Predicting Survival with Brain Metastases in the Stereotactic Radiosurgery Era: are Existing Prognostic Scores Still Relevant? Or Can we do Better?

Predicting survival is essential to tailoring treatment for patients diagnosed with brain metastases. We have evaluated the performance of widely used, validated prognostic scoring systems (Graded Prognostic Assessment and diagnosis-specific Graded Prognostic Assessment) in over 1000 'real-world' patients treated with stereotactic radiosurgery to the brain, selected according to National Health Service commissioning criteria. Survival outcomes from our dataset were consistent with those predicted by the prognostic systems, but with certain cancer subtypes showing a significantly better survival than predicted. Although performance status remains the simplest tool for prediction, total brain tumour volume emerges as an independent prognostic factor, and a new, improved, prognostic scoring system incorporating this has been developed.

Hypofractionated Stereotactic Ablative Radiotherapy for Recurrent or Oligometastatic Tumours in Children and Young Adults.

AIMS: Cancer remains a leading cause of death in children and adolescents in the developed world. Despite advances in oncological management, rates of primary treatment failure remain significant. Radiation of recurrent or metastatic disease improves survival in adults but there is little data to support clinical decision making in the paediatric/teenage and young adult population. MATERIALS AND METHODS: We present a retrospective case series of 14 patients treated with stereotactic ablative body radiotherapy or stereotactic radiosurgery at The Royal Marsden Hospital from September 2011 to December 2015. Eligible patients were aged <25 years, with Lansky/Karnofsky performance status ≥60 with confirmed relapsed or metastatic tumour in fewer than three sites. Follow-up was in accordance with standard clinical care and included regular outpatient review and radiological surveillance. Local control, progression-free survival and overall survival are presented. RESULTS: Data for 14 patients with 18 treated lesions were included. The median patient age was 15 years (range 5-20 years). Nine patients were treated for local recurrence and five for metastatic lesions. All patients had already undergone multiple previous treatments. Eleven patients had undergone previous radiotherapy. The median interval between the completion of initial radiotherapy and reirradiation was 29.0 months (range 0.2-49.5 months). The median follow-up was 3.4 years (range 0.28-6.4 years). The 1-year local control rate was 78.6% and the 2-year local control rate was 57.1%. Overall median survival was 58.4 months (95% confidence interval 33.8-82.9 months). Cumulative biologically effective doses (BED) over 200 Gy were associated with late toxicity (P = 0.04). CONCLUSION: Radical doses of short-course hypofractionated radiotherapy can achieve excellent local control and may contribute to the prolongation of overall survival. There is a need for prospective trials exploring the use of ablative radiotherapy in metastatic disease in paediatric/teenage and young adult patients in order to establish safe and effective treatment schedules.

Adopting Advanced Radiotherapy Techniques in the Treatment of Paediatric Extracranial Malignancies: Challenges and Future Directions.

Geometric uncertainties in radiotherapy are conventionally addressed by defining a safety margin around the radiotherapy target. Misappropriation of such margins could result in disease recurrence from geometric miss or unnecessary irradiation of normal tissue. Numerous quantitative organ motion studies in adults have been published, but the first paediatric-specific studies were only published in recent years. In the very near future, intensity-modulated proton beam therapy and magnetic resonance-guided radiotherapy will be clinically implemented in the UK. Such techniques offer the ability to deliver radiotherapy to the pinnacle of precision and accuracy, if geometric uncertainty relating to internal organ motion and deformation can be optimally managed. The optimal margin to account for internal organ motion in children remains largely undefined. Continuing efforts to characterise motion in children and young people is necessary to optimally define safety margins and to realise the full potential of intensity-modulated radiotherapy, magnetic resonance-guided radiotherapy and intensity-modulated proton beam therapy. This overview offers a timely review of published reports on paediatric organ motion, in anticipation of the increasing application of advanced radiotherapy techniques in paediatric radiotherapy.

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy.

Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally.

Challenges to Treating Older Glioblastoma Patients: the Influence of Clinical and Tumour Characteristics on Survival Outcomes.

