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.

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.

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.

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.

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.

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.

The use of a standardized positioning support cushion during daily routine of breast irradiation.

PURPOSE: The use of positioning and immobilization techniques during external beam irradiation of the female breast is time consuming and expensive. The currently available standardized positioning devices are insufficient. For this reason, we designed a new and generally useable hard foam positioning support cushion for the use during breast irradiation, and tested its clinical usefulness in a prospective study. METHODS AND MATERIALS: Fifty-five female breast cancer patients receiving adjuvant radiotherapy following breast-conservative surgery were irradiated either without immobilization (n = 27) or with the positioning support cushion (n = 28). The time necessary for patient setup, the lying subjective comfort and--comparing portal images with simulator images--the reproducibility of the set up were determined. RESULTS: Irradiation reproducibility was significantly improved (average deviation without positioning support cushion: 8.4 mm, with positioning support cushion: 6.1 mm, p < 0.001). The time required for the positioning of the patient with positioning support cushion was in average 73 s, without cushion it was 55 s. A significantly higher proportion of patients (72%) found the position with the positioning support cushion as pleasant, whereas only 46% of patients were pleased with the position without cushion. CONCLUSION: The positioning support cushion designed in our department makes a substantial contribution to quality assurance in breast irradiation. It significantly increases the patients' comfort in a supine position. In contrast to conventional positioning and fixation aids it may be quickly and easily applied at low costs. Therefore, its use can be recommended.

A Comparison of clinical target volumes determined by CT and MRI for the radiotherapy planning of base of skull meningiomas.

PURPOSE: To assess the utility of image registration and to compare the localization of clinical target volumes (CTV) using CT and MRI for patients with base of skull meningiomas undergoing radiotherapy. METHODS AND MATERIALS: Seven patients were imaged using CT and a T1-weighted MR volumetric sequence. Following image registration using a chamfer-matching algorithm, transaxial MR slices were reconstructed to match the planning CT slices. The accuracy of the image fusion was assessed in a preliminary study with matching accuracy better than 1.5 mm. The CTV in each patient was separately segmented by two independent observers for both CT and reconstructed MR image sets. Scalar and vector assessments were made of the difference in radial extent between the two outlines on each transaxial plane for all patients. A positive vector value corresponded to a greater extension of the tumor on MR compared to CT and vice versa. Scalar measurements compared the modulus of the differences between MR and CT, regardless of which volume was more extensive. Qualitative comparisons were also performed. RESULTS: Interobserver difference was small with a mean (+/- 1SD) volume difference of 1.5 +/- 1.5 cm(3) for CT and 0.5 +/- 1.0 cm(3) for MRI. The mean CT- and MR- CTVs were 17.6 +/-10.8 and 19.6 +/-14.2 cm(3) respectively. The mean overlap and composite volumes were 13.8 +/-10. 1 and 23.3 +/-14.8 cm(3) respectively. Average scalar differences in the left, right, anterior, and posterior directions were 6.0 +/- 7.0, 3.3 +/- 2.5, 4.9 +/- 3.9, and 4.5 +/- 5.0 mm respectively. The average vector differences were 3.3 +/- 8.5, -0.3 +/- 3.8, 1.1 +/- 5. 8, 1.5 +/- 6.4 mm (for left, right, anterior, and posterior directions respectively). Qualitatively, MR appeared to discern more tumor involvement in soft tissue regions adjacent to the skull base whereas CT appeared to provide larger target volumes within bony regions. CONCLUSIONS: MRI appeared to define CTVs that were larger but not inclusive of CT-defined CTVs. Although the average vector differences were small, the differences on individual borders could be large. In some instances, the CT or MR volumes were vastly different, each providing separate information. Therefore, the use of MRI and CT is complementary. Until accurate histological confirmation of disease extent is available, it is prudent to consider composite CT/MR volumes for the radiotherapy planning of base of skull meningiomas.

Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation.

PURPOSE: Very young children with medulloblastoma are considered to have a worse prognosis than older children. As radiotherapy remains an important part of the treatment, the adverse prognosis could be due to inadequate radiation treatment rather than biological factors. We analyzed the published literature to examine the impact of radiotherapy on survival in this group. METHODS AND MATERIALS: A Medline search was performed and we reviewed studies of treatment of medulloblastoma where radiotherapy was delivered using megavoltage equipment and the minimum follow-up allowed the calculation of 5-year survival rates. RESULTS: Thirty-nine studies were published between 1979 and 1996 with a treatment including craniospinal irradiation and boost to the posterior fossa. Eleven studies comprising 1366 patients analyzed survival by age at diagnosis. Eight of 11 studies showed a worse 5-year survival for the younger patient group which reached statistical significance in two. There is also a suggestion of a higher proportion of children with metastatic disease at presentation in the very young age group. The usual policy in younger children was to give a lower dose of radiotherapy to the craniospinal axis (CSA) and posterior fossa (PF) with reduction of dose in the range of 15 to 25% compared to standard treatment. As dose reduction to the posterior fossa is associated with worse survival and local recurrence is the predominant site of failure, the major determinant of worse survival in very young children with medulloblastoma may be suboptimal radiotherapy. Protocols including postoperative chemotherapy with delayed, omitted, or only local tumor irradiation do not reach survival rates of protocols with standard radiotherapy, also suggesting a continued importance for irradiation. CONCLUSION: Very young children with medulloblastoma have a worse prognosis than older children. Inadequate radiation dose and technique to the primary tumor region may be a major contributing factor. Current chemotherapeutic regimes alone are not sufficient to compensate for reduced radiation doses and volumes.

