- A 12-year-old boy presented with pain and swelling in his left tibia for one month with a history of intermittent fever. Differential diagnoses included osteomyelitis, osteoid osteoma, Ewing's sarcoma, and osteosarcoma.
- Ewing's sarcoma most commonly affects children and young adults between 5-25 years old and presents with pain, swelling, and sometimes pathological fractures. Definitive diagnosis is based on histology, immunohistochemistry, and detection of specific gene fusions.
- Treatment involves chemotherapy with VACA/IE cycles alternating every 2-3 weeks for 17 cycles along with possible surgery and/or radiation therapy based on response and margins. The goal is
Identified in 1921 by James Ewing
2nd most common bone tumor in children
Ewing’s Sarcoma Family of tumors:
Ewing’s sarcoma (Bone –87%)
Extraosseous Ewing’s sarcoma (8%)
Peripheral PNET(5%)
Askin’s tumor
Identified in 1921 by James Ewing
2nd most common bone tumor in children
Ewing’s Sarcoma Family of tumors:
Ewing’s sarcoma (Bone –87%)
Extraosseous Ewing’s sarcoma (8%)
Peripheral PNET(5%)
Askin’s tumor
This presentation demonstrates the current paradigm in the treatment of desmoid tumors. As the management is shifting from surgical approach to medical management.
This presentation demonstrates the current paradigm in the treatment of desmoid tumors. As the management is shifting from surgical approach to medical management.
Title: Understanding Giant Cell Tumor of Bone: A Comprehensive Overview
Introduction:
Giant Cell Tumor of Bone (GCTB) is a rare but potentially aggressive bone tumor that primarily affects young adults. While typically benign, it can be locally destructive and lead to significant morbidity if not managed appropriately. This presentation aims to provide a comprehensive understanding of GCTB, including its epidemiology, pathogenesis, clinical presentation, diagnostic modalities, treatment options, and prognosis.
Epidemiology:
GCTB accounts for approximately 5% of all primary bone tumors, with a peak incidence in the third and fourth decades of life. It shows a slight female predilection and commonly arises in the epiphyseal regions of long bones, particularly around the knee.
Pathogenesis:
The exact etiology of GCTB remains elusive, but it is thought to arise from mesenchymal stromal cells. Genetic alterations, including mutations in the H3F3A gene, have been implicated in its pathogenesis. Additionally, dysregulation of the RANK/RANKL/OPG pathway plays a crucial role in the development and progression of GCTB.
Clinical Presentation:
Patients with GCTB typically present with localized bone pain, swelling, and limited range of motion at the affected joint. Pathologic fractures may occur, especially in larger lesions. Rarely, patients may present with systemic symptoms such as fever and weight loss.
Diagnostic Modalities:
Diagnostic evaluation of GCTB includes imaging studies such as plain radiographs, which often show characteristic lytic lesions with well-defined margins and cortical thinning. Magnetic resonance imaging (MRI) provides detailed soft tissue evaluation and aids in surgical planning. Biopsy remains the gold standard for definitive diagnosis.
Treatment Options:
The management of GCTB is challenging and requires a multidisciplinary approach. Treatment options include curettage with or without adjuvant therapy (such as adjuvant bone cement, phenol, or cryotherapy), en bloc resection for aggressive or recurrent tumors, and denosumab therapy for unresectable or metastatic disease. Close surveillance is essential due to the risk of local recurrence.
Prognosis:
The prognosis of GCTB is generally favorable, with a low incidence of metastasis. However, local recurrence rates range from 10% to 50%, depending on the extent of surgical resection and the use of adjuvant therapy. Long-term follow-up is necessary to monitor for recurrence and late complications.
Conclusion:
In conclusion, Giant Cell Tumor of Bone poses a significant clinical challenge due to its potential for local recurrence and morbidity. Early diagnosis, appropriate staging, and a tailored treatment approach are crucial for optimizing patient outcomes. Continued research into the molecular mechanisms underlying GCTB pathogenesis and the development of targeted therapies are essential for improving treatment strategies and patient prognosis. Giant Cell Tumor of Bone (GCTB)
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
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2 Case Reports of Gastric Ultrasound
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Surgical Site Infections, pathophysiology, and prevention.pptx
Ewing's sarcoma
1. • An 12 year old boy
presents with history of
pain and diffuse bony
swelling over the mid
shaft of his Left Tibia since
one month.
