[Tunisian National Protocol for Adult Hodgkin's Lymphoma Treatment: Results of a therapeutic regimen adapted to the 2-cycle CT response, about 444 patients]. / Protocole national Tunisien prospectif de traitement du Lymphome de Hodgkin de l'adulte : résultats d'un schéma thérapeutique adapté à la réponse par tomodensitométrie à 2 cycles, à propos de 444 patients.

OBJECTIVE: In Tunisia, the management of Adult Hodgkin's Lymphoma (HL) has been standardized since 1999. We propose in this study to report the therapeutic results of the national protocol of adult HL treatment (MDH2008). PATIENTS AND METHODS: Our study is prospective multicenter interesting 444 patients followed for HL between July 2008 and June 2013 and treated according to the MDH2008 protocol. The median age of our patients was 30 years. B symptoms were present in 62.8 % of our patients. According to the Ann Arbor classification, our patients were in stages I, II, III and IV in 3 %, 42 %, 26 % and 29 %, respectively. The MDH2008 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of chemotherapy. RESULTS: Response≥75 % to 2 courses of chemotherapy was achieved in 43 % of patients and the response rate at the end of treatment was 92.1 %. Forty-eight patients (11.4 %) had primary failure. In the multi-variant study, bulky mediastinal mass (IMT≥0.35) was an independent predictive factor of primary failure (P: 0.000). Nineteen toxic deaths (4.35 %) were reported. The relapse rate was 7.8 %. Event free survival, relapse-free survival and overall survival at 5years were 75 %, 89 % and 90 %, respectively. Adaptation of the treatment to the 2 cycles response was effective in unfavorable early stages and advanced stages. CONCLUSION: Compared to MDH2002 (second version of Tunisian prospective protocol), the MDH2008 reduced the primary failure rate, the rate of toxic deaths with escalated BEACOPP and the rate of relapse in Tunisian patients.

Nomogram to predict rectal toxicity following prostate cancer radiotherapy.

BACKGROUND: To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction. METHODS: In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups. RESULTS: Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3-0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0-1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1-10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3-0.8, p<0.01). Based on these three parameters, a nomogram was generated. CONCLUSIONS: Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique.

Nomograms to predict late urinary toxicity after prostate cancer radiotherapy.

OBJECTIVE: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. METHODS: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.5 Gy/day) and techniques. Late urinary toxicity and the corresponding symptoms (urinary frequency, incontinence, dysuria/decreased stream, and hematuria) were prospectively assessed in half of the patients using the LENT-SOMA classification. Univariate and multivariate Cox regression models addressed patient or treatment-related predictors of late urinary toxicity (≥grade 2). Nomograms were built up, and their performance was assessed. RESULTS: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, dysuria, and urinary incontinence rates were 15, 10, 5, 3 and 1 %, respectively. The 5-year (≥grade 3) urinary toxicity rate was 3 %. The following parameters significantly increased the 5-year risk of global urinary toxicity (≥grade 2): anticoagulant treatment (RR = 2.35), total dose (RR = 1.09), and age (RR = 1.06). Urinary frequency was increased by the total dose (RR = 1.07) and diabetes (RR = 4). Hematuria was increased by anticoagulant treatment (RR = 2.9). Dysuria was increased by the total dose (RR = 1.1). Corresponding nomograms and their calibration plots were generated. Nomogram performance should be validated with external data. CONCLUSIONS: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.

[Atypical presentations of internal mammary chain involvement in breast cancer]. / Les aspects trompeurs de l'atteinte de la chaîne mammaire interne dans les cancers du sein.

BACKGROUND: Breast cancer is the first cancer in women. Lymphatic involvement in breast cancer is common, especially in our patients because of the frequency of locally advanced forms. This contrast with a weak rate of diagnosed internal mammary chain invasion. METHODS: We present observations of patients presenting atypical forms of internal mammary chain involvement. AIM: To clarify the atypical presentations of internal mammary chain involvement in breast cancer. RESULTS: The invasion of internal mammary chain is often underestimated. Indeed, this site of lymphatic spread is not accessible to the clinical exam and its radiological exploration is not systematic. Otherwise, different clinical, pathological and radiological presentations have to attract our attention to a potential internal mammary chain invasion. CONCLUSION: Our misrecognition of this site of spread and its different presentations can partly explain the lack of diagnosis.

