Paediatric medulloblastoma: patterns of care and radiotherapy quality assurance in Australia

The purpose of this study was to document how children in Australia with medulloblastoma are being treated and to evaluate the quality of radiotherapy (RT) delivered. The Radiotherapy Database of the Australian and New Zealand Children's Haematology and Oncology Group was used to identify 46 children with medulloblastoma younger than the age of 15 years treated with radical intent by craniospinal irradiation between 1997 and 1999 inclusively. Twenty-six patients had completely resected disease without evidence of disease spread. Of these, 16 patients received a craniospinal RT dose of <25 Gy in addition to chemotherapy. RT treatment immobilization methods varied, as did planning methods. RT dose to critical structures was recorded on treatment plans for only 15% of patients. The average systematic error in shield placement at the posterior orbit was 5.2 mm, and two-thirds of patients were 'overshielded' at this site. Adequate coverage of the distal end of the thecal sac was achieved in fewer than 50% of on-treatment verification films for 21 of 45 patients. With a reduction in RT dose to the craniospinal axis for paediatric medulloblastoma, greater attention is needed for patient immobilization, documentation of RT dose to critical structures and the placement and reproducibility of shielding.     

Craniospinal Radiotherapy in Adult Medulloblastoma

PURPOSE: To evaluate the outcome and prognostic factors of adult patients with medulloblastoma. PATIENTS AND METHODS: 26 adult medulloblastoma patients with a median age of 27 were subjected to craniospinal radiotherapy. A dose of 30.6 Gy with 1.8 Gy/fraction/day was prescribed to M0 patients, while 36 Gy were to be applied in patients with positive cerebrospinal liquor findings. The posterior fossa was boosted to 54 Gy. While 20 patients underwent external-beam radiotheray alone, only six received sequential adjuvant chemotherapy. RESULTS: Male/female ratio was 1.2. Preradiotherapy Karnofsky performance status was recorded as median 100%. 50% were classified as poor risk (n = 10, subtotal resection; n = 3, M+). The median follow-up time was 46.5 months. The 5-year actuarial survival rates for recurrence-free, distant metastasis-free, disease-free, and overall survival were 82.5%, 90.8%, 73.5%, and 89.7%, respectively. Patient characteristics, treatment factors and tumor characteristics failed to show any significance in univariate analysis. Grade 3 or 4 late morbidities were not observed. CONCLUSION: Yet, the current standard of care seems to remain craniospinal irradiation after maximal surgical resection of the primary neoplasm without clear indications for adjuvant chemotherapy.     

Medulloblastoma in adults

BACKGROUND AND PURPOSE: In this study, the clinical outcome and prognostic factors of adult medulloblastoma patients receiving multimodal treatment were investigated. PATIENTS AND METHODS: The clinical manifestations, treatment variables, and outcome of adult patients with medulloblastoma at our institution between 1983 and 2009 were retrospectively reviewed. RESULTS: A total of 20?adult patients were included (median age 22?years). Craniospinal irradiation (CSI) was given postoperatively. The craniospinal axis received a median of 30?Gy (range 23.4-39.6?Gy) in fractions of 1.6-2?Gy/day, and the tumor was boosted to a total median dose of 50?Gy (range 50-55.25?Gy). The 3-year disease-free survival (DFS) and overall survival (OS) rates for all patients were 45% and 50%, respectively. In univariate analysis, Karnofsky Performance Scale (KPS) >?70, neurologic symptoms duration >?30?days, lateral tumor location, standard risk patients, no hydrocephalus, radiotherapy (RT) treatment field (CSI?+?brain boost), and CSI dose ≥?30?Gy were associated with better DFS. Standard-risk patients, RT treatment field (CSI?+?brain boost), and CSI dose ≥?30?Gy were also significantly associated with better OS. CONCLUSION: The combined modality treatment results in a favorable outcome for adult medulloblastoma patients. Further investigation of the prognostic factors, radiation-related factors, and systemic chemotherapy is needed.     