• The mother gives history
of intermittent fever and
redness at the site of pain.
• No history of Trauma.
• Complaints of Loss of
weight, Loss of Appetite.
3. Osteomyelitis Osteoid
osteoma
Ewing’s
tumour
Osteosarcoma Eosinophilic
Granuloma
Presentation Pain, Redness,
Fever,
Weakness.
Dull pain,
Limping,
swelling.
Pain,
Swelling,
Pathological
fracture.
Pain, swelling,
worse at night
Pain
Age All ages 5-25 years 8-20 years Bimodal
distribution
(<25 &>60 yrs)
Adolesents/
Young adults.
Sex Males Males(3:1) Males(1.5-
2:1)
Males Equal
Duration Short/Long Long Short Short short
Benign/
Malignant
Infective origin Commonest
benign
Second most
Bone cancer
in childern.
Most common
Bone cancer in
childern.
Benign bone
lesion
soild
periosteal
reaction
Site Usually at
metaphysis
Diaphysis Diaphysis -
Femur, tibia,
flat bone
Metaphysis:
Femur, tibia
(knee)
Skull, ribs,
Femur.
(Metaphysis)
Others No h/o trauma Pain relieved
with NSAIDs
Can have H/O
Trauma
Most with
H/O Trauma
H/O fever,
Trauma.
5. • Ewing’s sarcoma is the second most common
bone cancer of children, following
osteosarcoma.
• The median age at presentation is 14 years
(usually 8–25 years)
• Boys are affected more than girls (1.5–2:1)
6. • American Pathologist
• Suffered from OM at the age of
14yrs.
• Confined to bed for 2 yrs.
• Served as Prof of Pathology for 33
yrs at Cornell Univ. New York.
• Died of bladder cancer at 76yrs.
• Described in 1921 as an
undifferentiated tumor involving the
diaphysis of long bones that is
radiation sensitive (in contrast to
osteosarcoma).
James Stephen Ewing (1866-1943)
7. At Presentation:
• Pain (>90%)
• Swelling or mass (65%)
• Limitation in movement (25%)
• Neurologic changes (15% overall, though 50% in
central tumors)
• Pathologic fracture (15%)
• Fever (10%)
• Approximately 25% have overt metastases at
presentation.
8.
9.
10. • Usually show an area of bone destruction which is predominantly in the mid-diaphysis.
• New bone formation may extend along the shaft and sometimes appears as fusiform layers of bone around the lesion
– ‘onion-peel’ effect.
• Often the tumour extends into the surrounding tissues, with radiating streaks of ossification (‘sunray’ appearance)
and reactive periosteal bone at the proximal and distal margins (Codman’s triangle).
11.
12. The definitive diagnosis is based on
• Histomorphologic findings
• Immunohistochemistry
• Molecular pathology
HISTOMORPHOLOGICAL FINDINGS:
• Neuroectodermal tissue is the embryonic tissue of origin for EWS and it is derived
from primordial BM mesenchymal stem cells.
• Ewing's sarcoma is a small-blue-round-cell tumors
• Have a clear cytoplasm on H&E staining, due to glycogen.
• The presence of the glycogen can be demonstrated with
• Positive PAS staining and
• Negative PAS diastase staining.
• Differential for small round blue cell tumors (mnemonic LEMONS): Lymphoma,
Ewing’s, Medulloblastoma, Other (rhabdomyosarcoma, pineoblastoma,
ependymoblastoma, etc.), Neuroblastoma, Small cell carcinoma.
13.
14.
15.
16. • The characteristic immunostain is CD99, which diffusely marks
the cell membrane.
