Pharmaceutical Supply chain Risk Assessment During COVID-19 Epidemic.

The global health products supply chain is negatively influenced by the COVID-19 pandemic. Moreover, the risks in the pharmaceutical supply chain (PSC) have increased. Assessment and mitigation risks in PSC are essential issues to control and counter these risks. In this study, a 2-Tuple ARAS-BWM approach, which combines ARAS and BWM methods under linguistic 2-Tuple environment, is proposed to evaluate and address various risks to the best mitigation strategies in the pharmaceutical industry in Tunisia during COVID-19. Noted that the main risk identified in the PSC is related to supply and suppliers and its best mitigation strategy is reducing risk.

[Cost effectiveness analysis of screening strategies for cervical cancer in Tunisia]. / Analyse coût-efficacité des stratégies de dépistage du cancer du col utérin en Tunisie.

We aimed to identify the most appropriate screening strategy for cervical cancer (periodicity of 3, 5 or 10 years) for Tunisia, taking into consideration the incidence of the disease, costs of screening and economic implications. We simulated follow-up of a fictitious cohort of 1 million women 35-39 years over 30 years. Computation of yearly medical care costs was based on data from medical files of patients diagnosed with cervical cancer in 2004 at the National Institute of Cancer, Tunis. For a 60% coverage level of screening, cervical cancer reduction would be 49.2% for a 3-year periodicity. The reduction would be 40.3% and 33.1% for 5 and 10 years periodicity respectively. Considering cost-effectiveness, 10-year screening gave the lowest annual cost to avoid 1 cervical cancer case.

[In vivo dosimetry study of semi-conductors EPD-20 in total body irradiation technique]. / Etude de la dosimétrie in vivo par semi-conducteurs EPD-20 dans les conditions de l'irradiation corporelle totale.

PURPOSE: The objective of this work was the study of in vivo dosimetry performed in a series of 54 patients receiving total body irradiation (TBI) at the Salah-Azaiz Institute of Tunis since 2004. In vivo dosimetry measurements were compared to analytically calculated doses from monitor units delivered. PATIENTS AND METHOD: The irradiation was conducted by a linear accelerator (Clinac 1800, Varian, Palo Alto, USA) using nominal X-rays energies of 6 MV and 18 MV, depending on the thickness of the patient at the abdomen. The dose was measured by semi-conductors p-type EPD-20. These diodes were calibrated in advance with an ionization chamber "PTW Farmer" type of 0.6cm(3) and were placed on the surface of plexiglas phantom in the same TBI conditions. A study of dosimetric characteristics of semi-conductors EPD-20 was carried out as a function of beam direction and temperature. Afterwards, we conducted a comparative analysis of doses measured using these detectors during irradiation to those calculated retrospectively from monitor units delivered to each patient conditioned by TBI. RESULTS: Experience showed that semi-conductors are sensitive to the angle of beam radiation (0-90 degrees ) and the temperature (22-40 degrees C). The maximum variation is respectively 5 and 7%, but in our irradiation conditions these correction factors are less than 1%. The analysis of the results of the in vivo dosimetry had shown that the ratio of the average measured doses and analytically calculated doses at the abdomen, mediastina, right lung and head are 1.005, 1.007, 1.0135 and 1.008 with a standard deviation "type A" respectively of 3.04, 2.37, 7.09 et 4.15%. CONCLUSION: In vivo dosimetry by semi-conductors is in perfect agreement with dosimetry by calculation. However, in vivo dosimetry using semiconductors is the only technique that can reflect the dose actually received instantly by the patient during TBI given the many factors that calculation can not take into account: patient and organs motions and the heterogeneity of the targets.

[Radiotherapy in the treatment of retinoblastoma: about 40 cases]. / Place de la radiothérapie dans le traitement du rétinoblastome : à propos de 40 cas.