Involved-node radiotherapy and modern radiation treatment techniques in patients with Hodgkin lymphoma.

PURPOSE: To assess the clinical outcome of the involved-node radiotherapy (INRT) concept using modern radiation treatments (intensity-modulated radiotherapy [IMRT] or deep-inspiration breath-hold radiotherapy [DIBH) in patients with localized supradiaphragmatic Hodgkin lymphoma. METHODS AND MATERIALS: All but 2 patients had early-stage Hodgkin lymphoma, and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the INRT concept according to European Organization for Research and Treatment of Cancer guidelines. IMRT was performed with the patient free-breathing. For the adapted breath-hold technique, a spirometer dedicated to DIBH radiotherapy was used. Three-dimensional conformal radiotherapy was performed with those patients. RESULTS: Fifty patients with Hodgkin lymphoma (48 patients with primary Hodgkin lymphoma, 1 patient with recurrent disease, and 1 patient with refractory disease) entered the study from January 2003 to August 2008. Thirty-two patients were treated with IMRT, and 18 patients were treated with the DIBH technique. The median age was 28 years (range, 17-62 years). Thirty-four (68%) patients had stage I - (I-IIA) IIA disease, and 16 (32%) patients had stage I - (I-IIB) IIB disease. All but 3 patients received three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). The median radiation doses to patients treated with IMRT and DIBH were, respectively, 40 Gy (range, 21.6-40 Gy) and 30.6 Gy (range, 19.8-40 Gy). Protection of various organs at risk was satisfactory. Median follow-up was 53.4 months (range, 19.1-93 months). The 5-year progression-free and overall survival rates for the whole population were 92% (95% confidence interval [CI], 80%-97%) and 94% (95% CI, 75%-98%), respectively. Recurrences occurred in 4 patients: 2 patients had in-field relapses, and 2 patients had visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in 1 case. CONCLUSIONS: Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the INRT concept and modern radiation treatment techniques such as IMRT and DIBH.

Technical aspects and perspectives of the vaginal mold applicator for brachytherapy of gynecologic malignancies.

PURPOSE: The importance of the quality of cervical cancer brachytherapy applicators has been reported, suggesting a direct influence of competent technical implant performance on outcome. In our institute, an original brachytherapy technique based on the use of a molded applicator for genital tract brachytherapy has been applied routinely in clinical practice. Here, we report the technical aspects of this customized applicator and perspectives on its use. TECHNICAL ASPECTS: The first step consists of a vaginal impression that accurately shows the topography and extension of the tumor as well as the anatomy of the vagina and cervix. From this impression, an acrylic applicator is made. Then, the intended positions of the vaginal catheters are drawn on the surface of the mold by the radiation oncologist. Two plastic vaginal catheters are introduced and fixed on the internal surface of the molded applicator. A hole for the cervical os is made through which the uterine probe will be positioned. PERSPECTIVES: This method allows for high specificity within the framework of a modern brachytherapy procedure, integrating the tumor topography, anatomy of the patient, and internal movements of target and critical volumes. This technique has been successfully extended to other tumor locations, such as genital tract rhabdomyosarcoma in children and postoperative endocavitary brachytherapy in patients with endometrial cancer. CONCLUSION: Customization of a vaginal brachytherapy applicator allows for the maintenance of morphologic optimization throughout the treatment course, which better takes into account a fourth dimension: internal organ motion during the course of brachytherapy.

Physics contributions and clinical outcome with 3D-MRI-based pulsed-dose-rate intracavitary brachytherapy in cervical cancer patients.

