Treatment of carcinoma of the penis by iridium 192 wire implant.

Since 1971, a group of 22 adult patients with squamous cell carcinoma of the penis have been treated by iridium 192 wires implant. There were 6 T1 tumors, 14 T2 tumors and 2 T3; only one patient (T3) presented with local failure after implant. Local necrosis occurred in 2 patients without local tumoral recurrence, but was sufficient enough to warrant amputation. Thus 19/22 (86%) patients were locally cured with penile conservation. In these patients the most frequent post-therapeutic complication is chronic urethral stenosis (9/19 patients, 47%) requiring repeated instrumental dilations. Four patients presented with initial inguinal metastatic nodes; only one was cured by radiosurgical treatment. Among patients without metastatic nodes at the time of diagnosis, none had delayed metastatic nodes. Three patients died of nodal evolution, 5 patients died of intercurrent disease without evidence of disease and 14 are now alive and NED. It appears that iridium 192 wires implant is the most effective conservative treatment of invasive squamous cell carcinoma of the penis; however, these results confirm that no particular treatment is required for inguinal nodal areas for patients who initially present with no disease.

Fractionated radiotherapy of small inoperable lesions of the brain using a non-invasive stereotactic frame.

Arteriovenous malformations (AVMs) and benign or low grade, small malignant tumors can be treated by stereotactic radiotherapy in a single fraction. This report describes a technique for stereotactic treatment of small lesions using conventional, fractionated, photon beam irradiation. The Laitinen's stereoadapter, non-invasive head frame was used. This device was tested for accuracy by serial mountings and found to be accurate within 1 mm. The accuracy of the dose delivered was within 2%. Adaptation of this device to the linear accelerator required the design of secondary circular collimators which decreased the penumbra from 3-4 mm to 2-3 mm. The dose fall off outside the target volume is steep enough when using two non-coplanar arcs (90 to 10% within 1 cm). Thermoluminescent dosimetry (TLD) in a humanoid phantom showed good correlation with the calculated dose. This system permits delivery of fractionated radiation therapy to small volumes, easily and accurately, under stereotactic conditions.

Radiosensitivity of jejunal mucosa after whole abdomen irradiation and CDDP pretreatment.

Pretreatment of mice with a single radiation dose of 11.5 Gy or with fractionated irradiation (2 x 6.5 or 7.5 Gy, with an interval time of 12 hr) led to a relative decrease in the radiosensitivity of jejunal crypt cells when a second single dose of radiation was delivered 2 months later. When the same irradiation pretreatment was combined with CDDP (6 mg/kg, i.p.) injected 12 hr after single radiation or between two equal doses of radiation, similar crypt cells resistance was obtained. The combination of CDDP with irradiation did not modify the radiosensitivity of jejunal crypts in comparison with irradiation alone, even when the total radiation dose was delivered in 2 split doses. This induced radioresistance was demonstrated to be a reflection of late injury on intestinal tissue, presumably due to hypoxia resulting from vascular damage. It seems that the administration of CDDP did not change the possible hypoxia suspected in crypt cells of mice pretreated with single radiation dose. However, mouse lethality increased significantly when CDDP was combined with irradiation.

Iridium-192 interstitial therapy for squamous cell carcinoma of the penis.

From February 1971 through February 1989, 51 patients with biopsy proven epidermoid carcinoma of the penis were treated with interstitial therapy (Iridium 192). The breakdown according to the stage was T1s = 3, T1 = 14, T2 = 28, T3 = 6, N0 = 43, N1 = 7, N2 = 1. The dose ranged from 50 to 65 Gy (mean: 60 Gy). Patients without clinical nodal involvement received no treatment to the nodes. Stage N1 and N2 patients had surgery and external irradiation to the inguinal and iliac nodes. Six of fifty-one (12%) patients developed nodal and/or metastatic disease following therapy. Five of six presented initially with clinical nodal involvement. Seven of fifty-one (14%) developed local recurrence only, requiring surgery (four partial penectomies, three total penectomies). Six of these seven patients are alive and free of disease with a mean follow-up of 5.5 years. Nine of thirty eight (23%) patients with local control developed local necrosis. The treatment consisted of local excision (one patient), partial amputation (six patients) or total amputation (two patients). Partial urethral stenosis was noted in 17/38 (45%) of the patients. Foreskin sclerosis occurred in 3/38 (8%) uncircumcised patients. Interstitial irradiation for penile carcinoma provided effective local control rates, especially for T1-T2 patients (91%). Local failures could be treated successfully with surgery. Complications could be treated conservatively in most patients. Local control with penile conservation was achieved in 67% of all patients and 75% of patients with T1-T2 disease.