PURPOSE: The aim of this study is to analyze the results and the complications of radiotherapy in the treatment of retinoblastoma. PATIENTS AND METHODS: Between 1994 and 2004, 40 children received radiotherapy for a retinoblastoma in Salah Azaiz Institute. The average age of the patients was 36 months (four to 132 months). There were 16 girls and 24 boys. Sixteen children presented a bilateral disease and 24 children a unilateral disease. Twenty eyes and thirty-six orbital cavities in 40 children with retinoblastoma were treated by radiotherapy. One child with a unilateral anterior retinoblastoma was treated with 106 ruthenium brachytherapy. External radiotherapy has been used to treat the 39 patients. In 20 cases the irradiation was conservative and in 36 cases postoperatively. The latter (n=36) presented at least one risk factor of relapses noted in the histological examination. The average dose was 44 Gy (1.8 to 2 Gy per fraction, five fractions weekly). This radiotherapy was associated with chemotherapy in 24 cases. RESULTS: Thirty-five children were followed with an average follow-up of 53 months (3-108 months). The average delay of relapses was of 10 months (two to 26 months). We found four orbital relapses and seven metastasis in nine children. The conservation of the eye with a useful visual field was noted in 18 cases among the 20 conservative irradiated eyes. The major therapeutic complication was the growth defect of the bones face. A femoral bone sarcoma was noted five years after the end of the irradiation and chemotherapy in one case. CONCLUSION: If the radiotherapy offers the advantage of the functional conservation and the improvement of the local control, its indications are more and more restricted in favor of the other therapeutic methods (chemotherapy, thermochemotherapy) and this considering the iatrogene risk. The development of new techniques of brachytherapy and the progresses of the conformational radiotherapy appear to reduce considerably this risk.

[Should chest wall irradiation be included after mastectomy and negative node breast cancer?]. / L'irradiation pariétale est-elle justifiée après mastectomie et curage négatif ?

PURPOSE: This study aims to evaluate local failure patterns in node negative breast cancer patients treated with post-mastectomy radiotherapy including internal mammary chain only. PATIENTS AND METHODS: Retrospective analysis of 92 internal or central-breast node-negative tumours with mastectomy and external irradiation of the internal mammary chain at the dose of 50 Gy, from 1994 to 1998. RESULTS: Local recurrence rate was 5 % (five cases). Recurrence sites were the operative scare and chest wall. Factors associated with increased risk of local failure were age < or = 40 years and tumour size greater than 20mm, without statistical significance. CONCLUSION: Post-mastectomy radiotherapy should be discussed for a sub-group of node-negative patients with predictors factors of local failure such as age < or = 40 years and larger tumour size.

Brachytherapy for primary and recurrent nasopharyngeal carcinoma: treatment techniques and results.

PURPOSE: Nasopharyngeal cancer is the commonest head and neck cancer in Tunisia treated with radiotherapy. A dose effect relationship is established in this tumor. The aim of this study is to describe our Low-dose-rate endocavitary brachytherapy using a personalized mold called Tunis applicator. PATIENTS AND METHODS: Seven patients (4 males and 3 females) with histologically confirmed undifferentiated nasopharyngeal carcinoma (UCNT) were treated between 2002 and 2005. Five patients with primary cancer and 2 with recurrent disease received external beam radiation followed by endocavitary brachytherapy. The mean applied dose of endocavitary brachytherapy was 5.5 Gy for primary site after external beam radiation (70-74 Gy) and 30 Gy for recurrent disease after external beam radiation (38 Gy). We have developed a personalized applicator with a balloon to optimize the placement of sources and a better conformity using the computer tomography scanning. Critical normal structures were identified on orthogonal radiographs and the dose was optimized to avoid excessive doses to these structures. RESULTS: With a follow up of 18 months (8-41), only one local failure was observed, 3 years after external beam radiation therapy for a recurrent disease. Moderate grade mucositis was seen in most patients. One patient was diagnosed with bulb necrosis. CONCLUSION: Endobrachytherapy can provide effective treatment for nasopharyngeal carcinoma with an easy application of the brachytherapy procedure.

[Primitive intracranial ependymomas. Salah-Azaîz institute experience].

PURPOSE: - To assess the outcome and prognostic factors of patients with primitive intracranial ependymomas treated at the department of radiotherapy of Salah-Azaîz Institute. METHODS AND MATERIAL: - Between 1972 and 1997, 31 patients aged one to 53 years received postoperative radiotherapy. There were 16 males and 15 females. Location of tumor was infratentorial in 24 cases and supratentoriel in seven cases. Surgical treatment consisted of complete resection in 14, incomplete resection in 13 and unknown type in four patients. All patients were treated with radiotherapy to the craniospinal axis in 26 cases, whole brain in five cases. RESULTS: - Five years survival rate was 63%. For infratentorial tumors, two patients failed locally, two patients failed locally and at distance and four patients failed only at distance, while one patient with supratentorial tumor relapsed locally. Age, performances status, tumor site, gender and extent of surgery had no impact on survival. The treatment field extent was the only variable predictive of outcome. Patients treated with craniospinal irradiation had a survival rate of 86% compared with 37,5% for patients treated with whole brain irradiation. CONCLUSION: - Infratentorial ependymomas seem to have a worse prognosis than supratentorial ones. Irradiation field extent should be correlated to prognostic factors.

