Concurrent Radiochemotherapy of Locally Recurrent or Advanced Sarcomas of the Uterus

BACKGROUND: Uterine sarcomas are rare tumors. Until now, no data on the treatment of recurrent or advanced uterine sarcomas using concurrent radiochemotherapy (RCT) has been available. PATIENTS AND METHODS: From 01/1997 to 03/2004, seven patients with locally recurrent (n = 6) or locally advanced uterine sarcomas (n = 1) received concurrent RCT after tumor surgery (R1/2 resection in 3/7 patients). A total radiation dose of 45 Gy was applied in single doses of 1.8 Gy using an external-beam technique; in addition, three to four intracavitary doses of 5 Gy were applied. Concurrent chemotherapy was generally administered as follows: 1.2 g/m(2) ifosfamide on days 1-5 and 29-33 in combination with 50 or 40 mg/m(2) adriamycin on days 2 and 30. 3/7 patients received further cycles of chemotherapy. The median follow- up was 35 months. RESULTS: All recurrences (before RCT) were localized either in the vagina or in or directly proximal to the vaginal stump. The main side effects of RCT were hemotoxicity (grade 3: n = 3/7; grade 4: n = 4/7; neutropenic fever n = 1/7) and diarrhea (grade 3: n = 5/7). At the median follow-up (35 months), 4/7 patients had recurrences (one local recurrence; one lymph node recurrence outside the irradiated field, two distant metastases). Local control in the irradiated field was 80% +/- 18% after 3 years. Disease-free survival calculated according to Kaplan-Meier was 57% +/- 19% after 3 years. Presently, 5/7 patients are still alive, corresponding to a 3-year survival rate of 83% +/- 15%. CONCLUSION: Concurrent RCT shows good local effectiveness with a good long-term survival. Further evaluation in phase II studies is recommended.     

Medulloblastoma

Medulloblastomas are primary malignant embryonal tumours of the central nervous system. They are the most common childhood central nervous system tumour, but are rare in the adult population. They arise infratentorially in the cerebellum or fourth ventricle and hence the most common presenting symptoms are those associated with raised intracranial pressure. Several histological subtypes have been described, although the classical and desmoplastic subtypes account for the majority. Recent advances in molecular biology and cytogenetics have led to an improved understanding of the genetic abnormalities and alterations in cell signalling pathways associated with medulloblastomas, including how these relate to patient outcome. The Modified Chang Staging System is still in use, but a number of other factors, including age, completeness of resection, histological subtype and genetic markers now contribute to treatment decisions and prognostication. Patients are currently classified as being either standard or high risk in order to stratify treatment. There has been an improvement in survival of all groups over the past 20 years. A multimodality approach is the cornerstone of treatment and recent trials have concentrated on ascertaining the most efficacious treatment combinations and timings for each patient group. Advances in surgical techniques have allowed a greater attainment of the two primary surgical goals: restoring normal cerebrospinal fluid (CSF) flow and maximal tumour resection. Radiotherapy to the craniospinal axis with a boost to the posterior fossa has been standard practice, but improvement in radiotherapy techniques and quality control has enabled optimisation of the trade-off between tumour control and normal tissue late toxicities. Combination chemotherapy is usually given adjuvantly, although it may be used to delay or avoid the use of radiotherapy in infants. In the future, the treatment of medulloblastoma will probably become increasingly individualised, based on patient-specific genetic features. Attention will be focussed not only on improving survival, but also on maintaining quality of life.     

Der besondere Fall

Traumatic chylothorax is a rare result of closed thoracic trauma, mainly because the thoracic duct is fairly well protected in the posterior mediastinum. However, this position explains an obvious vulnerability to high-velocity accidents with fractures or hyperextensions of the thoracic spine. We describe two cases of multiple injured patients with traumatic chylothoraces and spinal cord injuries. As mentioned in almost all other case reports, we also observed a significant diagnostic delay. Fortunately, one fistula resolved spontaneously, but the other needed ligature of the thoracic duct. Because treatment of traumatic chylothorax often results in the need for prolonged intensive care, we discuss options to optimize diagnostic and therapeutic procedures.     

