[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

Is proton beam therapy always better than photon irradiation? Lessons from two cases.

Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be difficult. There is a need to balance patient, tumour and treatment factors when making this decision. Comparing the dosimetry between these two modalities plays an important role in this process. PBT can reduce low to intermediate doses to organs at risk (OAR), but photon irradiation has its dosimetric advantages. We present two cases with brain tumours, one paediatric and one AYA, in which treatment plan comparison between photons and protons showed dosimetric advantages of photon irradiation. The first case was an 18-month-old child diagnosed with posterior fossa ependymoma requiring adjuvant radiotherapy. Photon irradiation using volumetric modulated arc therapy (VMAT) had lower doses to the hippocampi but higher doses to the pituitary gland. The second case was a 21-year-old with an optic pathway glioma. There was better sparing of the critical optic structures and pituitary gland using fractionated stereotactic radiation therapy over PBT. The dosimetric advantages of photon irradiation over PBT have been demonstrated in these cases. This highlights the role of proton-to-photon comparative treatment planning to better understand which patients might benefit from photon irradiation versus PBT.

Local hero: A phase II study of local therapy only (stereotactic radiosurgery and / or surgery) for treatment of up to five brain metastases from HER2+ breast cancer. (TROG study 16.02).

Introduction, A decade ago, stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) was emerging as preferred treatment for oligometastatic brain metastases. Studies of cavity SRS after neurosurgery were underway. Data specific to metastatic HER2 breast cancer (MHBC), describing intracranial, systemic and survival outcomes without WBRT, were lacking. A Phase II study was designed to address this gap. Method, Adults with MHBC, performance status 0-2, ≤ five BrM, receiving/planned to receive HER2-targeted therapy were eligible. Exclusions included leptomeningeal disease and prior WBRT. Neurosurgery allowed ≤6 weeks before registration and required for BrM >4 cm. Primary endpoint was 12-month requirement for WBRT. Secondary endpoints; freedom from (FF-) local failure (LF), distant brain failure (DBF), extracranial disease failure (ECDF), overall survival (OS), cause of death, mini-mental state examination (MMSE), adverse events (AE). Results, Twenty-five patients accrued Decembers 2016-2020. The study closed early after slow accrual. Thirty-seven BrM and four cavities received SRS. Four cavities and five BrM were observed. At 12 months: one patient required WBRT (FF-WBRT 95 %, 95 % CI 72-99), FFLF 91 % (95 % CI 69-98), FFDBF 57 % (95 % CI 34-74), FFECDF 64 % (95 % CI 45-84), OS 96 % (95 % CI 74-99). Two grade 3 AE occurred. MMSE was abnormal for 3/24 patients at baseline and 1/17 at 12 months. Conclusion, At 12 months, SRS and/or neurosurgery provided good control with low toxicity. WBRT was not required in 95 % of cases. This small study supports the practice change from WBRT to local therapies for MHBC BrM.

COVID-19 and social wellbeing in Malaysia: A case study.

The world has witnessed the largest single disruption to social wellbeing since the first known case of coronavirus disease 2019 (COVID-19) was reported in China in December 2019. In Malaysia, the government implemented the Movement Control Order (MCO) on 18 March 2020 in response to the COVID-19 pandemic. Thus, this paper highlights how the Malaysian government responded to COVID-19 in comparison with some Asian countries; and what has and has not worked for the MCO imposed by the government. The paper adopts a review approach that is supported by findings from both grey and academic literature. The findings reveal that the COVID-19 pandemic has significant impacts on the society's wellbeing in Malaysia, the most severe of which are negative mental health and job unemployment. On the other hand, COVID-19 has sparked a surge of volunteering in society. This paper presumably and hopefully represents a frontier review with more empirical research to be conducted to investigate the extent of the social impact of COVID-19, the outcomes of which are a call for re-envisioning of social policies in Malaysia. To the best knowledge of the authors, little empirical research has been conducted to explore the social-wellbeing implications of COVID-19 in Malaysia. By reflecting on the various scenarios-both detrimental and beneficial in the context of the COVID-19 pandemic, the paper identifies potential avenues for relevant research in the social wellbeing realm.

Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature.

