Sara Pedretti

Radiotherapy for adult medulloblastoma: Long term result from a single institution. A review of prognostic factors and why we do need a multi-institutional cooperative program

AIM We retrospectively analyzed our Institution experience with these patients. The endpoints of the analysis were overall survival (OS), disease-free survival (DFS), local control (LC), metastasis free survival (MFS); results were compared with the literature. BACKGROUND Medulloblastoma in adult patients is a very rare disease; the 5 and 10-year overall survival rates range between 33-78% and 27-56%, respectively. The collection of more clinical data is strongly needed. MATERIALS AND METHODS From September 1975 to October 2006, we treated 16 adult patients (9 males and 7 females) with a histological diagnosis of medulloblastoma. Acute and late toxicities were scored according to RTOG toxicity scale. Karnofski performance status (KPS) and neurological performance status (NPS) pre- and post-RT were reported. Median age was 27 years (range 18-53 years). All the patients received cranio-spinal irradiation, two patients were also given chemotherapy. Median follow-up period was 121.5 months. RESULTS In January 2014, 10/16 patients were alive without evidence of disease, 6/16 died with progressive disease (1 local and spinal, 3 spinal and 2 extraneural). Ten-year LC, OS, DFS, MFS were, respectively, 84%, 67%, 60% and 59%. Univariate analysis shows that gross total resection is associated with better survival. No acute or late G3-G4 toxicity was observed. CONCLUSIONS This experience and the analysis of the literature confirm the efficacy of postoperative RT but also the need of large datasets to better define prognostic factors and the possible role of the association of chemotherapy.

Three-dimensional conformal radiotherapy, static intensity-modulated and helical intensity-modulated radiotherapy in glioblastoma. Dosimetric comparison in patients with overlap between target volumes and organs at risk

Aims and Background Radiotherapy is the standard treatment of glioblastoma. Three-dimensional conformal radiotherapy is the standard technique to treat glioblastoma. Intensity-modulated radiotherapy and helical intensity-modulated radiotherapy (tomotherapy) are becoming widely used. The present study compared three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy in terms of target coverage and preservation of organs at risk. Methods Ten patients treated with three-dimensional conformal radiotherapy, with a target volume close to or superimposed to the organs at risk, were retrospectively selected. The plans were re-planned with step-and-shoot 3/5 fields intensity-modulated radiotherapy and tomotherapy. Target coverage and sparing of organs at risk were statistically compared. Results Mean planning target volume V95% improved with sophisticated techniques (87.2%, 93.2%, 97.6% with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively). The comparison of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy did not show significant differences, whereas differences were significant when three-dimensional conformal radiotherapy and tomotherapy as well as intensity-modulated radiotherapy and tomotherapy were compared. Mean planning target volume/clinical target volume D99-D98-D95 were not different between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, but they were different between tomotherapy and three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, with better clinical target volume/and planning target volume coverage with the tomotherapy plans. Brain D33/66 were 31.1/11.8 Gy, 37.5/18.3 Gy and 28.5/14.7 Gy with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively. Mean brainstem, optic nerves and chiasma Dmax were always within the defined constraints. The homogeneity index improved with intensity-modulated radiotherapy/tomotherapy compared to three-dimensional conformal radiotherapy. Tomotherapy was better than intensity-modulated radiotherapy in all patients. Conclusions In this selected group of patients, a significant dosimetric advantage was evident for tomotherapy compared with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Significant advantages were evident in terms of panning target volume coverage (V95), D99, D98 and D95. The clinical significance of the results should be defined.

Primary cutaneous non-Hodgkin lymphoma: results of a retrospective analysis in the light of the recent ILROG guidelines

Purpose: To analyze clinical outcome, local response, survival and toxicity in patients with primary cutaneous lymphoma (PCL) treated with radiotherapy. Methods: From 1995 to 2014, 112 patients were treated. B-cell lymphomas (CBCLs; n = 86) and T-cell lymphomas (CTCLs; n = 23) were analyzed separately. Clinical and therapeutic characteristics (age, sex, histology, primary treatment and radiotherapy modality) were related to response to treatment, survival and toxicity. Results: CBCLs were divided into 4 subgroups: marginal-zone lymphoma (n = 20), follicle center lymphoma (n = 32), diffuse large-cell lymphoma (DLBCL; n = 22) and DLBCL-leg type (n = 12). No significant correlation was found between doses and systemic treatments, extent of biopsy and number of lesions. DLBCL-leg type patients were older (p = 0.05), had disseminated disease (p = 0.034), and more frequently had local (p = 0.01) or systemic recurrence (p = 0.05). CTCLs were divided into 4 subgroups: α/β CTCL (n = 3), nasal type CTCL (n = 0), γ/δ CTCL (n = 10) and mycosis fungoides (n = 10). Longer disease-free survival was observed in patients obtaining complete remission (p<0.001). Conclusions: Radiotherapy is feasible, safe and effective for localized PCLs. The choice of dose is related to histological subgroups and the related prognoses. Survival results are very good also in relapsing disease. In advanced cutaneous lymphoma radiotherapy alone has mainly a role in symptom palliation.

A neuro-oncologic challenge: the case of a large, aggressive, malignant meningioma of the skull base with paranasal sinus involvement.

Background Malignant meningiomas, rare tumors that account for approximately 1%-3% of all meningioma, have high recurrence, morbidity, and mortality rate and a particularly poor outcome. Surgical excision followed by adjuvant radiotherapy is the current approach for the treatment of these tumors. Methods In the case reported, the disease, characterized by a high proliferative index (Ki67 60%-70%), was treated with endoscopic surgery limited to the extracranial portion; then the patient underwent radiotherapy, on the residual tumor volume, to a total dose of 66 Gy delivered in 33 fractions (2 Gy/fraction) by helical intensity-modulated radiation therapy with image-guided radiotherapy daily checks (tomotherapy). Results Two and a half years after the treatment, the patient is alive and a partial response is maintained. The patient is healthy overall with grade I fatigue and grade II hearing loss as late toxicity (Common Terminology Criteria for Adverse Events 4.1). Conclusions Within a multidisciplinary approach, new radiotherapy techniques confirm their effectiveness and reliability for the treatment of malignant meningioma.

Radio-Resistance and Cancer Stem Cells: The Glioblastoma Model

Glioblastoma Multiforme (GBM) is the most common and aggressive primary malignancy of the central nervous system (CNS). The best currently available treatment is radical surgical excision followed by association of radiotherapy and chemotherapy with Temozolomide (TMZ). Even with this aggressive treatment, almost all the patients have replace of disease, and this recurrence remains predominately local. The Cancer Stem Cells (CSC) hypothesis assumes the existence of a hierarchic tumour model with just few CSCs responsible both of the tumour growth and of the tumour resistance to radio and chemotherapy. We therefore reviewed some aspects of the complex GBM biology; these factors could potentially, in the future, impact on the design of new translational studies.