Survival Outcomes With Short-Course Radiation Therapy in Elderly Patients With Glioblastoma: Data From a Randomized Phase 3 Trial.

PURPOSE: To perform a subset analysis of survival outcomes in elderly patients with glioblastoma from a randomized phase 3 trial comparing 2 short-course radiation therapy (RT) regimens in elderly and/or frail patients. METHODS AND MATERIALS: The original trial population included elderly and/or frail patients with a diagnosis of glioblastoma. Patients joined the phase 3, randomized, multicenter, prospective, noninferiority trial; were assigned to 1 of 2 groups in a 1:1 ratio, either short-course RT (25 Gy in 5 fractions, arm 1) or commonly used RT (40 Gy in 15 fractions, arm 2); and were stratified by age (<65 years and ≥65 years), Karnofsky Performance Status (KPS), and extent of surgery. For the subset analysis in this study, only patients aged ≥65 years were evaluated (elderly and frail patients were defined as patients aged ≥65 years with KPS of 50%-70%; elderly and non-frail patients were defined as patients aged ≥65 years with KPS of 80%-100%); 61 of the 98 initial patients comprised the patient population, with 26 patients randomized to arm 1 and 35 to arm 2. RESULTS: In this unplanned analysis, the short-course RT results were not statistically significantly different from the results of commonly used RT in elderly patients. The median overall survival time was 6.8 months (95% confidence interval [CI], 4.5-9.1 months) in arm 1 and 6.2 months (95% CI, 4.7-7.7 months) in arm 2 (P=.936). The median progression-free survival time was 4.3 months (95% CI, 2.6-5.9 months) in arm 1 and 3.2 months (95% CI, 0.1-6.3 months) in arm 2 (P=.706). CONCLUSIONS: A short-course RT regimen of 25 Gy in 5 fractions is an acceptable treatment option for patients aged ≥65 years, mainly those with a poor performance status or contraindication to chemotherapy, which would be indicated in cases of methylated O6 methylguanine-DNA-methyltransferase promoter tumors.

Outcome of treatment of recurrent glioblastoma multiforme in elderly and/or frail patients.

Optimal treatment of recurrent glioblastoma multiforme (rGBM) in elderly and/or frail patients remains virtually unexplored, the best supportive care (BSC) only is routinely administered due to the fatal prognosis. We evaluated the impact of different treatment methods on post-progression survival (PPS) and overall survival (OS) of such patients. Data from 98 elderly and/or frail rGBM patients, treated initially with 1-week or 3-week radiotherapy (RT) within the phase III IAEA study (2010-2013), were analyzed. KPS at relapse and salvage treatment methods were recorded. Kaplan-Meier method was used to estimate PPS and OS for different treatment modalities. Eighty-four patients experienced recurrence: 47 (56%) received BSC, 21 (25%)-chemotherapy (CHT), 8 (9.5%)-surgery, 3 (3.5%)-RT, for 5 (6%) the data was unavailable. Median OS from randomization for all 84 patients was 35 weeks: 55 versus 30 weeks for any treatment versus BSC, p < 0.0001. Median PPS was 15 weeks: 23 weeks with any treatment versus 9 weeks with BSC, p < 0.0001. For local treatment (surgery and/or RT) median PPS was 51 versus 21 weeks for CHT, p = 0.36. In patients with poor KPS (≤60) at relapse median PPS was 9 weeks with BSC versus 21 weeks with any treatment, p = 0.014. In poor KPS patients median PPS for local treatment was 14 weeks versus 21 weeks with CHT, p = 0.88. An active therapeutic approach may be beneficial for selected elderly and/or frail rGBM patients. Poor KPS patients may also benefit from active treatment, but there is no benefit of local treatment over CHT.

International Atomic Energy Agency Randomized Phase III Study of Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme.

