Oral and oropharyngeal cancer surgery with free-flap reconstruction in the elderly: Factors associated with long-term quality of life, patient needs and concerns. A GETTEC cross-sectional study.

OBJECTIVES: To assess the factors associated with long-term quality of life (QoL) and patient concerns in elderly oral or oropharyngeal cancer (OOPC) patients after oncologic surgery and free-flap reconstruction. METHODS: Patients aged over 70 years who were still alive and disease-free at least 1 year after surgery were enrolled in this cross-sectional multicentric study. Patients completed the EORTC QLQ-C30, -H&N35 and -ELD14 QoL questionnaires, and the Hospital Anxiety and Depression Scale (HADS). Patient needs were evaluated using the Patient Concerns Inventory (PCI). Factors associated with these clinical outcomes were determined in univariate and multivariate analysis. RESULTS: Sixty-four patients were included in this study. Long-term QoL, functioning scales and patient autonomy were well-preserved. Main persistent symptoms were fatigue, constipation and oral function-related disorders. Salivary and mastication/swallowing problems were the main patient concerns. The mean number of patient concerns increased with the deterioration of their QoL. Psychological distress (HADS score ≥ 15) and patient frailty (G8 score < 15) were significantly associated with poor QoL outcomes. CONCLUSIONS: We found a negative correlation between the number of patient concerns and QoL. Dental rehabilitation and psychological and nutritional supportive measures are of critical importance in the multidisciplinary management of elderly OOPC patients.

Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study.

OBJECTIVES: In patients with N3 head and neck squamous cell carcinoma (HNSCC), N3 disease is associated with high regional relapse and metastatic risks. Patients with resectable N3 disease have better prognosis although their metastatic risk may be similar as in patients with unresectable disease. Neoadjuvant chemotherapy has been associated with lower metastatic rates, but N3 patients may die of rapid locoregional progression. We assessed outcomes with the three modalities in patients with low primary burden to better assess the specific prognosis of N3 disease. METHODS: This retrospective multicentric study included T0-2 N3 HNSCC patients. Outcomes and morbidity in upfront neck dissection (uND) vs non-surgical groups were analysed and oncological outcomes and morbidity compared between patients undergoing chemoradiation or neoadjuvant chemotherapy in patients with initially unresectable N3 nodes. RESULTS: Of 301 patients, 142 (47%) underwent uND, 68 (23%) neoadjuvant chemotherapy and 91 (30%) chemoradiation. The 24- and 60-month incidence of locoregional relapse was 23.2% [18.3%; 28.4%] and 27.4% [21.8%; 33.3%]; it was lower in patients undergoing uND (P = .006). In patients with non-surgical treatments, success rates were 57.8% [49.4%; 66.3%] after chemoradiation and 38.1% [29.6%; 46.7%] after neoadjuvant chemotherapy (P = .001). Overall morbidity was more frequent in patients undergoing uND (68.8%) (P < .001). CONCLUSION: uND improved locoregional control but increased morbidity and showed no survival benefit. Success rates were better after chemoradiation versus neoadjuvant chemotherapy. Neoadjuvant chemotherapy did not reduce metastatic rates but non-responders to chemoradiation had poor PFS and survival rate, suggesting that predictive criteria are warranted.

Surgery or Radiotherapy of the Primary Tumor in T1-2 Head and Neck Squamous Cell Carcinoma with Resectable N3 Nodes: A Multicenter GETTEC Study.