Results of the treatment of 165 lid carcinomas by iridium wire implant.

A group of 160 adult patients with epithelial tumors of the lid and/or canthi treated by iridium 192 wire implant are presented. There were 165 epithelial tumors, most of them were basocellular type (85%). In all cases, a nonradioactive procedure was used with disposable angiocatheters before introducing active wires. Respectively, 111/114 (97.4%) of "new" lesions and 48/51 (94%) of previously treated tumors were definitively cured by iridium wire implant. Among the 6 local recurrences, 4 were salvaged by a second iridium implant, and the two others by extensive surgery. Local side effects were present in 30 patients (18%): impairment of the eyelid aperture 9, stenosis of lacrymal ducts 7, eversion of the lid 7, lack of substance 7. These postherapeutic complications were significantly more frequent in treating recurrent lesions (15/48, 31.2%) than in previously untreated tumors (15/112, 13.4%). No visual complication was observed even in the early patients of this series.

Concomitant evaluation of efficiency, acute and delayed toxicities of combined treatment of radiation and CDDP on an in vivo model.

The efficiency, acute and delayed toxicities of different radio-chemotherapeutic combinations were assessed on an in vivo model (Krebs II ascitic carcinoma grafted to female Swiss mice). Mice were given whole abdomen irradiation (WAI) 2.5 to 10 Gy as a single dose (WAI). CDDP was given intraperitoneally at 0.5 to 4 mg/kg dose level, 12 hr before or after WAI. There was a relationship between dose of CDDP and increase of life span (ILS) of mice. However, WAI did not increase the life span. When a single dose of 2 mg/kg CDDP was given prior to a 2.5 Gy WAI, the ILS reached 47%. By contrast, it was only 37% when treatment sequence was reversed. When the WAI dose level was increased to 5 Gy, the ILS was not increased. The jejunal crypt cell number, determined 3 days after the last treatment, was not modified, regardless of the treatment sequence. There was no delayed renal toxicity. The study on the Krebs II ascites model confirms the tumor cell therapeutic potentiation without exacerbation of normal tissue damage.

Results of radiotherapy alone in 581 patients with Stage II carcinoma of the uterine cervix.

From January 1976 to December 1978, 581 previously untreated patients with Stage II carcinoma of the uterine cervix were treated by radiotherapy alone in nine departments of radiotherapy in France. This retrospective analysis was undertaken in an attempt to evaluate the therapeutic results and prognostically significant factors. The initial clinical staging and the therapeutic guidelines were as outlined at the U.T. M. D. Anderson Hospital in Houston; all our patients were treated by standardized protocols combining external beam irradiation and intracavitary irradiation with cesium sources. The overall locoregional control rate was 83.2%, with total disease control of 74.5%. Uncorrected actuarial survival rates are 76% at 3 years and 68% at 5 years. The incidence of severe posttherapeutic complications is 7.2%. Clinical substaging, patient's age at the time of the diagnosis, lymphangiogram findings, and tolerance to external irradiation were all found to have prognostic significance. According to those findings, the possibilities of improving the results are discussed.

A quantified approach to the analysis and prevention of urinary complications in radiotherapeutic treatment of cancer of the cervix.

This paper is the report of a dosimetric study of 79 urinary complications after radical radiation treatment (1975-1979) of 624 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit-Delclos applicator). Dosimetric-computerized studies were expressed as the maximum bladder dose on the trigone, as proposed by the I.C.R.U. Bladder doses were actually studied as a function of intracavitary irradiation and intracavitary + external irradiation. The results show a significant difference in patients with and without complications based on the dose reaching the bladder. The relative contribution of external therapy and intracavitary irradiation and their value can serve as one of the primary indicators for predicting complications. These values should be determined before placement of intracavitary sources. We found that the dose to the critical organs cannot be defined as a single number. These results argue in favor of adapting individual patient therapy based on rectal and bladder dosimetry and may be adjustable to all treatment modalities.

The incidence of severe chronic ileitis after abdominal and/or pelvic external irradiation with high energy photon beams.