PURPOSE: The optimal radiotherapy regimen for elderly and/or frail patients with newly diagnosed glioblastoma remains to be established. This study compared two radiotherapy regimens on the outcome of these patients. PATIENTS AND METHODS: Between 2010 and 2013, 98 patients (frail = age ≥ 50 years and Karnofsky performance status [KPS] of 50% to 70%; elderly and frail = age ≥ 65 years and KPS of 50% to 70%; elderly = age ≥ 65 years and KPS of 80% to 100%) were prospectively randomly assigned to two arms in a 1:1 ratio, stratified by age (< and ≥ 65 years old), KPS, and extent of surgical resection. Arm 1 received short-course radiotherapy (25 Gy in five daily fractions over 1 week), and arm 2 received commonly used radiotherapy (40 Gy in 15 daily fractions over 3 weeks). RESULTS: The short-course radiotherapy was noninferior to commonly used radiotherapy. The median overall survival time was 7.9 months (95% CI, 6.3 to 9.6 months) in arm 1 and 6.4 months (95% CI, 5.1 to 7.6 months) in arm 2 (P = .988). Median progression-free survival time was 4.2 months (95% CI, 2.5 to 5.9) in arm 1 and 4.2 months (95% CI, 2.6 to 5.7) in arm B (P = .716). With a median follow-up time of 6.3 months, the quality of life between both arms at 4 weeks after treatment and 8 weeks after treatment was not different. CONCLUSION: There were no differences in overall survival time, progression-free survival time, and quality of life between patients receiving the two radiotherapy regimens. In view of the reduced treatment time, the short 1-week radiotherapy regimen may be recommended as a treatment option for elderly and/or frail patients with newly diagnosed glioblastoma.

Sternal or parasternal involvement from breast cancer: a misleading clinical sign.

BACKGROUND: Sternal arch is a nonspecific clinical signs wich may arise during following of breast cancer, this sign reveals an involvement of internal mammary nodes secondary to breast cancer. AIM: To report a rare event such as a loco-regional sternal or parasternal invasion secondary to locally advanced cases of breast cancer (BC) about a Tunisian series. METHODS: We collected retrospectively from 1988 to 2012, 11 cases of BC treated at the Institut Salah Azaiez (ISA) of Tunis, with presence during the disease evolution (initial or at relapse) of a sternal or parasternal swelling. We analyzed their clinical history, clinical and imaging data (CT-scan and/or MRI), stage, time of occurrence, treatment and evolution RESULTS: All patients were females and their mean age was 46 years varying from 24 to 75 years. The sternal or parasternal swelling was found at diagnosis in 5 cases and on recurrence in 6 patients after a mean free interval of 24 months, > 12 months in 5 cases. The mean clinical tumor size of the primitive BC was 38 mm (24-75 mm) and lesions located in external quadrants in 3 cases and internal or central in 6 cases. Sternal involvement related to large Intrammmary Chain (IMC) adenopathies was diagnosed by CT-scan. 7 patients had synchronous metastases. 9 out of the 11 patients received a locoregional RT and two received chemotherapy (CT). CONCLUSION: Sternal or parasternal swelling is a clinical apparent symptom of advanced internal mammary lymph nodes in breast cancer. The first etiologic diagnosis in this context is an advanced internal mammary chain (IMC) node involvement from breast cancer.

[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.

[Radiation therapy in extra abdominal desmoid tumours]. / Radiothérapie des tumeurs desmoïdes extra abdominales.

BACKGROUND: Desmoid tumours are rare benign tumours that have local "malignity". They can be locally aggressive by infiltrating adjacent vascular, nervous and bony structures. AIM: To define the role of radiotherapy in the management of desmoid tumours. METHODS: Retrospective study of six extra-abdominal desmoid tumours treated with surgery and radiation therapy. RESULTS: Median age was 26.8 years (16-35 years). The tumor was located in the arm (1 case), in the legs (2 cases) and in the body (3 cases). Median tumoral sizes were 86.6 mm (60-100 mm). Five patients had local recurrence after surgical resection. Radiation therapy included Cobalt 60 in five cases and photons associated to linear acceleration in one case. Total dose was between 54 and 62 Gy. At the end of radiation therapy, tumoral control was obtained in five cases after a median follow-up of 26 months (1-83 months). CONCLUSION: Surgery is the main treatment of desmoids tumours but local recurrence rates remain high even after complete resection. The role of adjuvant radiation therapy is controversial.