[Primary intramedullary ependymomas: retrospective study of 16 cases]. / Les épendymomes intramédullaires primitifs: étude rétrospective de 16 cas.

PURPOSE: To review the radiotherapy department experience in treating primary spinal cord ependymomas (PSCE), analyse prognostic factors and provide treatment recommendations regarding literature review. MATERIALS AND METHODS: Sixteen patients with PSCE received postoperative radiotherapy between 1972 and 1997. There were 10 male and 6 female patients with a mean age of 34 years (range 2-63). Surgery was gross total resection in 2 cases, subtotal resection in 9, biopsy in 4 and of unknown type in one patient. All patients were treated with radiotherapy to the craniospinal axis (4 cases), spinal cord (1 case) and to the site of primary tumour in 11 cases. RESULTS: Five year-survival rate was 73%. Two patients had recurrent tumours within the primary site. Gender, extent of surgery and treatment field extent were not prognostic factors. Histologic type was the only variable predictive of outcome. Patients with myxopapillary type had a 5-year survival rate of 100% compared with 47% for those with other histology types. CONCLUSION: We conclude that aggressive surgery is not necessary in the management of PSCE, localised field radiotherapy is associated with favourable outcome, and tumour grade is an important prognostic factor.

[Indications for radiotherapy of benign lesions: yesterday, today and tomorrow]. / Indications de la radiotherapie des lesions benignes: hier, aujourd'hui et demain.

A better knowledge of the radiobiological effects and the control of the techniques of dosimetry led to a renewed interest for the radiotherapy of the benign lesions. The doses used for these indications are weaker than those recommended for treatment of cancer and the radiobiological mechanisms implied are different. The aim of this review of the literature is to specify the radiobiological mechanisms, the risks and the place of ionizing radiations during the processing of the benign lesions. Although the risk of radiation induced neoplasms remains a limiting factor of the indications, those are very varied. Some indications are well accepted such as keloid, cerebral arteriovenous malformations, graves' ophtalmopathy, prevention of postoperative heterotopic bone formations; and some others remain still controversial such as the prevention of the post angioplasty restenosis and age-related macular degeneration.

[Intraoperative brachytherapy in the management of keloids. Apropos of 114 cases] . / Place de la curiethérapie dans le traitement des chéloïdes. A propos de 114 cas.

PURPOSE: Keloid scars are unsightly, especially when located on the face or bare zones. The purpose of this study was to evaluate the therapeutic results of intraoperative brachytherapy in the management of keloids. MATERIAL AND METHODS: This retrospective study was based on the study of 82 patients with keloids treated in Salah Azaiz Institute (Tunisia) between 1982 and 1994 (65 women and 17 men). The mean age of patients was 23.4 years (+/- 8.4). A total of 114 lesions have been treated with surgical resection and intraoperative brachytherapy using an iridium source placed under the surgical scar. The length of iridium was chosen with the result that the radioactive thread exceeded 5 mm on each side of the surgical scar. The iridium source was loaded less than six hours after resection. Average iridium activity was 1.5 +/- 0.3 mCi/cm. Average iridium length was 56.8 +/- 34 mm. The referred isodose chosen for the target volume included the surgical scar and a margin of 5 mm around the iridium source, which was placed under the surgical scar. The average administered dose was 20.4 Gy (+/- 3.2 Gy). RESULTS: The 2-year local control rate was 87% for the whole group of lesions treated (n = 114). Local control rate of keloids processed by resection and intraoperative brachytherapy as the first treatment (59 cases) was 96% at two years. This rate was better than the local control of lesions that had been previously treated with anterior surgical resection (84% in 55 cases). For the latter group, lesions treated with a dose of more than 20 Gy had better local control, but the difference was not statistically significant (87 vs. 65% at two years, P = 0.41). CONCLUSION: Intraoperative brachytherapy is effective for improving local control of keloids and preventing a recurrence. A rigorous technique and an adequate dose according to previous surgical treatment allows very good results.

[Breast cancer in Tunisia: clinical and epidemiological study]. / Le cancer du sein en Tunisie: étude clinique et épidémiologie.

