B. Luboinski

Lymph node prognostic factors in head and neck squamous cell carcinomas

BACKGROUND This retrospective study included 914 patients who underwent a lymph node dissection at our institute between 1980 and 1985. The primary tumor sites were oral cavity, 287; hypopharynx, 249; larynx, 247; and oropharynx, 131. PATIENTS AND METHODS On the basis of anatomic considerations, the sentinel nodes for well-lateralized oral cavity tumors were defined as homolateral levels I, II, and III; for oropharyngeal, hypopharyngeal, and laryngeal tumors, the sentinel nodes were defined as levels II and III. We took into account the ipsilateral side of the neck for well-lateralized tumors, and both sides for medium or large tumors. For clinically positive nodes of more than 3 cm, a radical neck dissection was performed. Other patients underwent a selective neck dissection on sentinel nodes, with immediate pathologic evaluation. Modified radical neck dissections with contralateral selective dissection were performed when frozen sections were positive. Patients with positive nodes were given postoperative radiotherapy. RESULTS The prognostic factors studied, using the Cox survival model adjusted on the primary tumor site, surprisingly showed a nonsignificant value for extracapsular spread (P = 0.09), and a significant value for the number of positive nodes (P < 0.001) and for the positive node in or out of the sentinel node sites (P < 0.001). Although the node location factor can be used instead of positive node in or out of the sentinel node site, it has a less significant prognostic value. CONCLUSIONS The most significant prognostic factors are the site of the positive node in or out of the sentinel node and the number of positive nodes; and a more accurate approach can be obtained by combining both factors. Node location in the upper or lower neck remains a substitute prognostic factor for the site of the positive node in or out of the sentinel node.

Antitumor electrochemotherapy: New advances in the clinical protocol

Electrochemotherapy (ECT) is a new antitumor approach that combines systemic bleomycin (BLM) with electric pulses (EP) delivered locally at the tumor site. These EP permeabilize the cells in the tissue, allow BLM delivery inside the cells, and increase BLM cytotoxicity. As an extension of our initial Phase I trial on patients with head and neck squamous cell carcinoma (HNSCC) permeation nodules, we tested variations of ECT protocol to determine how to improve it.

Multiple synchronous and metachronous cancers of the upper aerodigestive tract: A nine‐year study

Three hundred fifty (42.1%) of these multiple cancers were considered synchronous, while 480 (57.9%) were classified as metachronous.

Changes in the oxygenation of head and neck tumors during carbogen breathing

The oxygenation of head and neck tumors and changes during carbogen breathing were assessed in 20 patients. The median oxygen tension (pO2) for each patient was lower in tumors before breathing carbogen than in normal tissues. The median pooled pO2 of all the tumors was 20 mmHg; for normal tissue it was 60 mmHg. Low values (below 10 mmHg) were found in 4 patients for the normal tissue and in 18 patients for tumors. During carbogen breathing, the median (61 mmHg) pO2 readings for all tumors was higher than that recorded before carbogen breathing. The frequency of low (< 10 mmHg) pO2 values decreased with carbogen breathing in 11 patients; only 4 patients still exhibited very low values (< 2 mmHg). Maximal effect was obtained within 1-6 min of gas exposure. The pO2 stayed high under carbogen breathing in 15 out of 16 patients. Return to pre-carbogen levels of oxygenation occurred in 1 min after the end of gas exposure. These data suggest that carbogen breathing increases tumor oxygenation as assessed by polarography. The breathing time appears to be important for therapeutical use and should to be taken into consideration.

Analysis of p53 Serum Antibodies in Patients With Head and Neck Squamous Cell Carcinoma

BACKGROUND Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Reconstruction with Free Jejunal Autograft after Circumferential Pharyngolaryngectomy: Eighty-Three Cases

The free jejunal autograft (FJA) has become a common procedure for pharyngeal reconstruction after circumferential pharyngolaryngectomy. In order to evaluate the postoperative outcome and the functional and carcinologic results, we retrospectively reviewed 83 cases of reconstruction with FJA. Fifty-one patients had received no prior radiotherapy, and 25 had received prior radiotherapy for their hypopharyngeal tumor or for another previous primary. Seven patients underwent a secondary reconstruction. In the postoperative course, there were 2 postoperative deaths, 4 graft failures (5%), and 11 salivary fistulas. The median time to removal of the nasogastric tube was 16 days, and to discharge, 23 days. Forty-eight patients received postoperative radiotherapy, with good tolerance. At 1 year postoperatively, 98% of the patients were able to eat a solid or soft diet. The postoperative radiotherapy did not impair the quality of the functional results in a long-term assessment. The vocal results were disappointing. The 3-year survival rate was 40%. The main carcinologic failures (45 patients) were locoregional recurrences (20 patients) and metastasis, which was the cause of death in 34% of the cases. It seems clear that FJA allows one-stage reconstruction and good swallowing rehabilitation, tolerates postoperative radiotherapy, and increases the quality of life in these patients with a poor prognosis.

