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
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
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
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
This PPT presentation talks about osteosarcoma from the clinical point of view, summarizing the recent guidelines in diagnosis and treatment of osteosarcoma.
When most normal cells grow
old or get damaged, they die, and new cells take their place. Sometimes, this
process goes wrong. New cells form when the body doesn't need them, and old or
damaged cells don't die as they should. The buildup of extra cells often forms
a mass of tissue called a growth or tumor.
Primary brain tumors can be benign or malignant:
Benign brain tumors do not contain cancer cells:
Usually, benign tumors can be removed, and
they seldom grow back.
Benign brain tumors usually have an obvious
border or edge. Cells from benign tumors rarely invade tissues around them.
They don't spread to other parts of the body. However, benign tumors can press
on sensitive areas of the brain and cause serious health problems.
Unlike benign tumors in most other parts of
the body, benign brain tumors are sometimes life threatening.
Benign brain tumors may become malignant.
Malignant brain tumors (also called brain
cancer) contain cancer cells:
Malignant brain tumors are generally more
serious and often are a threat to life.
They are likely to grow rapidly and crowd
or invade the nearby healthy brain tissue.
Cancer cells may break away from malignant
brain tumors and spread to other parts of the brain or to the spinal cord. They
rarely spread to other parts of the body.
Tumor Grade
Doctors group brain tumors by grade.
The grade of a tumor refers to the way the cells look under a microscope:
Grade I: The tissue is benign. The cells
look nearly like normal brain cells, and they grow slowly.
Grade II: The tissue is malignant. The
cells look less like normal cells than do the cells in a Grade I tumor.
Grade III: The malignant tissue has cells
that look very different from normal cells. The abnormal cells are actively
growing (anaplastic).
Grade IV: The malignant tissue has cells
that look most abnormal and tend to grow quickly.
Cells from low-grade tumors (grades I and
II) look more normal and generally grow more slowly than cells from high-grade
tumors (grades III and IV).
Over time, a low-grade tumor may become a
highgrade tumor. However, the change to a high-grade tumor happens more often
among adults than children.
You may want to read the NCI fact sheet Tumor
Grade.
Types of Primary Brain
Tumors
There are many types of primary brain
tumors. Primary brain tumors are named according to the type of cells or the
part of the brain in which they begin. For example, most primary brain tumors
begin in glial cells. This type of tumor is called a glioma.
Among adults, the most common types are:
Astrocytoma:
The tumor arises from star-shaped glial cells called astrocytes.
It can be any grade. In adults, an astrocytoma most often arises in the
cerebrum.
Grade I or II astrocytoma: It may be called
a low-grade glioma.
Grade III astrocytoma: It's sometimes
called a high-grade or an anaplastic astrocytoma.
Grade IV astrocytoma: It may be called a glioblastoma or
malignant astrocytic glioma.
Meningioma:
The tumor arises i
Malignant Bone Tumours - A lecture for undergraduate students and demonstrators / Tutors featuring general aspects and three common malignant bone tumours viz. Osteosarcoma, Ewing's Sarcoma and Multiple Myeloma
Conformal Radiotherapy in Head and neck cancers is essential in terms of improving quality of life and local control in this era. This presentation aimed at giving an overview of conformal radiotherapy and its role in HNC to a 'general audience'.
Presentation on bone tumors for undergraduate 2nd year MBBS medical students. The information for this presentation has been taken from texbook of Robbins & Cotran Pathologic Basis of Disease 8th ed.
It is about a disease called osteosarcoma which is a disease . It is about healthcare and health buisness . It was presented by Dr. Avinash gulati , a famous doctor in Norway.
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
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
- 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
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
5. Important Facts
• Most common benign tumor – Osteochondroma,
Osteoid Osteoma
• Most common Skeletal malignancy – Metastasis
• Most common bone tumor in Pediatric age group
and adolescence – Osteosarcoma and Ewing’s
sarcoma
• Most common tumors arising from bone marrow
elements – Ewing’s sarcoma and non-Hodgkin’s
lymphoma.