Decline in corpus callosum volume among pediatric patients with medulloblastoma: longitudinal MR imaging study

BACKGROUND AND PURPOSE: A decline in intrahemispheric cerebral white matter volume in children treated for brain tumors with cranial irradiation has been well documented. It was hypothesized that the development of the corpus callosum, the largest white matter commissure of the brain, would also be adversely affected after treatment with cranial irradiation in pediatric patients treated for medulloblastoma. METHODS: After diagnosis, 35 patients (22 male and 13 female patients) with histologically proved medulloblastoma were treated by maximal surgical resection, risk-adapted craniospinal irradiation, and chemotherapy. Using quantitative measurement techniques with MR imaging, corpus callosum volume was measured at multiple time points for each patient during a 4-year period. RESULTS: Quantitative MR imaging analyses of 239 examinations in 35 patients showed, in contrast to normal development, that the total midsagittal corpus callosum area decreased with time from craniospinal irradiation (-18.0 mm(2)/y; P <.0001). After examination of seven corpus callosum subregions, significant declines were also observed: genu (-2.2 mm(2)/y; P =.03), rostral body (-2.0 mm(2)/y; P =.04), anterior midbody (-1.4 mm(2)/y; P =.005), posterior midbody (-1.2 mm(2)/y; P =.004), isthmus (-2.4 mm(2)/y; P =.001), and splenium (-5.0 mm(2)/y; P =.007). CONCLUSION: The greatest deviation from normal development occurred in the most posterior subregions of the corpus callosum: the isthmus and the splenium. These corpus callosum subregions, associated with fibers traversing from the temporal, posterior parietal, and occipital lobes, are normally expected to have the highest rate of growth during childhood. However, these regions also received the highest total dose of irradiation, providing a possible explanation for atypical corpus callosum development observed in these 35 patients treated for medulloblastoma.     

Medulloblastoma in adults

Purpose

Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution.

Methods

Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients’ demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated.

Results

In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2?Gy) and a boost to the posterior fossa (median dose 19.8?Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5? and 10-year OS was 89 and 80%, respectively. Estimated 5? and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS.

Conclusions

The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible.

     

Multivariate analysis of dissemination relapse of medulloblastoma and estimation of its time parameter for craniospinal irradiation

PURPOSE: To examine in retrospect prognostic factors influencing meningeal dissemination relapse of medulloblastoma (MB) and to estimate time parameter gamma/alpha of the biologically effective dose for fractionated craniospinal irradiation (CSI). MATERIALS AND METHODS: Fifty-eight patients with MB who had been treated at our six hospitals from 1980 to 1990, were analyzed by the proportional hazards model consisting of radiation factors of both CSI and local irradiation (LI), sequential CSI time-lag, and eight non-radiation factors (gender, age, performance status, T-stage, dissemination score, extent of resection, and use of chemotherapy and immunotherapy). The gamma/alpha for CSI was estimated by the profile likelihood method using the maximum value of conditionally calculated time-incorporated biologically effective dose, tBEDmax, of the field treated with the least dose. RESULTS: Dissemination relapse was seen in 23 (40%) patients. Nineteen disseminations occurred within four years, and the cumulative dissemination-free rate was 64% at five years. The site of initial dissemination relapse was both cranial and spinal in 13 patients (57%). Dissemination relapse was accompanied with local failure in 43% (10/23) of patients, and four of them were seen later than four years. In the multivariate analysis, significant prognostic factors were dissemination score (p=0.0008) and total dose of CSI (p=0.018). The estimate of gamma/alpha for CSI was about 0.2 Gy/day in BED units. In another multivariate analysis including the best-fitted tBEDmax, significant prognostic factors were dissemination score and the tBEDmax of both CSI (p=0.021) and LI (p=0.024). CONCLUSION: This analysis indicated that the dissemination score, total dose of CSI, and tBEDmax of both CSI and LI were significantly prognostic for dissemination relapse of MB. The estimate of gamma/alpha for CSI was smaller than that derived from our previous analysis for LI. However, in order to estimate the time factor for CSI more precisely, a larger group of patients treated with concurrent CSI is needed.     

