Influence of radiotherapy on long-term relapse in clinically non-secreting pituitary adenomas. A retrospective study (1970-1988).

OBJECTIVE: We wished to evaluate the influence of postoperative radiotherapy on the incidence of tumour regrowth in non-secreting pituitary adenomas. METHODS: The cases of 57 patients with clinically non-secreting pituitary adenomas were retained for a retrospective study of long-term disease-free survival out of a series of 66 patients treated between 1970 and 1988. Thirty-three patients were treated by surgery only (Group A), and twenty-four by surgery followed by external radiotherapy (Group B). Disease-free survival curves were calculated according to the Kaplan-Meyer method and compared by the Logrank test. The impact of some supposed prognostic parameters--such as tumoural volume, macroscopic features of invasiveness and quality of surgical resection--on the disease-free survival was analyzed according to the Logrank adjusted test. RESULTS: The mean follow-up duration was 7.1 +/- 6.2 years, and eleven patients relapsed: nine in group A (27.0%) and two in group B (8.3%), with respective free intervals of 6.1 +/- 5.0 years and 9.6 +/- 2.4 years. Statistical analysis of the disease-free survival curves confirmed that this difference was significant (p < 0.01). Further analysis of putative risk factors (the importance of extrasellar extension and the estimated quality of surgical resection) was attempted, but it did not reach statistical significance. CONCLUSIONS: Radiotherapy is effective in preventing post-operative regrowth of non-secreting pituitary adenomas. Whether it should be systematically proposed or reserved to selected cases remains to be evaluated.

Radiotherapy in N0 head and neck cancer patients.

The efficacy of elective radiotherapy in N0 cancer of the oropharynx, hypopharynx and supraglottic larynx was assessed retrospectively in a large series of head and neck cancer patients treated at the Institut Curie between 1958 and 1976. Despite a significant incidence of false-negative cases accompanied by extra-capsular tumor spread, radiation tissue doses of 4500-5500 cGy were highly successful in preventing nodal disease in clinically negative necks. Isolated node failure occurred in only 2% of 611 cases of oropharyngeal and pharyngolaryngeal cancer from a total group of 1646 patients and 2% of 237 N0 cases of supraglottic vestibular cancer taken from a series of 340 patients. The impact of neck status on survival and disease-free survival is discussed. Present findings show that elective irradiation of the neck is easily integrated into the radiation management of primary pharyngeal and supraglottic laryngeal cancers and results in no additional morbidity to patients so treated.

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.

Chiasmal gliomas: results of irradiation management in 57 patients and review of literature.

Fifty-seven patients with optic gliomas, treated by megavoltage radiotherapy between May 1970 and March 1986, are retrospectively analyzed. The mean follow-up was 7.5 years (2.5-16.5). At presentation, 46% were under 10 years old, 40% had neurofibromatosis, and 51% had neurological and/or endocrinological signs. Twenty-one tumors (37%) were confined to the optic chiasm, and 36 tumors (63%) extended to the hypothalamus, the posterior optic tract, or the adjacent brain. Two among the 16 biopsy-proven tumors were high grade gliomas. Delivered tumor doses were 40 to 60 Gy in 5 to 7 weeks. Forty-nine patients were alive (five with tumor evolution) and eight had died (five from the tumor, one from cerebrovascular complication, two from intercurrent disease). Overall actuarial survival was 83.5% at 5 and 10 years. Control of the disease in 53 evaluables patients was: complete response in 8 (15%), partial response in 25 (46%), and no progression in 12 (22%). Progressive disease was observed in three patients and signs evocative of recurrence in five others. Stabilization of visual impairment or improvement of vision was recorded in 93% of patients who were evaluable. A critical review of the literature is presented and complications discussed. Radiotherapy seems thus effective in chiasmal gliomas and must be delivered in cases of rapidly developing symptoms visual, neurological, or endocrine.

Results of radiation therapy in carcinoma of the base of the tongue. The Curie Institute experience with about 166 cases.

Between 1960 and 1980, 166 patients with squamous cell carcinoma of the base of the tongue were treated with primary irradiation at the Curie Institute (Paris, France). Distribution according to the TNM system 1978 International Union Against Cancer (UICC) was the following: 22 T1 lesions, 47 T2 lesions, 64 T3 lesions, and 33 T4 lesions. Regional nodes were not palpable in 50 cases, 35 had N1 nodes, 12 had N2 nodes, and 69 had N3 nodes. All patients received external beam radiation. The 2-year, 3-year, and 5-year overall survival rates for all patients were, respectively, 45%, 37%, and 27%. Local control was significantly related to the initial status of the primary, to the tumor regression at the end of the radiation therapy, and to the histologic differentiation. The 2-year local control was 96% for T1 lesions, 57% for T2 lesions, 45% for T3 lesions, and 23% for T4 lesions. Local control was 70% if the tumor regression was complete at the end of the treatment and 27% if the tumor regression was partial. No significant differences were found in primary local control with respect to degree of infiltration, age, and dose of radiation therapy over a dose of 60 Gy in 6 weeks. The 3-year regional control was 86% for N0, 78% for N1, and 60% for N2 and N3. Among the tumor characteristics analyzed, the most useful ones for predicting local control and survival were clinical tumor staging parameters and tumor radiation-induced regression. A new therapeutic approach based on the evaluation of the tumor regression at 50/55 Gy is under discussion.