AIMS: There is now evidence to support giving single-agent chemotherapy, radiotherapy or hypofractionated concurrent chemoradiotherapy to older patients with glioblastoma (GBM). However, the clinical basis on which treatment decisions are made is under-researched and not standardised. This retrospective, multicentre study assessed whether pre-morbid characteristics or tumour imaging features could predict for overall survival in a cohort of older patients with GBM. MATERIALS AND METHODS: Patients aged > 70 years, diagnosed with GBM at three neuro-oncology centres from 2010 to 2015 were retrospectively analysed. Demographic, clinical, radiological and treatment details were included in a multivariate model to examine for predictors of overall survival. RESULTS: In total, 339 patients were included with a median overall survival of 3.8 months. One and 2 year overall survival rates were 13% and 4%, respectively. The median age at diagnosis was 75 years. Pre-treatment characteristics predicting for overall survival included Eastern Cooperative Oncology Group performance status over 0 (performance status 1, hazard ratio 1.66, P = 0.042; performance status 2, hazard ratio 1.78, P = 0.031; performance status 3, hazard ratio 2.20, P = 0.008; performance status 4, hazard ratio 2.40, P = 0.021), radiological evidence of mass effect (hazard ratio 1.31, P = 0.049), multifocal tumours (hazard ratio 3.419, P = 0.013), presenting with seizures (hazard ratio 0.63, P = 0.008) and tumours confined to the cerebral hemisphere (hazard ratio 0.59, P = 0.048). Subtotal resection decreased risk of death by 37% (P = 0.019) and total tumour resection by 44% (P = 0.019). Palliative radiotherapy decreased risk of death by 41% (P = 0.005), temozolomide alone by 60% (P = 0.004) and radical chemoradiotherapy by 81% (P < 0.001). CONCLUSION: Clinical presentation, performance status and imaging characteristics are independent prognostic indicators of overall survival in older GBM patients, irrespective of age or treatment received.

Stereotactic radiosurgery planning of vestibular schwannomas: Is MRI at 3 Tesla geometrically accurate?

PURPOSE: MRI is a mandatory requirement to accurately plan Stereotactic Radiosurgery (SRS) for Vestibular Schwannomas. However, MRI may be distorted due not only to inhomogeneity of the static magnetic field and gradients but also due to susceptibility-induced effects, which are more prominent at higher magnetic fields. We assess geometrical distortions around air spaces and consider MRI protocol requirements for SRS planning at 3 T. METHODS: Hardware-related distortion and the effect of incorrect shimming were investigated with structured test objects. The magnetic field was mapped over the head on five volunteers to assess susceptibility-related distortion in the naso-oro-pharyngeal cavities (NOPC) and around the internal ear canal (IAC). RESULTS: Hardware-related geometric displacements were found to be less than 0.45 mm within the head volume, after distortion correction. Shimming errors can lead to displacements of up to 4 mm, but errors of this magnitude are unlikely to arise in practice. Susceptibility-related field inhomogeneity was under 3.4 ppm, 2.8 ppm, and 2.7 ppm for the head, NOPC region and IAC region, respectively. For the SRS planning protocol (890 Hz/pixel, approximately 1 mm3 isotropic), susceptibility-related displacements were less than 0.5 mm (head), and 0.4 mm (IAC and NOPC). Large displacements are possible in MRI examinations undertaken with lower receiver bandwidth values, commonly used in clinical MRI. Higher receiver bandwidth makes the protocol less vulnerable to sub-optimal shimming. The shimming volume and the CT-MR co-registration must be considered jointly. CONCLUSION: Geometric displacements can be kept under 1 mm in the vicinity of air spaces within the head at 3 T with appropriate setting of the receiver bandwidth, correct shimming and employing distortion correction.

Validating a robust double-quantum-filtered (1) H MRS lactate measurement method in high-grade brain tumours.