PURPOSE: Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally fractionated radiation therapy (CF-RT) in glioblastoma (GBM). We report outcomes of young, fit GBM patients treated with HF-RT and CF-RT during the COVID-19 pandemic, and a meta-analysis of HF-RT literature in this patient subgroup. METHODS: Hospital records of patients with IDH-wildtype GBM treated with HF-RT (50 Gy/20 fractions) and CF-RT (60 Gy/30 fractions) between January 2020 and September 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariable analysis was performed using Cox regression analysis. A systematic search and meta-analysis of studies from January 2000 to January 2022 was performed. RESULTS: 41 patients were treated (HF-RT:15, CF-RT:26). For both HF-RT and CF-RT groups, median age was 58 years and 80-90% were ECOG 0-1. There were more methylated tumours in the HF-RT group. All patients received concurrent/adjuvant temozolomide. At 19.2 months median follow-up, median OS was 19.8 months and not-reached for HF-RT and CF-RT (p = 0.5), and median PFS was 7.7 and 5.8 months, respectively (p = 0.8). HF-RT or CF-RT did not influence OS/PFS on univariable analysis. Grade 3 radionecrosis rate was 6.7% and 7.7%, respectively. 15 of 1135 studies screened from a systematic search were eligible for meta-analysis. For studies involving temozolomide, pooled median OS and PFS with HF-RT were 17.5 and 9.9 months (927 and 862 patients). Studies using shortened HF-RT schedules reported 0-2% Grade 3 radionecrosis rates. CONCLUSION: HF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.

Improving the diagnosis of radiation necrosis after stereotactic radiosurgery to intracranial metastases with conventional MRI features: a case series.

BACKGROUND: The distinction between true disease progression and radiation necrosis after stereotactic radiosurgery to intracranial metastases is a common, but challenging, clinical scenario. Improvements in systemic therapies are increasing the importance of this distinction. A variety of imaging techniques have been investigated, but the value of any individual technique is limited. CASE PRESENTATION: Assessment should extend beyond simply the appearances of the lesion at a given timepoint, but also consider local anatomy and lesion evolution. Firstly, enlargement of a metastasis is affected by local anatomical boundaries, such as the dural reflections or cerebrospinal fluid spaces. In contrast, the radiation dose administered with stereotactic radiosurgery does not respect these anatomical boundaries and is largely concentric around the treated lesion. Therefore, new, non-contiguous enhancement across such a boundary can be confidently attributed to radiation necrosis. Secondly, the dynamic nature of radiation necrosis may result in a change in lesion shape, with different portions of the lesion simultaneously enlarging and regressing. Regression of part of a lesion indicates radiation necrosis, even if the overall lesion enlarges. This case series describes these two features and provides illustrative clinical examples in which these features allowed a confident diagnosis of radiation necrosis. CONCLUSIONS: The distinction between true disease progression and radiation necrosis should extend beyond just the appearances of the lesion. More nuanced interpretation incorporating a relationship to anatomical boundaries and a change in shape can improve accurate diagnosis of radiation necrosis.

Immunotherapy, radiation oncology and radiology: An alliance into the future.

AUTHOR BIOGRAPHIES: A/Prof Eric Hau is a clinician-scientist with interest in lung and CNS tumours. His clinical and laboratory research focuses on understanding the mechanisms of radiation resistance and investigating drugs which may be utilised for radiation sensitisation to improve outcomes for patients. Associate Professor Warren Clements is an Interventional Radiologist at Alfred Health and has an Adjunct appointment with the Department of Surgery, Central Clinical School, Monash University. A/Prof Clements completed post-fellowship subspecialty training in Interventional Radiology, consolidated by completion of the EBIR certification. A/Prof Clements is actively involved in medical research with over 80 peer-reviewed publications, and has presented his research at national and international conferences. He is an Associate Editor for JMIRO and editorial board member of both CVIR and CVIR Endovascular. He volunteers his time for RANZCR as a member of the Interventional Radiology Committee and as an editorial board member for RANZCR's Inside Radiology website. A/Prof Clements has a keen interest in education and training, and is the supervisor of Intern Training in the Radiology Department. Dr. Joseph (Joe) Sia is a Consultant Radiation Oncologist at the Peter MacCallum Cancer Centre, Melbourne, Australia. He obtained his medical degree from the University of Otago, New Zealand and completed his radiation oncology training in Melbourne in 2017. He then undertook a laboratory-based PhD in tumour immunology at the University of Melbourne, which was awarded in 2020.

Variations in whole brain radiation therapy fractionation for brain metastases in Victoria.

