Preoperative radiosurgery for brain metastases (PREOP-1): A feasibility trial.

Purpose: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1). Methods: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers. Results: Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm3 (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed. Conclusion: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

Optimized workflow to minimise intra-fractional motion during stereotactic body radiotherapy of spinal metastases.

Background and purpose: This study evaluated translational and rotational intra-fractional patient movement during spinal stereotactic body radiotherapy (SBRT) using 6D positioning based on 3D cone beam computerized tomography (CBCT) and stereoscopic kilovoltage imaging (ExacTrac). The aim was to determine whether additional intra-fractional image verification reduced intra-fractional motion without significantly prolonging treatment time, whilst maintaining acceptable imaging related dose. Materials and methods: A retrospective analysis of 38 patients with 41 primary tumour volumes treated with SBRT between September 2018 and May 2021 was performed. Three different image-guided radiotherapy (IGRT) workflows were assessed. The translational and rotational positioning errors for the different imaging workflows, 3D translational vectors and estimates of imaging dose delivered for the different imaging workflows were evaluated. Results: As the frequency of intra-fractional imaging increased from workflow 1 to 3, the mean intra-fraction 3D translational vector improved from 0.91 mm (±0.52 mm), to 0.64 (±0.34 mm). 85 %, 83 % and 97 % of images were within a tolerance of 1 mm/1° for workflows 1, 2 and 3 respectively, based on post treatment CBCT images. The average treatment time for workflow 3 was 13 min, as compared to 12 min for workflows 1 and 2. The effective dose per treatment for IGRT workflows 1, 2 and 3 measured 0.6 mSv, 0.95 mSv and 1.8 mSv respectively. Conclusion: The study demonstrated that the use of additional intra-fractional stereoscopic kilovoltage image-guidance during spinal SBRT, reduced the number of measurements deemed "out of tolerance" and treatment delivery could be optimized within a standard treatment timeslot without applying substantial additional radiation dose.

Five fraction stereotactic radiotherapy after brain metastasectomy: a single-institution experience and literature review.

PURPOSE: The outcomes of five fraction stereotactic radiotherapy (hfSRT) following brain metastasectomy were evaluated and compared with published series. METHODS: 30 Gy in 5 fractions HfSRT prescribed to the surgical cavity was reduced to 25 Gy if the volume of 'brain-GTV' receiving 20 Gy exceeded 20 cm3. Endpoints were local recurrence, nodular leptomeningeal recurrence, new brain metastases and radionecrosis. The literature was searched for reports of clinical and dosimetric outcomes following postoperative hfSRT in 3-5 fractions. RESULTS: 39 patients with 40 surgical cavities were analyzed. Cavity local control rate at 1 year was 33/40 (82.5%). 3 local failures followed 30 Gy/5 fractions and 4 with 25 Gy/5 fractions. The incidence of leptomeningeal disease (LMD) was 7/40 (17.5%). No grade 3-4 toxicities, particularly no radionecrosis, were reported. The incidence of distant brain metastases was 15/40 (37.5%). The median overall survival was 15 months. Across 13 published series, the weighted mean local control was 83.1% (adjusted for sample size), the mean incidence of LMD was 14.9% (7-34%) and the mean rate of radionecrosis was 10.3% (0-20.6%). CONCLUSION: Postoperative hfSRT can be delivered with 25-30 Gy in 5 fractions with efficacy in excess of 82% and no significant toxicity when the dose to 'brain-GTV' does not exceed 20 cm3.

Effective use of an audit tool devised to optimize the management of syphilis in an integrated sexual health clinic.

The objective of this study was to audit the management of syphilis in our integrated sexual health clinic according to the British Association for Sexual Health and HIV (BASHH) guideline using the 'Treponemal Infection Care' (TIC) audit tool devised by our clinic. The case notes of patients diagnosed with all stages of syphilis during an 18-month period were reviewed. At the time of diagnosis, the departmental TIC proforma was filled in: this proforma details BASHH auditable outcomes. The case notes of 83 patients diagnosed with syphilis during the audit period were reviewed. The majority of patients were men (76), men who had sex with men (69), HIV-negative (59) and were British (68). In line with current guidance all patients had a baseline Venereal Disease Research Laboratory (VDRL) titre at the start of treatment (target: 100%) and 97% of diagnosed patients completed treatment (target: 95%). A 'response to treatment' according to the decrease in VDRL was demonstrated in 50 (60%) patients with two (2%) patients failing to respond according to these criteria. However, 19 (23%) patients failed to return for their VDRL tests before demonstrating an adequate response to treatment, despite repeated attempts to contact them by letter and telephone. Fifty-four patients had at least 50% of their partners documented as traceable. Of those who were contactable, 100% attended for screening or treatment (target: 60%). In conclusion, our department performed well against BASHH auditable outcome targets. The introduction of the TIC proforma greatly facilitated the ease of audit and is a valuable tool within our clinic setting, which may have positively influenced our audit outcomes. Further action is required to highlight the importance of follow-up VDRLs to patients.