(1) H MRS measurements of lactate are often confounded by overlapping lipid signals. Double-quantum (DQ) filtering eliminates lipid signals and permits single-shot measurements, which avoid subtraction artefacts in moving tissues. This study evaluated a single-voxel-localized DQ filtering method qualitatively and quantitatively for measuring lactate concentrations in the presence of lipid, using high-grade brain tumours in which the results could be compared with standard acquisition as a reference. Paired standard acquisition and DQ-filtered (1) H MR spectra were acquired at 3T from patients receiving treatment for glioblastoma, using fLASER (localization by adiabatic selective refocusing using frequency offset corrected inversion pulses) single-voxel localization. Data were acquired from 2 × 2 × 2 cm(3) voxels, with a repetition time of 1 s and 128 averages (standard acquisition) or 256 averages (DQ-filtered acquisition), requiring 2.15 and 4.3 min respectively. Of 37 evaluated data pairs, 20 cases (54%) had measureable lactate (fitted Cramér-Rao lower bounds ≤ 20%) in either the DQ-filtered or the standard acquisition spectra. The measured DQ-filtered lactate signal was consistently downfield of lipid (1.33 ± 0.03 ppm vs 1.22 ± 0.08 ppm; p = 0.002), showing that it was not caused by lipid breakthrough, and that it matched the lactate signal seen in standard measurements (1.36 ± 0.02 ppm). In the absence of lipid, similar lactate concentrations were measured by the two methods (mean ratio DQ filtered/standard acquisition = 1.10 ± 0.21). In 7/20 cases with measurable lactate, signal was not measureable in the standard acquisition owing to lipid overlap but was quantified in the DQ-filtered acquisition. Conversely, lactate was undetected in seven DQ-filtered acquisitions but visible using the standard acquisition. In conclusion, the DQ filtering method has proven robust in eliminating lipid and permits uncontaminated measurement of lactate. This is important validation prior to use in tissues outside the brain, which contain large amounts of lipid and which are often susceptible to motion.

Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy--results of a United Kingdom phase II trial (CNS 2007 04).

Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28d) of temozolomide was studied with the aim of overcoming O(6)-methylguanine methyltransferase (MGMT) mediated resistance. Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75 mg/m(2)) after which up to 12 courses of 21d of adjuvant temozolomide (75-100mg/m(2)) were given 4 weekly. The trial used a 2-stage design and passed interim analysis. At diagnosis median age was 8 years (2-20 years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10-100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9 months, 35% (21%, 49%) at 1 year and 17% (7%, 30%) at 2 years. Median survival was 9.5 months (range 7.5-11.4 months). There were five 2-year survivors with a median age of 13.6 years at diagnosis. This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration.

Radiotherapy in craniopharyngiomas.

The optimal management of craniopharyngioma remains controversial. Although aggressive (i.e. attempted macroscopic complete/radical) primary surgery can be associated with significant morbidity and a noticeable recurrence rate, a conservative (limited) surgical approach followed by radiotherapy has increasingly been adopted after reports of excellent local control and a significant reduction in the incidence of complications by most multidisciplinary teams. A literature review from January 1990 to May 2012 was carried out identifying 43 studies with 1716 patients treated with irradiation for craniopharyngioma. The outcome and treatment-related toxicity were analysed in relation to the timing of radiotherapy, the target volume definition and radiotherapy dose and compared with the results of radical surgery. For patients undergoing limited surgery and postoperative radiotherapy, reported 10 year local control rates ranged between 77 and 100% and 20 year overall survival was reported as high as 66-92%. Comparable progression-free survival and overall survival were reported for radiotherapy delivered at first diagnosis or at progression. Long-term toxicity of combined limited surgery and irradiation seems to be less than that associated with radical surgery. The total recommended dose prescription to achieve long-term control while minimising adverse sequelae is 50-54 Gy delivered with conventional fractionation. Care should be provided by a multidisciplinary team in a specialised centre. However, national and international prospective co-operative trials are warranted to provide robust data to define an internationally multidisciplinary accepted risk-based management strategy.

Results of a phase II pilot study of moderate dose radiotherapy for inoperable desmoid-type fibromatosis--an EORTC STBSG and ROG study (EORTC 62991-22998).

BACKGROUND: To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out. MATERIALS AND METHODS: Patients with inoperable progressive disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months. The primary end point was local control rate at 3 years, estimated by a nonparametric method for interval-censored survival data. Secondary end points were objective tumor response, acute and late toxic effect. RESULTS: Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008. Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall response during the first 3 years was complete response (CR) 6 (13.6%), partial response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%) and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years, the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side-effects were limited to skin, mucosal membranes and pain. Late toxic effect consisted of mild edema in 10 patients. CONCLUSIONS: Moderate dose radiotherapy is an effective treatment of patients with DF. Response after radiation therapy is slow with continuing regression seen even after 3 years.

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.

Paraspinal volumetric modulated arc therapy.