INTRODUCTION: We aim to evaluate the use of different whole brain radiation therapy (WBRT) fractionation schedules for brain metastases (BM) in Victoria, and the factors associated with it. METHODS: This is a population-based cohort of patients who received radiation therapy for BM between 2012 and 2017, as captured in the Victorian Radiotherapy Minimum Dataset. We excluded patients with primary brain tumour and those who had 'prophylactic' intent treatment. The Cochran-Armitage test was used to evaluate changing trend in WBRT fractionation. Multivariate multinomial logistic regressions were used to evaluate factors associated with WBRT fractionation. RESULTS: Of the 3111 patients who had WBRT, 1048 (45%), 1291 (42%) and 312 (13%) had ≤5, 6-10 and >10 fractions WBRT respectively. There was progressive increase in ≤5 fractions WBRT use over time, from 37% in 2012 to 50% in 2017 (P-trend < 0.001). In multivariate analyses, increasing age, patients with gastrointestinal cancer, patients living in remote/regional areas and more recent treatment were associated with the use of shorter WBRT fractionation (≤5 fractions), while patients who had WBRT plus stereotactic radiosurgery, and those treated in private institutions were associated with the use of prolonged WBRT fractionation (≥6 fractions). Three hundred eighty-nine (13%) patients died within 30 days of WBRT, of which 241 (64%), 119 (32%) and 17 (5%) had ≤5, 6-10 and > 10 fractions WBRT respectively. CONCLUSION: We observed large variations in WBRT fractionation that are associated with patient, tumour, treatment and institutional factors. It is important to continuously monitor and benchmark our practice in order to reduce potentially unwarranted variations.

Basic cancer immunology for radiation oncologists.

Although the impressive clinical responses seen with modern cancer immunotherapy are currently limited to a subset of patients, the underlying paradigm shift has resulted in now hardly a segment in oncology that has not been touched by the immuno-oncology revolution. A growing body of data indicates that radiation therapy (RT) can modulate the tumour immune microenvironment and complement cancer immunotherapy via non-overlapping mechanisms to reinvigorate immunity against cancer. Thus, increasingly RT is viewed as a highly unique partner for immunotherapy across the spectrum of cancer settings, as radiobiology and cancer immunology foreseeably become more intertwined. Considering these developments, this review summarises the key concepts and terminology in immunology for the radiation oncologist, with a focus on the cancer setting and with reference to important recent advances. These concepts will provide a starting point for understanding the strategies that underlie current and emerging immunotherapy trials, as well as the indirect effects of RT by which immune responses against cancer are shaped.

Long-term Patterns of Failure and the Value of Blood Prognostic Markers in Anal Cancers Treated With Intensity-Modulated Radiation Therapy.

BACKGROUND: To analyze the long-term outcomes and prognostic value of hematological parameters in anal cancer patients receiving intensity-modulated radiation therapy (IMRT). MATERIALS: Hospital records of consecutive patients with anal squamous cell carcinoma who received curative-intent IMRT according to a standardized contouring protocol between 2010 and 2020 were reviewed. Locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Coverage of locoregional recurrences by the initial IMRT volumes were assessed. The prognostic value of pretreatment blood counts for PFS and OS were determined using Cox regression analysis. RESULTS: A total of 166 patients were analyzed with a median follow-up of 3.3 years. Forty-six percent and 54% of patients had Stage I-II and IIIA-B cancers, respectively. The 5-year LRFS, DMFS, PFS and OS were 81%, 89%, 65% and 76% respectively. Grade ≥ 3 toxicity occurred in 5% of patients. Of all patients who relapsed, 70% had only locoregional recurrence as first site of failure. Ninety percent of locoregional recurrences were in-field. Hemoglobin, neutrophil and platelet counts were associated with PFS on univariable analysis, but only cancer stage and p16 status remained prognostic on multivariable analysis. Patients with more advanced cancer stages also had higher baseline neutrophil counts. Performance status and neutrophil counts were prognostic for OS on multivariable analysis. CONCLUSION: This study affirms the long-term efficacy and safety of IMRT. Treatment resistance, rather than radiation geographic miss, is a major issue underpinning locoregional recurrences. Pretreatment blood counts were not validated to be independently prognostic for disease recurrence.

Molecular and genomic characterisation of a panel of human anal cancer cell lines.

Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.

Regulatory T Cells Shape the Differential Impact of Radiation Dose-Fractionation Schedules on Host Innate and Adaptive Antitumor Immune Defenses.