How do UK medical graduates rate their knowledge and skills in sexual health and HIV medicine? A national survey.

The objectives of this study are to determine self-assessed knowledge and skills in sexual health and HIV medicine in preregistration house officers and to explore undergraduate experiences of teaching and assessment in these subjects prior to the launch of National Core Learning Outcomes in Sexual and Reproductive Health and HIV. The study was designed as a postal questionnaire survey. The participants were all UK medical graduates of August 2004. The response rate 1737/4746 (36%). The main outcome measures were Doctors' views on their preparedness to manage patients with sexual health and HIV-related problems. Since graduation, 90% of respondents had seen at least one patient with a sexually transmitted infection or HIV-related issue. Seventy-six percent felt confident to take a sexual history. In all, 63% and 53% felt competent in male and female genital examination, respectively. Forty-three percent felt they could conduct an appropriate HIV pretest discussion and 59% felt they could recognize clinical indicators suggestive of HIV. Seventy-eight percent had been formally assessed in sexual health and 55% in HIV medicine. Increased confidence in sexual history taking, HIV pretest discussion and recognition of HIV indicators was associated with a longer duration of teaching and formal examination. In conclusion, although the proportion of recent graduates confident in sexual history taking is encouraging, their lack of skill in discussing HIV testing, risk assessment and recognition of possible HIV presentations must be addressed. Integration of National Core Learning Outcomes into all undergraduate curricula is a key step in reducing inconsistencies in undergraduate training.

A national review of assessment and monitoring of HIV-infected patients.

OBJECTIVES: The British HIV Association (BHIVA) audit subcommittee aimed to survey UK clinic policy and practice regarding baseline assessment and immunization of newly diagnosed HIV-positive patients, and frequency of follow-up and testing in established patients in the UK. METHODS: UK centres providing HIV care were requested to complete an online survey between October 2006 and March 2007. RESULTS: 111 centres participated in the survey. 89.2% of centres routinely performed baseline HIV resistance testing. 99% of centres had a policy of routine screening for hepatitis B. Only 91% of centres were routinely offering a sexual health screen at diagnosis. Frequency of routine follow-up for patients not requiring antiretroviral therapy (ART) and stable on ART varied between three and six months. DISCUSSION: This review showed variations in practice regarding the post diagnosis assessment and routine monitoring of HIV patients. It is of concern that not all centres perform baseline HIV resistance testing. It has also been noted that hepatitis B vaccination is not being offered to non-immune patients at diagnosis. Less frequent follw-up of stable patients (both on and off ART) should allow resources to be focussed on those with specific clinical needs.

Partner notification in pregnant women with HIV: findings from three inner-city clinics.

British HIV Association guidelines recommend that all HIV-positive pregnant women should be encouraged to disclose their HIV infection to their partner and that this should be viewed as a process rather than an event. The aim of this study was to describe local practice of partner notification (PN) and patterns of disclosure in a group of HIV-positive women in an antenatal setting. A retrospective case note and local pregnancy database review was undertaken. Women who had accessed specialist HIV antenatal care at one of three east London hospitals with an expected delivery date between 1 March 2004 and 30 June 2006 were identified. In total, 145 women were identified. HIV status had not been disclosed to a partner in 19% (n=27) of case notes reviewed. There was no documented discussion about PN in 18% (n=26) of case notes. Forty-three per cent (n=62) of case notes documented that the male partner had accessed HIV testing after PN was discussed. All HIV-positive pregnant women should have a documented discussion about PN. Concurrent HIV testing offered to both partners may improve HIV testing uptake in male partners and should be explored further. Care plans should include screening for intimate partner violence and housing problems; referral pathways should be established clearly when involving other agencies.

Management of a syphilis outbreak in street sex workers in east London.

OBJECTIVE: To describe the control and management of a syphilis outbreak in female street sex workers (SSWs) in east London. METHODS: Following the identification of several cases of infectious syphilis in SSWs in east London, a targeted service for screening and treatment of syphilis and other sexually transmitted infections was developed. A multidisciplinary team (MDT) joined an existing outreach service to facilitate this. Once it became apparent that this was not an isolated case, an outbreak control team (OCT) was established. RESULTS: Between April and December 2004 a total of 14 (58%) women with 15 cases of infectious syphilis were identified in 24 SSWs: 14/15 (93%) received treatment. Epidemiological treatment for syphilis was also given to the rest of SSWs at the initial visit. Several coexistent STIs were identified in this cohort. As part of the enhanced outbreak surveillance in north east London, 21 cases of infectious syphilis were reported in SSWs between April 2004 and December 2005. CONCLUSION: Outbreak management in this population was challenging: an MDT approach was crucial in identifying and treating syphilis to prevent onward transmission. There was a high prevalence of syphilis and other STIs in this cohort, and we treated the majority of cases. The formation of an OCT enabled us to monitor the outbreak and implement control measures more effectively. The novel intervention we describe has proved valuable in helping to control this syphilis outbreak.

