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Biomedical subjects

Frank Saran

Publications and source records attributed to Frank Saran.

12 recordsLinked to original sources
PubMed2006

Fractionated stereotactic conformal radiotherapy following conservative surgery in the control of craniopharyngiomas.

PURPOSE: To describe the technique and results of stereotactically guided conformal radiotherapy (SCRT) in patients with craniopharyngioma after conservative surgery. METHODS AND MATERIALS: Thirty-nine patients with craniopharyngioma aged 3-68 years (median age 18 years) were treated with SCRT between June 1994 and January 2003. All patients were referred for radiotherapy after undergoing one or more surgical procedures. Treatment was delivered in 30-33 daily fractions over 6-6.5 weeks to a total dose of 50 Gy using 6 MV photons. Outcome was assessed prospectively. RESULTS: At a median follow-up of 40 months (range 3-88 months) the 3- and 5-year progression-free survival (PFS) was 97% and 92%, and 3- and 5-year survival 100%. Two patients required further debulking surgery for progressive disease 8 and 41 months after radiotherapy. Twelve patients (30%) had acute clinical deterioration due to cystic enlargement of craniopharyngioma following SCRT and required cyst aspiration. One patient with severe visual impairment prior to radiotherapy had visual deterioration following SCRT. Seven out of 10 patients with a normal pituitary function before SCRT had no endocrine deficits following treatment. CONCLUSION: SCRT as a high-precision technique of localized RT is suitable for the treatment of incompletely excised craniopharyngioma. The local control, toxicity and survival outcomes are comparable to results reported following conventional external beam RT. Longer follow-up is required to assess long-term efficacy and toxicity, particularly in terms of potential reduction in treatment related late toxicity.

Adolescent↗
PubMed2006

Germinoma with synchronous lesions in the pineal and suprasellar regions.

BACKGROUND: Germinomas represent the most frequent tumour type in the pineal region and the synchronous involvement of the suprasellar region, frequently termed bifocal disease, is increasingly recognised. The incidence, pathogenesis, histomorphological, radiological, clinical features, and management strategies are discussed. CASE REPORT: A 6-year-old girl presented with clinical features of hypothalamic-pituitary axis dysfunction. MRI showed two distinct lesions in the pineal and suprasellar regions. Tumour markers for germ cell tumours from blood and cerebrospinal fluid were within the normal range. The suprasellar lesion was biopsied and the histology revealed a germinoma. She received a radical course of radiotherapy covering the entire craniospinal axis (24 Gy/15#) followed by focal boost to the sites of primary disease (16 Gy/10#). Three months after the completion of treatment, the patient achieved a complete clinical and radiological response, which was maintained during the 13-month follow-up period. CONCLUSIONS: The optimum management of primary intracranial pineal and suprasellar (bifocal) germinomas still remains controversial. The definition as either localised or disseminated disease has major implications on required treatment and its associated late morbidity. Prospective studies with large cooperative groups worldwide and consensus meetings may reduce uncertainties regarding available management options.

Child↗
PubMed2006

Analysis of patients with supratentorial primitive neuro-ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study.

The SIOP PNET 3 study was designed to determine whether 10 weeks of moderately intensive chemotherapy given after surgery and before radiotherapy (RT) would improve the outcome for patients with primitive neuroectodermal tumours (PNETs) compared with RT alone. Patients with a histological diagnosis of supratentorial PNET (StPNET) and no radiological evidence of metastatic disease were initially eligible for randomisation to either chemotherapy followed by craniospinal RT 35 Gy in 21 fractions with a boost of 20 Gy in 12 fractions to the primary site, or RT alone. In respect of the increasing recognition that StPNET were high-risk tumours, randomisation for this group closed in November 1999. This analysis includes both randomised and non-randomised patients with StPNET entered into the study database. Sixty-eight patients aged 2.9-16.6 years (median 6.5 years) were included in the analysis (chemotherapy+RT: 44, RT alone: 24). Fifty-four patients (79%) had a non-pineal and 14 (21%) a pineal site. At a median follow-up of 7.4 years, for all patients overall survival (OS) at 3 and 5 years was 54.4% and 48.3%, respectively. Event-free survival (EFS) at 3 and 5 years was 50.0% and 47.0%, respectively. There was no statistically significant difference in OS or EFS according to treatment received. OS (P=0.05) and EFS (P=0.03) were significantly better for patients with pineal primary sites. EFS for pineal tumours were 92.9% at 3 years and 71.4% at 5 years and for non-pineal primaries 40.7% at 3 years and 40.7% at 5 years. This study confirmed the relatively good survival for non-metastatic pineal PNETs but poor survival of non-pineal StPNETs. There was no evidence that pre-radiation chemotherapy improved outlook. Future treatment programs should be directed at the particular natural history of these tumours, to further define prognostic factors and to explore further biological characteristics.

Adolescent↗
PubMed2006

A multimodality approach to the treatment of craniopharyngiomas avoiding hypothalamic morbidity: a UK perspective.

The management of craniopharyngiomas is complex and controversial. The perception that they are benign tumours cured by radical surgical resection is not borne out by their often difficult excision, propensity to recur and invade, and high late morbidity and mortality from direct brain injury. Their central location makes visual or pituitary dysfunction and/or hydrocephalus common presenting features. The most important consequence of craniopharyngiomas is hypothalamic injury which may result in severe, crippling and life-threatening sequelae, such as adipsia, morbid obesity, sleep, and behavioural and cognitive disorders. Evidence suggests that unless the tumour is smaller than 2-4 cm in the mid-line and completely resectable without additional hypothalamic or visual compromise, the surgical approach should be conservative even if this leaves residual tumour. Adjuvant focal radiotherapy to residual or recurrent disease has proven efficacy in long-term tumour control. Thus concerns regarding the potential late toxicity of radiotherapy to the developing brain need to be balanced against the recognised morbidity and mortality of recurrent tumour and repeated neurosurgical interventions. Hypothalamic damage is in many cases surgically induced. Given the devastating consequences of such an injury this should be avoided at all costs. Thus the aims of primary treatment should be to relieve tumour-associated compression symptoms, preserve (or improve) vision and hypothalamo-pituitary function, and minimise tumour recurrence with its attendant high morbidity and mortality. National registration and management by multidisciplinary teams in specialised centres according to nationally agreed risk adapted treatment strategies are likely to improve outcomes, as has been demonstrated for example in adult pituitary tumours. Because of the rarity of craniopharyngiomas, international collaborative trials are necessary to properly inform future therapies.

