostic factors which define risks of recurrence after prostatectomy are: capsular invasion, invasion of resection margins, seminal vesicle invasion. Two randomized trials show that adjuvant radiotherapy improves local control and biochemical recurrence-free survival. Between 2005 and 2006, 12 patients of Centre François Baclesse have been irradiated on theprostatic loge. Immediate post-operative radiotherapy was preferably used. Late toxicity (grade 1) occurred only in one patient (1 case out of 8). Based on the literature, immediate postoperative irradiation is preferentially proposed in case of unfavourable factors, or possibly used secondly, in case of biological recurrence (in early situation i.e. PSA < 0.5).

[Localized prostatic cancer: treatment exclusive by radiotherapy guided by imagery, experiences in Luxembourg in 2005 and 2006]. / Cancer localisé de la prostate: traitement par radiothérapie exclusive guideée par l'imagerie, expérience au Luxembourg en 2005 et 2006.

Exclusive radiotherapy is one of therapeutic standard in the curative treatment of localized prostate cancer. Results are equivalent when compared with other treatment regimens (radical prostatectomy or curietherapy) in localized forms. However, the patients risks profiles to predict noxious effects are different. Between 2005 and 2006, 27 patients have been treated with intensity modulated radiation therapy and image-guided radiotherapy (IGRT), after implantation of gold markers to target prostate localization during daily radiotherapy seances. The total dose of radiation delivered in prostate is 74 Gy with respect to the maximal dose defined to the rectum and to the bladder. Late toxicity was limited to grade 2 (rectitis and cystitis). These symptoms were temporary. One patient out of 20 patients with one-year follow-up experienced biological recurrence with metastasis progression. New radiotherapy technologies have allowed to reduce the incidence of the toxicity especially late rectal toxicity (2.2% in 2006) within a limited time period (one-year minimum).

[Progress in radiotherapeutic approaches to anal, rectal, bronchial and prostatic cancers]. / Progrès récents dans l'approche radiothérapique des cancers anaux, rectaux, bronchiques et prostatiques.

During the last years, various progress has been made in the irradiation of cancers: combined treatment modalities with surgery and chemotherapy, the radiation technique itself (conformal radiotherapy, brachytherapy ...), alterations of the radiation fractionation, the use of radiosensitizers. These modifications will be illustrated through the treatment of anorectal, lung and prostatic cancers.