The Changing Landscape for the Treatment of Painful Spinal Metastases: is Stereotactic Body Radiation Therapy the New Standard of Care?

Due to advancements in systemic targeted and immunotherapies resulting in improved disease control and overall survival, and the increasing use of computed tomography and spine magnetic resonance imaging surveillance, the number of patients presenting with both asymptomatic and symptomatic spinal metastases is increasing. The need for versatile tumour ablative local management strategies, beyond the limits afforded by conventional palliative external beam radiation therapy (cEBRT), is increasingly more important. Stereotactic body radiation therapy (SBRT) was developed to meet such a need. This highly conformal technique allows the delivery of high biologically effective doses of radiation to the vertebral target, while controlling the differential dose exposure to the adjacent critical neural tissue. Identifying patients with painful spine metastases who would gain the most benefit from this important therapeutic option can be challenging. Here we summarise the randomised evidence specific to spine SBRT, comparing cEBRT with SBRT for pain control in patients with spine metastases in the palliative setting to better understand the role of spine SBRT in modern oncological spinal care.

Survey of current practices from an international task force for gynecological stereotactic ablative radiotherapy.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) is an effective treatment that improves local control for many tumours. However, the role of SABR in gynecological cancers (GYN) has not been well-established. We hypothesize that there exists considerable variation in GYN-SABR practice and technique. The goal of this study is to describe clinical and technical factors in utilization of GYN-SABR among 11 experienced radiation oncologists. MATERIALS AND METHODS: A 63 question survey on GYN-SABR was sent to 11 radiation oncologists (5 countries) who have published original research, conducted trials or have an established program at their institutions. Responses were combined and analyzed at a central institution. RESULTS: Most respondents indicated that salvage therapy (non-irradiated or re-irradiated field) for nodal (81%) and primary recurrent disease (91%) could be considered standard options for SABR in the setting of inability to administer brachytherapy. All other indications should be considered on clinical trials. Most would not offer SABR as a boost in primary treatment off-trial without absolute contraindications to brachytherapy. Multi-modality imaging is often (91%) used for planning including PET, CT contrast and MRI. There is a wide variation for OAR tolerances however small bowel is considered the dose-limiting structure for most experts (91%). Fractionation schedules range from 3 to 6 fractions for nodal/primary definitive and boost SABR. CONCLUSIONS: Although SABR has become increasingly standard in other oncology disease sites, there remains a wide variation in both clinical and technical factors when treating GYN cancers. Nodal and recurrent disease is considered a potential indication for SABR whereas other indications should be offered on clinical trials. This study summarizes SABR practices among GYN radiation oncologists while further studies are needed to establish consensus guidelines for GYN-SABR treatment.

Efficacy of ulipristal acetate for emergency contraception and its effect on the subsequent bleeding pattern when administered before or after ovulation.

STUDY QUESTION: Does ulipristal acetate (UPA) have similar efficacy as emergency contraception (EC) when administered before and after ovulation? SUMMARY ANSWER: The efficacy of UPA-EC was significantly better when administered before than after ovulation. WHAT IS KNOWN ALREADY: Levonorgestrel (LNG) is effective as EC only when administered before, but not after ovulation. LNG EC taken in the pre-ovulatory and post-ovulatory phase results in shortening and lengthening of the index menstrual cycle, respectively. Whether the same applies to UPA is not known. STUDY DESIGN, SIZE, DURATION: Prospective, open-label clinical cohort study conducted on 700 women between May 2011 and March 2014. PARTICIPANTS, SETTING, METHODS: Seven hundred women requesting EC within 120 h after a single act of unprotected sexual intercourse in the index menstrual cycle were recruited at a community family planning clinic in Hong Kong. Each subject received a single oral dose of UPA 30 mg, and 693 of them completed follow-up. Ovulatory status at the time of UPA administration was determined by serum progesterone level supplemented by menstrual history and ultrasound tracking. The main outcome measure was the percentage of pregnancies prevented (PPP). MAIN RESULTS AND THE ROLE OF CHANCE: The PPP was significantly higher in subjects who were pre-ovulatory (77.6%) compared with those who were post-ovulatory (36.4%) at the time of UPA administration (P < 0.0001). The observed pregnancy rate following UPA administration was significantly lower than the expected pregnancy rate only in the pre-ovulatory group (P < 0.0001), but not the post-ovulatory group (P = 0.281). The overall failure rate was 1.7% (1.4 versus 2.1% in the pre- and post-ovulatory groups, respectively). Pre-ovulatory administration of UPA resulted in a small delay (median of 3 days), whereas post-ovulatory administration resulted in a minimal advancement (median of 1 day) of the next menstruation, compared with that predicted from previous menstrual pattern. More pre-ovulatory subjects (19.1%) than post-ovulatory subjects (7.8%) had deviation of the next menses of more than 7 days (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The ovulatory status of the subjects was determined based only on menstrual history and a spot sonographic finding together with serum hormonal profile at the time of recruitment. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirmed comparable efficacy of UPA in the Asian population as in western populations. The comparison between pre- and post-ovulatory use of UPA is a novel finding, which provides insights to its possible pharmacological action. STUDY FUNDING/COMPETING INTERESTS: The UPA tablets were provided free of charge by Laboratoire HRA Pharma, who were not involved in the design and execution of the study, or the drafting and final approval of the manuscript. The authors have no other conflicts of interest to declare. TRIAL REGISTRATION NUMBER: The University of Hong Kong Clinical Trials Registry (reference number: HKUCTR-1197).

