Clinical Experience with Pulse Dose Rate Brachytherapy for Conservative Treatment of Penile Carcinoma and Comparison with Historical Data of Low Dose Rate Brachytherapy.

AIMS: To assess the efficacy of pulse dose rate (PDR) interstitial brachytherapy in the treatment of carcinoma of the penis and to compare with historical data of low dose rate (LDR) brachytherapy. MATERIALS AND METHODS: We reviewed the clinical records of 27 consecutive patients treated in our institution with exclusive PDR brachytherapy for a squamous cell carcinoma of the penis. The median tumour greatest diameter was 20 mm (range: 10-50 mm). Twenty-three patients (85%) had tumours limited to the glans and/or prepuce and four patients (15%) also had inguinal lymph node metastases. Implantations were carried out according to the Paris system and treatments were delivered with PDR brachytherapy. RESULTS: The median brachytherapy dose was 60 Gy (range: 60-70 Gy). The median treated volume was 28 cm(3) (range: 8-62 cm(3)). The median reference isodose rate was 0.4 Gy/pulse/h (range: 0.4-0.5 Gy/pulse/h). The median number of pulses was 150 (range: 120-175 pulses). With a median follow-up of 33 months (range: 6-64 months), tumour relapses in the penis were reported in four patients (15%). All patients with only local relapse (n = 3) were successfully salvaged with partial amputation. The estimated overall survival rate at 3 years was 95% (95% confidence interval: 83-100%). No grade 3 or more acute reaction was observed. Delayed ulcerations and stenoses requiring at least one meatal dilatation were reported in two (9%) and five (22%) patients without local relapse. The treated volume was significantly correlated to the risk of clinically relevant delayed toxicity. CONCLUSIONS: The efficacy/toxicity results of PDR brachytherapy for the treatment of penile carcinoma are comparable with those obtained with LDR brachytherapy in historical cohorts.

Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer.

PURPOSE: To evaluate an alternative dose point, so-called ALG (for Alain Gerbaulet), for the bladder in comparison to the International Commission on Radiation Units and Measurements (ICRU) point and D2cm(3) (minimal dose to maximally exposed 2 cm(3)) in a large cohort of patients with locally advanced cervical cancer treated with external beam radiotherapy followed by image-guided pulsed dose rate brachytherapy. METHODS AND MATERIALS: For each patient, the ALG point was constructed 1.5 cm above the ICRU bladder, parallel to the tandem (coronal and sagittal planes). The dosimetric data from 162 patients were reviewed. RESULTS: Average doses to ALG and bladder points were 19.40 Gy ± 7.93 and 17.14 ± 8.70, respectively (p=0.01). The 2 cm(3) bladder dose averaged 24.40 ± 6.77 Gy. Ratios between D2cm(3) and dose points were 1.37 ± 0.46 and 1.68 ± 0.74 (p<0.001) for ALG and ICRU points, respectively. Both dose points appeared correlated with D2cm(3) (p<0.001) with coefficients of determination (R(2)) of 0.331 and 0.399 respectively. The estimated dose to the ICRU point of the rectum was 12.77 ± 4.21 and 15.76 ± 5.94 for D2cm(3) (p<0.0001). Both values were significantly correlated (p<0.0001, R(2) = 0.485). CONCLUSION: The ALG point underestimates the D2cm(3), but its mean on a large cohort is closer to D2cm(3) than the dose to ICRU point. However, it shows great variability between cases and the weak strength of its correlation to D2cm(3) indicates that it is not a good surrogate for individual volumetric evaluation of the dose D2cm(3).

Management and clinical outcomes of pregnant patients with invasive cervical cancer.