Combined Modality Therapy↗
PubMed2005

Predicting age of ovarian failure after radiation to a field that includes the ovaries.

PURPOSE: To predict the age at which ovarian failure is likely to develop after radiation to a field that includes the ovary in women treated for cancer. METHODS AND MATERIALS: Modern computed tomography radiotherapy planning allows determination of the effective dose of radiation received by the ovaries. Together with our recent assessment of the radiosensitivity of the human oocyte, the effective surviving fraction of primordial oocytes can be determined and the age of ovarian failure, with 95% confidence limits, predicted for any given dose of radiotherapy. RESULTS: The effective sterilizing dose (ESD: dose of fractionated radiotherapy [Gy] at which premature ovarian failure occurs immediately after treatment in 97.5% of patients) decreases with increasing age at treatment. ESD at birth is 20.3 Gy; at 10 years 18.4 Gy, at 20 years 16.5 Gy, and at 30 years 14.3 Gy. We have calculated 95% confidence limits for age at premature ovarian failure for estimated radiation doses to the ovary from 1 Gy to the ESD from birth to 50 years. CONCLUSIONS: We report the first model to reliably predict the age of ovarian failure after treatment with a known dose of radiotherapy. Clinical application of this model will enable physicians to counsel women on their reproductive potential following successful treatment.

Age Factors↗
PubMed2004

Impact of radiotherapy parameters on outcome in the International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 study of preradiotherapy chemotherapy for M0-M1 medulloblastoma.

PURPOSE: To analyze the impact of radiotherapy (RT) parameters on outcome in a randomized study of pre-RT chemotherapy for M0-M1 medulloblastoma. METHODS AND MATERIALS: Patients were randomized to RT alone or RT preceded by chemotherapy with vincristine, etoposide, carboplatin, and cyclophosphamide. RT consisted of craniospinal RT, 35 Gy in 21 fractions, followed by a posterior fossa (PF) boost of 20 Gy in 12 fractions. The accuracy of cribriform fossa, skull base, and PF field placement was assessed. RESULTS: Between 1992 and 2000, 217 patients were randomized, of whom 179 were eligible for analysis. At a median follow-up of 5.4 years, the 3- and 5-year overall survival rate was 79.5% and 70.7%, respectively. The 3- and 5-year event-free survival (EFS) rate was 71.6% and 67.0%, respectively. EFS was significantly better for the chemotherapy plus RT group (3-year EFS rate 78.5% vs. 64.8%, p = 0.0366). Overall survival and EFS were significantly better for patients completing RT within 50 days compared with those taking >50 days to complete RT (3-year overall survival rate 84.1% vs. 70.9%, p = 0.0356, 3-year EFS rate 78.5% vs. 53.7%, p = 0.0092). Multivariate analysis identified the use of chemotherapy (p = 0.0248) and RT duration (p = 0.0100) as predictive of better EFS. Planning films were reviewed for 131 (74.4%) of 176 patients. Sixty-five (49.6%) had no targeting deviations and 58 (44.3%) had one or more deviations. PF recurrence occurred in 11 (34.4%) of 32 with a PF targeting deviation compared with 13 (16.3%) of 80 without (p = 0.043). No statistically significant impact of other targeting deviations on recurrence risk or EFS were found. CONCLUSION: The results of this study have confirmed the importance of the duration of RT for medulloblastoma. Also, attention to detail when planning RT is important, as illustrated in the case of PF field placement.

Adolescent↗
PubMed2002

Recent advances in paediatric neuro-oncology.

PURPOSE OF REVIEW: Primary central nervous system malignancies incorporate a variety of tumours with diverse biology and clinical behaviour and represent the most common solid tumour entity of childhood, accounting for approximate 20-25% of all primary paediatric malignancies. Recent findings regarding the underlying tumour biology may open up new avenues of clinical trial design, particularly identifying possible targets for biological modifiers. Over the last 12-18 months a significant number of institutional and national studies have been reported which are likely to impact on the design of future clinical trials. RECENT FINDINGS: In low-grade gliomas, stereotactically guided conformal radiotherapy should lead to a significant reduction in radiation-associated late toxicity, while in selected groups of high-grade gliomas the use of adjuvant or neo-adjuvant chemotherapy may improve survival. Completeness of resection and use of adjuvant focal radiotherapy remains the most important prognostic factor for outcome in patients with ependymomas, although in infants the use of post-surgical chemotherapy alone may allow the postponing of radiotherapy in selected cases. In primitive neuroectodermal tumours prognostic biological markers have been identified that are undergoing prospective evaluation. For patients with localized medulloblastomas a new standard treatment is emerging that uses reduced-dose craniospinal radiotherapy followed by platinum-based chemotherapy, while in supratentorial primitive neuroectodermal tumours future treatment will be aimed at improving local control. SUMMARY: Given the rarity of paediatric primary central nervous system malignancies, further progress can only be achieved in the context of national or multinational prospective clinical trials incorporating biological studies, and participation in these should be strongly encouraged.

Central Nervous System Neoplasms↗