External beam radiation therapy plays an important role in the treatment of central nervous system (CNS) tumors like glioblastoma multiforme (GBM). It involves using imaging like MRI and CT to delineate the tumor and plan radiation fields with margins around the enhanced lesion. Techniques like 3D-CRT, IMRT and Rapidarc are used to deliver precise radiation doses while sparing nearby organs-at-risk. Patient immobilization with a mask and daily image-guidance help ensure accurate targeting. Close multidisciplinary care is important due to the complexity and poor prognosis of CNS tumors.
This is a PDF of a presentation given to the Radiation Oncology department at the University of Minnesota in October 2015. This PDF focuses on evaluation, management, and state-of-the-art approach to non-glioma tumors from a medical neuro-oncology perspective.
This is a PDF of a presentation given to the Radiation Oncology department at the University of Minnesota in October 2015. This PDF focuses on evaluation, management, and state-of-the-art approach to non-glioma tumors from a medical neuro-oncology perspective.
This is a PDF of a presentation given to the Radiation Oncology department at the University of Minnesota in October 2015. This PDF focuses on evaluation, management, and state-of-the-art approach to gliomas from a medical neuro-oncology perspective.
Gliomas are the commonest tumor of brain arising from the supportive cells of the brain with diverse form and presentation the treatment of which is surgical and demands adjuvant therapy for most of circumstances.
General management
Management of low grade gliomas: overview
Pilocytic astrocytoma
non pilocytic/diffuse infiltrating gliomas
Management of high grade gliomas: overview
Anaplastic gliomas
Glioblastoma multiformae
This is a PDF of a presentation given to the Radiation Oncology department at the University of Minnesota in October 2015. This PDF focuses on evaluation, management, and state-of-the-art approach to gliomas from a medical neuro-oncology perspective.
Gliomas are the commonest tumor of brain arising from the supportive cells of the brain with diverse form and presentation the treatment of which is surgical and demands adjuvant therapy for most of circumstances.
General management
Management of low grade gliomas: overview
Pilocytic astrocytoma
non pilocytic/diffuse infiltrating gliomas
Management of high grade gliomas: overview
Anaplastic gliomas
Glioblastoma multiformae
A board-certified neurosurgeon, Ilyas Munshi received his doctor of medicine from Rush Medical College and has been practicing for almost 15 years. Through his clinic, Ilyas Munshi treats a range of brain and spine issues, including gliomas.
Games For Upper-limb Stroke Rehabilitation (Seminar)James Burke
A one hour seminar I gave at my university (University of Ulster) in February 2010. It looks at how video games can be applied to stroke rehabilitation and showcases some work we have conducted in the field, including some webcam games.
Treatment of Brain Metastases Using the Current Predictive Models: Is the Pro...CrimsonpublishersCancer
Brain metastases from solid tumours are the most common intracranial tumours [1] and it occur in 40% of patients with cancer [2]. The most common primary tumours that metastasize to the brain are lung(40%),breast (25%) and melanoma (20%) [3]. The incidence is expected to be on the increase, due to improved survival, with use of modern cytotoxic drugs, targeted therapy, immunotherapy and modern radiotherapy techniques, in addition to greater use of magnetic resonance imaging of the brain. Brain metastases are common in the elderly, defined as above 60 years [4], and the interval between diagnosis of the primary and the development of brain metastases is variable, however some reported an average of 19 months [5] and adenocarcinoma is the commonest histology that metastasizes to the brain [6].
The 2016 World Health Organization classification of tumors of the central nervous system broadly employs genetic alterations for diagnostic criteria including isocitrate dehydrogenase-1 (IDH1) mutation or IDH2 mutation, and 1p/19q codeletion,[1] with the goal of creating more homogeneous disease categories with greater prognostic value.[2-5] Molecular diagnostics is becoming an increasingly important aspect of clinical oncologic neuropathology practice.
Stereotactic Radiosurgery and Radiotherapy of Brain Metastases Clinical White...Brainlab
Learn more: https://www.brainlab.com/iplan-rt
Brain metastases are a common manifestation of systemic cancer constituting as much as 30% of all intracranial malignant tumors. Each year, 15 to 30% of cancer patients develop brain metastases, yielding an incidence of over 100,000 patients in the US. Development of brain metastases leads directly to the patient’s death in the majority of cases.