Relationship between laryngoceles and laryngeal carcinomas.

Because X‐ray evaluation of the larynx is an unreliable method of detecting laryngoceles, a study based on the systematic measurement of the ventricular depth in surgical specimens was carried out to determine the frequency of laryngoceles and their relationship to laryngeal carcinomas. The frequency of laryngoceles was found to be about 2% in the normal larynx. The frequency in laryngeal cancer specimens was about 18%. This difference demonstrated the role of cancer in the genesis of laryngoceles. A close relationship between the ventricular diverticuli and the tumors was observed on microscopic examination in half of the laryngeal carcinomas associated with laryngoceles. These carcinomas can be considered to have developed on the laryngoceles. Depending upon the degree of tumor spread and the number of laryngoceles involved, different types of carcinoma developing in laryngoceles can be recognized. This particular form of tumor can be misinterpreted as an ulcerated vestibular tumor, in which case inappropriate treatment may be tried.

Surgical salvage treatment of T1/T2 glottic carcinoma after failure of radiotherapy

PURPOSE To evaluate the use of conservative surgical salvage techniques (eg, vertical partial laryngectomy and subtotal laryngectomy with cricohyoidopexy) versus total laryngectomy for radiotherapeutic failure of early glottic cancer by retrospective review of medical records. PATIENTS AND METHODS Of 950 previously untreated endolaryngeal carcinomas managed at the Gustave-Roussy Institute in France between 1975 and 1984, 259 of 344 early glottic cancers (T1, N0 and T2, N0) received radiation therapy. Local failure rates were 14% in T1a cancers, 16% in T1b cancers, and 36% in T2 cancers with normal vocal-cord mobility. RESULTS Nine of 54 patients with treatment failure were ineligible for salvage surgery. Among the remaining 45 patients, 35 underwent a total laryngectomy; these patients had a 77% 5-year survival rate. Ten patients treated with partial surgery (6 vertical partial laryngectomies and 4 subtotal laryngectomies with cricohyoidopexy) had a 100% survival rate at 5 years. Seven of the 10 patients treated with partial surgery had healing problems that delayed canula and nasogastric tube removal for 30 to 60 days. CONCLUSIONS Salvage surgery is effective for radiotherapeutic failures of early glottic cancers. In some cases, partial surgery can be performed with good tumor control and satisfactory laryngeal functions. Subtotal laryngectomy is an alternative to total laryngectomy if vertical partial surgery is not suitable.

Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: A review of the institute gustave roussy experience

PURPOSE The aim of the study was to present the updated Institut Gustave Roussy experience of the predictive value of three biological parameters in patients with squamous cell carcinoma of the Head and Neck (HNSCC) treated with radiation therapy. METHODS AND MATERIALS Three parameters have been investigated independently: tumor cell kinetics (TS, Tpot and LI), oxygen tension measurements (PO2) and intrinsic radiosensitivity (SF2Gy). RESULTS No relationship has been found between local-regional control and Tpot or LI in a series of 74 patients. Our data also support that the surviving fraction at 2 Gy, (SF2) was unlikely to predict the clinical outcome in a series of 92 patients. Differences in PO2 measurements have been observed between tumors, and tumor oxygenation was lower than that of normal tissue for the majority of patients. However PO2 measurements did not predict clinical outcome, but further investigations are needed to draw definitive conclusions, given the limited number of patients entered in our study (35 patients). In addition, we were able to measure the three parameters in 10 patients showing no correlation between PO2, SF2 and Tpot. CONCLUSIONS The method used to evaluate Tpot and SF2 did not provide clinically relevant predictive parameters for this type of cancer. Further investigations are needed to assess the predictive value of PO2 measurements and of new biological parameters in a multiparametric approach, taking into account other possible clinical and biological confounding factors.

Modes of invasion of cancer of the larynx. A statistical, histological, and radioclinical analysis of 120 cases.

A statistical comparison between histologic and radioclinical data was performed on a series of 120 cases of total laryngectomies in order to study the modes of invasion of laryngeal cancer and to quantify the differences of results as evaluated by pathological and by clinical examinations. The first part of this study deals with the spread of cancer depending on its site of origin; the second part examines spread regardless of the primary location of the laryngeal tumor. The comparative results show that it was difficult to determine the deep invasion of structures such as the preepiglottic space and the cartilages from the radio‐clinical examination, especially in cases of cancer developed on a laryngocele. This study emphazises the importance of the histological examination of laryngeal specimens as described here in order to codify the modes of invasion and, as a result, to help the otorhinolarynglologist in the choice of the best treatment.