White matter anisotropy in childhood medulloblastoma survivors: association with neurotoxicity risk factors

PURPOSE: To prospectively evaluate the relationships between change in white matter (WM) anisotropy and (a) patient age at craniospinal irradiation (CSI), (b) CSI dose, and (c) time of magnetic resonance (MR) imaging since CSI and to determine the effect of these neurotoxicity risk factors on WM anisotropy in posttreatment medulloblastoma survivors. MATERIALS AND METHODS: Informed consent was obtained from the patients, control subjects, or their parents, and the study was approved by the institutional review board. Twenty consecutive medulloblastoma survivors (14 male, six female; mean age, 11.0 years +/- 4.6 [standard deviation]) and 36 control subjects (14 male, 22 female; mean age, 10.7 years +/- 3.5) were examined. Control subjects were divided into four groups according to age: 5.0-7.9 years, 8.0-10.9 years, 11.0-13.9 years, and 14.0-18.9 years. The authors calculated the histogram-derived mean WM fractional anisotropy (FA) value for each patient and compared it with the mean WM FA value for the control subjects in the corresponding age group to evaluate the percentage change in WM FA (DeltaFA) in each patient. Spearman rank correlation analysis was used to analyze the relationships between DeltaFA and (a) age at CSI, (b) CSI dose, and (c) time of MR imaging since CSI. Then, multiple linear regression analysis was performed to study the simultaneous influence of these factors on DeltaFA. RESULTS: There were significant correlations between DeltaFA and both age at CSI (r = 0.631, P = .003) and CSI dose (r = -0.586, P = .007) but not between DeltaFA and time of MR imaging since CSI. Multiple linear regression analysis revealed age at CSI to be the only independent variable that significantly affected DeltaFA (adjusted r2= 0.391, P = .012). CONCLUSION: Loss of WM anisotropy is significantly affected by age at CSI, and there is a trend toward increasing anisotropy loss with larger CSI dose. Both age at CSI and CSI dose are known risk factors of neurotoxicity.     

Influence of radioimmunoscintigraphy on postprostatectomy radiotherapy treatment decision making.

The aim of this study was to evaluate the role of radioimmunoscintigraphy (RIS) directed against prostate-specific membrane antigen (PSMA) in influencing postradical retropubic prostatectomy (RRP) radiotherapy (RT) decision making. METHODS: The records of consecutive patients who underwent RRP, who were referred for consideration of RT, and for whom an RIS scan was obtained were reviewed. The RT decisions, with regard to (a) the decision to offer RT and (b) the general volume to be treated [prostate fossa (PF) only versus PF + pelvis (P)] before knowledge of the RIS findings were charted. The RIS findings, with regard to uptake in the PF, uptake in the P, or extrapelvic (EP) uptake were tabulated. Then, the RT treatment decisions based on the RIS knowledge were evaluated and compared with the pre-RIS RT treatment decisions. RESULTS: Of the 54 patients originally referred for post-RRP RT, the initial decision was to recommend RT to the PF only in 52 cases and to PF+P in 2 cases. The RIS findings were as follows: PF only, 43 patients; PF+P, 8 patients; PF+EP, 2 patients; PF+P+EP, 1 patient. After knowledge of these RIS results, the decision to offer RT was withdrawn in 4 of 54 patients (7.4%; P = 0.046). Furthermore, RIS changed the general treatment volume (PF only to PF+P) in 6 of 54 patients (11.1%; P = 0.015). In total, RIS altered the RT decision in 10 of 54 patients (18.5%; P = 0.0067). Three-year biochemical failure-free survival (with failure defined as 2 consecutive prostate-specific antigen [PSA] rises above 0.2 ng/mL after PSA nadir) was 78%; no patient, disease, or treatment factor reached statistical significance on univariate or multivariate analysis. CONCLUSION: RIS was found to influence post-RRP RT decision making for the identification of patients not likely to benefit from RT and for guiding general target volume definition.     

Radiochemotherapy with temozolomide for patients with glioblastoma

Background

The objective of this retrospective analysis was to assess long-term outcome and prognostic factors of unselected patients treated for glioblastoma (GB) at a single center with surgery, standard radiotherapy (RT), and concomitant temozolomide (TMZ). From 1999?C2005, the institutional protocol included surgery and RT with TMZ. From 2005 on, adjuvant TMZ was routinely added.