[Superior vena cava syndrome and internal mammary nodes in breast cancer: two cases]. / Syndrome cave superieur avec atteinte de la chaine mammaire interne au cours d'un cancer du sein: a propos de deux observations.

BACKGROUND: The association of superior vena cava syndrome with involvement of the internal mammary lymph nodes in breast cancer has not been reported in the literature. AIM: To report two cases of association of superior vena cava with involvement of the internal mammary lymph nodes in breast cancer. CASES REPORT: We report two observations in two patients 45 and 52 years with breast cancer classified T4N2M0 and T3N2M0 treated. Both patients had clinical features compatible with the diagnosis of superior vena cava confirmed by the initial clinical appearance (observation 1) and after treatment (observation 2) to the CT scan. CONCLUSION: The combination of superior vena cava with the achievement of the internal mammary chain in breast cancer worse prognosis.

Clear cell carcinoma of the uterus.

AIM: The aim of this study was to determine the characteristics and outcome of patients presenting with clear cell carcinoma (CCC) of the endometrium treated in a single institution. METHODS: We reviewed the records of patients treated in the Salah-Azaiz institute for CCC of the endometrium. A histopathological stage was retrospectively assigned to these patients according to the FIGO classification and was compared to the clinical stage. Pathological features were studied in order to determine predictif factors of extrauterine disease extention and failure patterns. RESULTS: 12 patients were included in the study. The mean age at diagnosis was 64 years (50 to 84 yers). Upstaging after surgery was found in 9 patients. 9 patients had extrauterine extension. Deap myometrial invasion was not correlated with extrauterine extension. After a median follw up of 32 months, 4 patients presented with recurrences: one vaginal recurrence, two cases of pelvic and abdominal recurrence and abdominal recurrence in one patient. All recurrences occurred during the first year after surgery. Tumor recurrence was located within the radiation field in one case. Two patients with abdomino-pelvic recurrences progressed despite the association of surgery, radiation therapy and chemotherapy. CONCLUSION: Extrauterine extension is frequent at diagnosis and not correlated to classical risk factors observed in endometrioid carcinoma. A comptlete surgical staging is necessary for adjuvant treatment. Locoregional and distant recurrences are frequent and have a poor outcome.

[Internal mammary lymph node invasion in breast cancer: myth or reality?]. / L'atteinte de la chaîne mammaire interne dans le cancer du sein: mythe ou réalite?

The internal mammary nodes are often underestimated as breast cancer lymphatic pathway spread. It is yet the first site of lymphatic invasion in central or internal tumors and the second site in external tumors. The intra-thoracic situation of internal mammary nodes explains partly, the difficulty of its exploration. To evaluate the risk of internal mammary node invasion, some predictive factors are established (tumor size, internal or central tumor location, axillary node invasion and young age). Prognostic and therapeutic impact of invasion justifies its systematic research. Without exploring internal mammary nodes status, TNM classification remains, incomplete. CT scanner, magnetic resonnance imaging, positron emission tomography scanner and sentinel node exploration technique are helpful to explore this region and to adapt its irradiation.

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.

Effect of once-a-day fractionated total body irradiation on the risk of relapse after non-T-cell-depleted HLA-matched sibling transplantation.