PERSONALIZED MEDICINE 66515 2013Molecular Imaging .docxherbertwilson5999
PERSONALIZED MEDICINE
665
15 2013
Molecular Imaging in the Framework of Personalized
Cancer Medicine
Dževad Belkić PhD1 and Karen Belkić MD PhD1,2,3
1Department of Oncology/Pathology, Karolinska Institute, Stockholm, Sweden
2Claremont Graduate University, School of Community and Global Health, and 3Institute for Prevention Research, University of Southern California School of Medicine, Los
Angeles, CA, USA
M olecular imaging is an emerging medical discipline that integrates cellular and molecular biology with diagnos-
tic imaging. It encompasses several imaging modalities that
provide critical information for early detection and progres-
sion of disease, for predicting response to therapy and for
evaluating treatment efficacy through its cellular and molecu-
lar pathways. Given the rapidly growing sophistication in
our understanding of the cell biology of cancer, molecular
imaging offers a strategic bridge to clinical oncology. It is of
critical importance to non-invasively assess the behavior of
tumors, for which in vivo molecular imaging is a key meth-
odology. Molecular imaging detects not only the presence
of the disease process, but can potentially also quantify its
extent and severity, as well as follow the course of disease over
time. Besides its diagnostic possibilities, molecular imaging
is vital for target definition within dose-planning systems
for radiotherapy. Molecular imaging is also an invaluable
tool during and after therapy for assessing dose delivery
and the overall success of treatment, as well as for deciding
post-radiotherapy whether the patient needs further treat-
ment and, if so, with which modalities. Recently, molecular
imaging has proven to be pivotal, as well, for image-guided
biopsy and surgery. This is particularly crucial since there
may be multiple sites of cancer and image guiding can help
detect them. Imaging is likely to become an important tool
for cancer staging. Molecular targeting can be especially help-
ful in visualizing the extent of certain malignancies such as
androgen-sensitive prostate cancers, neuroendocrine tumors,
among others.
The strategic importance of molecular imaging in provid-
ing the best possible care for patients with or at risk for cancer
has been emphasized [1-3]. As recently stated: “Molecular
imaging is rapidly gaining recognition as a tool that has the
capacity to improve every facet of cancer care. The growing
demands among physicians, patients and society for per-
sonalized care are increasing the importance of molecular
imaging and shaping the development of biomedical imaging
as a whole.” [3] (p. 182)
LIMITATIONS OF PURELY ANATOMIC IMAGING
Anatomic imaging is vital for cancer detection, as well as for
staging and evaluation of response to therapy. Magnetic reso-
nance imaging, ultrasound and computerized tomography
are anatomic imaging modalities used routinely in clinical
With our increased understanding of cancer cell biology, .
Intensity-modulated radiotherapy with simultaneous modulated accelerated boos...Enrique Moreno Gonzalez
To present our experience of intensity-modulated radiotherapy (IMRT) with simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC).
Radiation Oncology in 21st Century - Changing the ParadigmsApollo Hospitals
Since its inception radiation therapy has been used as one of
the essential treatment options in the management of malignant and some benign tumors. With better understanding of tumor biology many new molecules have been added to the armamentarium of an oncologist. There is continuous improvement in surgical techniques with more emphasis on minimally invasive, organ- and function-preserving techniques. Neoadjuvant chemotherapy with or without addition of radiation therapy has helped surgeon downsizing the tumor and obtaining clearer margins.
Precision Radiotherapy: Tailoring Treatment for Individualised Cancer Care.pptxDr. Rituparna Biswas
Precision radiotherapy, also known as precision radiation therapy or targeted radiotherapy, is a cutting-edge approach in the field of radiation oncology that aims to deliver highly focused and accurate doses of radiation to cancerous cells while minimizing damage to surrounding healthy tissues.
Stereotactic Radiotherapy of Recurrent Malignant Gliomas Clinical White PaperBrainlab
Learn more: https://www.brainlab.com/intraoperative-mri
Tumors of the central nervous system (CNS) represent approximately 176,000 newly diagnosed cases worldwide per year, with an estimated annual mortality of 128,000. Malignant gliomas comprise 30% of all primary CNS tumors and remain one of the greatest challenges in oncology today, despite access to state-of-the-art surgery, imaging, radiotherapy and chemotherapy.