This study has been realized to determine epidemiological profile and clinicopathologic aspect of breast cancer in Tunisia. We have counted and analyzed all cancers of the breast diagnosed in Tunisia with proof pathologic or to defect cytologic of malignancy, between first January 1994 and 31 December 1994. In the course of this year, 689 new cases of mammary cancers have been diagnosed at the women. The average patient age was 50.0 years, the incidence standardized on the age of the cancer of the breast in Tunisia was 16.7/100,000 women. The average size of the tumor was 49.5 mm (35.8 mm at patients processed in private clinics and 50.7 mm at patients processed in the public hospitals). According to TNM classification of 1988, 7.2% of tumors were classified T1, 48.9% T2, 18.5% T3, and 23.4% T4 (6.2% T4d and 16.1% T4b). 22.1% of tumors were M1. 3.3% were in situ carcinoma. For the infiltrants cancers, the grade II SBR has been the most frequent (53.6%). On the therapeutic plan, the conservative processing has been practiced only at 17.6% of patients. The cancer of the breast in Tunisia rest again relatively little frequent, and its clinic profile resides alarming. The inflammatory cancer notion of the breast (equal T4d) intimately linked to Tunisia overestimates probably the reality. Cancers that were classified "PEV" in many publications would be in reality only for most of locally evolved and neglected cancers.

[Cutaneous lymphoma in Tunisia: clinical profile and therapeutic results]. / Lymphomes cutanés en Tunisie: profil clinique et résultats thérapeutiques.

PURPOSE: The aim of this retrospective study was to investigate therapeutic result of cutaneous lymphoma in Tunisia. PATIENTS AND METHODS: Between January 1969 and June 1994, 100 patients with cutaneous lymphoma were referred either to Salah Azaiz Institute or the other University Hospitals of Tunisia. Fifty-one patients had epidermotropic lymphoma and 49 non-epidermotropic lesions. Eighty-seven patients received complete treatment. Puvatherapy and other local dermatologic treatments were used for early stage mycosis fungoïdes. Thirty-two patients benefited from radiotherapy, with curative dose in 28 cases. Chemotherapy including anthracyclin agents was used for high grade lymphoma. Thirteen patients had association of radiotherapy and chemotherapy. RESULTS: Five-year survival rates were 50% for patients with epidermotropic lesions and 56% for patients with non-epidermotropic cutaneous lymphoma. Statistical study has not identified any significant prognosis factor. CONCLUSION: Radiotherapy and chemotherapy are both effective. Treatment should depend on stage and histologic type.

[Radiotherapy of epidemic Kaposi's sarcoma: the experience of the Henri-Mondor Hospital (643 patients)]. / Radiothérapie du sarcome de Kaposi épidémique: l'expérience de l'hôpital Henri-Mondor (643 patients).

PURPOSE: Retrospective analysis of results of radiotherapy in epidemic Kaposi sarcoma at the Henri-Mondor hospital. MATERIAL AND METHODS: From June 1986 to December 1996, 643 patients presenting with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma were treated with irradiation at the Oncology Department of Henri Mondor University Hospital. Three-hundred eighty-seven patients (60%) had previously received a treatment with interferon (259 patients, 40.2%), vinblastine (225 patients, 34.5%), doxorubicin (22 patients, 3.4%), bleomycin (19 patients, 2.9%), and/or antiviral treatment (216, 33.5%). The radiotherapy was delivered by 4 MeV or 8 MeV electron beam for extended cutaneous fields and 45-100 kV x-ray for localized fields. The delivered dose was 20 Gy in 2 weeks (2.5 Gy/fraction, 4 fractions/week) followed by 2 weeks rest and second series of 10 Gy in 1 week. For oral cavity lesions, we used a series of 15.2 Gy was delivered (1.9 Gy/fraction, 4 fractions/week), followed for three patients by a 3 week rest and by a similar second series of 15.2 Gy. RESULTS: Six-hundred and twenty-one patients were evaluable and the objective response rate was 92%, with a complete regression of clinical and functional symptoms for all patients. The skin tolerance was good, with 7.3% grade I reactions, 69.3% of grade II reactions, and 23.4% grade III reactions. There was a correlation between recurrence rate and the occurrence of opportunistic infections. CONCLUSION: This analysis shows the efficacy of dose radiotherapy for treatment of epidemic Kaposi sarcoma.

Radiotherapy in the management of epidemic Kaposi's sarcoma: a retrospective study of 643 cases.

