This document provides information on the management of soft tissue sarcoma. It discusses the clinical presentation, patterns of spread, imaging, histology, grading, staging, prognostic factors and management of soft tissue sarcomas. The key points are:
1) Soft tissue sarcomas most commonly present as painless swellings in the extremities and can invade locally along fascial planes. Imaging like MRI is important for assessing tumor extent.
2) Histologically, the most common subtypes are undifferentiated pleomorphic sarcoma and liposarcoma. Grading systems consider tumor differentiation, mitosis and necrosis.
3) Staging is based on tumor size, depth, nodal status and metastasis
A multidisciplinary approach that includes surgery, medical oncology, and radiation oncology is required for optimal treatment of patients with rectal cancer
A multidisciplinary approach that includes surgery, medical oncology, and radiation oncology is required for optimal treatment of patients with rectal cancer
Introduction .
Statics.
Risk factors.
survival rate.
Staging , Grading.
Special investigations.
WHO Classification .
Most common Benign and Malignant salivary gland Tumors
Clinical presentation and prognosis.
Surgical Treatment .
Summary.
Salivary gland tumors account for 2% to 6.5% of all head and neck neoplasms, are more common in female with a peak incidence in their 60s and 70s, but can occur in all age groups.
The majority of neoplasms occur in the parotid, and pleomorphic adenoma is the most common benign tumor and mucoepidermoid carcinoma the most common malignant tumor.
Irregular margins, bony invasions, the presence of metastatic lymph nodes and perineural spread can all be signs of malignancy.
Necrosis can also characterize malignancy.
Benign tumors were more common than malignant ones.
The prevalent benign tumor was PA, and the prevalent malignant tumors were ACC and MEC.
The smaller the gland more likely that a mass is malignant.
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
- 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
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.
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.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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.
2. Natural History
STS can occur anywhere in the body.
The most common site of presentation is an
extremity, specifically the thigh.
The approximate distribution of STS sites at presentation is extremity,
60% (lower extremity, 45%, upper extremity, 15%); trunk, 15% to 20%;
retroperitoneum, 10% to 15%; and head and neck, 8%.
Perez and Brady’s 6TH
3. Clinical presentation
• Extremity:-
• M.C symptom:- a painless swelling.
• Other symptoms – d/t involvement of surrounding structures.
• Pain due to invasion of neurovascular
structures.
• Distal edema pressure effect on vascular
structures.
• Joint compliants restriction of joint movements
and bone # can occur .
Perez and Brady’s 6TH
4. Retroperitoneal:-
• Usually asymptomatic until reaching large sizes.
• Identified on imaging for unrelated complaints.
• May present with
i. Nonspecific abdominal pain
ii. Palpable abdominal mass.
iii. Anorexia and
iv. Chronic subacute intestinal obstruction
with subsequent weight loss.
Perez and Brady’s 6TH
5. Patterns of spread
• Local spread :
• Tends to invade longitudinally along musculoaponeurotic planes
• Rarely transgress fascial boundaries or invade bone
• Compresses surrounding normal tissue to form a pseudocapsule –
• Contains a compression zone and a reactive zone
• The Reactive zone consists of edema, inflammatory cells and tumor cells
Perez and Brady’s 6TH
6. LN SPREAD
• STS rarely spread to lymph nodes 1.8% to 3.7% of lymph node involvement at the
time of initial presentation.
• Notable lymph node involvement rates have been demonstrated for epithelioid
sarcoma (20% to 35%), clear cell sarcoma (10% to 18%), rhabdomyosarcoma
(20% to 25%), and cutaneous angiosarcoma (10% to 15%).
• 23% of patients had metastatic disease at presentation.
• The single most common site of distant metastasis (34%) lung,
Bone(24%),liver(16%),brain(2%).
• Retroperitoneal sarcoma and intra-abdominal visceral sarcomas1st site is Liver.
Perez and Brady’s 6TH
7. Imaging workup
• MRI is the preferred modality
• T1 weighted images – For disease extent
• T2 weighted images – For peritumoral edema
• CT scan
• Not good soft tissue delineation
• Chest CT scan is recommended to rule out pulmonary metastases for all cases
except low-grade tumour's or small (<5 cm) high-grade lesions
• CT of the abdomen and pelvis : Myxoid liposarcoma (predilection for spread
to the retroperitoneum)
Perez and Brady’s 6TH
8. CT MRI(T1)
Perez and Brady’s 6TH
MRIScanvs CTScan(Demas et al. compared MRI and CT for STS lesions in the
extremity and reported that for 23% of cases, the MRI scans showed tumor
involvement in muscles that appeared normal on CT scan)
9. Imaging Workup
• PET CT
• Used in cases of recurrence
• Also used for follow up purposes.
• Potential utility to help distinguish malignant peripheral nerve sheath tumors
from benign neurofibromas in patients with neurofibromatosis.
• the detection of malignant transformation in neurofibromatosis.
• the presence of regional or distant metastases
• the response to initial (i.e., neoadjuvant) treatment as a surrogate to
prognosticate on future outcome.