8. Osteosarcoma
• Tumor is characterised by production of osteoid by
malignant mesenchymal cells.
• Most common primary malignant bone tumor (35%).
• Most common radiation induced sarcoma.
• 10%-20% present with metastatic disease at diagnosis.
Spreads hematogenously, with lung being the most
common metastatic site.
• 5 year survival rate is 5% - 23%
9. • Bimodal distribution as a function of age : Primary
high grade osteosarcoma – 10–20 years, Parosteal
osteosarcoma – 3rd and 4th decade, Secondary
osteosarcoma in older population associated with
other conditions (Paget Disease, fibrous dysplasia)
that arise in an older population (age >65 years).
• more common in boys (> girls) (with the exception
that parosteal osteosarcoma is more common in
females)
• more common in blacks (> whites).
11. Tumor is located at the typical metaphyseal site
A. Tumor is largely restricted to bone
B. Tumor is accompanied by massive soft tissue extension.
12. skip metastasis located in the upper half of the femur. The
primary tumor was located in the lower metaphysis of the same
bone
13. • The exact cause of osteosarcoma is unknown
Risk factors –
• Rapid bone growth
• Environmental
• Genetic
• Pre-existing benign /malignant lesions
Etiology
14. • Rapid bone growth
- increased incidence during the adolescent
growth spurt
- location in the metaphyseal area adjacent to
the growth plate of long bones
• Genetic
Li-Fraumeni syndrome (p53 mutation)
Rothmund-Thomson syndrome
Mutation of the RB gene (retinoblastoma)
15. • Environmental
Radiation – localised radiation >2000 cGy
latent period - 4 to 40 years
Chemicals – methylcholanthrene
acetylaminofluorene
beryllium compounds
Virus - RNA : mouse sarcoma virus
DNA : polyoma ,SV 40 virus
17. – Intramedullary (80%) : typically presents within areas
of rapidly proliferating skeletal bone.
– Juxtacortical/Surface (7-10%) : arise adjacent to the
outer surface of cortical bone.
– Intracortical (2%)
Sub-types
18. • Intramedullary
– conventional
a. Osteoblastic
b. Chondroblastic
c. Fibroblastic
d. Small-cell
e. Epithelioid
– Telangiectatic
– Well-differentiated
• Juxtacortical Osteosarcoma
– Parosteal
– Periosteal
– High Grade Surface
• Intracortical
20. www.eyst.org
Conventional Osteosarcoma
• High grade
• Common type of
Osteosarcoma
• Common radiographic
appearance is aggressive
lesion producing osteoid
matrix. Periosteal reaction
may take the form of
“codmans triangle” or
“sunbrust” or “hair on end”
appearence
21. www.eyst.org
Small Cell Osteosarcoma
• Rare
• High grade
• Uniform small size tumor
cells.
• Diffuse pattern of growth.
• Resemble Ewing sarcoma or
Lymphoma
22. Telangiectatic
• Blood filled cystic space and radiologically
appears as pure lytic lesion.
• Pathological fractures.
• Grossly the lesion simulate aneurysmal bone
cyst.
• Detection of malignant stroma in the septa
that separate the blood cysts.
23.
24. Well differentiated intramedullary
• This tumor is microscopically bland - underdiagnosed as a
benign lesion.
• In contrast to fibrous dysplasia:
– this tumor shows radiographic evidence of cortical
destruction.
– Microscopically, atypia is minimal but still present.
– Invasive growth pattern.
26. www.eyst.org
Parosteal Osteosarcoma
• Low grade malignancy
• Rare
• Arises on surface of bone
and invades medullary
cavity only at later stages.