Improvement of radiation treatment planning in squamous-cell head and neck cancer by immuno-SPECT.

UNLABELLED: Previous studies have shown high accuracy for immunoscintigraphy with 99mTc-MAb-174 in patients with squamous-cell carcinoma of the head and neck region compared to CT and MRI. We conducted a prospective study to determine if immunoscintigraphy provides additional diagnostic information for radiation treatment planning. METHODS: Radioimmunoscintigraphy (RIS) was performed on 40 patients (planar, whole-body, SPECT) with histologically confirmed squamous-cell carcinoma (30 primary tumors, 10 recurrences) after injection of the 99mTc (1.1 GBq) labeled monoclonal anti-squamous-cell cancer antibody 174H0.64 (murine IgG1). Results were combined with information obtained by clinical examination, sonography, panendoscopy and x-ray CT. The strategy for radiation treatment and the required treatment volumes were defined with and without immunoscintigraphical findings. RESULTS: Additional diagnostically relevant information from RIS was obtained from 10 patients (25%) with advanced tumors or recurrences. In three patients (7.5%), the treatment volume had to be extended. The therapeutic strategy for seven patients (17.5%) had to be changed due to the detection of metastatic disease beyond the head and neck region. RIS of patients with squamous-cell cancers of the head and neck region with 99mTcMAb-174H0.64 enabled the detection of tumors that were not depicted by other conventional diagnostic imaging procedures. CONCLUSION: The use of RIS in radiation treatment planning of advanced tumors of the head and neck region appears to yield important diagnostic information that may alter patient management.

Design and implementation of a system for treating paediatric patients with stereotactically-guided conformal radiotherapy.

BACKGROUND AND PURPOSE: Stereotactically-guided conformal radiotherapy (SCRT) allows the delivery of highly conformal dose distributions to localised brain tumours. This is of particular importance for children, whose often excellent long-term prognosis should be accompanied by low toxicity. The commercial immobilisation system in use at our hospital for adults was felt to be too heavy for children, and precluded the use of anaesthesia, which is sometimes required for paediatric patients. This paper therefore describes the design and implementation of a system for treating children with SCRT. This system needed to be well tolerated by patients, with good access for treating typical childhood malignancies. MATERIALS AND METHODS: A lightweight frame was developed for immobilisation, with a shell-based alternative for patients requiring general anaesthetic. Procedures were set up to introduce the patients to the frame system in order to maximise patient co-operation and comfort. Film measurements were made to assess the impact of the frame on transmission and surface dose. The reproducibility of the systems was assessed using electronic portal images. RESULTS: Both frame and shell systems are in clinical use. The frame weighs 0.6 kg and is well tolerated. It has a transmission of 92-96%, and fields which pass through it deliver surface doses of 58-82% of the dose at d(max), compared to 18% when no frame is present. However, the frame is constructed to maximise the availability of unobstructed beam directions. Reproducibility measurements for the frame showed a mean random error of 1.0+/-0.2mm in two dimensions (2D) and 1.4+/-0.7 mm in 3D. The mean systematic error in 3D was 2.2mm, and 90% of all overall 3D errors were less than 3.4mm. For the shell system, the mean 2D random error was 1.5+/-0.2mm. CONCLUSIONS: Two well-tolerated immobilisation devices have been developed for fractionated SCRT treatment of paediatric patients. A lightweight frame system gives a wide range of possible unobstructed beam directions, although beams that intersect the frame are not precluded, provided that output corrections are applied. A shell system allows the use of general anaesthesia. Both systems give reproducible immobilisation to complement the high-precision treatment delivery.

Increase of surface dose using wound dressings during percutaneous radiotherapy with photons and electrons.

Different wound dressings are used for the supportive treatment of patients with radiation-induced skin lesions. Depending on beam quality and energy, an increase of the dose administered to the skin and thus an aggravated skin reaction is to be expected during percutaneous irradiation. The increase of the skin dose during irradiation with photons (Co60, 6 MV, 42 MV) and electrons (7 MeV, 20 MeV, 42 MeV) was determined using thermoluminescence dosimetry. The use of wound dressings during electron irradiation and during soft irradiation therapy does not significantly increase the dose administered to the skin and does not therefore cause any problems. During irradiation with high energy photons only extremely thin dressings should be used; if there is an aggravated skin reaction, the dressing should be taken off before irradiation commences.