BACKGROUND: The objective of this study was to evaluate the clinical outcomes and to discuss the management of women presenting with an invasive cervical cancer during pregnancy. PATIENTS AND METHODS: We retrospectively reviewed patients treated for an invasive cervical cancer diagnosed during pregnancy between 1985 and 2000 in our institution. RESULTS: Twenty-one pregnant patients among a total of 487 women were treated. Thirteen, five, two and one, respectively, were diagnosed during the first, second and third pregnancy trimester and post-partum. The FIGO stage was IB in 15 cases, IIB in five cases and IVA in one case. Mean follow-up was 64 months (range 2-165). Overall and disease-free survival at 5 years were 82% and 79%, respectively. All five patients diagnosed in the second trimester were alive. Two of the 13 patients and one of the two patients diagnosed during the first trimester and the third trimester, respectively, died of their disease. No difference was observed between the nine patients whose treatment was delayed or not. CONCLUSIONS: Invasive cervical cancer during pregnancy is rare but is a dilemma for women and their physicians. The present study and review of the literature suggest that pregnancy does not seem to influence the prognosis of cervical cancer. Delayed treatment could be proposed to selected patients diagnosed at the end of the second trimester or at the beginning of the third trimester, with a small tumor (<2 cm) and negative nodes, after a multidisciplinary approach.

High-dose-rate brachytherapy as sole modality for early-stage endobronchial carcinoma.

PURPOSE: To evaluate exclusive high-dose-rate brachytherapy for localized early-stage non-small-cell bronchial carcinoma; to develop new insights in treatment-catheter positioning and tumor-volume assessment by computed tomography (CT) scan. METHODS AND MATERIALS: Between 1992 and 1996, 34 patients with non-small-cell bronchial carcinoma were treated by brachytherapy alone. All patients were medically inoperable and had contraindications for external beam irradiation. The treatment protocol was six sessions of 5 Gy over 6 weeks. The treatment catheter was placed under fiberoscopy and was positioned with the help of spacer catheters or with a surrounding plastic tube; CT scan was performed in 50% of the cases to measure the spacing between the applicator and the bronchial wall. Dose prescription was individually based on clinical and radiologic evaluation of tumor volume. RESULTS: Local disease failure occurred in 5 patients (15%). With a median follow-up of 2 years, the local control rate was 85% and the survival rate 78%. No acute toxicity was found, except one pneumothorax. CONCLUSION: Brachytherapy alone can give an optimal therapeutic ratio in small endobronchial carcinomas without radiation-induced morbidity. Such results are achieved after careful tumor volume evaluation and individualized treatment catheter positioning.

Isolated para-aortic node involvement in stage IB/II cervical carcinoma.

The aim of this report was to describe exceptional cases of patients treated for stage Ib and II cervical carcinoma with isolated para-aortic node involvement and to deduce therapeutic implications. Between 1985 and 1998, 491 women with stage IB or II cervical carcinoma underwent radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy. Five patients had para-aortic metastatic nodes but no external iliac, obturator or common iliac node involvement. These five patients had a tumor size >3 cm. According to these cases, in patients with bulky cervical carcinoma systematic complete lymphadenectomy should be performed in order to avoid misdiagnosis of para-aortic node involvement.

Evaluation of cosmetic results of a randomized trial comparing surgery and radiotherapy in the treatment of basal cell carcinoma of the face.

Basal cell carcinoma is the most frequent cutaneous carcinoma, and it is characterized by its local spreading and an exceptional tendency to metastasize. Radical excision or destruction ensures the highest chance of cure. The most frequent site of this tumor is the face, where radical excision is limited by the proximity of essential anatomic structures. The main difficulty is to avoid mutilation and to provide good cosmetic results despite the vicinity of the eyes, the nose, and the mouth. Surgery and radiotherapy are known to provide similar chances of cure, but results concerning cosmetic sequelae are controversial, depending sometimes on the specialty of the physician in charge of the treatment. A randomized trial was performed at the Gustave-Roussy Institute to compare basal cell carcinomas of the face treated either by surgery or by radiotherapy. In summary, a significant advantage was observed in favor of surgery, as has been published elsewhere. Looking at the details of the cosmetic results, we analyzed the specific methodology of the cosmetic evaluation set up to eradicate the usual bias owing to subjective judgments. We looked also to the evolution of the cosmetic results with time. A panel of five judges performed repeated evaluations during the follow-up, and standardized photographs were taken at each visit and rated later by three nonmedical judges. In total, 174 patients were treated by surgery and 173 by radiotherapy; the choice of the treatment was allocated by randomization. Postoperative complications were higher in the radiotherapy group. The final cosmetic results after 4 years of follow-up were rated significantly better with surgery than with radiotherapy (good in 87 percent versus 69 percent according to the patient, 79 percent versus 40 percent according to the dermatologist, and respectively for each of the observers). Evolution of the ratings during the follow-up demonstrated an improvement of the cosmesis after surgery and stable or deteriorated results after radiotherapy. The same trend was observed regardless of the site of the tumor on the face, except for the nose, where the difference--still in favor of the surgery--was not significant. Concordance of all assessments in our study was the main guarantee of reliability of our methodology for cosmetic evaluation.