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk.

The clinical applications of stereotactic body radiotherapy or stereotactic ablative radiotherapy (SABR) for the treatment of primary and metastatic tumours of different organ sites have been expanding rapidly in the recent decade. SABR requires advanced technology in radiotherapy planning and image guidance to deliver a highly conformal ablative dose precisely to targets (or tumours) in the body. Although this treatment modality has shown promising results with regard to tumour control, some serious complications have been observed and reported. In order to achieve a favourable therapeutic ratio, strategies to mitigate the risk of complications must be in place. This overview will summarise the reported serious complications caused by SABR and strategies to mitigate the risk will be discussed.

Ultrasound-guided thrombin injection for pseudoaneurysms: a case series at a local hospital.

Post-catheterization pseudoaneurysms are increasingly prevalent due to widespread use of endovascular procedures. Ultrasound-guided thrombin injection has emerged as a treatment of choice for these pseudoaneurysms. We review our experience performing this procedure for a series of cases from 2007 to 2010 with different clinical manifestations at a single hospital in Hong Kong. We achieved a high technical success rate with no complications.

International practice survey on the management of brain metastases: Third International Consensus Workshop on Palliative Radiotherapy and Symptom Control.

AIM: To evaluate international patterns of practice for the management of metastatic disease to the brain. MATERIALS AND METHODS: An online international practice survey was conducted from April to June 2010. Most of the survey questions were based on common management issues for which optimal management using level 1 evidence was lacking. The survey consisted of three sections: respondent demographics, 13 general questions regarding surgery, whole brain radiotherapy (WBRT) and radiosurgery and 13 questions related to specific scenarios. RESULTS: In total, 445 individuals responded to the survey over a 3 month period. Ninety per cent of respondents worked in a hospital-based setting. Ninety-three per cent of respondents were radiation oncologists. Thirty-seven per cent worked in an academic setting. Only three of 26 survey questions generated at least 70% agreement for a favoured response. Eighty-eight per cent of respondents chose comfort measures only for patients with multiple brain metastases who have been previously treated with WBRT and who now present 6 months later with two to four brain metastases (all less than 4 cm in size) with uncontrolled extracranial disease and bedridden state. Seventy-eight per cent of respondents would use WBRT alone for initial treatment in patients with two to four brain metastases (all less than 4 cm in size), with active, uncontrolled extracranial disease and a Karnofsky performance status of 70. Seventy-eight per cent of respondents chose surgical resection for an enlarging single brain metastasis that has been previously treated with radiosurgery. The enlarging single brain metastasis is in a surgically accessible site and is now symptomatic. The patient has controlled extracranial disease, good performance status and magnetic resonance spectroscopy was not diagnostic. CONCLUSIONS: There is a lack of uniform agreement for many common management issues (not well answered by level 1 evidence) in patients with metastatic disease to the brain.

Overexpression of miR-370 and downregulation of its novel target TGFß-RII contribute to the progression of gastric carcinoma.

MicroRNAs (miRNAs) are endogenous non-coding RNAs that are known to be involved in the pathogenesis of tumors. Gastric carcinoma (GC) is a common malignancy worldwide. The aim of this study was the identification of the expression signature and functional roles of aberrant miRNAs in GC. Initial screening established a profile of aberrantly expressed miRNAs in tumors. miR-370 was confirmed to be overexpressed in GC tissues. Higher expression of miR-370 in GC tissues was associated with more advanced nodal metastasis and a higher clinical stage compared with controls. In addition, significantly higher level of miR-370 was noted in the plasma of GC patients compared with controls. Patients having more invasive or advanced tumors also exhibited a higher plasma level of miR-370. In vitro assays indicated that exogenous miR-370 expression enhanced the oncogenic potential of GC cells. The AGS-GFPM2 cells with exogenous miR-370 expression also exhibited enhanced abdominal metastatic dissemination in nude mice. Reporter assays confirmed that miR-370 targeted predicted sites in 3'UTR of transforming growth factor-ß receptor II (TGFß-RII) gene. The exogenous miR-370 expression decreased TGFß-RII expression and the phosphorylation of Smad3 elicited by TGFß1. The TGFß1-mediated repression in cell migration was reverted by exogenous miR-370 expression. A reverse correlation between miR-370 and TGFß-RII expression was noted in GC tissues. This study concludes that miR-370 is a miRNA that is associated with GC progression by downregulating TGFß-RII. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in GC.