(CD99 is not specific for Ewing's sarcoma)
• The most common translocation, present in about 90% of Ewing
sarcoma cases, is t(11;22)(q24;q12)
• Generates an aberrant transcription factor through fusion of the
EWSR1 gene with the FLI1 gene.[FLI1(11): EWS(22)]
• Other minor translocations include:
• t(21;22), c-Myc proto-oncogene(chromosome 21) and EWS
gene(chromosome 22) in 10% of cases.
• t(7;22)
17. • Ewing’s family of tumors includes
• Ewing’s sarcoma (bone 87%),
• Extraosseous Ewing’s sarcoma (8%),
• Peripheral PNET (5%), and
• Askin’s tumor (PNET of chest wall).
• Markers that differentiate EWS:
1. Vimentin
2. HBA-71
3. β2-microglobulin
4. ↑c-myc (vs. n-myc in NB)
• PNET and EWS have similar translocations and are both CD99 (MIC2)+ and
vimentin+.
• PNET is NSE+, S100+, more differentiated, and has more neuroendocrine
features.
• EWS is NSE−, S100 variable, and Homer Wright rosettes+.
18. At presentation
• 75-80% of patients present with localized disease.
• 25% of EWS pts present with mets.
Lung (25%–40%) ≥ Bone/BM (∼25%) and LNs (<10%).
• Bone Marrow micromets are seen in 25% (localized) &
40% (lung mets)
5-yr OS:
• Localised disease is 60-70%
• Metastatic EWS:
1. Lung mets: ∼35%
2. Bone/BM mets: ∼25%
3. Lung + bone/BM mets: ∼15%
(Paulussen M et al., Ann Oncol 2009)
19. Poor prognosis in EWS
• Male gender
• Age >15 yrs (>17 yrs in some)
• Pelvic/axial Site or rib origin
• Size (>8 cm per St. Jude or >100 cc per CESS-
81 [Cooperative Ewing Sarcoma Studies])
• Stage (presence/absence of metastatic Dz is
strongest prognostic factor)
• ↑LDH
• Poor response to chemo (>10% viable tumor)
• No surgery
20.
21. Chemotherapy
• IESS-1 (JCO 1990):
– Nonrandomized comparison of 342 patients with localized disease treated with VAC + D vs.
VAC vs. VAC + prophylactic bilateral whole lung RT plus noncontrolled local intervention.
– 5-year RFS was best with VAC + D (60%) vs. VAC (24%) vs. VAC + RT (44%).
– VACA is superior to VAC or VAC + BPR. VAC + bilateral pulmonary RT is superior to VAC. No
improvement between treatment modalities was noted for pelvic cases.
• IESS-2 (JCO 1991):
– 214 patients with localized nonpelvic primaries randomized to high-dose, intermittent VAC + D
vs. moderate dose continuous VAC + D.
– Local treatment was surgery ± postoperative RT or RT alone (whole bone to 45 Gy with
primary boost to 55 Gy).
– High-dose VAC + D improved OS (63 → 77%); no difference in OS for local control modalities.
– High dose intermittent VACA is superior to the IESS-I regimen, even for pelvic tumors. OS
actually superior to nonpelvic pts in IESS-I.
– Take home: Intermittent VACA is standard of care.
• IESS-3/INT 0091 (NEJM 2003):
– 518 patients with localized or metastatic disease randomized to VDCA vs. VDCA alternating
with IE.
– Local treatment was given at week 9–15 with RT, surgery, or both.
– Adding IE improved 5-year OS (61 → 72%) for localized disease, but not for metastatic disease
(25%).
– VACA+IE superior to VACA for OS and localized disease, but no benefit in metastatic disease.
– Take home: high dose, intermittent VACA+IE is standard of care.
22. • IESS-IV tested dose intensification of VAdriaC+IE
• AEWS0031 tested interval compression of VAdriaC+IE
These showed that VAdriaC+IE q2wks was superior and forms the
current standard of care in the definitive setting.
• COG protocol AEWS0031 a randomized trial for patients with
newly diagnosed localized Ewing sarcoma.
• This trial sought to intensify therapy not by dose escalation, but
by decreasing the interval between chemotherapy cycles (interval
compression).
• Patients randomized to receive VDC/IE cycles alternating every 3
weeks vs 2 weeks.
