[Impact of nutrition management in patients with head and neck cancers treated with irradiation: is the nutritional intervention useful?]. / Intérêt de la prise en charge nutritionnelle des patients traités par irradiation des voies aérodigestives supérieures: la consultation diététique est-elle utile?

AIMS: The head and neck tumors are most often associated with a precarious nutritional status. Radiotherapy increases the risk of denutrition because of its secondary effects on the secretory and sensorial mucous membranes. The purpose of our retrospectively study was to evaluate the interest of a precocious and regular nutritional therapy on the ability to maintain the nutritional status of the patient during the radiotherapy. PATIENTS AND METHODS: The fifty-two patients included in the survey have been classified retrospectively in two different groups based on their observance to the nutritional therapy: group 1 "good observance", group 2 "bad observance". RESULTS: The 31 patients of group 1 have lost an average of 1.9 kg by the end of the irradiation, whereas the 21 patients of group 2 have lost an average of 6.1 kg (p<0.001). The almost stability in weight of patients in group 1 was linked to a lower frequency of breaks in the radiotherapy (6 vs 33% p=0.03) and in a decrease in grade of inflammatory mucous membranes (10% of grade 3 in group 1 vs 52% in group 2, p=0.006). The quantity of calories ingested in form of nutritional supplements was greater in group 1 and consequently enabled patients to stabilized their weight (1200 calories in group 1 versus 850 calories in group 2, p<0.005). CONCLUSIONS: The given nutritional advice and the prescription of adapted nutritional supplements consequently allowed limiting efficiently the weight lost during the irradiation and the grade of mucositis. The systematization of a precocious nutritional therapy for patients irradiated for head and neck tumors seems absolutely essential.

Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: tentative multivariate modelling system to predict the radiocurability of neck nodes.

In a series of 1251 cases of squamous cell carcinomas of oropharynx and pharyngolarynx with clinically positive neck and treated primarily by radiation therapy a determinate group of 798 cases remained eligible for a multivariate analysis of the prognostic factors related to the regional outcome. Node size (p less than 0.0001), node fixity (p = 0.016) and T stage (p = 0.02) were the significant pretreatment factors independently predictive of neck node control. when regarding the treatment modalities in this determinate group of patients who received tumor doses of at least 55 Gy, only the treatment duration was found to be predictive (p = 0.002). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various groups of patients. The predictive accuracy of the equation was assessed by the log-rank test significance levels. The model may help to select, in many clinical situations, the appropriate approach of the management of metastatic neck disease, either by definitive radiation therapy or by combined modalities.

Impact of neck node radioresponsiveness on the regional control probability in patients with oropharynx and pharyngolarynx cancers managed by definitive radiotherapy.

We reviewed a series of 1,666 patients with squamous cell carcinoma of the oropharynx and pharyngolarynx treated with definitive radiation therapy to determine whether or not radioresponsiveness of the metastatic neck nodes is a reliable indicator of their radiocurability. In a determined group of 708 patients with clinically positive neck nodes, only one third of the adenopathies (247/759) completely regressed at the completion of the treatment. At 6 months, only ten percent of the nodes remained palpable. Lymph node clearance rates and halving diameter times were tumor size-dependent. Node clearance rate was also influenced by the site of the primary lesion. The impact of various parameters, both intrinsic and extrinsic to the tumor behavior, is discussed. Neck control probability was significantly higher for complete responders. In this group, the ultimate node control was as good for adenopathies larger than 6 cm as for the smaller ones. Tumor control probability directly related to clearance rate following radiotherapy. Finally, therapeutic implications are derived for nodal dose adjustments and optimal applicability of radiosurgical combinations.

Is reseeding from the primary a plausible cause of node failure?