Otitis media in adults with chlamydial conjunctivitis.

The aim of this study was to assess the prevalence of otological symptoms in patients with chlamydial conjunctivitis. We report four cases of chlamydial conjunctivitis, in association with otitis media, that were investigated by an otologist.

Symptomatic trichomoniasis, metronidazole allergic and pregnant--a management dilemma.

A case of persistent Trichomonas vaginalis (TV) in a pregnant, metronidazole-allergic woman is described. This case posed a management dilemma as untreated TV has been associated with adverse pregnancy outcomes but antibiotic desensitization is potentially dangerous during pregnancy.

High precision radiosurgery and technical standards.

BACKGROUND: A high degree of precision and accuracy in radiosurgery is a fundamental requirement for therapeutic success. Small radiation fields and steep dose gradients are clinically applied thus necessitating a dedicated quality assurance program in order to guarantee dosimetric and geometric accuracy. MATERIAL AND METHODS: A detailed analysis of the course of treatment independent of the irradiation technique used results in the so-called chain of uncertainties in radiosurgery (immobilisation, imaging, treatment planning system, definition of regions of interest, mechanical accuracy, dose planning, dose verification). Each link in this chain is analysed for accuracy and the established quality assurance procedures are discussed. A "System Test" was used to check the whole chain of uncertainties simultaneously. RESULTS: The tests described are compatible with published reports on quality assurance in radiosurgery. In terms of accuracy the weakest link in the chain of uncertainties is stereotactic MR imaging. Geometric overall accuracy measured in the "System Test" is less than 0.7 mm. CONCLUSION: The established quality assurance routines have clinically been validated. MR imaging dominates geometric overall accuracy in radiosurgery, which can be limited to less than 1 mm by an adequate quality assurance protocol.

Quality assurance in stereotactic radiosurgery/radiotherapy according to DIN 6875-1.

The new DIN ('Deutsche Industrie-Norm') 6875-1, which is currently being finalised, deals with quality assurance (QA) criteria and tests methods for linear accelerator and Gamma Knife stereotactic radiosurgery/radiotherapy including treatment planning, stereotactic frame and stereotactic imaging and a system test to check the whole chain of uncertainties. Our existing QA program, based on dedicated phantoms and test procedures, has been refined to fulfill the demands of this new DIN. The radiological and mechanical isocentre corresponded within 0.2 mm and the measured 50% isodose lines were in agreement with the calculated ones within less than 0.5 mm. The measured absorbed dose was within 3%. The resultant output factors measured for the 14-, 8- and 4-mm collimator helmet were 0.9870 +/- 0.0086, 0.9578 +/- 0.0057 and 0.8741 +/- 0.0202, respectively. For 170 consecutive tests, the mean geometrical accuracy was 0.48 +/- 0.23 mm. Besides QA phantoms and analysis software developed in-house, the use of commercially available tools facilitated the QA according to the DIN 6875-1 with which our results complied.

[Palliative treatment of brain metastases with gamma knife]. / Palliative Behandlung von Hirnmetastasen mit dem Gamma Knife.

The gamma knife is a stereotactic radiosurgery device which allows well defined, deep seated brain tumors or arteriovenous malformations with a maximal volume of about 25 ccm and a diameter not greater than 3.5 cm, to be treated in a single session under local anesthesia. The gamma knife offers an alternative treatment method to the classical approach of treating brain metastases by surgical excision and/or whole brain radiotherapy. The advantages of this technique are evident: the method is non-invasive, the treatment is carried out in a single session with a very short hospitalisation of two to three days, it is exempt from physical and psychical stress, the head does not need to be shaved and no hair loss occurs, a good quality of life is obtained for a reasonably prolonged survival time and it offers an economically favourable treatment method. Up to December 1999, over 30,000 patients suffering from brain metastases have been treated worldwide using the gamma knife. In Zürich, from September 1994 to December 2000 140 received this treatment. In the literature selection criteria may differ, and this may have determined some of differences in outcome. However, our results are comparable with those in the majority of publications with an average survival time of 263 days and a maximum survival of 1080 days. Good prognostic factors for survival and local control of brain metastases are a Karnofsky Performance Scale Score approaching 90 to 100, but not lower than 70, tumour volume, controlled primary cancer, and absence or stable extracranial metastases.

Octreotide may act as a radioprotective agent in acromegaly.