• 5-year event-free survival (73% versus 65% for patients
randomized to the standard arm).
• This trial established interval compressed VDC/IE as a new
standard approach for patients with localized Ewing sarcoma.
23. • VAC/IE (vincristine + doxorubicin [Adriamycin] +
cyclophosphamide alternating with ifosfamide + etoposide)
• Alternating VAC and IE cycles.
• Repeat each cycle every 3 weeks for 17 cycles.
VAC cycles
• Day 1: Vincristine 2mg/m2 (max 2mg) IV + doxorubicin
75mg/m2 IV bolus + cyclophosphamide 1,200mg/m2 IV.
– Dactinomycin can be substituted for doxorubicin if there are
concerns regarding cardiotoxicity
– Dactinomycin 1.25mg/m2 IV can be substituted for doxorubicin
when a total doxorubicin dose of 375mg/m2 is reached.
IE cycles
• Days 1–5: Ifosfamide 1,800mg/m2 IV + mesna + etoposide
100mg/m2 IV.
24.
25. Surgery:
• For local control, Surgery preferred unless poor functional results
are anticipated.
• Resection provides pathologic information post-chemotherapy,
avoids second malignancy and late effects of RT.
• Resection without reconstruction can be done in small bones such
as rib, clavicle, proximal fibula, distal scapula, metatarsals,
metacarpals, and small iliac wing or pubic bone lesions.
• Results are typically very good for these “dispensable bones.”
• Large lesions may require allograft or endoprosthetic
reconstructions.
• Metastatic setting:
– Limited pulmonary metastases
– Palliation at primary site
• Nodal dissection is not routinely indicated.
LOCAL THERAPY
26. • Adequate surgical margins in EWS Per COG protocol AEWS0031(Womer RB
et al., JCO 2012)
– >1 cm for bone
– >0.5 cm for Sdft Tissue
– >0.20 cm for fascia
• Sg is preferred
– Expendable bones are involved
– If there is a pathologic fracture
• 3 indications for adj RT after Sg in EWS:
– +Margin
– Tumor spill
– >10% viable tumor after induction chemo (poor chemo response).
27. Radiation:
• RT potentially indicated pre-op, post-op, or definitively for the
primary tumor and for treatment of pulmonary and skeletal
metastases.
• Indications for postoperative RT
– Close margins (<1 cm)
– Poor histologic response (<90% necrosis)
– Tumor spill.
• Preoperative RT considered when close/positive margins are
expected.
• Treat pre-chemo volume due to high rate of local failure if limited to
post-chemo volume.
• Involved field rather than whole bone is sufficient.
• Hyperfractionation does not improve outcomes, but may improve
fracture rate, range of motion, and muscle atrophy.
• Adjuvant RT starts at the time of consolidation CHT (week 14).
• VC-IE CHT is given during RT (doxorubicin held during RT).
28. No randomized trials have directly compared RT to surgery
for LC of Ewing’s sarcoma.
• CESS 86 (JCO 2001):
– 177 patients with localized Ewing’s treated with chemotherapy
– Nonrandomized local control arms of
• Surgery alone
• Surgery plus 45 Gy RT
• Definitive RT of 60 Gy (randomized to qd vs. b.i.d.).
– RT used 5 cm proximal/distal margins and 2 cm lateral/deep
margins.
– 5-year OS was 69% with no differences in OS or RFS according
to local therapy.
– Local control was 100% for surgery, 95% for surgery plus RT,
and 86% for RT alone (no difference for qd vs. b.i.d. RT).
29. • POG-8346 (Donaldson SS et al., IJROBP 1998)
– Osseous EWS pts after induction chemo rcvd
definitive RT for local therapy randomized to
• Whole bone RT (39.6 Gy → 55.8 Gy boost to GTV +2 cm)
vs.
• Involved-field RT (GTV + 2 cm to 55.8 Gy)
• All pts then rcvd maintenance chemo.
• The RT Tx techniques had similar 5-yr EFS
(∼41%) and LC (∼53%).