Patients and Methods

Between April 1999 and September 2009, 181 patients with GB were treated with RT (60 Gy in 30 fractions) and concomitant TMZ (75 mg/m²/day throughout RT). Biopsy only had been performed in 53 patients (29.3%), 128 patients (70.7%) had undergone resection, which was complete based on postoperative MRI in 51 patients (28.2%). Adjuvant TMZ was applied in 67 of 181 patients (37%).

Results

Median overall survival (OS) and progression-free survival (PFS) were 15.0 (95% CI, 13.1?C16.8) and 7.2 months (95% CI, 5.9?C8.5), respectively. After complete resection, partial/subtotal resection and biopsy, median OS was 23.20, 14.75, and 7.89 months (p < 0.001), respectively. In multivariate Cox proportional hazards regression models, extent of resection (p < 0.0001), Karnofsky??s performance score (p < 0.0001) and adjuvant TMZ (p = 0.001) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 146 patients (80.7%), while 11 patients (6.1%) discontinued RT. Another 35 patients (19.3%) interrupted concomitant chemotherapy.

Conclusion

RT with concomitant TMZ is a feasible regimen with acceptable toxicity in routine practice. Our data are compatible with a beneficial effect of adjuvant TMZ on OS and PFS.     

Radio-chemotherapy for bladder cancer: Contribution of chemotherapy on local control

The purpose of this study was to review the magnitude of contribution of chemotherapy(CT) in the local control of muscle invasive bladder carcinoma in the studies where a combined radio-chemotherapy(RCT) was used(how much higher local control rates are obtained with RCT compared to RT alone).Studies on radiotherapy(RT) and combined RCT,neo-adjuvant,concurrent,adjuvant or combinations,reported after 1990 were reviewed.The mean complete response(CR) rates were significantly higher for the RCT studies compared to RT-alone studies:75.9% vs 64.4%(Wilcoxon ranksum test,P = 0.001).Eleven of the included RCT studies involved 2-3 cycles of neo-adjuvant CT,in addition to concurrent RCT.The RCT studies included the onephase type(where a full dose of RCT was given and then assessment of response and cystectomy for nonresponders followed) and the two-phase types(where an assessment of response was undertaken after an initial RCT course,followed 6 wk later by a consolidation RCT for those patients with a CR).CR rates between the two subgroups of RCT studies were 79.6%(one phase) vs 71.6%(two-phase)(P = 0.015).Theaverage achievable tumour control rates,with an acceptable rate of side effects have been around 70%,which may represent a plateau.Further increase in CR response rates demands for new chemotherapeutic agents,targeted therapies,or modified fractionation in various combinations.Quantification of RT and CT contribution to local control using radiobiological modelling in trial designs would enhance the potential for both improved outcomes and the estimation of the potential gain.     

Management of non-Hodgkin's lymphoma of the thyroid: the Royal Marsden Hospital experience

A retrospective review was conducted of patients treated for thyroid non-Hodgkin's lymphoma (TNHL) at the Royal Marsden Hospital between 1936 and 1996 to determine the effect of radiotherapy (RT) on outcome. 91 patients were identified from the Thyroid Unit Database. There were 77 females and 14 males with a median age of 65 years (range 22-87 years). RT was delivered according to two separate policies: (1) involved field radiotherapy (IFRT) to the thyroid bed and cervical lymph nodes; (2) extended field radiotherapy (EFRT) covering the thyroid bed, cervical and mediastinal lymph nodes. 89 patients received RT as part of definitive treatment following surgery, to a dose of approximately 40 Gy. 25 patients received IFRT and 64 patients EFRT. 27 patients received cytotoxic chemotherapy. 18 patients (72%) treated with IFRT died of TNHL with a median relapse free survival (RFS) of 10 months and a median overall survival (OS) of 21 months. In contrast, only 29 patients (46%) treated with EFRT died of TNHL with a median RFS of 76 months (p = 0.01 for RFS with respect to IFRT and p = 0.04 for OS). Significantly more patients treated with IFRT relapsed locally (52% vs 27%). There was no difference in the rates of systemic relapse (20% vs 22%). EFRT alone for Stage I, but not for Stage II disease, yielded acceptable rates of local control and disease free survival with doses of at least 40 Gy. These historical data strongly support the addition of combination chemotherapy to the treatment regimen in all patients with Stage II disease. Indeed, in recent years this has become the standard of care for all cases of thyroid lymphoma unless the histology is of marginal zone type (mucosa associated lymphoma tissue (MALT) lymphoma).     