Further analysis of the time factor in squamous cell carcinoma of the tonsillar region.

Recently, Bataini et al. reported that overall time was the major treatment-related determinant of local control in 465 squamous carcinomas of the tonsillar region. They did not, however, quantify the relationship or relate it to the doubling time of tumorigenic cells, except qualitatively. This note reports an attempt at that quantification.

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.

[Cerebral necrosis found 13 years after irradiation of osteosarcoma of the cranial vault]. / Nécrose cérébrale découverte 13 ans après irradiation d'un ostéosarcome de la voûte du crâne.

Delayed cerebral radiation necrosis was discovered 13 years after irradiation of the skull for osteosarcoma. Conservative treatment with glucocorticoids is discussed.

Significance and therapeutic implications of tumor regression following radiotherapy in patients treated for squamous cell carcinoma of the oropharynx and pharyngolarynx.

The prognostic significance of tumor regression following radiotherapy was evaluated in 1,897 patients with oro- and pharyngolaryngeal cancer. Complete tumor regression occurred in 62% and 80% at the end of treatment and 2 months later, respectively. Complete regression was significantly higher for early tumors than for advanced stages and for exophytic lesions compared to deeply infiltrative cancers. Depending on tumor location, 75% to 90% of T1, T2 stages and 50% to 80% of more advanced tumors were locally controlled in patients who experienced complete tumor regression at 2 months. The local failure rate was at least 80% for those who did not have complete regression. The local failure rate for the incomplete responder was the same for early and advanced tumors. Complete tumor clearance following radiotherapy is a reliable indicator of permanent local control. Tumor regression after a dose of 5,000 to 5,500 cGy should be used as a guide to select patients who could be treated by either radical irradiation or surgery.

[Incidence of mandibular osteoradionecrosis in a series of 13 cases of carcinoma of the mouth floor]. / Incidence des ostéo-radio-nécroses mandibulaires sur une série de 13 cas de carcinomes du plancher buccal.

In a 13-case series of epithelioma of the floor of the mouth given cobalt-therapy irrespective of the selected therapeutic protocol, the authors recorded 5 cases of osteoradionecrosis. In this study, they review both risk and prevention factors linked with radionecrosis at the localization site of this particular type of tumor. They also stress the importance of adapting the treatments, when introducing so-called néo-adjuvant systemic chemotherapy, the high efficacy rate of which is likely to reduce the risks of radionecrosis. This can be achieved either by eliminating completely or limiting the surgical step, or by bringing modifications to the post-operative radiation regimen.

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.

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.

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.

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%.

Anal margin carcinoma: 21 cases treated at the Institut Curie by exclusive conservative radiotherapy.

Between 1962 and 1980, 21 patients with anal margin carcinoma were treated with exclusive radiotherapy. They were divided into 4 T1, 7 T2, 8 T3 and 2 T4 cases; only 3 cases presented with an N1 lymph node involvement (1 T2 and 2 T3). The tumor dose was 65 Gy in 22 fractions and 55 days; the inguinal dose was 50 Gy in 15 sessions and 50 days for prophylactic irradiation performed in 9/18 N0 patients, and 65 Gy with a limited 15 Gy boost for the 3 N1 cases. The results are: for T1, 4 patients alive and well out of 4; for T2, 3 out of 7; for T3, 2 out of 8; for T4, 2 out of 2. The overall survival was 11 out of 21 after 5 years. Severe complications occurred in 2 patients out of 21. Sphincter preservation was obtained in 9 patients out of 10 cured cases.

[Colloid cancers of the breast. Value of radiotherapy. A series of 138 cases treated at the Curie Institute]. / Cancers colloides du sein. Intérêt de la radiothérapie. Série de 138 cas traités à l'Institut Curie.

A series of 138 mucinous breast carcinomas was treated at the Institut Curie from 1970 to 1980: 107 were diagnosed as "pure" mucinous carcinoma and 31 as "mixed" mucinous carcinomas. Fifty per cent of the cases were stage T2 and 78% N0-N1a. Treatment methods were radical mastectomy in 113 cases (82%) with pre-operative irradiation for 37 patients and post-operative irradiation for 14 patients. A conservative treatment was used for 25 patients, consisting either of lumpectomy followed by radiotherapy (in 15 cases) or radiotherapy alone (in 10 cases). The five-year actuarial survival rate was 81% for the "pure" group and 87% for the "mixed" group; it was 70 and 75%, respectively, at ten years follow-up. In this series, survival was not influenced by the type of treatment. The efficacy of radiotherapy was evaluated from the local recurrence rate: only four local failures among the 25 conservative treatments were noted. Our conclusion is that radiotherapy, with or without lumpectomy, is efficient in mucinous breast carcinoma and could be useful in selected cases.

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.

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.