BACKGROUND: The prognosis of advanced nodal (N3) squamous cell carcinoma of the head and neck (HNSCC) is poor. We investigated whether surgery or radiotherapy of early (T1-2) primary stage HSNCC is preferable to limit the overall morbidity after upfront neck dissection (uND) for N3 disease. METHODS: This retrospective multicentric Groupe d'Étude des Tumeurs de la Tête Et du Cou study included patients undergoing uND and surgery or radiotherapy of their primary. Prognostic factors were evaluated using propensity score matching to account for biases in performing surgery depending on primary site and stage. RESULTS: Of 189 T1-2, N3 HNSCC patients, 70 (37.0%) underwent uND: 42 with surgery of their primary and 28 with radiotherapy only. Radiotherapy alone was more frequent in patients with hypopharyngeal primaries. All local (N = 3) and regional (N = 10) relapses (included 2 locoregional relapses) occurred within the first 2 years. There were 16 distant metastatic failures. Five-year locoregional relapse and survival incidences were 15.7% and 66.5% and were similar regardless of the treatment of the primary. The overall morbidity rate was 65.2% and was similar after weighting by the inverse propensity score (p = 0.148). The only prognostic factor for morbidity was the radicality of the uND. Prolonged parenteral feeding was not more frequent in patients only irradiated to their primary (p = 0.118). Prolonged tracheostomy was more frequent after surgery of the primary. CONCLUSIONS: In patients with T1-2, N3 HNSCC undergoing uND, radiotherapy and surgery of the primary yield similar oncological outcomes. Morbidity was related to the extent of neck dissection.

Curative treatment can be an option for patients with metastatic squamous cell cancer of the head and neck.

BACKGROUND: No specific study has focused on patients with metastatic squamous cell carcinoma of the head and neck (SCCHN) at diagnosis. Due to high response rates of induction chemotherapy in chemo-naïve patients with localized disease, their prognosis should be better than patients with recurrent disease. METHODS: From January 1, 2008 to July 1, 2012, we retrospectively collected all patients' records with SCCHN diagnosed as metastatic. Patients, disease, treatment and its results were analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of the 749 new patients treated for SCCHN in our institution, 16 (2.1%) were metastatic at diagnosis, of whom five had cytological results to prove it. Six patients died before treatment or had palliative care and ten received initial chemotherapy and then surgery and/or radiotherapy according to the primary response. Four patients treated with first-line chemotherapy with docetaxel-5FU-cisplatin (TPF) showed a complete response of metastatic lesions allowing locoregional treatment. The overall survival at 1 year and 3 years was 50% and 24%, respectively. The median survival was 7 months (1-72 months). Seven patients (43.7%) had a higher survival at 12 months, including five (31.5%) who are still alive without recurrence with a mean follow-up of 30 months. There was a significant difference in overall survival (P<0.01) between patients who had chemotherapy with TPF versus other therapeutic protocols. The median survival of patients with lung metastases only was 15 months (1-72 months), significantly higher than that of patients with liver and/or bone localizations, which was 2 months (1-9 months). CONCLUSION: Patients with metastatic SCCHN treated by TPF followed by multimodal treatment could achieve long survival.

A pyriform sinus cancer organ preservation strategy comprising induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, followed by potentiated radiotherapy: a multicenter, retrospective study.

No specific study has evaluated the role of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) followed by radiotherapy in pyriform sinus cancer, which are often included in studies focusing on laryngeal and hypopharyngeal cancer. We assessed the proportion of patients treated sequentially for a pyriform sinus cancer with a preserved larynx. Overall survival, event-free survival (EFS), survival with 'local control', and treatment tolerance were assessed as well. We retrospectively reviewed 88 patients with advanced pyriform sinus squamous cell carcinoma treated with DCF between 2005 and 2010. After induction, radiation could be potentiated with cetuximab or cisplatin. Most patients (82%) had been treated with organ preservation intent. The response rate to DCF was 85%, including 42% with complete response. Primary tumor was operated in 13 patients (eight with total laryngectomy). Radiotherapy had been delivered to 78 (89%) patients (30 with cisplatin, 39 with cetuximab). Potentiation had been achieved as planned in 52 and 79% of patients treated with cisplatin and cetuximab, respectively. Twenty-three local and three neck recurrences were found. Median overall survival was 16.8 months and 38.3% at 3 years. EFS at 3 years was 29.1% with a hazard ratio for partial responders versus nonresponders of 0.18 (P<0.001), and 0.13 (P<0.001) for complete responders versus nonresponders. Thirty-five percent of patients were alive with their larynx preserved at 3 years. This study confirms the efficacy of induction followed by chemoradiation for pyriform sinus cancer and that response to DCF is predictive of EFS.

Vertebroepidural metastasis of an ethmoid adenocarcinoma: A case report.