Absence of adverse early quality of life outcomes of radiation therapy in breast conservation therapy for early breast cancer

The New South Wales Breast Radiation Oncology Group has completed a prospective multicentre study of the impact of radiation therapy (RT) on acute toxicity and quality of life (QoL) in women with early breast cancer treated with breast conservation therapy. The patient group received adjuvant breast tangential RT after wide local excision of breast cancer. Acute toxicity and cosmesis was assessed quantitatively and qualitatively. European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) and Perceived Adjustment to Chronic Illness Scale (PACIS) were the QoL instruments used. Of 175 women, 34.3% described lethargy leading to a significant disruption to normal activity during RT. At week 6, this had reduced to 7.5% reporting significant lethargy. No negative effects on QoL were noted over the time period of RT; EORTC demonstrated no difference (P = 0.79). PACIS recorded a significant improvement in functioning (P < 0.001) from baseline to week 6. Univariate analysis on potential predictive patient, tumour and treatment factors demonstrated an association of baseline pre-RT breast discomfort with worse lethargy (P = 0.03), EORTC (P < 0.01) and PACIS (P < 0.01) measures. This study confirms the minimal impact of RT on patient functioning at 6 weeks post-treatment.     

Radiation therapy combined with or without chemotherapy for limited extent of non-small cell lung carcinoma

From July 1977 to December 1983, 130 patients with limited extent of non-small cell lung carcinoma received radiotherapy of more then 30 Gy combined with or without chemotherapy at the Center for Adult Diseases, Osaka, Japan. Four treatment arms were evaluated: RT alone, RT following chemotherapy, RT following low dose concurrent irradiation with chemotherapy (LDC-RT), and RT concurrently used with chemotherapy. Complete regression of local and regional tumor was produced in 5% and partial regression 58%. Among these four treatment arms LDC-RT showed the highest response rate (88%), while no difference in long-term survival was apparent. According to the RT dose, survival of cases who received RT doses above 50 Gy was better than that of cases under 50 Gy in spite of the combination with chemotherapy. These data suggest that adjuvant chemotherapy has no favorable impact against the survival. Concerning the prognostic factor, tumor response after treatment, general performance status and N stage were important.     

局部晚期鼻咽癌同步化疗与诱导化疗联合调强放疗的疗效分析

目的比较同步化疗与诱导化疗联合调强放疗治疗局部晚期鼻咽癌的疗效和毒副反应。方法将60例局部晚期鼻咽癌患者随机分为诱导化疗联合调强放疗组30例（诱放组）与同步化疗联合调强放疗组30例（同放组）。两组放疗方法相同,均采用调强放疗。鼻咽癌原发病灶（GTV1）给予70Gy,2.10～2.25Gy/次;达诊断标准的颈部淋巴结（GTV2）给予65～68Gy,2.0～2.18Gy/次;高危预防区（CTV1）给予60～62Gy,1.8～2.0Gy/次;低危预防区（CTV2）给予50.4Gy,1.8Gy/次。化疗方法为紫杉醇150mg/m2d1,顺铂90mg/m2（每日30mg/m2）d2～4。诱放组为先诱导化疗两周期＋放疗＋辅助化疗两周期。诱导化疗为每21天1周期。同放组为先同步放化疗＋辅助化疗两周期。同步化疗为每28天1周期。两组辅助化疗均为每28天1周期。结果中位随访时间46个月。诱放组与同放组5年总生存率,无复发生存率,无转移生存率分别为59.1%和74.5%（χ2=0.24,P=0.624）,40.4%和74.5%（χ2=1.959,P=0.162）,35.6%和74.5%（χ2=2.491,P=0.114）。毒性反应观察：同放组发生3～4级口腔黏膜反应为53.3%,诱放组为36.7%（P=0.032）,同放组发生骨髓抑制率为50.0%,诱放组为20.0%（P=0.024）,同放组的副作用明显要高于诱放组。结论同步放化疗和诱导化疗＋放疗这两种治疗方法对于局部晚期鼻咽癌特别是T3～4N0～3的患者在总生存率、无复发生存率和无转移生存率上无统计学差异。同放组较诱放组治疗毒性反应大,但能耐受。     