OBJECTIVES: The processes involved in the treatment of paraspinal tumours by volumetric modulated arc therapy (VMAT) are described here by means of an illustrative case. METHODS: Az single anticlockwise arc from gantry angle 179° to 181° was constructed using SmartArc (Philips Radiation Oncology Systems, Fitchburg, WI) with control points spaced at 2°. The dose prescription was 60 Gy in 30 fractions to cover the planning target volume (PTV) as uniformly as possible while sparing the 0.3-cm planning risk volume (PRV) around the spinal cord. The plan was verified before treatment using a diode array phantom and radiochromic film. Treatment delivery was on a Synergy linear accelerator with a beam modulator head (Elekta Ltd, Crawley, UK). RESULTS: Homogeneous dose coverage of the PTV was achieved with a D(2%) of 62.0 Gy and D(98%) of 55.6 Gy. Maximum spinal cord dose was 49.9 Gy to 0.1 cm(3) and maximum dose to the spinal cord PRV was 55.4 Gy to 0.1 cm(3). At pre-treatment verification, the percentage of the high-dose region receiving a dose within 3% and 3 mm of the planned dose was 98.8% with the diode array and 93.4% with film. Delivery time was 2 min 15 s and the course of treatment was successfully completed. CONCLUSIONS: VMAT was successfully planned, verified and delivered for this challenging tumour site. VMAT provides a very suitable method of treating complex paraspinal tumours, offering a high-quality conformal dose distribution with a short delivery time.

Clinical applications of dosimetry for mIBG therapy.

Metaiodobenzylguanidine (mIBG), developed 30 years ago, is taken up by tumours expressing the noradrenaline transporter. Radiolabelled with I-123 or I-131, mIBG has become a gold standard for diagnostic imaging of pediatric and adult neuroendocrine cancer. Within a few years of its clinical introduction, I-131 mIBG was found to be an effective palliative treatment with minimal toxicity that in some cases could produce a complete response. The importance of internal dosimetry for I-131 mIBG therapy has been demonstrated by a number of studies showing that absorbed doses delivered to tumours and organs-at-risk from standard and weight-based activities can vary by an order of magnitude. However, significant correlations between the whole-body absorbed dose and myelotoxicity have been demonstrated and studies based on this relationship have enabled treatments to be tailored to the individual. Ongoing developments include patient-specific treatment planning based on tumour dosimetry and cocktails of radionuclides and radiosensitisers.

Radiotherapy planning in high-grade gliomas: a survey of current UK practice.

AIMS: Primary brain tumours in adults are rare, with high-grade gliomas (HGG) being the most common and most aggressive type. The clinical management of rare tumours such as HGG can be heterogeneous across different cancer centres. The aim of this survey was to determine current UK practice in the primary management of HGG, particularly in light of the improved outcomes reported recently. MATERIALS AND METHODS: In February 2009, a questionnaire was sent to 71 consultant clinical oncologists in the UK who were reported to have a neuro-oncology practice. Questions focussed on the radiotherapeutic management of HGG. RESULTS: In total, 46/71 (65%) completed questionnaires were returned; 31/46 (67%) routinely used magnetic resonance imaging/computed tomography fusion for radiotherapy planning; 34/36 (94%) routinely prescribed 60Gy in 30 fractions in a single phase; 7/36 (19%) would consider 54-55Gy in 30 fractions in selected clinical scenarios; 42/46 (91%) defined the planning target volume (PTV) as the gross tumour volume (GTV)+2-3cm margin and 42/46 (91%) outlined at least one 'organ at risk' (OAR). Accepted tolerance doses varied considerably, e.g. retina range: 30-54Gy. Sixty-four per cent of clinicians (27/42) compromise the PTV and 30% (14/42) the GTV in order to keep OARs within preset tolerances. Nearly one-third (14/42) involve the patient in this decision-making process, e.g. weighing up the risk of late toxicity with the risks of reducing the dose to the PTV. CONCLUSION: The results of this survey show areas of strong agreement as well as areas of variation in clinical practice of aspects of treatment planning for HGG between UK neuro-oncologists.

Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome.

Relapsed ependymoma in children poses difficult dilemmas in management. Clinico-pathological and treatment data of 108 children with relapsed ependymoma in the United Kingdom (UK) treated between 1985 and 2002 were reviewed to identify prognostic factors affecting survival. The primary site was the most common site of relapse (84%). Overall 25% had metastatic relapse. Surgery at relapse was attempted in only 55%. Radiotherapy was delivered at relapse in 66% infants and 50% of older children were re-irradiated. Overall 5-year survival was 24% and 27% for children less than 3 years of age at initial diagnosis and older children, respectively. Multivariate analysis showed that, for infants, surgery (p=0.01) and radiotherapy (p=0.001) at relapse were independent predictors of survival. For older children regardless of the previous radiotherapy, repeat irradiation was associated with better outcome (p=0.05). Relapse was associated with poor outcome in both age groups. A survival advantage conferred by both radiotherapy and surgery at relapse is independently significant.