In a previous analysis of node failures in 1251 consecutive patients with node positive oropharyngeal and pharyngolaryngeal squamous cell carcinomas treated by external radiotherapy alone at the Institut Curie, the main reasons for patient exclusion were node recurrence associated with primary failure (N+T failures) and doses less than 55 Gy. These exclusions reduced the number of node failures from 399/1251 (32%) to 77/798 (10%). Multivariate analysis of node recurrence indicated that node size and fixity, treatment duration, and T stage of primary were significant (higher probability of isolated node failure for the T1-T2 primaries). In the present analysis, it is noted that 60% of the N+T failures were observed less than 1 month after the completion of the irradiation and, therefore, were not likely the result of reseeding from the primary tumor. When all 1251 patients were included in the analysis, the probability of nodal failure increased for larger nodes, T4 primaries, lower nodal doses, presence of contralateral node metastases, and nodal fixation to the surrounding structures. No influence of the primary site was found. Treatment duration was closely associated with total dose to the nodes. The best description of the data was obtained with a model including total dose and not treatment time. However, as in the previous analysis, the exclusion of low-dose (less than 55 Gy) treatments resulted in the loss of a significant dose-control relationship. We conclude that the majority of node failures is unlikely to result from reseeding from the primary tumor, and therefore should not be excluded from local-control analyses. From a more radiobiological point of view, the exclusion of palliative treatments is questionable when studying the effect of dose on local control.

Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study.

OBJECTIVE: Prospective evaluation of tumor regression during external irradiation for head and neck squamous cell carcinomas and its association with long-term local control. METHODS AND MATERIALS: Two hundred twenty-eight patients with histologically confirmed squamous cell carcinoma [oral cavity: 59 (26%), oropharynx: 65 (29%), hypopharynx: 37 (16%), larynx: 67 (29%)] were included between January 1986 and December 1990. Curative intent external irradiation delivered 65-70 Gy over a period of 7 weeks (five 2 Gy fractions per week). Tumor regression was evaluated clinically and endoscopically every week. RESULTS: Tumor regression, assessed at 2 weeks, was as follows: no response: 62 (30%), 25% response: 121 (59%); 50% response: 23 (11%). At 5 weeks, 9 (4%) patients showed 0-25% regression, 75 (33%) showed 50% regression, 115 (50%) showed 75% regression, and 29 (13%) showed complete regression. Median follow-up was 79 months (range: 6-96 months). The local control probability was 68% (62-74%) at 2 years, 65% (59-70%) at 5 years. Univariate analysis showed that, at 2 weeks, local control was significantly different between the nonresponders and the patients with 25% or greater response (p < 0.025) and that, at the fifth week, local control was very different between the major responders (75 and 100%) and the minor responders (0-50%) (p < 0.0001). Multivariate analysis (Cox Proportional Hazards Model) showed that the probability of local relapse was significantly and independently increased for minor regression at 5 weeks [Relative risk (RR) of failure was 2.3 (1.4-3.7)], for nonlaryngeal tumors [RR: 2.4 (1.3-4.5)], and for Stage T3-T4 [RR:2.4 (1.4-4)]. Three prognostic groups can, therefore, be proposed: 1) low risk of recurrence when regression > or = 75% and laryngeal tumor or T1-T2 tumors in other sites: 106 (46.5%) patients, 2-year local control probability: 84% (77-92%); 2) high risk of recurrence: regression < or = 50% and T3-T4 nonlaryngeal tumors: 44 (19%) patients, 2-year local control probability: 27% (13-41%); 3) intermediate risk of recurrence: 78 (34.5%) patients, 2-year local control probability: 69% (58-80%). CONCLUSION: The present study suggests that tumor regression during external radiotherapy is an independent predictive factor of local control in head and neck carcinomas.

Induction chemotherapy in advanced head and neck tumors: results of two randomized trials.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two randomized induction chemotherapy trials. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine and mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil by continuous infusion and vindesine. Local treatment was the same in the two trials: primary radiotherapy in all patients. The response was then evaluated; in the case of a poor response at 55 Grays surgery was performed; otherwise, radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial than in the first: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. The significance of the complete response at the end of the irradiation varies with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval were very similar in the two groups. The incidence of distant metastasis was significantly reduced (p less than 0.03) with chemotherapy. This trial suggests the need to test new chemotherapy protocols according to new schemes of treatment, with chemotherapy given concurrently with or following the completion of standard treatment by means of multicenter randomized trials.

Conventional megavoltage radiotherapy in the management of malignant epithelial tumours of the parotid gland.

This is an evaluation of definitive conventional megavoltage radiotherapy in a consecutive series of 35 patients presenting malignant epithelial tumours of the parotid gland. In this series, the 5-year actuarial locoregional control rate was 41% with a 5-year crude survival rate of 36%. The results are analyzed according to tumour presentation and tumour doses. Six of 15 patients with tumours larger than 6 cm have had a lasting locoregional control. During the same period 43 other patients received radiotherapy as a post-operative modality. Results obtained in this group confirm the previously published data. While recent studies tend to demonstrate the specific efficacy of high LET radiation in the management of locally advanced salivary gland tumours, radical conventional radiotherapy can still be employed with a curative intent when neutron facilities are not available.