Ethmoid adenocarcinoma is the most frequent ethmoid tumor. To date, only a single case of spinal cord compression resulting from ethmoid adenocarcinoma has been reported. The current case study presents a recent case of vertebroepidural metastasis of an ethmoid adenocarcinoma leading to spinal cord compression. Modern imaging studies, including magnetic resonance imaging (MRI) and 18 fludeoxyglucose positron emission tomography (FDG PET), as well as histological and immunohistochemical analyses, have led to diagnoses of a metastasis of an ethmoid adenocarcinoma, which is a mucinous variant, dedifferentiated when compared to the primary tumor. The present case discusses current diagnostic and treatment protocols of this condition. Since survival rates associated with the primary tumor are improving, the incidence of spinal metastasis of ethmoid carcinomas is likely to increase in the future, therefore requiring appropriate diagnostic and therapeutic management.

Adenoid cystic carcinoma of the nasopharynx: a case report and a discussion about prognostic factors and the role of local treatments.

Adenoid cystic carcinoma (ACC) is a rare epithelioid malignancy. It occurs most frequently in the salivary glands, while its localization in the nasopharynx is rare and few cases have been reported in the literature. We report the case of a 32-year-old woman presenting with ACC of the nasopharynx who was treated with surgery and adjuvant intensity-modulated radiation therapy (IMRT, total dose: 68 Gy) and concomitant chemotherapy (cisplatin 100 mg/m² on the first and 21st days of IMRT). During irradiation, the patient developed G1 dermatitis and G2 mucositis (RTOG). Clinical and instrumental reevaluation 17 months after the end of radiotherapy did not show any signs of relapse, and she did not show any sign of local mild-severe toxicity. Adjuvant radiotherapy after standard complete surgical resection seems to be effective and well tolerated and should be strongly considered in the multidisciplinary approach to this infrequent carcinoma.

Management of the neck in the setting of definitive chemoradiation: is there a consensus? A GETTEC study.

BACKGROUND: The management of the neck remains controversial in the definitive chemoradiation setting of advanced N2-3 head and neck squamous cell carcinoma. Most published data favor omission of neck dissection (ND) after complete response for N2-3 or selective ND for residual disease METHODS: We studied the patterns of care in the French-Belgian Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC) through a questionnaire-based survey. RESULTS: Eighteen percent of institutions never performed up-front ND, 20% rarely, 40% sometimes, 14% often, and 8% systematically. Induction chemotherapy was indicated in 30% of the cases, and most ND were performed either between induction and radiation or after chemoradiation for residual disease. Response to chemoradiation was assessed by computed tomographic scan and positron emission tomography in 72% of cases. Selective ND was more common than radical ND. CONCLUSIONS: Omission of ND based on computed tomographic scan and positron emission tomography-based complete response to chemoradiation is the most common strategy for advanced nodal disease among centers. However, neck management strategies vary among institutions, and some institutions continue advocating systematic ND before irradiation. The new treatment options and the changing epidemiology, namely docetaxel-based induction chemotherapy and human papilloma virus-related head and neck squamous cell carcinoma having better response profiles and prognosis, are adding to the nonconsensual approach. The best therapeutic index in terms of neck management remains to be defined in this evolving context.

Role of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.

OBJECTIVE: To assess the efficacy of radiotherapy in the treatment of nasoethmoidal adenocarcinoma. DESIGN: Multicenter, retrospective study. SETTING: Eleven French hospitals. PATIENTS: The medical records of 418 patients who presented with nasoethmoidal adenocarcinoma from January 1, 1976, through December 31, 2001, were evaluated. A total of 324 patients were treated with a combination of surgery and radiotherapy, and 55 were treated with surgery only. MAIN OUTCOME MEASURES: Survival rates, disease recurrence, and postoperative complications. RESULTS: The 5-year Kaplan-Meier survey revealed survival rates of 64.5% for the surgery-only group and 70.8% for the combined-treatment group. In the surgery-only group, 28 patients (51%) had disease recurrence (24 local, 2 regional, and 2 distant). Of the 55 patients in the combined-treatment group, 31 patients (56%) had disease recurrence (29 local, 1 regional, and 1 distant). Immediate postoperative complications in the combined-treatment group were hemorrhages in 2 patients, meningitis in 3 patients, and cerebrospinal fluid leakage in 4 patients, but no deaths occurred. In the surgery-only group, 1 patient had meningitis, 2 had cerebrospinal fluid leaking but no hemorrhage, and 5 died postoperatively. CONCLUSION: The results of this retrospective study suggest that radiotherapy can be used to treat nasoethmoidal adenocarcinoma, but its usefulness should be confirmed with further prospective studies.