30. CESS-81 and -86 and EICESS 92 (European Intergroup CESS)
• Schuck et al. (IJROBP 2003)
• Performed a secondary analysis of 1,085 pts
• Compared PreOP RT vs. PORT vs. Definitive RT
• Local Failure
– Similar b/t preop and postop RT (5.3% vs. 7.5%) but
– Significantly worse in the definitive RT arm (26%)
• Criticism: There was a strong negative selection bias against
the definitive RT cohort.
• There was no difference in LF b/t RT alone and Sg + post-RT if
only partial resection was achieved.
• In CESS-81, Disease free survival after 41 months for patients
with
– Tumor volume <100 ml was 75%
– Tumor volume greater than or equal to 100 ml was 10%
• Preop RT may improve LC if unresectable.
31. • Talleur (IJROBP 2016):
–St. Judes phase II trial of 45 EWS patients
–Randomised to 55.8 vs. 64.8 Gy based on
tumor size <8 vs. ≥8 cm, respectively.
–All patients treated with 1 cm margins on
gross tumor.
–LF rate 4.4% at 10 year.
32. Chest wall Ewings Sarcoma
(Rib primary & Askin’s tumor)
• More commonly seen in females.
• Preoperative CHT
– Improves negative margins (50% vs. 77%)
– Decreased need for post-op RT (5-yr EFS 56%)
• Schuck A et al. retrospectively reviewed 138 pts with localized CW
EWS treated in CESS-86 and EICESS 92. (IJROBP 2002)
– 42 pts rcv hemithorax RT.
– If <14 yo, then 15 Gy; otherwise, 20 Gy at 1.5 Gy/fx or 1.25 Gy bid.
– All RT pts rcv a boost to the primary site of 45–60 Gy.
– 7-yr EFS trended in its favor (63% vs. 46%).
– Improvements in EFS appeared to be d/t reductions in pulmonary mets.
– A major criticism of this study is that the RT group had sup chemo.
33. METASTATIC DISEASE
• If patient has Lung Mets:
• Chemotherapy → WLI or surgical resection (if <5 mets).
• EICESS secondary analyses: Paulussen et al.
(a) isolated pulmonary mets or
(b) combined lung + bone/BM mets
– Treated +/– WLI as part of a series of protocols from the EICESS.
– WLI was associated with improved EFS in both subgroups. (Ann Oncol
1998)
• St. Jude’s retrospective study: Rodriguez-Galindo et al.
– EWS pts with isolated pulmonary recurrence.
– Pts who rcvd WLI had improved 5-yr postrecurrence survival (30% vs.
17%). (Cancer 2002)
34. • The WLI dose in EWS depends on age:
– If <14 yo, then 15 Gy (1.5 Gy/fx)
– If ≥14 yo, then 18 Gy (mostly in European
protocols, but US protocols still use 15 Gy).
The field borders used in WLI for EWS.
• Superior–Inferior: 1 cm above 1st rib to L2
(Block PA kidney at 7.5 Gy)
• Lateral: 1 cm lat rib cage.
35. RADIATION DOSES
• Radiation fields customized depending on primary site
• MRI is recommended for treatment planning in all cases
• Definitive RT for bone tumors with no soft-tissue involvement:
– Prechemotherapy GTV plus a 2 cm margin to 55.8 Gy.
• Definitive RT for bone tumors with a soft-tissue component:
– Prechemotherapy GTV plus a 2 cm margin to 45 Gy boost to 55.8 Gy
to the initial bony GTV + postchemotherapy soft-tissue extent with a
minimal margin.
• For postoperative RT
– Pretreatment GTV plus a 2 cm margin to 45 Gy boost
-Postoperative microscopic/tumor spill + 2 cm margin to 50.4 Gy
-Gross residual disease + 2 cm margin to 55.8 Gy.
• 45 Gy for vertebral body involvement b/c of SC tolerance.