• Peculiar tendency to occur
as a lobulated mass on the
posterior aspect of femur
• Occur in slightly older age
group
28. www.eyst.org
High grade surface Osteosarcoma
• High grade
• Least Common
• Radiographs show invasive lesions with ill defined borders
29. • Very rare
• High grade
• confined to the
cortex
• Sites : Diaphysis of
femur or tibia
Intracortical Osteosarcoma
30. www.eyst.org
Secondary Osteosarcoma
• These occur at the site of another disease process
• E.g. Pagets disease, previous radiation treatment, fibrous
dysplasia, bone infarcts, osteochondromas, chronic
osteomyelitis, dedifferentiated chondrosarcomas,
melorhestosis and osteogenesis imperfecta.
• Older patients
• Prognosis poor
• Long history of dull aching pain and recent lytic destruction
31. Osteosarcoma of jaw :
• Slightly older population is affected (average age, 34
years)
• Most lesions show a prominent chondroblastic
component.
• Most common sites of involvement: body of the
mandible and alveolar ridge of the maxilla.
Osteosarcoma in Paget’s disease :
• Polyostotic type
• Pelvis, humerus, femur, tibia and skull.
• Large number of osteoclasts alternating with atypical
osteoblast.
32. • Synchronous Osteosarcoma:
Lesions that affect multiple bones
discovered within 6 months of each other.
• Metachronous Osteosarcoma:
Lesions involving multiple bones
discovered more than 6 months apart.
Multicentricity
33. Clinical Features
• Presenting complaints :
- pain (night pain)
-sometimes only tiredness & limp
-palpable, painless mass
-skin conditions to be examined
carefully
• History of trauma sometimes draws attention.
34. Associated Features
• Effusion and swelling of nearby joints
• Fever
• Pallor and cachexia
• Regional lymph nodes
• Symptoms associated with pulmonary metastasis
• Pathological fracture: unusual presentation
35.
36. Laboratory Studies
• Full blood count, ESR, CRP.
• LDH (elevated level is associated with poor prognosis)
• ALP (highly osteogenic)
• Platelet count
• Electrolyte levels
• Liver function tests
• Renal function tests
• Urinalysis
36
38. Plain X-ray (Most valuable)
• Lesions are usually permeative
• Associated with destruction of the cancellous and
cortical elements of the bone
• Ossification within the soft tissue component, if tumor
has broken through cortex
• Intra medullary extension may be present
• Borders are ill defined
38
42. CT scan
• Approximately 10% to 20% of
patients present with
radiographically detectable
metastases at diagnosis mostly in
the lungs.
• Conventional radiographs of the
chest show metastatic nodules 10
mm or greater in diameter.
• Pulmonary metastases 3 to 7 mm
or greater in diameter are
identified with CT.
• Spiral CT is superior to
conventional CT for this purpose.
43. MRI
• Excellent for describing lesions in the marrow cavity
• Helpful to determine the level of resection
• Useful for screening skip lesions of 2mm or more
• Can detect medullary invasion in case of juxtacortical
tumors
• Can detect epiphyseal involvement and penetration of
cartilage.
• MRI demonstrates relationship of the extra-
compartmental tumor to fascial planes and
neurovascular structures.
46. Bone scan
• Bone scan with technetium 99m
shows a marked increase in the
uptake of radionuclide in tumor.
• Increased uptake is due to active
formation of new tumor and host
bone as well as the vascularity of the
lesion.
• Used to look for bony metastases in
the involved bone (skip
metastases)and at other skeletal
sites.
• Detect local recurrence of tumor
• Mineralized metastases are more
likely to be detected by bone scans
than are non-mineralized ones at
extra-pulmonary sites.
46
47. Biopsy
• to confirm the diagnosis.
• Types :
– Fine needle aspiration
– Core needle biopsy
– Open incisional biopsy
47
50. Prognostic Factors
• Extent of the disease
– Patients with pulmonary, non-pulmonary ( like bone) or skip
metastasis have poor prognosis
• Grade of the tumor
– High grade tumor have poor prognosis
• Size of the primary lesion
– Large size tumors have worse prognosis then small size
tumors
• Skeletal location
– proximal tumors do worse than distal tumors.