PURPOSE: We examined how radiation dose per fraction (DPF) and total dose, as represented by biological effective dose (BED), can independently and differentially affect the immunomodulatory capacity of radiation therapy (RT). METHODS AND MATERIALS: AT3-OVA mammary and MC38 colorectal tumors in C57BL/6 mice were irradiated with rationally selected dose-fractionation schedules, alone or with immune-modulating or -depleting agents. Tumor growth was monitored as a readout of therapeutic response. Flow cytometry and RNA sequencing of mouse tumors and analysis of transcriptomic data sets from irradiated human cancers were used to examine the immunomodulatory effects of the different radiation schedules. RESULTS: In AT3-OVA tumors, radiation DPF rather than BED determined the ability of RT to evoke local antitumor CD8+ T cell responses and synergize with anti-PD-1 therapy. Natural killer cell-mediated control of irradiated tumors was more sensitive to radiation BED. Radiation-induced regulatory T cell (Treg) responses, which were detected in both mouse and human tumors, were a major factor underlying the differential activation of adaptive immunity by radiation DPF and the activity of natural killer cells during the early phase of response to RT. Targeted inhibition of Treg responses within irradiated tumors rescued and enhanced local tumor control by RT and permitted the generation of abscopal and immunologic memory responses, irrespective of radiation schedule. MC38 tumors did not support the induction of an amplified Treg response to RT and were highly vulnerable to its immunoadjuvant effects. CONCLUSIONS: Local radiation-induced Treg responses are influenced by radiation schedule and tumor type and are a critical determinant of the immunoadjuvant potential of RT and its ability to synergize with T cell-targeted immunotherapy.

Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer.

Radiation therapy (RT) is responsible for at least 40% of cancer cures, however treatment resistance remains a clinical problem. There have been recent advances in understanding the molecular mechanisms of radiation-induced cell death. The type of cell death after radiation depends on a number of factors including cell type, radiation dose and quality, oxygen tension, TP53 status, DNA repair capacity, cell cycle phase at time of radiation exposure, and the microenvironment. Mitotic catastrophe (a pathway preceding cell death that happens in mitosis or as a consequence of aberrant mitotic progression) is the primary context of radiation-induced cell death in solid cancers, although in a small subset of cancers such as haematopoietic malignancies, radiation results in immediate interphase apoptosis, occurring within hours after exposure. There is intense therapeutic interest in using stereotactic ablative body radiotherapy (SABR), a precise, high-dose form of RT given in a small number of fractions, to prime the immune system for cancer cell killing, but the optimal radiation dose and fractionation remain unclear. Additionally, promising novel radiosensitisers targeting the cell cycle and DNA repair pathways are being trialled. In the context of the increasing use of SABR and such novel agents in the clinic, we provide an updated primer on the major types of radiation-induced cell death, focussing on their molecular mechanisms, factors affecting their initiation, and their implications on immunogenicity.

Extracting tumour prognostic factors from a diverse electronic record dataset in genito-urinary oncology.

OBJECTIVES: To implement a system for unsupervised extraction of tumor stage and prognostic data in patients with genitourinary cancers using clinicopathological and radiology text. METHODS: A corpus of 1054 electronic notes (clinician notes, radiology reports and pathology reports) was annotated for tumor stage, prostate specific antigen (PSA) and Gleason grade. Annotations from five clinicians were reconciled to form a gold standard dataset. A training dataset of 386 documents was sequestered. The Medtex algorithm was adapted using the training dataset. RESULTS: Adapted Medtex equaled or exceeded human performance in most annotations, except for implicit M stage (F-measure of 0.69 vs 0.84) and PSA (0.92 vs 0.96). Overall Medtex performed with an F-measure of 0.86 compared to human annotations of 0.92. There was significant inter-observer variability when comparing human annotators to the gold standard. CONCLUSIONS: The Medtex algorithm performed similarly to human annotators for extracting stage and prognostic data from varied clinical texts.

Reduced dose to small bowel with the prone position and a belly board versus the supine position in neoadjuvant 3D conformal radiotherapy for rectal adenocarcinoma.