The authors report a 7.9% incidence of late severe ileal complications after abdominal and/or pelvic external radiation therapy in 188 consecutive patients. All treatments were performed using 25 MV photon beams, with AP-PA field technique, a daily dose of 1.8-2 Gy, 5 times a week. One hundred and two (54.3%) patients were given whole pelvic irradiation up to 45-55 Gy without a boost, 64 patients (34%) received boost doses on limited volumes up to 60-65 Gy. The analysis of factors which could be useful in predicting a high risk of severe ileal sequellae, has shown that the main factor was the past history of previous laparotomy. Thus, the incidence of chronic ileitis in patients who have never been laparotomized in the past and who were treated by radiotherapy alone, was 2.2% (2/97); in contrast patients with previous abdominal surgery whatever its purpose, showed in 13/91 cases (14.3%) severe ileal complications (p less than 0.05). In addition, the risk of chronic ileitis increases with the number of previous laparotomies irrespective of delay or purpose: 10.1% after one laparotomy, 22.2% after two and 50% after three or more laparotomies. The influence of these data on the planning of abdominal and/or pelvic external irradiation is discussed.

Non-randomized comparative study of irradiation alone or in combination with surgery in stage Ib, IIa and "proximal" IIb carcinoma of the cervix.

252 evaluable patients were treated in the Centre Claudius Regaud from January 1974 to December 1983 for stage Ib, IIa or proximal IIb carcinoma of the uterine cervix. This retrospective analysis compares results obtained either by radio-surgical combination therapy (113 patients = RS group) or by exclusive irradiation (139 patients = RT group). The comparison of the two groups in terms of patient age, obesity, associated vascular pathology and previous abdomino-pelvic surgery favored the RS group significantly. The distribution according to clinical stage also significantly favored the RS group. The proportion of patients with stage IIb disease was 12% in the RS group as opposed to 25% for the RT group. Despite unfavorable patient and tumor characteristics, therapeutic results in the RT group were similar to those of the RS group. Pelvic recurrences developed in 18/110 (16%) and 18/139 (13%) of the patients in the RS and RT groups, respectively. Distant metastases occurred in 5/92 (5%) patients in the RS group and 13/121 (11%) patients in the RT group, but the difference was not significant (p less than 0.1). Five year corrected actuarial disease-free survival was 82% in both groups. There were no major early complications in the RT group while four were found in the RS group, of which three were fatal. 2% of patients had major late complications in the RS group versus 6% in the RT group and none were lethal. 25% of the RT group patients had a moderate or mild complication versus 10% in the RS group but 2/3 of these complications recovered without sequellae.

Stage I cutaneous malignant melanoma: risk factors of loco-regional recurrence after wide local excision and clinical perspectives.

Two hundred and nineteen patients admitted to the Centre Claudius Regaud over a 14-year period for a stage I cutaneous malignant melanoma were retrospectively evaluated for loco-regional recurrence rates, risk factors and survival rates following wide primary excision. Five and 8 year survival rates corrected for deaths owing to concurrent illness were 77% and 73%. The loco-regional control rate was 69% (151/219). Distant metastases occurred in 59% (40/68) of patients who had a loco-regional recurrence, versus 11% (16/151) of patients when loco-regional control was obtained (P < 0.001). Multivariate analysis was used to ascertain which risk factors act independently as predictors of poor loco-regional control. Anatomical location of the primary ('head and neck-trunk-hands and feet' vs 'proximal limb') and thickness formed the best model in this respect among 11 prognostic factors studied. Since loco-regional recurrence may be associated with an increased risk of distant metastatic disease, we advocate the use of elective regional lymph node dissection in stage I patients at high risk of loco-regional recurrence in the hope that a portion of these patients may have increased survival owing to lack of development of widespread metastases.

Misonidazole-induced radio-resistance in normal and preirradiated jejunal mucosa.

Pretreatment of mice with a single dose of whole-abdomen irradiation led to a relative decrease in radiosensitivity in jejunal crypts given a second single dose of irradiation 2 months later. Hyperbaric oxygen (3.5 bars) restored the survival level to initial values, suggesting that there was radiation-induced hypoxia in the primed jejunum. However, misonidazole did not sensitize primed jejunal crypts; it reduced the radiosensitivity of both normal and primed crypts. This 'paradoxical' effect of misonidazole could well be due to the acute toxic side-effects of 1 mg/g body weight misonidazole i.p., as there was a sharp drop in the core temperature of mice immediately after drug injection. Artificially maintaining the temperature of miso-treated animals at a normal level produced crypt survival levels similar to those of both normal controls and primed controls. Thus, although the primed gut is chronically hypoxic, as suggested by the effects of hyperbaric oxygen, misonidazole is not a reliable tool for the study of this tissue hypoxia. In all in vivo experiments with misonidazole, core temperature must be controlled in order to avoid misleading interpretations of experimental results.

