Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

CT-scan prediction of thyroid cartilage invasion for early laryngeal squamous cell carcinoma

Treatment choice for laryngeal cancer may be influenced by the diagnosis of thyroid cartilage invasion on preoperative computed tomography (CT). Our objective was to determine the predictive value of CT for thyroid cartilage invasion in early- to mid-stage laryngeal cancer. Retrospective study (1992–2008) of laryngeal squamous cell carcinoma treated with open partial laryngectomy and resection of at least part of the thyroid cartilage. Previous laser surgery, radiation therapy, chemotherapy and second primaries were excluded. CT prediction of thyroid cartilage invasion was determined by specialized radiologists. Tumor characteristics and pathologic thyroid cartilage invasion were compared to the radiologic assessment. 236 patients were treated by vertical (20 %), supracricoid (67 %) or supraglottic partial laryngectomy (13 %) for tumors staged cT1 (26 %), cT2 (55 %), and cT3 (19 %). The thyroid cartilage was invaded on pathology in 19 cases (8 %). CT’s sensitivity was 10.5 %, specificity 94 %, positive predictive value 13 %, and negative predictive value 92 %. CT correctly predicted thyroid cartilage invasion in only two cases for an overall accuracy of 87 %. Among the false-positive CT’s, tumors involving the anterior commissure were significantly over-represented (61.5 % vs. 27 %, p = .004). Tumors with decreased vocal fold (VF) mobility were significantly over-represented in the group of false-negatives (41 vs. 13 %, p = .0035). Preoperative CT was not effective in predicting thyroid cartilage invasion in these early- to mid-stage lesions, overestimating cartilage invasion for AC lesions and underestimating invasion for lesions with decreased VF mobility.     

Locoregional effects of pegylated liposomal doxorubicin (Caelyx) in irradiated area: a phase I-II study in patients with recurrent squamous cell carcinoma of the head and neck

Aim of this study was to determine the antitumour activity and toxicity of pegylated liposomal doxorubicin (Caelyx) in pretreated patients with locally recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). Caelyx was administrated as 1 h infusion every 3 weeks at doses of 35 mg/m2 (group A) and then subsequently given at 45 mg/m2 (group B). 26 patients received a total of 87 cycles. The median number of cycles was 3 (range 1-7). Four out of 24 evaluable patients (17%, 95% confidence interval (CI) 0.5-32%) showed significant evidence of antitumour activity, with tumour necrosis being observed in 2 patients. Grade 3-4 neutropenia was observed in only 2 patients. There were no grade 3-4 mucosal, skin, digestive, cardiac or hepatic toxicities. Caelyx has activity against locally recurrent SCCHN and is well tolerated up to 45 mg/m2, but a careful utilisation of this drug is required for tumours relapsing in irradiated areas.     

Locoregional recurrence of ORL cancer: the place of surgery

Surgery of locoregional failures is mainly represented by salvage surgery after radiotherapy. Due to progress of radiotherapy, especially modification of fractionation and association with chemotherapy, the problem of salvage surgery is nowadays emphasized. Despite the reduction of postoperative mortality and morbidity by the use of myocutaneous flaps the complications are still frequent and the rehabilitation long and difficult. Oncologic results are disappointing too, especially in salvage surgery for oropharyngeal and hypopharyngeal tumors with less than a half of patients being candidates for salvage surgery and 5 year survival rates inferior to 30% in these patients. Laryngeal tumors are more favorable for salvage surgery but in the majority of the cases recurrences after radiotherapy require a total laryngectomy. The poor postoperative, functional and oncologic results after salvage surgery, especially in pharyngeal tumors must be taken into account for the decision of primary treatment. Regarding the important locoregional aggressivity of squamous cell carcinomas of the upper aerodigestive tract, these results must be kept in mind when preservation protocols are in question.     