Gunderson
10. Investigation:
• Following appropriate imaging assessment, the standard approach to
diagnosis consists of multiple core needle biopsies.
• However, an excisional biopsy may be the most practical option for < 3 cm
superficial lesions.
( Excisional biopsy should be avoided, especially for lesions >3 cm in size, as the contamination of
surrounding tissue planes may require the definitive resection to be more extensive.)-DEVITA
• An open biopsy may be another option in selected cases.
• A biopsy may underestimate the tumor malignancy grade. Therefore, when
preoperative treatment is an option, radiological imaging [PET] may be
useful, in addition to pathology, in providing the clinician with information
that helps to estimate the malignancy grade
ESMO-2018
14. WHO Classification
• Benign
• Do not recur locally, and those that do recur usually are not locally invasive
and can be cured with complete surgical excision.
• Intermediate, locally aggressive soft tissue tumors
• often recur locally and are associated with a locally infiltrative growth pattern.
• Do not have any potential to metastasize but typically require wide excision
with a margin of normal tissue for good local control.
WHO 2013
15. • Intermediate rarely metastasizing tumors
• Often locally aggressive but in addition can occasionally give rise to distant
metastases. The risk of metastasis, usually to lymph nodes or lung, is typically
less than 2%, but is not reliably predictable based on histology
• Malignant
• potential for local invasion and recurrence, have a significant risk of distant
metastasis, ranging in most instances from 10% to 100%, depending on
histological type and grade.
• Some low-grade sarcomas have a metastatic risk of only 2% to 10%, but these
tumor types may progress to more aggressive tumors
WHO 2013
16. Histologic Diagnoses
•Malignant Fibrous Histiocytoma (MFH)
a) Undifferentiated pleomorphic sarcoma.
b) Myxofibrosarcoma
c) With inflammation
d) Angiomatoid malignant fibrous
histiocytoma
•Low-grade Fibromyxoid Sarcoma
(Fibrosarcoma)
Sarcomas of Fibrous Tissue Sarcomas of Blood and Lymph Vessels
•Angiosarcoma
•Hemangiosarcoma
•Lymphangiosarcoma
•Epithelioid Hemangioendothelioma
•Hemangiopericytoma
•Kaposi’s Sarcoma
Sarcomas of Peripheral Nervous Tissue
•Malignant Peripheral Nerve Sheath Tumor
(Neurofibrosarcoma).
Malignant granulosa cell tumour
Primtive neuroectodermal tumour.(PNET)
Sarcomas of Unknown Tissue
•Synovial Sarcoma
•Monophasic
•Biphasic
•Alveolar Soft Part Sarcoma
•Epithelioid Sarcoma
•Unclassified Sarcoma
Extraskeletal Sarcomas of Bone
•Extraskeletal Osteosarcoma
•Extraskeletal Chondrosarcoma
•Extraskeletal Ewing’s Sarcoma (PNET)
•Dermatofibrosarcoma Protruberans
•Desmoid Fibromatosis
•Nodular Fasciitis
SOFT-TISSUE SARCOMA
WHO 2013
17. • Leiomyosarcoma
• GI
• GU
• Skin
• Vessel
• Other
Sarcomas of Smooth Muscle
•Liposarcoma
•Atypical Lipomatous Tumor
•Myxoid Liposarcoma
•Cellular Myxoid Liposarcoma
•Dedifferentiated Liposarcoma
•Pleomorphic Liposarcoma
Sarcomas of Adipose Tissue
Sarcomas of Skeletal Muscle
•Embryonal Rhabdomyosarcoma
•Botryoid RMS
•Spindle cell RMS
•Alveolar Rhabdomyosarcoma
•Pleomorphic Rhabdomyosarcoma
Soft-tissue Tumors of Melanocytic Tissue
•Melanoma of Soft Parts
•AKA - Clear Cell Sarcoma
WHO 2013
19. Grading
• Under histological grading , the two most important criteria appear to be the mitotic
index and the extent of tumor necrosis.
• The two systems most favoured by pathologists are those designated as
the French Federation of Cancer Centres Sarcoma Group (FNCLCC)
[tumour differentiation , mitotic count and necrosis]
The National Cancer Institute (NCI)
[tumor histology and amount of tumor necrosis ]
22. Staging
• AJCC 8th edition
• Based on
• Size of tumor
• Extent of tumor (Superficial / Deep)
• Lymph node status
• Presence or absence of metastasis
• Grade of tumor
28. Prognostic Factors for Survival and Local Recurrence
• The most powerful predictor for DFS and OS is the TNM stage of the
tumor.
• Five-year DFS rates for stages I, II, and III STS are 86%, 72%, and
52%, respectively.
• Grade.
• Tumor size, depth, and site.
Poor Prognostic factors :
- Age > 50 years
- Size > 8 cm
- Vascular invasion
- Local infiltration
- Tumour necrosis
- Deep location
- High grade tumors
- Recurrent disease
Perez and Brady’s 6TH
29. Significant predictors for LR include positive margins of resection,
presentation with locally recurrent disease, older age, and head and neck
or retroperitoneal location.