[Radiation therapy for stage IV carcinoma of the cervix (author's transl)]. / Traitement par agents physiques des cancers du col utérin stage IVa.

Fifty four cases of stage IVa carcinoma of the cervix and treated with radiotherapy were collected between 1971 and 1977. Overall actuarial survival was 16 per cent at 3 years and almost all the deaths occurred before that time. Amongst the factors studied, the initial size of the pelvis tumour and lumbo-aortic lymphography findings were the determing factors in the prognosis. To a lesser extent, the age of the patient, tumour differentiation and the amount of irradiation modified the prognosis. It was thus possible to define, within the stage IVa category, several prognostic groups, the determination of which has therapeutic consequences.

[Role and results of radiotherapy in the treatment of pancreatic adenocarcinoma]. / Place et résultats de la radiothérapie dans le traitement des adénocarcinomes pancréatiques.

Most pancreatic carcinomas are clinically observed when the tumoral spread is well advanced. Consequently, surgical excision is very often either partial or unfeasible. However, evolutive patterns of pancreatic carcinomas show a long past history of loco-regional spread before the onset of visceral metastasis. Consequently, radiotherapy could be proposed to treat locally advanced pancreatic tumors or residual disease after surgical excision in curative intend. The major challenge dealing with radiotherapeutic management of pancreatic carcinomas is to safely deliver doses as high as 60-70 Gy into the upper half of the abdominal cavity. Several technical conditions must be fulfilled before this can take place: high energy and multiple convergent photon beams, precise surgical and/or radiological description of tumoral extent, careful sparing of critical tissues such as spinal cord and kidneys. Usually, radiotherapeutic planning is administered in 2 successive sessions: 40-45 Gy are first administered to the tumor and main nodal drainage over 4-6 weeks, then a 15-25 Gy boost dose is given to the primary tumor bed only. However, postoperative irradiation after complete removal of a gross tumor gives a 10% survival rate only at 2 years. Improvement of these results, are eventually expected from intra-operative irradiation techniques or radiochemotherapy combined treatments.

[Postoperative external irradiation of epidermoid epitheliomas of the larynx and hypopharynx. Analysis of tumor control factors in and outside of the neck]. / Irradiation externe postopératoire des épithéliomas épidermoöides du larynx et de l'hypopharynx. Analyse de facteurs du contrôle tumoral dans et hors du cou.

The authors present a retrospective analysis of 138 patients with squamous cell carcinoma of the hypopharynx and larynx treated with post-operative irradiation. Overall tumoral control rate within the treated areas was 73.9%, uncorrected actuarial survival rates at 3 years and at 5 years were respectively 49.4 and 37.6%. The clinical status (TNM-UICC, 4th edition, 1987) seems to be the main determinant for the prognosis in terms of cervical tumoral control. Patients with N0-N1 nodal stage presented 14/88 (15.9%) cervical failures, while patients staged as N2-N3 presented 22/50 (44%) tumoral recurrences within the treated areas (P less than 0.001). Pyriform sinus tumors were found to present cervical relapses in 13/32 cases (40.6%). This recurrence rate was significantly higher than cervical failure risk in other tumoral sites (P less than 0.05). Cervical relapse (P less than 0.0001), N2-N3 nodal stage and pyriform sinus localization (P less than 0.05) were all found to increase metastasis rate. On the other hand, our results show that the use of post-operative irradiation reduces the prognostic influence of the primary tumor volume; in the same manner, the use of modulated post-operative external irradiation permits the control of microscopically positive surgical margins. In conclusion, the initial staging alone is sufficient to safely evaluate the risk of cervical relapse or metastatic spread; the use of these clinical parameters for selecting patients who could benefit from adjunctive chemotherapy is discussed.

Experimental studies of the resolution of acoustic rhinometry in vivo.