INTRODUCTION: No consensus exists regarding the optimal treatment setup for neoadjuvant radiotherapy of rectal cancer using a 3D conformal (3D CRT) technique. Positioning the patient prone with a belly board aims to reduce the amount of small bowel irradiated. METHODS: Twenty-five patients with locally advanced rectal cancer underwent computed tomography (CT) planning for neoadjuvant chemoradiotherapy. Patients were simulated prone with a belly board and then in the supine position. Questionnaires rating the comfort of each position were completed. 3D CRT plans were generated for both positions to a prescribed dose of 50.4 Gy in 1.8 Gy daily fractions. Dose-volume parameters in 5 Gy increments for small bowel, large bowel and bladder wall were compared. RESULTS: Small bowel V5 Gy, V10 Gy, V15 Gy and V20 Gy values were significantly higher in the supine position (398, 366, 245, 151 cm3 for supine vs. 243, 213, 161, 122 cm3 for prone respectively; P < 0.001, <0.001, <0.001 and 0.025). Large bowel V5 Gy, V10 Gy and V15 Gy values were significantly higher in the supine position (266, 209, 147 cm3 supine, 175, 139, 108 cm3 prone respectively; P = 0.001, <0.001, 0.003). There was a significant difference in comfort scores favouring the supine position (P = 0.015). CONCLUSION: A significant increase in small and large bowel dose was seen in the supine plans. Treatment in the prone position with a belly board may reduce toxicity when using a 3D CRT technique. Whilst both setup positions were tolerable the supine was more comfortable.

A prospective study comparing digital breast tomosynthesis with digital mammography in surveillance after breast cancer treatment.

BACKGROUND: Although the benefit of adjunct digital breast tomosynthesis (DBT) is established in population screening, its benefit in surveillance after breast cancer treatment is not well defined. We prospectively evaluated whether the addition of DBT to digital mammography (DM) reduced the rate of indeterminate findings compared to DM alone in patients after breast cancer treatment. METHODS: Patients had both DM and DBT for routine surveillance. Two-dimensional synthesised mammogram (SM) was generated for each patient from DBT data. DM, SM, and DBT images were read for each patient by one of four radiologists credentialed for DBT. We compared the rates of indeterminate findings between DM+DBT with DM alone in patients with a range of breast densities and between DM and SM. RESULTS: A total of 618 patients and 1069 breasts were analysed. The rates of indeterminate findings for DM+DBT versus DM alone were 10.5% and 13.1%, respectively (p=0.018). In breasts treated with surgery and radiotherapy (n=558), the corresponding rates of indeterminate findings were 4.9% and 6.9%, respectively (p=0.039). The rate of indeterminate findings for DM+DBT increased with increasing breast density (p=0.019). There was no significant difference in the rates of indeterminate findings between DM and SM (13.1% versus 11.5%, p=0.1). CONCLUSION: The addition of DBT to DM reduced the rate of indeterminate findings in surveillance of patients after breast cancer treatment. Further research is required to confirm whether DBT and SM could replace DM for patients undergoing surveillance.

Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance.

BACKGROUND: Vertical human immunodeficiency virus (HIV) transmission is a public health problem in Burkina Faso. The main objective of this study on the prevention of mother-to-child HIV-1 transmission was to determine the residual risk of HIV transmission in infants born to mothers receiving highly active antiretroviral therapy (HAART). Moreover, we detect HIV antiretroviral (ARV) drug resistance among mother-infant pairs and identify subtypes and circulating recombinant forms (CRF) in Burkina Faso. DESIGN: In this study, 3,215 samples of pregnant women were analyzed for HIV using rapid tests. Vertical transmission was estimated by polymerase chain reaction in 6-month-old infants born to women who tested HIV positive. HIV-1 resistance to ARV, subtypes, and CRFs was determined through ViroSeq kit using the ABI PRISM 3,130 sequencer. RESULTS: In this study, 12.26% (394/3,215) of the pregnant women were diagnosed HIV positive. There was 0.52% (2/388) overall vertical transmission of HIV, with rates of 1.75% (2/114) among mothers under prophylaxis and 0.00% (0/274) for those under HAART. Genetic mutations were also isolated that induce resistance to ARV such as M184V, Y115F, K103N, Y181C, V179E, and G190A. There were subtypes and CRF of HIV-1 present, the most common being: CRF06_CPX (58.8%), CRF02_AG (35.3%), and subtype G (5.9%). CONCLUSIONS: ARV drugs reduce the residual rate of HIV vertical transmission. However, the virus has developed resistance to ARV, which could limit future therapeutic options when treatment is needed. Resistance to ARV therefore requires a permanent interaction between researchers, physicians, and pharmacists, to strengthen the network of monitoring and surveillance of drug resistance in Burkina Faso.