Radiation-induced osteochondroma of the T4 vertebra causing spinal cord compression

A case of a radiation-induced osteochondroma arising from the vertebral body of T4 in an 18-year-old man is reported. The patient presented with a history of progressive left lower extremity weakness. At 7 years of age, he had undergone resection of a cerebellar medulloblastoma and received adjunctive craniospinal irradiation and systemic chemotherapy. Both CT and MR imaging revealed an extradural mass contiguous with the posteroinferior endplate of the T4 vertebral body. This case indicates that radiation-induced osteochondroma should be considered in the differential diagnosis of patients with symptoms of myelopathy or nerve root compression and a history of radiation therapy involving the spine in childhood.     

What’s in a name?

Background

Intracranial peripheral primitive neuroectodermal tumors (P-PNET) are extremely rare. They can be easily misdiagnosed as central nervous system primitive neuroectodermal tumors (CNS-PNET) or meningiomas. Little is known about the optimal treatment and prognosis of these tumors.

Patients and methods

We evaluated the treatment and outcome of 17 patients with intracranial, nonmetastatic, genetically confirmed P-PNET. Three patients were treated at our institutions. Thirteen other cases providing sufficient treatment and follow-up information were extracted from the literature.

Results

The median age at diagnosis was 17 years. All patients underwent initial surgery. Complete resection was achieved in 9 of the 17 cases (53?%). Combined adjuvant treatment consisting of radiotherapy (focal, n?=?10; craniospinal, n?=?1) and chemotherapy was administered to 11 of the 17 patients (59?%). The median follow-up time was 1.4 years. In 8 of the 17 patients (47?%), the disease progressed; 4 of the 17 patients (24?%) died. The 2-year progression-free and overall survival rates were 64?% and 76?%, respectively.

Conclusion

The differential diagnosis for intracranial, meningeal-based, small, round-cell tumors should include P-PNET. It is highly probable that complete resection has a positive impact on survival—as previously reported for extracranial P–PNET—but this cannot be shown by our data. Intensive adjuvant treatment consisting of radiotherapy and chemotherapy seems to be essential. A statistically grounded recommendation for the appropriate target volume and radiation dose is not yet possible. However, in most case reports of primary intracranial P-PNET published to date, patients were treated with focal irradiation. The optimal chemotherapy regimen has yet to be established, with both the Ewing tumor and CNS-PNET protocols being promising candidates for effective treatment.     

Incidence and clinical course of radionecrosis in children with brain tumors

Radionecrosis (RN) in children treated for brain tumors represents a potentially severe long-term complication. Its diagnosis is challenging, since magnetic resonance imaging (MRI) cannot clearly discriminate between RN and tumor recurrence. A retrospective single-center study was undertaken to describe the incidence and clinical course of RN in a cohort of 107 children treated with external radiotherapy (RT) for various brain tumors between 1992 and 2012. During a median follow-up of 4.6 years (range 0.29–20.1 years), RN was implied by suspicious MRI findings in in 5 children (4.7?%), 5–131 months after RT. Suspicion was confirmed histologically (1 patient) or substantiated by FDG positron-emission tomography (FDG-PET, 2 patients) or by FDG-PET and MR spectroscopy (1 patient). Before developing RN, all 5 patients had received cytotoxic chemotherapy in addition to RT. In addition to standard treatment protocols, 2 patients had received further chemotherapy for progression or relapse. Median radiation dose expressed as the biologically equivalent total dose applied in 2 Gy fractions (EQD2) was 51.7 Gy (range 51.0–60.0 Gy). At RN onset, 4 children presented with neurological symptoms. Treatment of RN included resection (n?=?1), corticosteroids (n?=?2) and a combination of corticosteroids, hyperbaric oxygen (HBO) and bevacizumab (n?=?1). One patient with asymptomatic RN was not treated. Complete radiological regression of the lesions was observed in all patients. Clinical symptoms normalized in 3 patients, whereas 2 developed permanent severe neurological deficits. RN represents a severe long-term treatment complication in children with brain tumors. The spectrum of clinical presentation is wide; ranging from asymptomatic lesions to progressive neurological deterioration. FDG-PET and MR spectroscopy may be useful for distinguishing between RN and tumor recurrence. Treatment options in patients with symptomatic RN include conservative management (steroids, HBO, bevacizumab) and surgical resection.     