SU-E-T-04: Repair Kinetics of Sublethal Damage in Rat Cervical Spinal Cord - Application of the GLQ Model Incorporating Reciprocal Time Pattern.

PURPOSE: The repair rate conventionally assumed to be constant during the entire radiation course. However, increasing evidences from animal studies show that the repair process may slow down with time and the experimental data does not fit an exponential pattern. To address this enigma, we presented a generalized linear-quadratic (gLQ) model incorporating reciprocal time repair pattern of sublethal damage and fit the model to published experimental data. METHODS: In the gLQ model, the parameter G in the surviving fraction represents the repair process of sublethal damage with Tr as the repair half-time. When a reciprocal time pattern of repair process was adopted, a generalized form of G was derived analytically for arbitrary radiation schemes (I(t) = Ii, ti-1 < t < ti, where i=1 to N, Ii is the dose rate of the ith segment to the voxel in question, and N is the total number of segments for the entire treatment course). The published animal data was used to test the reciprocal formulas. RESULTS: The gLQ model incorporating a reciprocal time pattern to describe the repair process was used to fit the experimental data. The reciprocal model showed better fit to the animal data than the exponential model, particularly for the ED50 data, resulting in the following parameters: the reduced chi-square of 1.52, α/ß=0.9 Gy, Tr =1.0 h for the reciprocal model and reduced chi-square of 3.39, α/ß=1.6 Gy, Tr=3.5 h for the exponential model. CONCLUSIONS: The modeling results suggest that the gLQ model incorporating the reciprocal time pattern of sublethal damage repair facilitates the interpretation of complex experimental designs, especially for irregular dose delivery schedules. These formulas can be used to analyze experimental and clinical data, where a slowing-down of the repair process occurs during the radiation therapy course.

Arachnoiditis ossificans.

Arachnoiditis ossificans is a rare type of chronic arachnoiditis characterised by the presence of calcification or ossification of the spinal arachnoid. There are a few reports of this condition in Japanese and western populations but no case has been reported in a Chinese population before. We describe a 35-year-old woman with typical findings of arachnoiditis ossificans. A brief review of the literature is also presented.

Acceptability of human papillomavirus vaccination among Chinese women: concerns and implications.

OBJECTIVE: To explore Chinese women's perceptions of human papillomavirus (HPV) vaccination and their intention to be vaccinated. DESIGN: A cross-sectional community-based survey study. SETTING: Thirteen community women's health centres of The Family Planning Association of Hong Kong. SAMPLE: A total of 1450 ethnic Chinese women aged 18 or above who attended the health centres. METHODS: Participants completed a written consent and an anonymous questionnaire onsite. MAIN OUTCOME MEASURES: Knowledge and beliefs about HPV and HPV vaccination against cervical cancer and participants' own intention to be vaccinated. RESULTS: About 38% of the participants (n = 527) had heard of HPV and 50% (n = 697) had heard of vaccination against cervical cancer. HPV infection was perceived to be stigmatising and detrimental to intimate, family and social relationships. Despite misconceptions and a grossly inadequate knowledge about HPV and HPV vaccination, 88% of the participants (n = 1219) indicated that they would likely be vaccinated. Majority of the participants believed that sexually experienced women should be vaccinated, while 27% opposed vaccinating sexually naive women. Younger age women who perceived a disruptive impact of HPV infection on intimate relationship and their partners' approval were significantly associated with a positive intention to be HPV vaccinated. CONCLUSIONS: The easy acceptability of HPV vaccination among the mostly sexually experienced Chinese participants and their knowledge deficit on the subject may implicate potential misuse of the vaccines and a false sense of security against cervical cancer. There is a dire need for culturally sensitive and tailored education for the public, women of different ages and their partners about HPV and HPV vaccination. Emphasis must be placed on the prophylactic nature of the current vaccines, the uncertain effects when given to sexually experienced women, the importance of adolescent vaccination and the need for continued cervical screening whether vaccinated or not.

Quality of life after curative gastrectomy for gastric cancer in a randomised controlled trial.