2. Brain, Spinal cord, Meninges
Primary or Metastatic
Metastatic cancers of the CNS are more
common
Types of CNS tumours:
Gliomas
Spinal cord tumours
Intracranial germ cell
tumours
Figure 1. The brain and spinal cord of the CNS
http://www.encognitive.com/node/1115
3. Figure 2. Frequency of all primary CNS gliomas. Adamson, C., et al. (2009) Glioblastoma multiforme: A
review of where we have been and where we are going. Expert Opinion on Investigational Drugs, 18(8): 1061-
1083
5. Diagnostic workup
Patient history and physical examination
Magnetic Resonance Imaging (MRI)
Contrast-enhanced CT
Biopsy – pathologic confirmation
Staged according to the World Health
Organisation (WHO) classification system
6. Table 1. WHO classification system for CNS tumours
8. External beam vs. Stereotactic, Brachytherapy,
Hyperfractionation, Radioenhancers, BCNT,
Accelerated, Dose escalation
3DCRT vs. IMRT vs. Rapidarc
Table 2. Recommended techniques for malignant glioma planning and their respective advantages and disadvantages.
Wagner, D. et al. (2009) Radiotherapy of malignant gliomas: Comparison of volumetric single arc technique (Rapidarc), dynamic intensity-
modulated technique and 3D conformal technique. Radiotherapy and Oncology, 93:593-596
9. Supine
Thermoplastic
immobilization mask
CT with intravenous
contrast
Figure 4. Contrast enhanced CT of brain. Arrow indicates
GBM multiforme. Drislane, F. et al. (2006) Chapter 19: Brain
Tumors. Blueprints Neurology, Philadelphia: Lippincott Williams &
Wilkins
11. Figure 5. (A) Target delineation of a GBM. GTV outlined in blue. CTV with an additional 2cm margin to cover microscopic
disease is represented by the green line. An additional 0.5cm margin is added to create the PTV for daily setup variability. (B)
3 field 3DCRT planned treatment for the same patient. Preusser, M. et al. (2011) Current concepts and management of glioblastoma.
Annals of Neurology, 70: 9-21
12.
13. Recommendations for 2-6 weeks post-surgery
Treatment position same as in simulation
Immobilisation mask accuracy within order of 5mm
Appropriate QA procedures and treatment
verification carried out
2D-2D matching IGRT can reduce PTV margin to 3mm
Dependent on available imaging modalities at each
centre
14.
15. Patients with GBM have a relatively poor prognosis and
much research is needed in the way of improved
treatment standards, especially to do with recurrent GBM
Requires MDT approach for treatment
Care must be taken in the planning of GBM
Be aware of proximity of OAR, need for partial or whole brain
RT and the advantages/disadvantages of different EBRT
techniques which may assist in planning
If performing IMRT or Rapidarc, additional QA measure must be
taken
Be aware of associated side effects and flag to appropriate
member of MDT if thought necessary
16. http://www.encognitive.com/node/1115
Adamson, C., et al. (2009) Glioblastoma multiforme: A review of where we have been and where we are going. Expert Opinion on Investigational Drugs, 18(8): 1061-
1083
Al-Mohammed, H.I. (2011) Patient specific quality assurance for glioblastoma multiforme brain tumours treated with intensity modulated radiation therapy.
International Journal of Medical Sciences, 8(6): 461-466
Amelio, D. et al. (2010) Intensity-modulated radiation therapy in newly diagnosed glioblastoma: A systematic review on clinical and technical issues. Radiotherapy
and Oncology, 97: 361-369
Barrett, A. et al. (2009) Chapter 4: Organs at risk and tolerance of normal tissues. Practical Radiotherapy Planning, London: Hodder Arnold
Brandes, A.A. et al. (2008) Glioblastoma in adults. Critical Reviews in Oncology/Hematology, 67: 139-152
Drislane, F. et al. (2006) Chapter 19: Brain Tumors. Blueprints Neurology, Philadelphia: Lippincott Williams & Wilkins
Fiveash, J.B. & Spencer, S.A. (2005) Role of radiation therapy and radiosurgery in glioblastoma multiforme. Glioblastoma Multiforme, Massachusetts: Jones and
Bartlett Publishers
Greene, F.L. et al. (2002) Chapter 47: Brain and spinal cord. AJCC Cancer Staging Handbook, New York: Springer
Hansen, E.K. & Roach III, M. (2010) Part II: Central nervous system. Handbook of Evidence-Based Radiation Oncology, London: Springer
Hermanto, U. et al. (2007) Intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy for high-grade gliomas: Does IMRT
increase the integral dose to normal brain? International Journal of Radiation Oncology Biology Physics, 67(4): 1135-1144
Kuo, L. et al. (2008) Setup accuracy of a thermoplastic mask system using two-dimensional (2D) on-board imager (OBI) for fractionated stereotactic radiotherapy
(FSRT). Medical Physics, 35(6): 2825