PURPOSE: To assess the physics contributions and clinical outcome with three-dimensional magnetic resonance imaging-guided pulsed-dose-rate (PDR) intracavitary brachytherapy in cervical cancer patients. METHODS AND MATERIALS: The data from 45 patients with primary locally advanced cervical carcinoma were analyzed. The median tumor cervical volume was 64.0 cm(3) (range, 3-178). Of the 45 patients, 24 (53%) had histologic and/or radiologic pelvic involvement. After pelvic with or without para-aortic concomitant chemoradiotherapy, a PDR brachytherapy boost was delivered to a three-dimensional magnetic resonance imaging-based clinical target volume, taking into account the dose-volume constraints for critical organs and optimization of the target volume coverage. RESULTS: At a median follow-up of 26 months (range, 9-47), the 2-year overall survival and disease-free survival rate was 78% and 73%, respectively. At the last follow-up visit, the disease of all patients remained locally controlled. Adding external beam radiotherapy and PDR using the equivalent dose in 2-Gy fractions model, the median dose received by 100% and 90% of the target was 54.4 Gy(alpha/beta10) and 63.5 Gy(alpha/beta10) for the intermediate-risk clinical target volume and 61.6 Gy(alpha/beta10) and 74.9 Gy(alpha/beta10) for the high-risk clinical target volume, respectively. Of the 45 patients, 23 and 2 developed acute Grade 1-2 and Grade 3 complications, respectively; 21 patients presented with delayed Grade 1-2 complications. One other patient presented with Grade 3 vesicovaginal fistula. No Grade 4 or greater complications, whether acute or delayed, were observed. CONCLUSION: Magnetic resonance imaging-guided PDR brachytherapy with optimization integrating the limits of tolerance to critical organs allows for excellent local control rates. Moreover, the present results have confirmed that the ability to optimize dwell times can contribute to an improvement in local control rates with a low level of late side effects.

New trends in the evaluation and treatment of cervix cancer: the role of FDG-PET.

INTRODUCTION: Positron emission tomography (PET) with F18 Flurodeoxyglucose (FDG) has been evaluated and found to be a useful diagnostic tool in a certain number of malignancies, particularly in providing crucial assessment of metabolic activity of the tumour. We herein review and discuss the place and role of FDG-PET scan in cervix carcinoma patients' management. MATERIALS AND METHODS: Data for this review were identified by searches of Medline with and without MeSH database and Cancerlit. Studies were selected only if they were randomised clinical trials or historical reports. References were also identified from reference lists in relevant previously published articles. Recent guidelines and meta-analyses were included. Only published articles were taken into consideration. RESULTS: Although FDG-PET may be useful in the primary cervical tumours morphologic and metabolic evaluation, it seems to have limited place for disease staging in patients with early-stage disease (less than 4 cm). Hybrid PET/CT is an effective imaging technique in the lymph node staging of locally advanced cervix carcinoma with negative CT findings and may lead to substantial changes in treatment planning for several patients. FDG-PET provides meaningful information for the early evaluation of therapeutic response and long-term follow-up. CONCLUSION: Several reports have demonstrated the efficacy of FDG-PET in both pre-treatment staging and post-treatment evaluation of patients with cervical carcinoma. Further evaluation in prospective clinical trials will be required to assess the clinical benefit of this strategy.

Breast cancer in Tunisia in 2004: a comparative clinical and epidemiological study.

The aim of this study was to determine the epidemiological, clinical and anatomopathological aspects of breast cancer in Tunisia. We censored and analyzed all cases of breast cancer newly diagnosed in Tunisia during the year 2004. During that year, 1437 new cases of invasive breast cancer were diagnosed and 35 cases of non invasive breast cancer. There were 1408 women and 29 men. The accrual incidence was 27.1 and the standardized incidence was 28.5. The mean age for women was 51 years. The mean tumour size was 40.8 mm (32.3 mm and 42.5 mm for private and public sectors respectively). Tumour stage was T1 in 12.2% cases, T2 in 46.9% cases, T3 in 11.2% cases and T4 in 24.7% cases. Invasive ductal carcinoma was the most frequent (86,6%) with SBR II grade representing 54.5%. 27.7% of the patients had undergone conservative treatment. There was an unexpected increase of the incidence since 1994 where the standardized incidence was 16.9. We have noticed a moderate decrease of the tumour size of 8 mm during the last decade. This national epidemiological study on breast cancer showed an increase in the incidence of this cancer with a moderate decrease in the clinical tumour size. The relative young mean age of our patients may be explained by the age distribution in our population or by risk factors that may be particular to our country.