PURPOSE: To report to the literature the largest published series of epidemic Kaposi's sarcoma (EKS), treated with radiation therapy, to summarize and discuss our 10 years experience in the treatment of this malignancy. METHODS AND MATERIALS: From June 1986 to December 1996, 643 patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma were treated with radiation therapy (RT) at the Cancerology Department of Henri Mondor University Hospital. The patients, 640 men and 3 women had an average age of 38.5 years (range 20-68 years). Three hundred eighty-seven patients (60.1 %) had received previous treatment for their Kaposi's sarcoma (KS). In total, 6777 fields were irradiated, as follows: face 1342 (19.8%), eyelid and conjunctiva 362 (5.3%), trunk 1903 (28.1%), upper and lower limbs 2866 (42.3%), genitals 189 (2.8%). and oral cavity 115 fields (1.7%). Radiation therapy consisted of 4 MV or 45-70 kV X-rays, depending on tumor size and location. Doses ranged from 10 to 30 Gy, according to tumor response and toxicity. RESULTS: Objective response (CR and PR) was observed in 92% (5947/6464) of all cases, treated for cutaneous form of EKS. All patients with irradiated oral lesions had an objective response. The overall tolerance was acceptable for the cutaneous lesions. By contrast, in oral lesions, mucosal reactions were often observed after relatively low doses of radiotherapy. CONCLUSIONS: Doses of 15 Gy for oral lesions, 20 Gy for lesions involving eyelids, conjunctiva, and genitals, have been shown to be sufficient to produce shrinkage of the tumor and good palliation of the symptoms. For the cutaneous EKS, we propose 30 Gy given in a local field, using a fractionated scheme with small size applicators. Radiotherapy has its own place in the management of EKS, as an efficient treatment.

[Kaposi sarcoma]. / Sarcome de Kaposi.

Moriz Kaposi was the first who, in 1872, described five patients presenting with "sarcoma idiopathicum multiple hemorrhagicum". In 1912 Sternberg termed this disease Kaposi's sarcoma. Since then various forms of this rare disease have been observed. In 1914 Hallenberg described the first cases of African or endemic Kaposi's sarcoma. In the 1960s the first reports discussing Kaposi's sarcoma following organ transplantation and immunosuppressive therapy were published. After 1981, the epidemic form associated with the acquired immunodeficiency syndrome (AIDS) was described. All these forms, their history, treatment methods and the role of radiation therapy in the management of this rare malignancy are discussed, and the literature is reviewed.

[Invasive carcinoma of the cervix in young women in Tunisia]. / Le cancer invasif du col utérin chez la femme jeune en Tunisie.

A series of 133 patients, 35 years or less in age (mean: 31.8) presenting with a carcinoma of the cervix and treated at Salah Azaiz Institute from 1969 to 1989 was analysed and compared to a control group of patients older than 35 years (mean: 54). Neither clinical nor epidemiological particularities were found in the younger patients group, except an early sexual life and a high proportion of early stage tumours (33% versus 15.9% in the older women group). Overall survival of the younger women was dramatically worse than that of the older women: 40% and 50% at 5 years, 20% and 40% at 10 years, and 14% and 30% at 15 years, respectively. This difference is statistically significant in stage I-II patients. Young age, non-sterilization of the tumour after brachytherapy, and anemia, are associated with a poor prognosis.

[Clinical and evolutive aspects of nasopharyngeal T4 N0 neoplasms]. / Aspects cliniques et évolutifs des T4 N0 du nasopharhnx.

Nasopharyngeal carcinoma (NPC) is the primary cancer of the head and neck localisations in the Salah Azaiz Institute (Tunisia). From 1970 to 1987, 80 patients with histologically proven T4 N0 NPC, were treated with exclusive radiation (70-75 Gy to the primary lesion and 50-55 Gy to cervical lymph nodes). The T4 N0 represents 7% of all NPC and 16% of the T4 treated in our Institute. Ninety percent of the patients are over 20 years old with a mean age of 52 years. The sex-ratio was 4:1. Extension to the brain was observed in 55% of the cases. Local control was 70% at 2 months after the end of irradiation. The actuarial survival at 5 years was 47%. Distant metastasis represent 13% (30% of all NPC). The main failure of treatment was local recurrence. The T4 N0 is probably a particular entity concerning the age, the response to radiotherapy and the low rate of distant metastasis.

[Cancers associated with AIDS]. / Cancers associés au SIDA.

The acquired immunodeficiency syndrome (AIDS) defining conditions were expanded to include three malignancies: epidemic Kaposi's sarcoma recognized in 1981, high and intermediate grade lymphoma included in 1985 and cervical carcinoma considered since January 1993. Progression in the management of these neoplasms depends on detailed knowledge of their pathogenesis and natural history. Treatment should take into consideration adverse factors such as the immunocompromised state and the clinical course of AIDS, particularly opportunistic infections.