Clinical experience shows that an increasing number of patients undergoing radiation treatment for recurring acromegaly or acromegaly persisting after surgery are treated with octreotide. We, therefore, performed a follow-up study of patients undergoing stereotactic radiosurgery (Gamma Knife) to determine whether this medication has an influence on the ultimate result of radiation therapy in either a positive or negative sense. It has been suggested that the combination of radiation with antisecretory drugs may increase the effectiveness of radiation. A follow-up study of 31 patients suffering from recurrent acromegaly and acromegaly persisting after surgery, and who had been treated with stereotactic radiosurgery, showed that patients treated with octreotide at the time of radiation application simultaneously reached a normal level of growth hormone and insulin-like growth factor-I only after a significantly longer interval than patients who did not receive the drug. The two groups of patients did not demonstrate significant differences in the main clinical findings (age, sex, target volume, radiation dose, baseline growth hormone, and baseline insulin-like growth factor-I).

Gamma knife radiosurgery for prolactinomas.

OBJECT: In this retrospective investigation the authors examined the results of gamma knife radiosurgery (GKS) for tumor remnants after unsuccessful open surgery and medical treatment in 20 patients with prolactinomas. Particular attention is paid to a possible radioprotective action of dopamine agonists similar to the action of octreotide in acromegaly. METHODS: Twenty patients with prolactinomas were followed after GKS. Five patients were treated successfully; their prolactin (PRL) levels dropped into the normal range and dopaminergic drugs could be discontinued. Two spontaneous pregnancies were observed and 11 patients experienced improvement. Improvement was defined as normal PRL levels with the continued possibility of reduced medical treatment or a substantially reduced medical treatment dose with some degree of hyperprolactinemia maintained. The treatment failed in three patients who experienced no improvement. Patients treated with dopaminergic drugs during GKS did significantly less well in comparison with the untreated group when a cumulative distribution function (Kaplan-Meier estimate) was used. CONCLUSIONS: The results of GKS for prolactinomas in this investigation are better than the results published by others. This may be an effect of case selection because there were no "salvage cases" in our group of patients. Because a dopamine agonist seemed to induce radioprotection in this series, it is suggested that GKS be performed during an intermission in drug therapy when the dopamine agonist is discontinued.

Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy.

OBJECT: The authors tested the assumption that gamma knife radiosurgery is more effective than fractionated radiotherapy for the treatment of patients with acromegaly who have undergone unsuccessful resective surgery. Untreated and uncured acromegaly causes illness and death. Acromegalic patients in whom growth hormone and, particularly, insulin-like growth factor I are not normalized must undergo further treatment. METHODS: After unsuccessful operations, 16 patients suffering from recurrent and uncured acromegaly underwent stereotactic radiosurgery (25 Gy to the tumor margin, 50 Gy maximum), the outcome of which was compared with the result obtained in 50 patients who received fractionated radiotherapy (40 Gy). The cumulative distribution functions of the two groups (Kaplan-Meier estimate) differed significantly (p < 0.0001 in the log-rank test of Mantel). The mean time to simultaneous normalization of both parameters was 1.4 years in the group treated with the gamma knife and 7.1 years in the group treated with fractionated radiotherapy. CONCLUSIONS: The authors suggest the use of stereotactic radiosurgery as the preferred treatment for recurrent acromegaly resulting from unsuccessfully resected tumors.

[Gamma knife radiosurgery in neurosurgery]. / Das Gamma-Knife im Dienste der Neurochirurgie.

The gamma knife is a stereotactic radiosurgery device which allows well defined, deep seated brain tumors, or arteriovenous malformations having a diameter of less than 3 cm, to be treated in a single session under local anesthesia. This technique, which was first described over 40 years ago, has undergone major development in recent years and is the most commonly used method for radiosurgery worldwide. The principle relies on the over-lapping of narrow collimated beams from 201 cobalt-60 sources. The technique, which was introduced into Switzerland in September 1994, has rapidly gained recognition. 184 patients have been treated by 30 April 1997. An average follow-up period of 15 months is much too short for analysis of patients treated by radiosurgery. However, our series of benign tumors shows stabilization of volume in the first few months followed by a slow reduction of the tumor volume, in all but two cases. The gamma knife represents the treatment of choice for recurrent and unsuccessfully operated patients with endocrine active pituitary adenomas. With brain metastases, a rapid reduction in tumor volume is seen in the first few weeks in the majority of cases. The tumor volume may then remain stable or reduce further until complete disappearance. In the case of arteriovenous malformations complete obliteration of the nidus is not seen, on average, for 2-3 years. Individual patient follow-up studies illustrate these results. To date our results have shown zero morbidity and mortality. International statistics from 58,766 cases (as of December 1996) from 77 gamma knife centers demonstrate the value of this technique as a complement or, depending on the indication, an alternative to classical microsurgery.