Stereotactically guided conformal radiotherapy for meningiomas.

PURPOSE: Stereotactically guided conformal radiotherapy, (SCRT) is a high precision technique of conformal radiotherapy (RT) which reduces the volume of normal tissue irradiated compared to conventional RT and may lead to a reduction in long-term toxicity We describe the technique and the preliminary results in patients with inoperable, residual or recurrent meningiomas. MATERIAL AND METHODS: From July 1993 to November 1997, 24 patients (median age: 56 years, range: 28-72) with base of skull (n = 21). falx or upper skull (n = 3) meningiomas were treated with SCRT. The technique employed immobilization in a Gill-Thomas-Cosman (GTC) frame and CT localization with a Brown-Roberts-Wells (BRW) fiducial system for stereotactic space definition. The planning target volume (PTV) was defined as gross tumour volume (GTV) and a 0.5-1 cm margin. Treatment was delivered with three (12 patients) or four non-coplanar conformal fixed fields (12 patients) Conformal blocking was achieved either with lead alloy blocks (n = 11) or with a multi-leaf collimator (MLC) (n = 13). Patients were treated on a 6 MV linear accelerator to doses of 50-55 Gy, in 30-33 daily fractions. The treatments were carried out as part of a routine work of a busy radiotherapy department. RESULTS: Median GTV for 24 meningiomas was 21.7 cm3 (range: 4.4-183 cm3). SCRT was well tolerated with minimal toxicity Three months after the end of radiotherapy, seven of 15 patients with neurological deficit had an improvement and eight remained unchanged. Two patients experienced early side effects (one VII nerve palsy, one Addisonian state). At a median follow-up of 13-months (range: 3-43) the 1 year progression free survival and overall survival are 100%. which is within the range expected for conventional fractionated radiotherapy for meningiomas. CONCLUSIONS: SCRT is a feasible technique of high precision conformal RT for patients with meningiomas. Potential advantages in tumour control, survival and toxicity over conventional RT, require evaluation in long-term prospective studies.

Radiotherapy in the treatment of benign meningioma of the skull base.

OBJECT: This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma. METHODS: This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy. CONCLUSIONS: The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

Bilateral breast carcinoma versus unilateral disease. Review of 498 patients.

In literature data, an uncertainty exists whether occurrence of bilateral breast cancer decreases the survival probability of affected patients. Therefore, we analyzed the medical records of 498 postoperatively irradiated (1977-1982) female breast cancer patients (T1-4,N0-3,M0). In the follow-up time, in 36 patients a bilateral breast carcinoma treated by surgery with or without radiotherapy was found. The 10-year overall survival rates were 54% in patients who had unilateral disease, compared with 56% in bilateral carcinoma patients, respectively. The incidence of metastasis did not differ between both groups: 24.2% versus 38.8%. Eleven percent of unilateral cancers recurred; in the other group, local failure of the first and second tumor was observed in 19.4% and 11.1%, respectively. We conclude that the occurrence of bilateral breast cancer has no significant impact on survival, although the development of local failures and metastases seems to be more frequent. The therapeutic strategy in bilateral carcinoma should resemble the treatment procedure in unilaterally affected patients.

Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis?

Therapeutic application of immunoglobulin is reported to be successful in radiation-induced oral and oropharyngeal mucositis. In this study the efficacy of prophylactic application of immunoglobulin was investigated. In 42 patients with head and neck cancer, postoperative radiation treatment or radiation combined with chemotherapy was performed. In 20 consecutive patients, prophylactic mucositis treatment consisted of panthenol (4 x 10 ml/day) and nystatin (4 x 1 ml/day). The 22 following patients received, supplementary to panthenol and nystatin, 800 mg (5 ml) human immunoglobulin intramuscularly once weekly. During the treatment time, the degree of mucositis was examined 3 times a week. The distribution of maximal mucositis degree revealed slightly more severe mucous membrane reaction in the control group compared with the immunoglobulin group (n.s.). The analysis of mean mucositis degrees in both groups demonstrated statistically significant differences (t test, p = 0.031) related to the entire group (n = 42) and to those 16 patients receiving radiation combined with chemotherapy. There was no significant immunoglobulin-induced effect on mucositis in patients treated by radiation alone. The time from the beginning of therapy to the first interruption could be prolonged 5 days in the immunoglobulin group (n.s.). In conclusion, it is demonstrated that the prophylactic application of immunoglobulin seems to lower the degree of radiation-induced mucositis. In comparison to the published data about therapeutically given immunoglobulin, the clinical efficacy of the prophylactic application of immunoglobulin as it is performed in this study is less evident.