Louis, D.N. et al. (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathologica, 114: 97-109
Manoj, L. et al. (2011) Review of brain and brain cancer treatment. International Journal of Pharma and Bio Sciences, 2(1): 468-477
Mason, W.P. et al. (2007) Canadian recommendations for the treatment of glioblastoma multiforme. Current Oncology, 14(3): 110-117
Mirimanoff, R.O. et al. (2006) Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC
CE3 phase III randomised trial. Journal of Clinical Oncology, 24: 2563-2569
Mundt, A.J. & Roeske, J. (2011) Chapter 15: Central nervous system tumors: Overview. Image-Guided Radiation Therapy: A Clinical Perspective, Connecticut: People's
Medical Publishing House – USA
Preusser, M. et al. (2011) Current concepts and management of glioblastoma. Annals of Neurology, 70: 9-21
Rinne, M.L., Lee, E.Q. & Wen, P.Y. (2012) Central nervous system complications of cancer therapy. The Journal of Supportive Oncology, 10(4): 133-141
Schiff, D. & Wen, P. (2006) Central nervous system toxicity from cancer therapies. Hematology Oncology Clinics of North America, 20: 1377-1398
Stupp, R. et al. (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England Journal of Medicine, 352: 987-996
Stupp, R. et al. (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised
phase III study: 5-year analysis of the EORTC-NCIC trial. The Lancet Oncology, 10: 459-466
Wagner, D. et al. (2009) Radiotherapy of malignant gliomas: Comparison of volumetric single arc technique (Rapidarc), dynamic intensity-modulated technique and
3D conformal technique. Radiotherapy and Oncology, 93:593-596
Editor's Notes
The Central Nervous System is made up of the brain, spinal cord and the meninges. Cancers of the CNS present as either primary tumours originating from the CNS or as secondary, metastatic cancers originating from areas such as the breast. Of these forms of CNS cancers, however, metastatic cancers present more commonly (Manoj, L. et al., 2011). Some primary CNS tumours include gliomas, spinal cord tumours or intracranial germ cell tumours.
Of the different types of gliomas, glioblastoma is the most common and aggressive. It is classified as a WHO grade IV glioma and generally has a poor prognosis, although this has improved with advancements in treatment regimes. With current treatment regimes, median progression-free survival is quoted to be 7 months and overall survival to be 15 months ( Stupp, R. et al., 2005, Stupp, R. et al, 2009) . This is of course determined by a multitude of factors such as patient age and extent of tumour resection (Mirimanoff, R.O. et al., 2006).
GBMs are also found to have extensive microvascular infiltration, high rates of proliferation and of recurrence which all contribute to the poor prognosis of patients with GBM as well as age, histologic features and performance status (Mason, W.P. et al., 2007). Clinically, patients generally present with headaches, focal neurologic deficits and seizures but this is highly dependent on the location of the tumour. Often, diagnosis results as a consequence of these presenting symptoms rather than as an incidental discovery due to the aggressive nature of GBM (Adamson, C. et al., 2009). The etiology of GBM is greatly unknown but correlations between GBM incidence and ionising radiation and the genetic makeup of patients has been made. These genetic links have opened up a pathway for gene-based therapies, none of which have yet become the standard (Brandes, A.A. et al., 2008).
The diagnostic workup of CNS tumours typically involves: Patient history and physical examination Magnetic Resonance Imaging (MRI) T1 weighted imaging with or without gadolinium T2 weighted images Contrast-enhanced CT if patient is unable to undergo MRI Biopsy for pathologic confirmation (Adamson, C. et al., 2009) They are staged according to the WHO classification system as there is no existent TNM staging system for CNS tumours. Previous attempts to use the TNM staging system were unsuccessful in the prediction of outcomes. This is largely because the size of the tumour is less relevant than the location and histology, the CNS does not have lymphatics and patients with primary CNS tumours are less likely to survive and develop metastases (Greene, F.L. et al. 2002).
The WHO classification of CNS tumours segregates tumours by malignancy. It can be used to determine prognosis and response to therapy and consequentially determines survival (Louis, D.N. et al., 2007). Prognosis and treatment regime is also determined by: Tumour type Location Surgical margins Spread of disease (Manoj, L. et al., 2011).