An evaluation of conformal and intensity-modulated radiotherapy in whole ventricular radiotherapy for localised primary intracranial germinomas.

AIMS: To evaluate different treatment techniques in whole ventricular radiotherapy (WVRT) for localised intracranial germinomas with respect to target volume and organ at risk (OAR) dose. As a second end point, a comparison of OAR doses between WVRT and whole brain radiotherapy was made. MATERIALS AND METHODS: Co-registered computed tomography-magnetic resonance images (MRI) of five patients were studied. Planning target volumes for whole ventricles (phase 1, PTV(1)) and boost to the primary tumour (phase 2, PTV(2)) were prescribed to 24 and 16 Gy. For phase 1, lateral parallel-opposed pairs (PP), non-coplanar three- and four-field (3F and 4F) and optimised four- and seven-field intensity-modulated radiotherapy (4FIMRT and 7FIMRT) plans were compared. A conformal non-coplanar six-field technique was used for phase 2. RESULTS: For phase 1, statistically significant high-dose sparing of normal brain was achieved with increasing treatment complexity for supratentorial brain (STB) minus PTV(1) (STB-PTV(1)) and infratentorial brain (ITB) minus PTV(1) (ITB-PTV(1)). Median pituitary gland dose sparing was 1 Gy with IMRT techniques (P=not significant). CONCLUSION: WVRT using 7FIMRT is the most conformal technique, which offers significant sparing of normal brain from high-dose irradiation, a mean reduction of 1 Gy in the pituitary gland (P<0.05) with no significant reduction in other OARs. Yet even with the most complex technique the absolute reduction in mean dose to normal brain tissue achieved was modest in clinical terms. Whether this could translate into a reduction in late sequelae in a predominantly adolescent patient population remains hypothetical.

Children's Cancer and Leukaemia Group (CCLG): guidelines for the management of intracranial meningioma in children and young people.

Primary tumours of the meninges occur extremely rarely in children and young people (less than five new cases annually in the UK) and have remained a poorly defined group compared with the common diagnosis of meningiomas in adults. Because of the rarity in children, paediatric meningiomas are often treated according to the adult practice. This may lead to inappropriate treatment considerations since paediatric meningiomas exhibit peculiarities that distinguish them from their adult counterpart. Striking the balance between late toxicities of adjuvant radiotherapy on the growing brain versus the risk of repeated recurrences necessitating surgical interventions in young patients is of importance and will require a clinical decision making process in the paediatric neuro-oncological/neurosurgical MDT tailored to each patient's age and clinical setting. The paediatric literature is based on small, single institution retrospective studies over extensive time periods during which the imaging facilities, pathological criteria and surgical advances have led to shifts in definitions of disease making comparison of results difficult to interpret. These guidelines have been developed following a comprehensive appraisal of the literature. Primary treatment is surgical resection. Careful pathological review and multidisciplinary discussions should be undertaken before considering postoperative treatment, such as radiotherapy for histologically anaplastic or clinically aggressive, relapsing meningioma.

Radiotherapy of localised intracranial germinoma: time to sever historical ties?

The optimum management of localised intracranial germinoma remains controversial. Cure rates for this rare CNS tumour, which arises mainly in adolescents, exceed 90% at 10 years, and limitation of treatment-related late morbidity is therefore essential. Craniospinal radiotherapy plus boost is perceived to be the gold-standard treatment, but there have been suggestions that reduced-volume radiotherapy could be adequate for cure. We reviewed publications since 1988 to compare patterns of disease relapse and cure rates after craniospinal radiotherapy, reduced-volume irradiation alone (i.e., whole-brain or whole-ventricular irradiation followed by a boost), and focal or localised irradiation alone. The recurrence rate after whole-brain or whole-ventricular radiotherapy plus boost was 7.6% compared with 3.8% after craniospinal radiotherapy, with no predilection for isolated spinal relapses (2.9% vs 1.2%). We challenge the consensus that craniospinal radiotherapy is the best treatment for localised germinomas and conclude that reduced-volume radiotherapy plus boost should replace craniospinal radiotherapy when a radiotherapy-only approach is used.