• Secondary osteosarcoma
• Proximity to neurovascular structures
• Elevated LDH and Alkaline phosphatase
50
Poor prognosis
51. Management
Radiological staging
Biopsy to confirm diagnosis
Preoperative chemotherapy x 6weeks
Repeat radiological staging (access chemotherapy response, plan surgical
treatment)
Surgical resection with wide margin (3-4 weeks after chemotherapy)
Reconstruction
Adjuvant chemotherapy based on pre-operative response (2 weeks after
surgery) x 32weeks
51
52. • Low grade osteosarcoma - treated by surgery alone.
• Pulmonary metastatic disease - treated as for non-metastatic
disease. If possible, resection of nodules after completion of
chemotherapy.
53. Chemotherapy
• Chemotherapy has excellent role in terminating these
lesions.
• Historical data suggests that survival rate with ablative
surgery alone is <20%.
• When combined with chemotherapy it is almost 65%.
• Multidrug chemotherapy found to be more effective than
single agent (39% vs 68%)
• Chemotherapy given in two modalities :
– Neoadjuvant chemotherapy
– Adjuvant chemotherapy
55. • First line therapy
– Cisplatin, Doxorubicin
– MAP (HD-Mtx, Doxorubicin, Cisplatin)
– HD-Mtx, Doxorubicin, Cisplatin, Ifosfamide
– Cisplatin, Ifosfamide, Epirubicin
• Second line therapy
– Docetaxel, Gemcitabine
– Cyclophosphamide, Etoposide
– Cyclophosphamide, Topotecan
– Gemcitabine
– Ifosfamide, Etoposide
– Ifosfamide, Etoposide, Carboplatin
– HD-Mtx, Ifosfamide, Etoposide
– 153 Sm-EDTMP for disease beyond second line therapy
– Sorafenib
56. • High dose methotrexate (HDMTX) with leucovorin
regresses pulmonary metastasis.
• Efficacy of HDMTX mostly depends on dosage (minimum
of 8-12g/m2 is required to get tumoricidal effect).
• Chemotherapeutic agents under clinical trials are
– High dose Ifosfomide
– Muramyl tripeptide phosphatidylethanolamine (MTP-
PE)
57. Neoadjuvant Chemotherapy
• Advantages
– Regression of primary tumor, making limb salvage surgery easier.
– Effectively treat micro-metastases at earliest possible.
– Avoid tumor progression, which may occur due to any delay in surgery.
– Determination of pathologic response : Percent of necrosis after
neoadjuvant chemotherapy is a prognostic factor (> 90% necrosis has
significant survival advantage).
• Disadvantages
– May increase peri-operative complications (delayed wound healing,
infection)
– nausea, vomiting and other toxicities may cause delay in surgery.
57
59. Restaging after Neoadjuvant
Chemotherapy
• Clinical : Pain
ALP
Tumor size
• Radiographic response : increased ossification, marked
thickening and new bone formation of periosteum and
tumor border and decreased soft tissue mass.
• Angiographic : vascularity
• Bone Scintigraphy : in activity
• PET Scan : SUV < 2 : good response
SUV > 5 : poor response
60. Histologic Grading for Neoadjuvant
Chemotherapy Response
Salzer-Kuntschik Picci Huvos
I No viable
tumor cells
Total response No viable
tumor
IV No histologic evidence of
viable tumor
II Single viable
tumor cells or
cluster <0.5 cm
Good response 90%–99%
tumor necrosis
III Only scattered foci of viable
tumor cells
III Viable tumor
<10%
Fair response 60%–89%
tumor necrosis
II Areas of necrosis due to
chemotherapy with areas of
viable tumor
IV Viable tumor
10%–50%
Poor response <60% tumor
necrosis
I Little or no chemotherapy
effect
V Viable tumor
>50%
VI No effect of
chemotherapy
61. Memorial Sloan-Kettering Cancer Centre T10 regimen is
frequently used for non-protocol patients : high-dose
methotrexate, doxorubicin, bleomycin, cyclophosphamide and
actinomycin D.