A multivariate primary tumour control analysis in 465 patients treated by radical radiotherapy for cancer of the tonsillar region: clinical and treatment parameters as prognostic factors.

Out of a consecutive series of 698 cases of squamous cell carcinomas of the tonsillar region treated by radical megavoltage radiotherapy, a determinate group of 465 cases remained eligible for a multivariate analysis of the pretreatment features of the disease and treatment-related parameters predictive of lasting control of the disease at the primary site. T-stage and initial site within the tonsillar region, were the significant pretreatment factors. Tumours arising from the glossopalatine sulcus which are characterized by involvement of the tongue, do significantly worse than those arising from other sites within the tonsillar region: i.e. the tonsil itself, posterior pillar and to a lesser extent the anterior pillar. As regards treatment-related parameters in the 465 cases which received tumour doses of at least 55 Gy, only the length of overall treatment time was found to be predictive. Combining both pretreatment and treatment variables, T-stage (p less than 0.0001), overall treatment time (p less than 0.0001) were by decreasing order of significance the predicting factors, followed by initial site (p = 0.006). When present, tumour extension to the anatomical structures anterior to the tonsillar region was also found to be significant (p = 0.05). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various categories of patients. Four groups are individualized with 3 years local control rates ranging from 90 to 21%. The predictive accuracy of the model was assessed by log-rank test significance levels. The model may help to select patients for whom conventional radical radiotherapy is inadequate, and combined modality or altered fractionation regimes should be tried particularly for advanced tumours of the glossopalatine sulcus, and any case with significant invasion of the oral cavity.

Results of irradiation in squamous cell carcinoma of the soft palate and uvula.

Out of a series of 235 patients presenting with tumours of the soft palate at the Institut Curie, between 1958 and 1980, 146 cases were analysed to evaluate the results of radical radiation therapy. Seventy patients (48%) had advanced T3-T4 disease and 40 patients (27%) had clinically involved metastatic nodes. All patients had a minimum follow-up of 5 years. In 103 cases, megavoltage X-ray therapy was employed. For 43 patients, presenting with small or moderately advanced tumours, a combination of megavoltage and intra-oral orthovoltage X-rays was used. The local control rate at 3 years was 92% for T1, 70% for T2, 58% for T3 and 49% for T4 lesions. Nodal failure was seen in 19 patients. In 9 of these, it was not associated with failure at the primary site, 7 out of 9 occurring marginally or outside the treatment portals. Complications were observed in 16 patients, 7 requiring surgery. The crude 3 and 5 year survival rate was 52 and 40%, respectively, and the disease-free survival 59 and 53%.

Natural history of neck disease in patients with squamous cell carcinoma of oropharynx and pharyngolarynx.

Out of a series of 2040 patients referred to the Institut Curie with squamous cell carcinoma of oropharynx and pharyngolarynx, 1666 cases were evaluated on admission regarding the characteristic metastases patterns to their cervical lymph nodes. Incidence and topographic distribution of lymph nodes are correlated with the anatomic sites of primary lesions. Biological virulence of these tumors is emphasized since the overall incidence of positive neck nodes attains 63% (1048/1666) and advanced disease, stage IV in the UICC classification, 61%. Cervical status is also related to several characteristics of the primary: clinical staging and variety, and histopathological differentiation. Ipsilateral cervical involvement is characterized by the high incidence of metastases in the jugular chain for the whole series, in the submaxillary group for oropharyngeal carcinomas and in the spinal accessory chain for cancer of the pharyngolarynx (pyriform sinus and lateral epilarynx). Preliminary therapeutic implications are derived from this nodal distribution. Comparisons are established between the 1978 UICC and 1976 AJC classifications, showing a good correlation despite multiple differences in staging criteria. It is shown that assessment combining both the multiplicity and the volume of cervical metastases allows to evaluate more accurately the aggressiveness of the primary.

Desmoid tumors in adults: the role of radiotherapy in their management.