[Curietherapy in uterine cervix cancers: what therapeutic trends?]. / Curiethérapie dans des cancers du col utérin. Quelles orientations thérapeutiques?

Brachytherapy is a fundamental step in the treatment of patients with cervical cancer. Brachytherapy allows a significant increase in the local control rate as well as the survival rate. Brachytherapy has to be performed as soon as possible after external irradiation in order to maintain the overall treatment time below 53 days. Technical and dosimetric data characterizing low dose-rate brachytherapy using ICRU 38 recommendations have led to an improvement in local control and a decrease in complications. Data are less well known for other dose rates. The role of interstitial brachytherapy is not clearly defined and its potential benefit is probably balanced by an increase in severe complications. Concomitant brachy-chemotherapy requires further clinical investigations, even if concomitant radio-chemotherapy has become a standard in advanced cervical cancers.

[Brachytherapy in the treatment of vesicoprostatic rhabdomyosarcomas in children]. / Curiethérapie dans le traitement des rhabdomyosarcomes vésicoprostatiques de l'enfant.

Brachytherapy has been widely used at the Institut Gustave-Roussy since 1972 in pediatric oncology. In genitourinary rhabdomyosarcoma, because of its ballistic and physical characteristics, it represents the optimal treatment whenever irradiation is required and brachytherapy feasible. Between 1976 and 1998, 23 children with bladder or prostate rhabdomyosarcoma were treated with a protocol including brachytherapy, with five of them treated with a salvage brachytherapy. All but one brachytherapy was performed during the surgery. Among the 18 brachytherapies performed as a first-line treatment, eight presented a tumoral evolution: five presented a local evolution, one a local and nodal evolution and two a nodal evolution. Brachytherapy allowed a conservative treatment among ten out of 11 children alive with no evidence of disease. Among the five patients with salvage brachytherapy, two presented a second recurrence. Sequelae were minimal, consisting of one grade I rectitis and one asymptomatic vesical and ureteral reflux. These results are consistent with the published data using more radical treatment. Brachytherapy can represent an alternative to radical surgery, when indications are clearly defined in bladder or prostate rhabdomyosarcoma. This type of treatment can be performed only integrated with other treatments, more particularly with surgery. This approach requires a close cooperation between the different specialists: pediatricians, surgeons and brachytherapists.

Radiotherapy and radical surgery for treatment of patients with bulky stage IB and II cervical carcinoma.

The aim of this study was to evaluate prognostic factors and to study combination radiotherapy-surgery as treatment for patients with bulky stage Ib and II cervical carcinoma. From 1985 to 1994, 187 patients with cervical cancer >/= 4 cm, were treated by combined radiation therapy and radical surgery including systematic para-aortic lymphadenectomy. Complications were observed in 34 (18%) patients. In a multivariate analysis, young age, tumor size less than 5 cm, metastatic nodes with capsular rupture, and bilateral nodes were independent prognostic factors. Overall survival at 3 years was 85%, 56%, and 40% in patients with negative nodes, positive pelvic nodes, and positive para-aortic nodes, respectively (P < 0.001). These results confirm the prognostic significance of young age, tumor size, and nodal involvement. Radical surgery combined with radiotherapy is feasible, with an acceptable rate of complications and yields satisfactory survival results in patients with bulky stage IB and II cervical carcinoma. Recent randomized published studies have demonstrated that concomitant chemotherapy and radiotherapy should be the gold standard in this setting. The role of surgery is questioned.

Laparoscopic prophylactic oophorectomy in women with inherited risk of ovarian cancer.