Stereotactic radiosurgery for 318 brain metastases in a single Australian centre: the impact of histology and other factors.

While melanoma brain metastases (BM) are consistently associated with worse survival compared to other histologies, whether they correlate with worse local control (LC) following stereotactic radiosurgery (SRS) is not yet well-defined. In this study of prospectively and retrospectively collected data we investigated the impact of histology and other host, tumour and treatment factors on overall survival (OS) and LC. We analysed 162 patients and 318 BM lesions from various histologies treated with SRS between 2005 and 2011. We included patients who received SRS as first-line treatment, as well as patients who received SRS for residual or recurrent BM following prior surgery, whole brain radiotherapy (WBRT) or both. Median OS for the entire cohort was 8.4 months. Median OS for tumour histologies of melanoma, lung and breast cancer were 5.1, 12.2, and 14.7 months, respectively. On multivariate analysis, melanoma predicted for worse OS (hazard ratio [HR] 1.515, p = 0.003) together with performance status (HR 1.662, p < 0.001) and uncontrolled systemic disease (HR 1.755, p = 0.003). Melanoma histology was also negatively predictive for LC (HR 1.828, p = 0.021) together with increasing tumour size (HR 1.038, p = 0.017). Other factors, including the use of WBRT with SRS, the use of planning treatment volume margins, and prescription dose were not significantly predictive for OS and LC. We conclude melanoma histology also portends poorer LC in the SRS setting. While survival depends significantly on the systemic behaviour of the disease, treatment refinements to reduce local failure still merit exploration, especially in the era of targeted therapies.

A pilot study of EUS-guided fiducial insertion for the multidisciplinary management of gastric cancer.

BACKGROUND AND STUDY AIMS: The 5-year survival rates for gastric cancer remain poor despite evolving therapies, and fiducial insertion via endoscopic ultrasound (EUS) is novel within this setting. We aimed to assess the feasibility of fiducial insertion for response assessment and anatomic localization in patients with gastric cancer. PATIENTS AND METHODS: A prospective phase II feasibility study was undertaken at Austin Health (Victoria, Australia) from February 2011 to November 2012. Consecutive adult patients were enrolled who had primary adenocarcinoma of the stomach with American Joint Committee on Cancer stage T1 - 3,N0 - 1,M0 - 1a and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. In addition, the patients were medically suitable for gastrectomy and chemotherapy/chemoradiotherapy. Gold fiducial markers were inserted under EUS guidance into the margins of the gastric cancer primary. The main outcome was successful insertion of the fiducial without complications for response assessment and anatomic localization. RESULTS: A total of 15 fiducials were successfully inserted into 7 (88 %) of 8 patients. No immediate or delayed complications were noted. One patient proceeded to image-guided radiotherapy through the use of fiducials and is disease free at 12 months. Fiducials were used to assess treatment response in all patients who underwent computed tomographic imaging after insertion. Follow-up computed tomography with fiducial placement improved anatomic localization and estimation of the gastric cancer primary size in 3 (60 %) of 5 patients. CONCLUSIONS: Within the limitations of our small study cohort, fiducials were placed in gastric cancers under EUS guidance without complications, and placement was successful in the majority of our patients. Although potential benefits exist, there remain substantial limitations to the generalization of this technique across our patient population.

The use of fiducial markers in image-guided radiotherapy for gastric cancer.

The use of fiducial markers (FM) in image-guided radiotherapy (IGRT) to increase treatment precision is emerging for upper gastrointestinal malignancies. To our knowledge there is no data beyond technical reports for the use of FMs in IGRT for gastric cancers in the current literature. We report a case of an 89-year old gentleman with localised gastric cancer who was deemed unfit for surgery and chemotherapy. He had FMs inserted endoscopically around the tumour via ultrasound guidance and received radiotherapy with a high-dose palliative intent via a two-phase technique to 54 Gy in 30 fractions with IGRT. The use of FMs allowed confidence in tumour delineation and together with IGRT enabled precise and safe delivery of a higher dose. The patient tolerated the treatment without significant toxicity and had no evidence of residual or recurrent tumour 12 months following radiotherapy. The use of FMs with IGRT in upper gastrointestinal malignancies warrants further collaborative studies.