Twenty-six adult patients with the pathologic diagnosis of desmoid tumor were treated between 1964 and 1983 at the Institut Curie in Paris with megavoltage irradiation. Twenty of these patients (76 percent) had extraabdominal tumors. Definitive surgical resection was performed on nine patients (one received preoperative radiotherapy). At last follow-up 1 1/2 to 10 years after treatment, all of the patients had no evidence of disease. Seven of the nine had follow-up examinations from 5 to 10 years after treatment. Seven patients had postoperative radiotherapy with doses from 4,700 to 6,500 rads (47 to 65 Gy) for either microscopic (three patients) or gross (four patients) residual disease. All but one patient had no evidence of disease from 2 to 8 years after treatment. Nine patients had radiotherapy for recurrent inoperable tumors and six had no evidence of disease from 3 to 20 years after treatment. Recurrences developed in three patients; outside the treatment portal in one, and the other two had received less than 5,000 rads (50 Gy). Clinical regression of tumors after treatment was slow, with complete regression taking up to 2 years. Postoperative radiotherapy with doses of at least 5,000 to 6,000 rads (50 to 60 Gy) was effective in achieving local control of inoperable or incompletely resected tumors, thus the need for repeated resections was avoided. Computerized tomography has greatly improved the assessment of tumor extension and should be used routinely before either operation or radiotherapy to obtain adequate margins and minimize the chance of missing disease.

Impact of cervical disease and its definitive radiotherapeutic management on survival: experience in 2013 patients with squamous cell carcinomas of the oropharynx and pharyngolarynx.

Two thousand thirteen patients with squamous cell carcinoma of oropharynx and pharyngolarynx were reviewed with regard to neck disease presentation and disease-free survival after radical radiotherapy. All patients were staged according to both the AJCC 1976 and the UICC 1978 classifications. Causes of failure, disease-free survival, and complication rates were assessed. Sixty percent had a clinically positive neck. The 3-year disease-free survival rates were 58%, 44%, 38%, and 25% for AJCC N0, N1, N2, and N3 cases, respectively. Corresponding UICC figures were 58%, 46%, 26%, and 29%. Analyzed parameters were nodal stage, size, site and fixity, and location of primary. Complications attributed to neck disease did not exceed 3%. A critical appraisal of the nodal staging systems is derived from these sets of data.

Treatment of metastatic neck nodes secondary to an occult epidermoid carcinoma of the head and neck.

One hundred thirty-eight patients, who were followed for a minimum of 5 years, had either surgery and postoperative radiotherapy (48 patients) or radiotherapy only (90 patients) for metastatic epidermoid carcinoma in cervical nodes from an unknown head and neck primary. All received radiotherapy to the presumed occult sites. Forty-five percent presented with a single unilateral adenopathy. Those who were initially operable had a neck recurrence rate of 17% and a survival rate of 53%. Forty-three percent of initially inoperable patients recurred and only 25% survived. Patients with adenopathy which completely regressed or became resectable after irradiation had an 80% locoregional control. Only 4% developed an overt cancer at an occult site within 5 years.

Radiation treatment of lateral epilaryngeal cancer. Prognostic factors and results.

Treatment results of epilaryngeal cancer are rarely individualized in the world literature. For this purpose, we have reviewed the records of 167 patients with squamous cell carcinoma of the lateral epilarynx who received radical radiotherapy at the Institut Curie on a megavoltage unit, between 1959-1975. Two-thirds of the lesions were located at the junction of the ary- and pharyngo-epiglottic folds and lateral border of the epiglottis. Forty-four percent of patients had advanced primary lesions (T3, T4) and over 50% had palpable neck nodes at the time of presentation. The absolute survival for the entire patient population at 3 and 5 years was 44% and 32%. Local control for T1 and T2 tumors at 3 years was about 80%. Survival at 5 years for the N0 Stage patient was 40%, whereas it was about 20% for those with clinically palpable nodes. Patients with exophytic tumors and lesions which regressed completely within 8 weeks following irradiation had a significantly better 3-year survival and local control than those with nonexophytic tumors and with tumors which had incompletely regressed after irradiation. Radiotherapy remains the treatment of choice for the small tumors (T1, T2) but the association of radical surgery with pre- or postoperative radiotherapy should be considered for advanced disease.

[Laryngeal cancer and conservative treatment. Place of combined radiotherapy chemotherapy and modified fractionation radiotherapy]. / Cancer du larynx et traitement conservateur. Place des associations radiochimiothérapiques et des fractionnements modifiés en radiothérapie.