The aim of this study was to specify the surgical procedure most adapted for prophylactic laparoscopic oophorectomy in patients with an inherited risk of ovarian cancer. This prospective study was based on a series of 27 patients who underwent prophylactic bilateral laparoscopic oophorectomy between September 1995 and January 1998. Nine patients underwent an oophorectomy (33%) and 18 patients an adnexectomy (67%). The laparoscopic procedure was converted into a laparotomy in one patient in whom an ovarian adenocarcinoma was detected during the surgical procedure. During final histologic examination of the ovaries, 23 patients were found to have benign atypical histologic alterations, one patient had an ovarian adenocarcinoma and only three patients (11%) had normal ovaries. In women with an inherited risk of ovarian cancer, during the laparoscopic procedure for prophylactic oophorectomy, the abdomino-pelvic cavity should be thoroughly explored with peritoneal cytology and systematic peritoneal biopsies. The laparoscopic procedure could be converted into a laparotomy if an ovarian cancer is discovered.

How can laparoscopic management assist radiation treatment in cervix carcinoma?

PURPOSE: To determine the role of laparoscopic lymphadenectomy (pelvis +/- para-aortic nodes) and laparoscopic hysterectomy in cervical cancer compared to 'classic radical surgery' in patients undergoing surgery in comparison with modern imaging in patients treated with radiotherapy alone. MATERIALS AND METHODS: The limitations of modern imaging are presented as well as how complication rates can be increased when classic laparotomy is followed by radiation therapy. Laparoscopic procedures are described with particular emphasis on how to provide information on lymph node metastases with the risk of overlooking microscopic involvement. A number of clinical experiences are cited to illustrate this problem and show how treatment approaches can be adapted. RESULTS: The role of laparoscopy is evaluated according to different clinical situations and treatment protocols emphasizing the possibilities offered by this method to the radiotherapist. CONCLUSION: When developing laparoscopic techniques for the management of cervical carcinoma, caution must be exercised to ensure that these techniques are not detrimental to the prognosis.

[The centenary of the discovery of radium]. / Le centenaire de la découverte du radium.

Henri Becquerel presented the discovery of radium by Pierre and Marie Curie at the Paris Académie des Sciences on 26th December 1898. One century later, radium has been abandoned, mainly for the reason of radiation safety concerns. It is, however, likely that modern techniques of brachytherapy are the successors of those designed for radium sources, and that radium has cured thousands and thousands patients all over the word for about 80 years. The history of discovery and medical use of radium is summarised.

How to optimize therapeutic ratio in brachytherapy of head and neck squamous cell carcinoma?

Considerable experience has been accumulated with low dose rate (LDR) brachytherapy in the treatment of squamous cell carcinoma of the oral cavity and oropharynx, 4 cm or less in diameter. Recent analysis of large clinical series provided data indicating that modalities of LDR brachytherapy should be optimized in treating these tumours for increasing therapeutic ratio. LDR brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with the last two modalities are discussed in comparison with those achieved with LDR brachytherapy.

Laparoscopic ovarian transposition for pelvic malignancies: indications and functional outcomes.

OBJECTIVE: To assess the indications and effectiveness of laparoscopic ovarian transposition before pelvic irradiation for a gynecologic cancer. DESIGN: Prospective study. SETTING: A gynecologic oncology department in a French anti-cancer center. PATIENT(S): Twenty-four patients treated for pelvic cancer. INTERVENTION(S): Laparoscopic ovarian transposition to paracolic gutters. Uterine conservation in 18 patients. MAIN OUTCOME MEASURE(S): Clinical and laboratory follow-up tests of ovarian function. RESULT(S): Bilateral laparoscopic ovarian transposition was achieved in 22 patients (94%). Twelve patients were treated for clear cell adenocarcinoma of the cervix and/or upper vagina, 6 patients for invasive squamous cervical carcinoma, 3 patients for pelvic sarcoma, 1 patient for recurrent cervical cancer to the upper vagina, 1 patient for ependymoma of the cauda equina, and 1 patient for ovarian dysgerminoma. Ovarian preservation was achieved in 79%. Three pregnancies were obtained. CONCLUSION(S): Laparoscopic ovarian transposition is a safe and effective procedure for preserving ovarian function. Bilateral ovarian transposition should be performed. The main indications for laparoscopic ovarian transposition are a patient with a small invasive cervical carcinoma (<2 cm) in a patient <40 years of age who is treated by initial laparoscopically assisted vaginal radical hysterectomy and a patient with a clear cell adenocarcinoma of the cervix and upper vagina.