The ability of acoustic rhinometry to detect objects of defined size in nasal cavities has hitherto been investigated only in cadavers and models. We aimed to determine the resolution of the technique in the nose of living subjects. Silicone spheres of 3.0, 5.0, and 7.0 mm diameter were placed at two sites in the decongested and locally anaesthetised nasal cavities of 3 healthy adults. Acoustic rhinometry area-distance functions were obtained before and after insertion of the spheres, with further control data obtained after removal of the sphere from the nasal cavity. Six nasal cavities were studied in each test state on two separate occasions. The 3.0 mm sphere caused a statistically significant change in cavity volumes in only 17% of cases when placed in the middle meatus and in 8% at the nasal value (Mann-Whitney U-test; p < 0.05). The detection rates for the 5.0 mm sphere were 50% in the middle meatus and 50% at the nasal valve. When the control and test curves were compared by superimposition and the cross-sectional areas at the site of perturbations compared statistically (Mann-Whitney U-test) the detection rates in the middle meatus were: 33%-3.0 mm and 67%-5.0 mm sphere. The detection rate at the nasal valve region was 25%-3.0 mm sphere and 58%-5.0 mm. The 7.0 mm sphere was detected in 100% cases by volume changes, and 80% by area changes. Acoustic rhinometry can reliably detect changes of volume and area in the living nose resulting from the introduction of a 7 mm sphere into the nasal valve or middle meatal region in most cases. Smaller spheres are detected in only a fraction of cases. The resolution of the technique is therefore close to 7.0 mm (1.44 cm3). These findings are important when interpreting acoustic rhinometry data in monitoring patients with nasal pathology.

Acoustic rhinometry in the pre-operative assessment of adenoidectomy candidates.

Claims have been made for the potential of acoustic rhinometry (AR) in the evaluation of adenoidectomy patients. Little evidence has been presented to support such claims, and evidence is accumulating that AR is inaccurate in reflecting anatomical reality in the nasopharynx. We set out to establish whether acoustic rhinometry studies could predict operative decision-making sufficiently for it to be of assistance to the clinician, despite these theoretical and practical obstacles. A total of 101 patients aged 2-13 years were examined by AR using the impulse technique. Parameters were chosen from the area-distance function to indicate nasopharyngeal volumes and areas (decongested and non-decongested). This information was compared with findings at EUA (examination under anaesthesia-obstruction categories: A-'good airway' to D-'severe obstruction'), operative decision (2 categories-'obstructive' = remove, versus 'non obstructive' = leave in situ) and parents' symptom scores. Twenty-one patients were also evaluated post-operatively. There was considerable overlap between the AR parameters in the groups classified at EUA as 'obstructive' or 'non obstructive', but this overlap diminished after decongestion. Logistic regression demonstrated that the decongested volume and area parameters were of significant predictive value with respect to operative decision (odds ratio for unit change in volume = 0.82; 95% C.I. = 0.70-0.97; p = 0.018). Parents' analogue scores for snoring and for [snoring+obstruction+ mouthbreathing] were also of significant predictive value. The presence of rhinitis diminishes the predictive value of AR. Acoustic rhinometry has potential as a pre-operative evaluation of the nasopharyngeal airway in adenoidectomy candidates, but the predictive value is low unless combined with clinical factors.

[Epidermoid epitheliomas of the upper respiratory and digestive pathways in females]. / Epithéliomas épidermoïdes des voies aérodigestives supérieures chez la femme.

Ninety-five females with squamous cell carcinoma of the head and neck are reported. Tobacco and alcohol habits were present in only 18% of patients; in these cases tumoral behavior and prognosis are quite similar to those of male patients. When no particular epidemiology was found, female patients present special tumoral localizations as gum, cheek or palate. In addition these patients are elderly, mean age above 75 years. Radiotherapeutic management of female patients allow the same results than in treating males; consequently, since female patients are more elderly than males, these therapeutic results advocate aggressive therapy even in female patients above 80 years old.

[Epidermoid carcinoma of paranasal sinuses. 61 cases treated at the Claudius-Reguad Center from 1961 to 1976 (author's transl)]. / Epithéliomas épidermoïdes du sinus maxillaire. A propos de 61 malades traités au Centre Claudius-Regaud, de 1961 à 1976.

Authors present a critical review of 61 cases of squamous carcinoma of paranasal sinuses. Most of these cases were diagnosed at an advanced stage, allowing only external radiotherapy to be proposed. The mean delivred dose was 6,000 to 6,500 rads, mainly to telecobaltherapy. Survival rates are poor (SVI = 50%, SV3 = 14%, SV5 = 8%) in the same range than values previously published by others. However, it seems possible to point out some practical trends in order to improve the management of the disease:--in all cases, irradiated volumes must be large;--prophylactic irradiation of cervical nodes in also a key point, especially when tumor reaches the oral cavity, the skin or the pterygomaxillary fossa.