PURPOSE: The aim of this study was to assess the impact of fractionated total body irradiation (F-TBI) on treatment-related mortality (TRM) and relapse in patients who received a non-T-cell-depleted allogeneic stem cell transplantation (ASCT) for hematological malignancies. MATERIALS AND METHODS: Between March 2003 and December 2004, a total of 24 patients with HLA-identical sibling donors entered this study and received three doses of 3.33 Gy F-TBI separated by 24 h and cyclophosphamide or etoposide. RESULTS: At a median follow-up of 37 months (range 29-47 months), 4 of the 24 patients (16.6%) died of TRM. Relapse occurred in 10 patients at a median of 9 months (range 2-18 months). Overall, 13 of 24 patients (54%) died. Relapse was the most common cause of death (9/13). The 2-year actuarial survival rate was 46% (+/-11%). CONCLUSION: In our experience, ASCT conditioned with F-TBI was associated with low TRM but a high early relapse rate in patients with hematological malignancies.

[Skin cancer in Tunisia: a retrospective study: 1379 cases and risk factors]. / Les cancers cutanés en Tunisie: une étude rétrospective de 1379 cas et facteurs de risques.

UNLABELLED: The aim of this study was to determine the clinical and epidemiological aspects of skin cancer in Tunisia. METHODS: we analysed the clinical files of all cases of skin cancer registrated at the ISA institute between 1975 and 1984. RESULTS: 1379 cases of skin cancer were referred to ISA, representing 9.02% of all cancer cases referred to the institute during the same period. Basal cell carcinoma (CBC) was the most frequent type (57.5%) followed by squamous cell carcinoma (CSC): 32.6% and melanomas: 4%. The sex ratio was 1.7 with a mean age of 61 years in men and 60 years in women. The face was the most frequent involved sites in CBC (92%). This region is usually exposed to the sun. The distribution of CSC in the body was different. The lesions were multiple in 11% of the cases. 13.7% of the CSC were developped on a burn scar. 21 cases were radio-induced and 45 patients had a xeroderma pigmentosum. CONCLUSION: skin cancer is relatively frequent in Tunisia. However, our incidence is inferior to other countries. Sun exposure is the main risk factor.

[Medulloblastoma with extracentral nervous system metastases: clinical presentation and risk factors]. / Medulloblastoma with extracentral nervous system metastases: clinical presentation and risk factors.

PURPOSE: Extra-central nervous system (extra-CNS) metastases are relatively unknown failure patterns in medulloblastoma. The aim of this study was to analyse epidemiological, clinical and aetiopathological aspects of these extra-CNS localisations. PATIENTS AND METHODS: Extra-CNS metastases were retrospectively identified in patients treated in the department of radiation therapy at Salah-Azaïz institute (ISA) for medulloblastoma. These metastases were diagnosed as extra-CNS for all secondary localisations not related to other tumour aetiology. Aetiopathological aspects are discussed with a literature review. RESULTS: Among 103 patients treated and followed-up in the department of radiation therapy of ISA from 1970 to 1992, 8 developed extra-CNS metastases (7.7%). Age at diagnosis of primitive tumour varied from 3 to 23 years. Sex ratio was 1. Primitive tumour treatment was: complete surgical resection in 4 patients with preoperative cerebrospinal fluid shunting in two, cerebrospinal axis irradiation in 7 patients and a cerebral-limited irradiation in 1. Two patients received chemotherapy for their initial treatment (systemic in one case and intrathecal in the other). The mean free-interval from diagnosis of primitive tumour to extra-CNS metastases was 23 months, varying from 8 to 53 months. These metastases were located in the liver (1 case), cervical lymph nodes (2 cases), bone marrow (1 case) and bone (2 cases). Two patients had multiple metastases: bone and bone marrow (in one), lung, pleura, cervical lymph node and bone localisations (in one). Treatment of these metastases was: chemotherapy in 5 cases, chemotherapy and radiation in one, radiation therapy in one and 2 patients were given only supportive care treatment. All patients died or are in progressive disease in less than one year from the diagnosis of extra-CNS metastases. CONCLUSION: Extra-CNS metastases are not rare and have a poor prognosis. The most commonly involved sites are bone, cervical lymph nodes and bone marrow. A complete work-up at initial diagnosis is recommended to screen early metastases. Literature review showed that histopathologic grading might help to identify groups at risk.