[Epidermoid carcinoma of the penis]. / Carcinome épidermoïde de la verge.

Squamous cell carcinoma is the most common tumour of the penis. It is a rare disease in Western countries, and occurs in patients after the sixth decade. The pattern of spread is loco-regional, and prognosis is poor when nodal metastases appear. The etiology of penis cancer is discussed, however human papillomavirus infection, tobacco, poor hygiene and phimosis are often associated with this disease. Radical surgery gives the best control of the primary tumour, but it is mutilating. Conservative therapies (laser, radiotherapy, and particularly brachytherapy...) are an attracting option. Regional lymph nodes management is extremely controversial. Lymph node metastases, invasion of corpus cavernosum, and poor differentiation are pejorative prognostic factors. More than half patients are responsive to modern polychemotherapy combinations. However responses are transient and chemotherapy alone is not curative for metastatic disease. Etiologic factors, clinical presentation, staging work-up requirements, prognostic factors and therapeutic modalities are detailed.

[Role of intravascular brachytherapy in the prevention of vascular restenosis after angioplasty]. / Rôle de la curiethérapie endovasculaire dans la prévention de la resténose vasculaire après angioplastie.

About 30% of patients who underwent percutaneous transluminal coronary angioplasty show evidence of restenosis, which appears to be independent of the angioplasty method used. The restenosis is due of two factors, firstly migration of smooth vascular muscle cells of the vascular media to the intima and multiplication which lead to the formation of a neo-intima. Irradiation limits the proliferation by acting of the cells in the mitotic stage. The vascular target volume is not very thick and is difficult to define it, that why brachytherapy seems to be the best procedure to prevent restenosis. However, the development of this treatment present many difficulties. Different irradiation techniques have been studied. Such techniques include catheter containing radioactive sealed source, radioactive stent, or balloon containing radioactive liquid inside. Each of these methods have their own advantages, inconveniences, problems and risks. Radioisotope may be either beta or gamma emitters. Gamma emitter presents problems for radioprotection but the satisfactory dose distribution may be difficult to obtain using beta emitter. Choice of dose, dose rate and delay between the end of angioplasty and the beginning of brachytherapy is subject to some discuss. Animal experiments using radioisotope have shown reduction in cell proliferation. Human trials showed feasibility, safety of the method and real impact on restenosis prevention. However, long-term efficacy has not been proved because the follow-up of the patients is too short. A randomized trial of 192Ir brachytherapy for prevention of restenosis has recently shown the efficacy in short and median term. However, long term efficiency and secondary effects have not yet been established as the follow up time of this study is still too short. That is why, collaboration between cardiologists and radiotherapists and physicists is indispensable to enable the development of an optimal technique.

Squamous cell carcinoma of the penis

Squamous cell carcinoma is the most common tumour of the penis. It is a rare disease in Western countries, and occurs in patients after the sixth decade. The pattern of spread is loco-regional, and prognosis is poor when nodal metastases appear. The etiology of penis cancer is discussed, however human papillomavirus infection, tobacco, poor hygiene and phimosis are often associated with this disease. Radical surgery gives the best control of the primary tumour, but it is mutilating. Conservative therapies (laser, radiotherapy, and particularly brachytherapy.) are an attracting option. Regional lymph nodes management is extremely controversial. Lymph node metastases, invasion of corpus cavernosum, and poor differentiation are pejorative prognostic factors. More than half patients are responsive to modern polychemotherpy combinations. However responses are transient and chemotherapy alone is not curative for metastatic disease. Etiologic factors, clinical presentation, staging work-up requirements, prognostic factors and therapeutic modalities are detailed.

[Prognostic factors of cancer of the endometrium and therapeutic implications]. / Facteurs pronostiques du cancer de l'endomètre et déductions thérapeutiques.

Tumor differentiation, myometrial invasion and lymph node metastasis are the most important prognostic factors in endometrial carcinoma. Tumor stage, positive peritoneal cytology, obesity and race seems to be also prognostic factors. The surgical treatment of stage I and II endometrial carcinoma is hysterectomy with bilateral adnexectomy and pelvic lymphadenectomy (obturator group). This procedure can be performed by laparotomy or laparoscopy.