Circumferential pharyngolaryngectomy with total esophagectomy for locally advanced carcinomas

Background: Forty-nine cases of circumferential pharyngolaryngectomy with total esophagectomy (PLTE) done between 1982 and 1996 were studied retrospectively. These procedures were performed for advanced squamous cell tumors of the superior esophageal sphincter (n=23), for hypopharyngeal tumors with synchronous esophageal carcinoma (n=15), and for hypopharyngeal tumors extensively invading the cervical esophagus (n=11). Methods: Ninety-six percent of the patients had T3–4 lesions, and it was impossible to use a free jejunal graft reconstruction. Patients underwent primary surgery in 70% of the cases, and salvage surgery (after failure of chemoradiotherapy) in 30%. In most patients, esophagectomy was performed without thoractomy (n=45). Resection was curative (R0) in 70% of the cases, in spite of lymph node invasion in 94%. Reconstruction of the digestive tract was achieved with the stomach in 33 patients (67%) or with the colon in 16 patients (33%). Results: Before 1989, postoperative mortality was high, was correlated with the high frequency of palliative surgery, and resulted in unsatisfactory survival results (overall 5-year survival rate of 7%). After 1989, as a result of better selection of patients and appropriate training of our team, postoperative mortality decreased from 33% to 10%, R1–2 resections decreased from 39% to 26%, and a 3-year overall survival rate of 28% was obtained for the last 25 patients, all of whom were able to eat without difficulty. These results are superior to the survival rates and functional results obtained with radiochemotherapy alone for such advanced tumors, even though the voice is preserved with radiochemotherapy alone. Conclusions: PLTE for advanced pharyngeal or cervical esophageal tumors is the best treatment currently available, but it is indicated only in very selected cases: when it is technically impossible to perform reconstruction with a free jejunal graft after circumferential pharyngolaryngectomy; as primary surgery, rather than as salvage surgery following chemoradiotherapy; after careful preoperative morphologic and endoscopic assessment of the extent of the tumor; and in patients able to tolerate a thoracotomy for an esophagectomy with lymphadenectomy. Selection according to these guidelines should improve results.     

Reconstructive surgery in head and neck oncology: indication and technic]

Oncologic cervicofacial surgery and plastic surgery have had a common evolution over the last 50 years where progress erasing from one was beneficial to the other one. We review here the historical evolution of these specialties and present the state of the art of plastic surgery in the field of cervicofacial oncology.     

Salvage surgery by composite resection for epidermoid carcinoma of the tonsillar region.

Radiation therapy has usually been used as the primary treatment of squamous cell carcinoma of the posterior aspect of the oral cavity and the lateral aspect of the oropharyngeal walls. However, local failure occurs in a certain number of cases, depending on the initial tumor stage. One hundred thirty-four composite resections (transmaxillary buccopharyngectomies) have been performed as a salvage treatment at the Institut Gustave-Roussy, Villejuif, France, from January 1, 1976, through December 31, 1985, for local failure of epidermoid carcinomas treated initially by radiotherapy. Average time between primary irradiation and salvage surgery was 18 months. Most of the patients underwent some kind of supraomohyoid neck dissection. A myocutaneous flap was used in 18% of cases, which significantly reduced the rate of local complications. The nasogastric tube and the tracheostomy cannula were removed after a median delay of 23 days and 24 days, respectively. Early postoperative local complications occurred in 45% of cases; most of them were minor. A new locoregional recurrence occurred in approximately half of the patients and was usually fatal. Overall survival after salvage surgery was 34% at 3 years and 23% at 5 years. The only statistically significant prognostic factor was the adequacy of surgical margins.     

Preoperative sequential chemotherapy in locally advanced squamous cell carcinoma of the head and neck

BACKGROUND: Induction chemotherapy may contribute to decreased local and distant recurrences in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) resectable for cure. METHODS: Patients with previously untreated locally advanced stage III-IV (N0-2, M0) SCCHN received a dose-dense sequential regimen combining cisplatin/5-fluorouracil followed by bleomycin/methotrexate/hydroxyurea. Induction chemotherapy was followed by locoregional surgery and/or radiation therapy. RESULTS: Among 37 patients, 23 (62%) had T4 primary tumors. Grade 3 to 4 asymptomatic hematologic toxicity occurred in less than 15% of patients. Nonhematologic toxicities were limited to grade 1 to 2 in less than 20% of patients. In the overall cohort (intent-to-treat; n = 35), 24 (68.5%) of 35 patients had objective clinical responses, including nine complete responses (25.7%). Fifty-seven percent of patients were free of disease at 2.5 years. CONCLUSIONS: Sequential induction chemotherapy is feasible and active in patients with locally advanced head and neck cancers and may further include recent compounds such as taxanes.