62. Surgery
• Goal of the surgery: Remove the tumor en-bloc and achieve
adequate negative margins.
• Small Tumors : can be removed adequately by resection with or
without reconstruction.
• Large Tumors : may mean loss of ipsilateral lower extremity and
compromising bowel and bladder function.
63. Principles of Surgery
• Choice between limb salvage surgery and amputation must
be made on the basis of the expectations and desires of the
individual patient and the family.
• Points to be stressed
– survival after the procedure
– short and long term morbidity
– function of salvaged limb compared to prosthetics
– psychosocial consequences
64. Options for Surgery
• Non Functioning Limb : Amputation
• Limb sparing procedure (preferred)
• Reconstruction Options :
– Autologous Bone Grafts
– Allografts
– Endoprosthesis
• Less commonly :
– Rotationplasty
– Arthrodesis
65. Limb Salvage Surgery
• Removal of tumor and reconstruction of the limb with an
acceptable oncologic, functional and cosmetic results.
• Goal is to safely and completely remove the tumor while
preserving vascular and nerve supply to the extremity.
• Historically - amputation.
• Over the past few years - limb-sparing procedures have become
the standard, mainly due to advances in chemotherapy and
sophisticated imaging techniques
• Limb salvage procedures now can provide rates of local control
and long-term survival equal to amputation.
66. • Guidelines :
– No major neurovascular involvement
– Wide resection of affected bone with a normal muscle cuff all
around
– En-bloc removal of all biopsy sites and contaminated tissue
– Resection of bone 3-4 cm beyond abnormal uptake
– Resection of adjoining joint and capsule
– Adequate motor reconstruction
– Adequate soft tissue coverage.
67. • Contraindications
– Displaced pathological fracture
– Inappropriate biopsy site
– Infection
– Skeletal immaturity
– Major neurovascular involvement
– Extensive muscle involvement
Predicted leg-length discrepancy should not be greater than 6-
8cm.
68. Amputation
• Amputation involves removal of the limb with a safe margin
between the end of the retained portion and the tumor.
• Indications :
– Grossly displaced pathologic fracture
– Encasement of neurovascular bundle
– Tumor that enlarges during pre-operative chemotherapy and
is adjacent to neurovascular bundle
– Palliative measure in metastatic disease
– If the tumor has caused massive necrosis, fungation,
infection, or vascular compromise.
68
70. • The skeletal defect must be reconstructed by :
– Endoprosthesis (most common) – replacing the removed bone
with a metal implant
– Allograft (cadaveric) bone
– Vascularized bone acquired from the patient
– Allograft-prosthetic composite constructions
70
A B
71. Rotationplasty
• Most commonly used for osteosarcoma of distal femur in skeletally
immature patients
• Neurovascular structures and distal aspect of limb (leg) are retained
and re-attached to the proximal portion after the tumor has been
removed.
• Principle is to excise the diseased part of the limb and then join the
ramainning parts together but in so doing, rotating them through
180 degrees.
71
• Main vessels are divided and re-
anastamosed but sciatic nerve is
retained in anastamosed segments
• Here the ankle becomes knee and the
foot becomes a useful attachment for
a below knee prosthesis
72. • Pelvic tumors require hemipelvectomy for en bloc resection.
Adjuvant radiation has been used to improve outcomes in
patients with incomplete resections.
• Spinal tumors are difficult to resect with negative margins.
Typically, an en bloc resection with vertebrectomy is performed,
combined with mechanical stabilization. Postoperative radiation
therapy used when negative margins cannot be obtained,
particularly when there is microscopic dural involvement.
73. Radiation Therapy
• Role is limited in treatment of osteosarcoma : relatively radio-
resistant tumor.
• Indications :
– Patients who refuses surgery
– Those with positive margins after resection.