Quality of life (QOL) was studied in gastric cancer patients treated on a randomised, controlled trial comparing D1 (level 1) with D3 (levels 1, 2 and 3) lymphadenectomy. A total of 221 patients were randomly assigned to D1 (n=110) and D3 (n=111) surgery. Quality-of-life assessments included functional outcomes (a 14-item survey about treatment-specific symptoms) and health perception (Spitzer QOL Index) was performed before and after surgery at disease-free status. Patients suffered from irrelative events such as loss of partners was excluded thereafter. Main analyses were done by intention-to-treat. Thus, 214 D1 (106/110=96.4%) and D3 (108/111=97.3%) R0 patients were assessed. Longitudinal analysis showed that functional outcomes decreased at 6 months after surgery and increased over time thereafter, while health perceptions increased over time in general. On the basis of linear mixed model analyses, patients having total gastrectomy, advanced cancer and hemipancreaticosplenectomy, but not complications had poorer QOL than those without. D1 and D3 patients showed no significant difference in QOL. The results suggest that changes of QOL were largely due to scope of gastric resection, disease status and distal pancreaticosplenectomy, rather than the extent of lymph node dissection. This indicates that nodal dissection can be performed for a potentially curable gastric cancer.

The conjoint junction of the triceps surae: implications for gastrocnemius tendon lengthening.

Forty embalmed cadaver lower limbs were dissected to identify the morphology of the conjoint junction of the tendons of gastrocnemius and soleus and the location of the gastrocnemius tendon relative to bony landmarks. Five patterns of conjoint junction morphology were found: transverse (25%), oblique passing distally and medially (45%), oblique passing distally and laterally (5%) and arcuate as an inverted U (17.5%) and a U-shape (7.5%). Left-right asymmetry of the junction was observed in 31.6% of 19 paired cadaver legs. On the medial side of the calf the gastrocnemius tendon could be located between 38 and 46% of the proportion of the distance between the upper border of the calcaneus and the fibular head. Corresponding values for the midline and lateral side of the calf were 45-58% and 48-51%. The location of the gastrocnemius tendon relative to bony landmarks may help to guide incision planning for open or endoscopic division of the tendon.

Outcome of distal gastric cancer with pyloric stenosis after curative resection.

AIMS: Pyloric stenosis usually presents with symptoms, and this may lead patients to consult their physician. We evaluate whether distal gastric cancer patients with pyloric stenosis had a better outcome than those without. METHODS: A total of 551 distal gastric cancer patients who received curative subtotal gastrectomy between January 1988 and December 2003 at Taipei Veterans General Hospital were analyzed. Among them, 174 patients were sorted into the pyloric stenosis group according to obstructive symptoms. Their clinicopathological features, survival and prognostic factors were evaluated. RESULTS: The 5-year overall and disease-free survival rate of distal third gastric adenocarcinoma for the pyloric stenosis group was significantly lower than those without pyloric stenosis. Multivariate analysis revealed the pyloric stenosis group had deeper cancer invasion (relative to pT1, RR of pT2 3.1, p=0.009; pT3 6.1, p<0.001; pT4 16.5, p<0.001), and more lymph node metastasis (RR 3.6; p=0.001). The pyloric stenosis group had a tendency to lymph node metastasis toward the hepatoduodenal ligament, but this did not reach statistical difference. However, the pyloric stenosis group had significantly higher lymph node metastasis in the retropancreatic region (5.17% vs. 0.53%; p=0.001). CONCLUSIONS: Distal gastric cancers with pyloric stenosis have worse biological behavior than those without, and consequently have a poor outcome.

Effect of local lignocaine gel application for pain relief during suction termination of first-trimester pregnancy: a randomized controlled trial.

BACKGROUND: This study evaluated the effectiveness of local lignocaine gel application in pain control during first-trimester suction termination of pregnancy (STOP). METHODS: In this prospective randomized placebo-controlled double-blind trial, 131 women undergoing STOP between 7 and 10 weeks of gestation were studied. They were computer-randomized to receive 2% lignocaine gel or placebo (KY Jelly) locally applied to the cervix 1 min before cervical manipulation/dilatation. They all had cervical priming with misoprostol and premedication with diazepam and pethidine. Pain scores on a verbal analogue scale preoperative, at cervical manipulation/dilatation, intraoperative and 1 h post-operative, as well as the patients' satisfaction level towards pain control, were compared. RESULTS: The lignocaine gel group had significantly reduced overall intraoperative pain score compared with placebo group (P = 0.021). No significant difference in pain score between the two groups was demonstrated at other time points. Subgroup analysis revealed that the difference in overall intraoperative pain scores between the two groups was evident in the multiparous (P = 0.015) but not the nulliparous subjects. CONCLUSION: The use of local lignocaine gel application reduces overall intraoperative pain in multiparous women undergoing first-trimester STOP preceded by misoprostol cervical priming and premedication for conscious sedation.