Validation of CollaboRATE and SURE – two short questionnaires to measure shared decision making during CPAP initiation

Adherence to continuous positive airway pressure (CPAP) treatment tends to be low. Brief validated instruments focusing on shared decision making have not been used in a CPAP context. The aim was to investigate factorial structure, categorical functioning of the response scale and differential item functioning across sub‐populations of the CollaboRATE and Sure questionnaires among patients with obstructive sleep apnea (OSA) before CPAP treatment is initiated. A prospective design, including 193 objectively diagnosed (polygraphy) OSA patients (68% men, 59.7 years, SD 11.5) from two CPAP clinics was used. Data were collected with the following questionnaires; Sure, CollaboRATE, Attitudes to CPAP Inventory, Epworth sleepiness scale, minimal insomnia symptoms scale, and hospital anxiety and depression scale. Objective CPAP use was collected after 6 months; 49% demonstrated decisional conflict on SURE and 51% scored low levels of shared decision making on CollaboRATE. Unidimensionality was found for both CollaboRATE (one factor explaining 57.4%) and SURE (one factor explaining 53.7%), as well as local independence. Differential item functioning showed both to be invariant across both male and female patients. Internal consistency (Cronbach's alpha 0.83) and composite reliability (0.89) were good. Latent class analyses showed that patients with low decisional conflict and high shared decision making were more adherent to CPAP treatment. CollaboRATE and SURE provided good validity and reliability scores to measure shared decision making and decisional conflict in relation to CPAP treatment. The questionnaires can be used by healthcare personnel as a tool to simplify the assessment of shared decision making.     

High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D Pilot study

We conducted a phase II study to test methotrexate (5 g/m²), as a single agent prior to radiochemotherapy for pediatric high-grade glioma and diffuse intrinsic pontine glioma. Thirty patients (19 male, median age 10.8) were enrolled. Tumors were located as follows: cortex 10, pons 7, other 13. Tumor resection was classified as gross total in 6, subtotal in 6, partial in 4, biopsy in 11 and not performed in 3. WHO grading of the histology was: IV: 11, III: 12 and II: 3. Patients received methotrexate 5 g/m² in 24-hour infusions on days 1 and 15. Subsequently 54 Gy radiation was administered with simultaneous chemotherapy including cisplatin, etoposide, vincristine and ifosfamide as previously described. Eight 6-weeks cycles of maintenance chemotherapy consisted of vincristine 1.5 mg/m² on days 1, 8 and 15; lomustine 100 mg/m² on day 2 and prednisone 40 mg/kg on days 1–17. Event-free survival rates in the whole group of 30 patients were: 43, 20, and 13% after 1, 2 and 5 years, respectively. The response evaluation after methotrexate was available in 19 of the 24 patients who started treatment with measurable disease: CR: 0, PR: 1, SD 18, PD: 0. After radiochemotherapy the response of 24 patients with measurable disease was CR: 1, PR 10, SD 12, PD 1. Both response and event-free survival were superior to the control group of 330 patients treated in various protocols of the same cooperative group. In subgroup analyses the use of dexamethasone during early treatment was linked to poor event free survival. Giving two cycles of high-dose methotrexate prior to radiochemotherapy was feasible, and the approach was taken forward to a randomized phase III trial.     

Mental health and psychosocial support aspects in disaster preparedness: Nepal

To improve mental health care in Nepal, a National Mental Health Policy, Strategy and Plan of Action was approved by the Government in 1997. Nepal has high vulnerability to natural disasters compounded by a prolonged violent civil conflict affecting almost all districts of the country. Floods, landslides and earthquakes are the most regularly occurring disasters in Nepal. There is a Health Sector Emergency and Disaster Response Plan of the Ministry of Health, but mental health and psychosocial relief is not adequately addressed in this plan. In 2003 guidelines on best public health practices in emergencies for district health workers was developed in which the minimum standard and indicators include aspects of mental and social aspects of health. The experience of the complex emergency in April 2005 showed that in general the emergency preparedness plan has not been prepared well enough, but on the other hand the health system was able to cope quite well because of past training. Further strengthening of the mental health and psychosocial aspects of disaster preparedness is strongly recommended.     

Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91.

PURPOSE: To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.