For patients with early stages of laryngeal carcinomas, the local therapeutic modalities of surgery and/or radiation are the accepted standards of treatment. Recently, combined chemotherapy-radiotherapy and new fractionation schedules have received much attention as an alternative to surgery in patients with resectable locally advanced cancer of the larynx to preserve the larynx function. This article is intended to update the reader on the most recent articles written about the treatment of laryngeal carcinomas. The different points are: the results of conventional radiotherapy, the importance of parameters of radiotherapy (dose, fractionation, overall treatment time), new fractionation schedules, combined chemo-radiotherapy, randomized trial results.

[Preliminary results for a 434 MHz microwave hyperthermia applicator (author's transl)]. / Résultats préliminaires d'un applicateur d'ondes électromagnétiques à 434 MHz pour hyperthermie.

Laboratory tests on inert gel and gel of different compositions were conducted to determine the distribution of isothermal temperature zones. The repartition in depth and along a perpendicular plane to the applicator axis was studied as a function of different parameters: the skin cooling water temperature of the applicator, the incident microwave power, the application time, the gel composition and the antenna position. Experimental results were compared to theoretical values corresponding to a plane microwave penetrating into a tissue-equivalent medium. To take into account in vivo temperature regulation phenomena, the same measurements were made in vivo in pigs and humans and compared to in vitro results.

[Carcinomas of the nasopharynx in adults]. / Carcinomes du rhinopharynx de l'adulte.

From 1959 through 1980, 139 MO adult patients (greater than 15 Y.) presenting with nasopharyngeal cancer were treated by definitive radiotherapy: 103 (74%) undifferentiated carcinomas and 36 (26%) squamous cell carcinomas. Chemotherapy was prescribed only in case of failure of treatment. Case distribution is the following according to UICC classification: stages I and II: 12%, stage III: 16%, stage IV: 72%. Survival rate is respectively 70%, 45%, 20%. The overall 3 and 5 year survival rate is 46% and 30%. Almost 80% of the failures occur by the end of the second year. Local control is 95% for T1-T2, 73% for T3 and around 50% for T4 cases. Isolated node failure occurs in 2% and distant metastases in 30%.

[Present clinical status of hyperthermia associated with radiotherapy (author's transl)]. / Etat actuel des applications cliniques de l'hyperthermie associée à la radiothérapie.

Improved techniques for inducing heat: ultrasound, microwaves, diathermy with different application modalities, capable of producing localized superficial or deep, regional or total body hyperthermia have been responsible for the multiplication of clinical trials. These studies have confirmed the tumoricidal effect of hyperthermia alone, or more especially when combined with radiotherapy, and the good tolerance of normal tissues to localized temperatures of 42 to 43.5 degrees C even in previously irradiated cases. Localized heating does not seem to increase the incidence of metastasis. Enhancement ratios and therapeutic gain with respect to normal tissues are not yet well documented. Many problems, including the heterogenicity of tissues to be heated, difficulties with temperature monitoring, and selection of appropriate sequential scheduling of radiation and hyperthermia remain unsolved and further investigations are required.

[Treatment of epitheliomas of the parotid. Apropos of 93 cases treated at the Curie Institute]. / Traitement des épithéliomas de la parotide. A propos de 93 cas traités à l'Institut Curie.

From 1955 through 1982, a series of 93 cases of parotid gland carcinoma were treated at the Institut Curie: 55 primarily and 28 for recurrent tumors. Treatment modalities included surgery alone (n : 14), surgery followed by radiotherapy (n : 43), and radiotherapy alone (n : 36). The most advanced cases were mostly in the latter group. With a mean follow-up of 13 years, the actuarial loco-regional control is 67% (62/93) and the median survival 10 years. Ultimate loco-regional control was achieved in 86% of cases managed by surgery alone, 88% of cases managed by surgery and radiotherapy and 33% of cases managed by radiotherapy. In the latter group, control rate was 42% (8/19) in those primarily treated by radiotherapy. Prognosis was related to histology. Twenty patients (22%) presented distant metastasis. The potential advantages of neutron irradiation for parotid neoplasms is discussed.

[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients]. / Place de la chimiothérapie néoadjuvante dans le traitement des tumeurs avancées de la tête et du cou. Résultats de deux essais thérapeutiques randomisés effectués à l'Institut Curie sur 208 patients.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.