36. • LN positive—resected: Nodal Bed-50.4 Gy in 1.8 Gy/fx
• LN positive—unresected: Nodal level: 45 Gy, Gross node: 55.8 Gy in 1.8 Gy/fx
• Malignant ascites/diffuse peritoneal involvement:
– Whole abdomen RT: 25 Gy in 1.5 Gy/ fx
• Lung metastases: Whole lung RT: 15 Gy in 1.5 Gy/fx
– (if <6 years, then 12 Gy in 1.5 Gy/fx)
• Chest wall tumor/pleural nodules/effusion:
– Hemithorax RT: 15 Gy in 1.5 Gy/fx
– Chest wall tumor:
• Prechemo volume +1.5-2cm=30.6 Gy
• Postchemo Volume+1.5-2cm=36 Gy in 1.8 Gy/fx
– Pleural nodule:
• Prechemo volume +1.5-2cm=21.6 Gy
• Postchemo Volume+1.5-2cm=36 Gy in 1.8 Gy/fx.
AEWS1031 contouring guidelines
37. COMPLICATIONS
1) Dermatitis and recall reaction: ADR and dactinomycin A.
2) Cystitis: Cyclophosphamide or ifosfamide or RT cystitis.
3) Abnormal bone and soft-tissue growth and
development.
– Premature epiphyseal closure: occurs at >20 Gy.
– Decreased bone growth can occur at ∼10 Gy.
– Limb length discrepancy of 2–6 cm can be managed with a shoe
lift.
– Consider amputation and prosthesis in the very young as they
recover function well.
38. 4) Permanent weakening of affected bone.
– The highest risk for fracture is within 18 months of RT, during
which time patients should avoid contact and high-impact
sports.
– Factors that influence fracture risk
• Total dose, extent of cortical disruption at Dx, younger age, and 2nd
bone malignancy in the RT field.
5) Decreased range of motion secondary to soft-tissue and/or
joint fibrosis.
6) Lymphedema can be prevented by
– Sparing a 1–2-cm strip of skin on the extremity or
– Minimize the circumferential RT dose to 20–30 Gy
39. 7) Second malignancy
• Kuttesch et al. retrospectively reviewed 266
EWS pts treated at St. Jude’s Hospital.
• 20-yr cumulative incidence of 2nd malignancies
was
– 9.2% for any malignancy and
– 6.5% for sarcoma
• RT dose–response relationship with a 2nd
malignancy RR of 40 if RT was >60 Gy and
minimal for <48 Gy. (JCO 1996)
• Most common second tumor is osteosarcoma.
40. Chemotherapy Side effects:
– Vincristine (neuropathy, constipation, myalgias,
arthralgias, and cholestasis)
– Cyclophosphamide (pancytopenia and dose-dependent
hemorrhagic cystitis, infertility)
– Doxorubicin (myocardial dysfunction and pancytopenia)
– Ifosfamide (high incidence of hemorrhagic cystitis
requiring use of Mesna and Fanconi syndrome of
electrolyte wasting)
– Etoposide (pancytopenia, anaphylactic reactions, and
second malignancies such as AML).
41. FOLLOW-UP
• H&P + CXR every 3 months for 2 years.
• X-ray primary every 3 months (and/or MRI
every 6 months) for 2 years.
• After 2 years, may increase follow-up
intervals, but should obtain CBC annually.
Editor's Notes
Ewing’s sarcoma commonly presents in
Lower extremity (femur 15–20%, tibia or fibula 5–10%),
Pelvis (20–30%),
Upper extremity (humerus 5–10%),
Ribs (9–13%), and
Spine (6–8%).
S100 calcium binding protein B
Neuron-Specific Enolase
75-80% of patients present with localized disease, but 20–25% have gross metastases to the lung, bone, or bone marrow, and nearly all patients have micrometastases at diagnosis, so all patients require chemotherapy.
dose intensity defined as the amount of drug delivered per unit of time [mg/m²/week].
Local Failure rate for EWS after definitive RT: 5%–25%
Worse with pelvic sites (LF 15%–70%)
Worse with large (>8 cm) lesions (LF 20%).
Cooperative Ewing Sarcoma Study
In a recent review of RT-induced osteosarcoma, most common primary was Ewing’s (25%), median latency was 8 years.
5-yr OS was 40% overall, with aggressive CHT and surgery 5-yr OS 68% versus chemo alone 17%.