GBMs can either manifest as primary (de novo) or secondary GBMs. They are also highly likely to recur either at the primary site or at another tumour focus due to migration of proliferating cells away from the primary site. Current therapies and imaging modalities are unable to detect these migrating cells which may partially explain the high incidence of recurrence. There is no current standard for the treatment of recurrent GBM (Brandes, A.A. et al., 2008). Both primary and secondary GBMs are histologically identical and as such are treated in the same way. They differ only in their rate of development and age of presentation. The mainstay treatment for these forms of GBM is surgical resection of the tumour followed by concomitant chemoradiotherapy. Resection of more than 98% of the tumour has shown to double survival rates compared to biopsy alone but this can be affected by proximity to adjacent critical structures. GBM is relatively chemoresistant and so the search for the appropriate chemotherapy drug has been relatively disappointing. Currently, the only drug found to be particularly effective is temozolomide which is prescribed concomittantly with radiotherapy and post-radiotherapy for maintenance. Radiotherapy has also been found to double survival time and is generally prescribed at 60Gy in 30 fractions (Brandes, A.A. et al., 2008, Preusser, M. et al., 2011) . A multidisciplinary team approach is required for the treatment of GBM.
Different techniques for the delivery of radiation therapy have been explored, none of which have so far proved any survival advantage over external beam therapy (Brandes, A.A. et al., 2008). Comparisons between 3DCRT, IMRT and Rapidarc have also been explored and recommended applications for each technique are outlined in table 2 (Wagner, D. et al., 2009, Amelio, D. et al., 2010, Hermanto, U. et al., 2007).
For simulation of radiotherapy, the patient lays supine and a thermoplastic immobilisation mask is fashioned. A c ontrast enhanced CT scan is then taken for accurate delineation of the tumour (Preusser, M. et al., 2011).
For planning, a post-operative MRI scan and the CT scan is fused. This still does not, however, provide accurate imaging of GBM as it is not specific for infiltration (Mundt, A.J. & Roeske, J., 2011). A 2-3cm margin is included around the GTV as about 90% of GBMs recur within 2cm of the primary site of the tumour or progress at the same site as the primary. A 0.5cm margin is then added to create the PTV. This is added to compensate for inter- and intra-fractional errors (Fiveash, J.B. & Spencer, S.A., 2005). Partial and whole brain have been found to have similar results but long-term survivors are more likely to benefit from partial brain RT due to the reduction in radiation of normal brain tissue. There is, however, still a place for the use of whole brain radiotherapy (Adamson, C. et al., 2009).
Example: MRI/CT fusion GTV + 2-3cm margin for microscopic disease + 0.5cm margin for inter/intrafractional movement 3DCRT planned
Tolerance table: (Barrett, et al., 2009, Hansen, E.K. & Roach III, M., 2010) The organs at risk to be aware of when treating GBM are dependent on the area of intended treatment and its proximity to the surrounding critical structures. This slide presents some of the possible organs at risk and their associated tolerance doses. Patient positioning and conformal planning of treatment can assist in reducing dose to or sparing these organs, thus providing the potential clinical benefit of reduction in side effects and in risk of developing secondary cancers later on.
It is recommended that treatment begins 2-6 weeks post-surgery so that any wounds from surgery are allowed to completely heal. Patients will be treated in the same position as they were simulated in where the immobilisation mask will increase the accuracy of tumour localisation, as will daily 2D-2D image matching ( Mundt, A.J. & Roeske, J., 2011, Kuo, L. et al., 2008). Appropriate QA procedures must also be carried out prior to and during treatment. These may include: MLC QA IMRT fluence maps tool calibration reproducibility of patient positioning (Al-Mohammed, H.I., 2011).
CNS irradiation complications: (Rinne, M.L., Lee, E.Q. & Wen, P.Y., 2012, Schiff, D. & Wen, P., 2006, Hansen, E.K. & Roach III, M., 2010) Side effects of irradiation of the CNS present themselves as either acute complications, early delayed complications or late delayed complications. Listed are some of the complications a patient undergoing CNS irradiation may experience. The side effects experienced depend highly upon the area of treatment and the dose (Hansen, E.K. & Roach III, M., 2010). Other treatment modalities such as chemotherapy can also exacerbate the side effects produced by radiation therapy. Acute complications have been hypothesised to occur because of blood brain barrier disruption, causing increased intracranial pressure and cerebral edema. Early delayed complications on the other hand, are hypothesised to be caused by demyelination of oligodendrocytes and late delayed complications are said to be caused by necrosis, axonal, oligodendrocytic and vascular injury, gliosis and demyelination (Rinne, M.L., Lee, E.Q. & Wen, P.Y., 2012, ) . Treatment for acute and early delayed side effects of CNS irradiation usually involves surgical debulking or corticosteroids. Other methods of management currently being researched include anticoagulation drugs or hyperbaric oxygen treatment ( Schiff, D. & Wen, P., 2006). Treatments for the other typical effects of irradiation to the body are treated in the same way as they would be for other parts of the body. For example, treatment of nausea and vomiting with antiemetics.