– Those with sites not amenable to resection and
reconstruction (skull, vertebra, ilium, sacrum).
– Palliate symptomatic metastasis and local recurrence
– Bilateral lung irradiation in pulmonary metastasis.
74. 1. Modern external beam radiotherapy
– 3-D treatment planning with aid of presurgical and
postsurgical imaging.
– Typically, 2cm margin for axial tumors, which can be
extended to 4 to 5cm for extremity tumors.
– These margins can be restricted at natural tissue and fascial
boundaries.
– Chemotherapy should not be interrupted to deliver local
radiation therapy.
– Radiation can be given concurrently but is usually delivered
after chemotherapy due to increased acute toxicity with
concurrent administration.
75. Dose
• 60Gy at 2Gy/# for microscopically involved margins
• 66Gy for macroscopic residual disease
• 70Gy for inoperable tumors.
A non-irradiated strip of limb – length should be maintained
and wherever possible, overlie lymphatic drainage pathways
located medially in extremity (or atleast restricted to
maximum dose to less than 40Gy).
76. 2. Extracorporeal and definitive IORT :
– Extracorporal technique includes en-bloc resection of the
tumor and surrounding soft tissues, irradiation of the
specimen (30Gy) and re-implantation with aid of prosthesis.
– Associated with low rate of recurrence (<5%) but higher rate
of complications.
3. Particle therapy :
– Neutrons
– Protons
77. • Neutrons :
– Higher relative biologic effectiveness and o2
enhancement ratio.
– Complications: severe fibrosis, scarring of soft tissues
and adjacent organs.
• Protons :
– Largest study was done by Massachusettes general
hospital: 15 patients with osteosarcoma of base of
skull or vertebra - 5 year local control was reported to
be 59%
– Advantage: physical property of Bragg peak.
78. 4. Whole lung irradiation :
– 3 arm EORTC/SIOP study compared chemotherapy and
whole lung irradiation or combination of both which
showed same disease free survival and overall survival in
both arms.
– WLI following completion of chemotherapy/
metastatectomy (NCCN guidelines)
• 15Gy (1.5Gy/#) for patients < 14 years
• 18Gy for patients > 14 years
79. 5. Radionuclide therapy :
– Rhenium, strontium, samarium
– used for palliation of extensive bone metastases.
– Major toxicity : decreased platelet and white blood cell
counts, transient hypocalcemia.
– Radium-223 dichloride is bone seeking radiopharmaceutical
,under investigation for treatment of metastatic or recurrent
osteosarcoma. This agent is approved in US for treating bone
metastasis associated with castration resistant prostate
cancer.
80. Extracorporeal Irradiation (ECI)
• en-bloc removal of tumor bearing bone segment, removal of tumor
from bone, irradiation and re-implantation back in body.
• Advantages :
– Avoidance of radiation injury to un-irradiated bone, muscles,
joint, and other healthy tissues of body.
– Delivery of very high doses of radiation to tumor bearing bone
by ECI, which is otherwise not possible in the intact bone.
– Provides an anatomically size-matched graft for biological
reconstruction.
– Cost effective as compared to the prosthetic devices.
– Psychological advantage as patients feel that their own bone is
being used as prosthesis.
81. Davidson et al (2005)
• Reported a series of 50 patients with malignant bone tumor
mainly ESFT (21 patients) and OS (16 patients) using en bloc
resection and ECI (50Gy).
• Mean time of ECI process was 35min.
• With a mean follow-up of 38 months (range 12-92), 84%
patients were alive without any disease and only 8% developed
LR.
82. Poffyn et al (2011)
• Retrospective analysis of 107 patients with 108 malignant or
locally aggressive bone tumors treated by ECI with 300Gy,
and re-implantation of the bone as autograft.
• At 5 year follow-up, there was no LR and 64% of patients had
well healed graft. The 0% LR rate could be due to relatively
very high dose of ECI (300Gy) used in their study.