Head and neck cancer in young people: a series of 52 SCCs of the oral tongue in patients aged 35 years or less.

CONCLUSION: Prognosis was very poor as soon as a local failure developed. Up-front treatment should be optimized to control this rare disease. We propose producing and reporting recommendations via a concerted oncologic physician referral network. OBJECTIVES: Squamous cell carcinoma (SCC) in young people is rare and the literature is confusing. This study was carried out to assess the demographics, clinical features, and treatment outcome in a cohort of patients aged 35 years or less with SCC of the oral tongue (SCCOT). PATIENTS AND METHODS: This was a multicenter retrospective study. Fifty-two patients treated between 1990 and 2000 were identified. Descriptive statistics were analyzed to assess demographic and tumor variables. RESULTS: The WHO performance status was excellent for all patients. Thirty-seven were classified as T1-T2 and 38 were N0. All of them except one were treated with curative intent. Treatment failures were observed in 25 patients (48%). Four patients could be successfully salvaged after SCCOT recurrence or progression. The disease-free survival (DFS) was 52% at 5 years. The 5-year overall survival (OS) rate was 64%. Factors that affected the OS were invasion of the floor (p=0.009), cross over of the midline (p=0.02), positive lymph nodes (p=0.02), and the lack of disease control (p=0.0001).

Adenocarcinoma of Ethmoid: a GETTEC retrospective multicenter study of 418 cases.

OBJECTIVE: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature. MATERIALS AND METHODS: A multicenter and retrospective study. The medical records of 418 patients who had presented with ethmoid adenocarcinoma at 11 French hospitals from 1976 to 2001 were analyzed to determine the clinical characteristics and treatment of the disease. RESULTS: The gender ratio was 2.8 men per 1 woman. Toxic exposure was classic for this lesion, exposure to wood and leather for most cases. The mean age was 63 years (range 31-91). Symptoms were nonspecific and based on clinical rhinologic signs. Nasal endoscopy after mucosal retraction was found useful to evaluate the extension of the lesion and to perform biopsies. Computed tomography scan and magnetic resonance imagery must be carried out prior to treatment to define extra nasal extension. The survival rate was significantly influenced by the size of the lesion (T4, N+) and extension to brain or dura. Surgery with postoperative radiotherapy remains the treatment of choice. Total excision must be a major priority, as confirmed in our series. CONCLUSION: This retrospective study was, to our knowledge, the largest ever reported in the literature. This series confirmed the risk factor of this lesion as well as the lesion's influence on the survival rate. Surgery is the most important part of the treatment. Local recurrences were responsible for the poor prognosis of this lesion.

Squamous cell carcinoma of the nasal columella: a retrospective study of 66 cases from the GETTEC.

Squamous cell carcinoma of the nasal columella (SCCNC) is a rare disease. We aimed to define a strategy for the diagnosis and management of nasal columella squamous cell carcinoma. Medical records of 66 patients presenting with columella squamous cell carcinoma in nine French hospitals, from 1980 to 2003, were evaluated to determine the clinical characteristics and current treatment of the disease. Mean age was 69 years. The sex ratio was one female for three males. Majority of the lesions were T1 N0 according to the classification international union against cancer. Patients underwent one of the three treatments: surgery alone for the T1 lesions, radiotherapy for tumors of T2-T3 and combined (surgery and radiotherapy) for T4 lesions. The 5-year Kaplan-Meier survival test was 39% and no difference was found between the therapeutic groups. Thirty-five (53%) tumor recurrences were observed with a median time of 43 months. As regards TNM classification and treatment, no significant difference between the two groups disease free/recurrence was found. Prognosis of early lesions was considered better than the advanced lesions. SCCNC is difficult to manage and has a poor prognosis. No therapeutic solution has yet been confirmed in the treatment of this pathology.