Primary spinal epidural extraosseous Ewing's sarcoma: report of five cases and literature review

Ewing's sarcoma is the most common malignant bone tumour occurring in children and adolescents and exists in two different clinicopathological entities: osseous Ewing's sarcoma (OES) and extraosseous Ewing's sarcoma (EES). Five cases of primary epidural EES are described, which presented with non-specific symptoms leading to a long diagnostic delay. The median age at diagnosis was 22 years (range 13-36 years). The median diagnostic delay was 3 months. All patients had one or more neurological deficits. All underwent surgical exploration with a laminectomy and partial resection followed by adjuvant radiotherapy to a dose of 46-50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide) alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six cycles. The mean follow-up period is 21.2 months (range 11-32 months). Four of the five patients achieved a complete remission and are disease free at the time of writing this report. Two patients have a residual neurological deficit--both having presented with long history of neurological deficit. Primary spinal epidural EES should be suspected whenever young patients present with back pain and/or radicular pain, have abnormal neurology and an extradural mass is demonstrated on MRI. Surgical excision followed by adjuvant radiotherapy (50 Gy) and combination chemotherapy (VAC alternating with ICE) achieved local and systemic control in these patients. A greater number of patients and longer follow up are required to evolve a generally accepted treatment policy for this aggressive but potentially curable malignancy.     

Can the Addition of Regional Radiotherapy Counterbalance Important Risk Factors in Breast Cancer Patients with Extracapsular Invasion of Axillary Lymph- Node Metastases?

PURPOSE: To evaluate if locoregional radiotherapy (RT) versus local irradiation only can alter the pattern of failure in breast cancer patients with extranodal invasion. PATIENTS AND METHODS: From 08/1988 to 06/1998, 81 patients with extranodal invasion were treated with adjuvant RT (median total dose: 50.4 Gy), 46/81 only locally, 35/81 loco regionally due to presumed adverse parameters. The mean number of resected (positive) lymph nodes was 17 (seven). 78 patients received adjuvant systemic treatment(s). RESULTS: Patients treated with locoregional RT had significantly more often lymphatic vessel invasion (LVI; 63% vs. 28%; p = 0.003), T3/T4 tumors (43% vs. 17%; p = 0.014), and four or more positive lymph nodes (91% vs. 46%; p < 0.001) than patients irradiated only locally. Disease progression occurred in 24/81 patients (locoregional RT: 26% vs. local RT: 33%). The above risk factors were highly significant of worse outcome. Despite their overrepresentation in the locoregional RT group, no difference was found between both groups in regard to disease-free survival (DFS; p = 0.83) and overall survival (OS; p = 0.56), suggesting that regional RT was able to counterbalance the increased risk. There was even a trend toward a better 3-year DFS, 61% in locoregional RT and 37% in local RT, in the subgroup of patients with four or more positive lymph nodes. In a Cox regression model, higher T-stage, four or more positive lymph nodes, and LVI remained significant. For DFS and distant metastasis-free survival (DMFS), the absence of estrogen receptors and the omission of regional RT were also significant. CONCLUSION: Our data suggest that the addition of regional RT might be beneficial in selected subgroups of patients with extranodal invasion and other poor prognostic factors.