Phase 2 study of intratumoral cisplatin and epinephrine treatment for locally recurrent head and neck tumors.

Local relapses of head and neck tumors are not often eligible for surgical and/or radiotherapy retreatment, and the efficacy of systemic chemotherapy is poor. A greater accumulation and efficacy of anticancer drugs with lower systemic toxicity is theoretically obtained with intratumoral chemotherapy. In experimental studies, epinephrine has been shown to increase the concentration and antitumor effect of intratumoral cisplatin. Fourteen patients with locally recurrent head and neck tumors (median age, 58.7 years) were included in this phase 2 trial. Recurrent tumors (squamous cell carcinomas) were located on the tongue, oral pharynx, or cervical nodes. Prior therapy was surgery and/or radiotherapy with or without intravenous chemotherapy. Inclusion criteria included an Eastern Cooperative Oncology Group/World Health Organization performance status of 0, 1, or 2, an anticipated survival of >3 months, adequate cardiac, kidney, liver, and bone marrow function, and no coagulopathy or carotid invasion. Fifty intratumoral injections of cisplatin-epinephrine (average, 3.6 injections per patient; range, 1 to 5 injections) were given to the 14 patients from November 1998 to July 2000. Patients were treated with cisplatin (1 mg/mL; maximum dose, 50 mg) at an injection volume corresponding to the tumor volume (1 mL/cm3 of tumor; maximum volume, 50 mL). Epinephrine was added at a concentration of 0.02 mg/mL. Intratumoral injections were repeated every 2 to 3 weeks at different locations in the tumors to obtain a homogeneous distribution. Tumor response was evaluated by clinical examination and computed tomography. Eight objective responses were registered among the 14 patients. Four were complete responses, and 4 were partial responses. The average time to disease progression was 11.5 +/- 8.9 weeks. Local adverse effects were transient pain, swelling, and erythema at the site of the injection. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Intratumoral injection of cisplatin and epinephrine in an aqueous solution has a definite antitumor activity in recurrent head and neck cancer with acceptable local tolerance and no major systemic toxic effects except for transient tachycardia and high blood pressure at the time of injection.

T1-T2 NO oropharyngeal cancers treated with surgery alone. A GETTEC study.

The aim of this study is to show that surgical treatment of early-stage squamous cell carcinomas of the oropharynx gives identical, if not better, oncological results than the classic radiotherapy treatment in terms of locoregional control and survival. Fifty-three patients (32 T1, 21 T2, all N0) were operated on during the years 1995-2000. Surgical treatment consisted in a resection by the transoral approach in 43 patients (81.13%); ten patients (18.87%) benefited from a pharyngectomy with (seven) or without (three) mandibular resection. A level I to V selective neck dissection was performed on 35 patients, and 5 patients underwent a level II to V selective neck dissection. The 1-, 3- and 5-year overall survival rates were 100, 94.6 and 73%, respectively. There was no significant difference concerning the tumor stage ( P=0.69), the initial localization ( P=0.64), the macroscopic aspect ( P=0.65) and the management undertaken in the different centers ( P=0.19). The 5-year rate of specific survival was 100%. The 1-, 3- and 5-year locoregional control rates were 96.22, 92.45 and 88.68, respectively. The oncological occurrences observed were 2 persistent diseases, 5 local recurrences, 11 second primary cancers and 0 nodal recurrences. Seven local failures were observed, all of which were controlled after a second treatment. Eleven patients presented second primary cancers; three died, two are alive with an extension of this second localization, and six are alive and free of disease. The locoregional control provided by surgery alone on T1-T2 N0 oropharyngeal cancers is as good as radiotherapy. Moreover surgery alone makes it possible to spare patients the complications and aftereffects of radiotherapy. It also makes it possible during the recurrences to operate on patients in non-irradiated areas with lower morbidity and mortality. It is all the more beneficial since it will be possible to resort to radiotherapy after surgery if need be.