Patients who present with locally recurrent disease are at higher risk for
LR (25% to 47%)
Perez and Brady’s 6TH
32. • Marginal resection-simple removal of the tumor with its pseudocapsule.
(LR-42% to 93%)
• Radical resection-removal of all of the muscles and neurovascular structures
within the compartment where the tumor resides or amputation. (LR-0% to
18%)
• Wide resection (conservative surgery (CS) limb-sparing surgery, or function
sparing surgery)-
It involves en bloc removal of tumor with a rim of normal tissue varying in
width from about 1 cm to several centimeters depending on anatomic
constraints. (LR- 25% to 60%)
Perez and Brady’s 6TH
33. Radiation Therapy
• Historically, all patients underwent amputation for extremity sarcomas
• NCI randomized study demonstrated that high grade lesions could be
treated with limb-sparing surgery with concurrent adjuvant RT.
• Rates of amputation fell to <10% as postop RT became widely used
after limb-sparing surgery
Perez and Brady’s 6TH
36. Wide resection/CS combined with pre- or postoperative
radiation therapy (RT) is the current standard of care for most
high-grade STS.
Most low-grade STS of the extremity and trunk is wide
excision alone.
Perez and Brady’s 6TH
38. Preoperative Versus Postoperative EBRT:
• Recently, examination of data from 27,969 patients with extremity STS in
the NCDB identified both preoperative and postoperative RT as factors
associated with increased OS.
• However, that data showed that preoperative RT was predictive of achieving
R0 resection.
• In a phase III randomized study conducted by the Canadian Sarcoma
Group, local control and progression-free survival (PFS) rates were similar
in patients receiving either preoperative or postoperative RT in patients with
localized primary or recurrent disease.
• However, preoperative RT was associated with a greater incidence of acute
wound complications (35% vs 17% for postoperative RT), especially in
lower-extremity tumors (43% vs 5% for upper extremity tumors).
• Late-treatment–related side effects were more common in patients receiving
postoperative RT, which is believed to be related to the higher RT dose (66
vs 50 Gy for preoperative RT) and the larger treatment volume.
NCCN 2018
39. Updated Results of NCI Trial
• 2005
• Late radiation morbidity following randomization to preoperative
versus postoperative radiotherapy in extremity soft tissue sarcoma Davis
AM, Radiotherapy Oncol.2005 Apr;75(1):48-53
• Post-op RT associated with worse fibrosis as well as joint stiffness (although
not statistically significant).
• Outcome: Grade 2+ fibrosis pre-op RT 31% vs. post-op RT 48% (p=0.07)
• Edema, and joint stiffness also more severe in post-op arm
• Joint stiffness and fibrosis worse with larger field size
40. • 5 studies (1 RCT and 4 retrospective cohort) -1098 patients
• Localized, resectable, STS.
• Comparis5 studies (1 RCT and 4 retrospective cohort) -1098 patients
• Localized, resectable, STS.
• Comparison of pre operative versus and post operative Radiaotherapy
• Outcome:
• Local recurrence better in pre operative group (HR = 0.6, Significant)
• Survival : Pre operative - 76% vs Post operative - 67%
• Conclusion:
Delay in surgical resection for pre operative Radiation therapy does not increase mortality
Local recurrence lower after pre operative Radiation therapy
Annals of Surgical Oncology
May 2010, Volume 17, Issue 5, pp 1367-1374
41. Indications for Radiotherapy
• Post Operative :
• All Deep seated tumors
• All High grade tumors
• Intermediate grade tumor, size >5cm
• Low grade tumors :
• Positive or close (<1cm) resection margins
. Tumor location that would not be
amenable to subsequent salvage surgery
Recurrent disease following
initial wide excision
Pre Operative
• Unresectable disease
• Resectable disease but resection
will lead to significant functional loss
Perez and Brady’s 6TH
43. Radiation Therapy
• Positioning the Patient: the limb is positioned as far away from the
trunk (for upper extremities) or from the opposite limb (for lower
extremities) as possible.
Perez and Brady’s 6TH
44.
45. Target Volumes and Treatment Fields
Preoperative Radiation Therapy:
• Fusion of the diagnostic MRI and planning CT for optimal target definition is
strongly encouraged.
• GTV is defined as the gross tumor delineated by the T1 postgadolinium MRI.
• Clinical target volume (CTV) is defined as the GTV plus 3-cm margins in the
longitudinal directions and 1.5-cm margins radially.
• PTV: CTV plus 5 to 10 mm
46.
47. Postoperative Radiation Therapy
• The CTV should encompass all the tissues handled during the surgery including the
incision and any drain sites. (Postoperative changes seen on MRI help define the
operative bed.)
• An additional longitudinal margin of 2 to 4 cm and a radial margin of 1.5 to 2 cm is
generally added to the operative bed to form the CTV.
• The PTV is typically CTV plus 5 to 10 mm.
• A second (and sometimes third) course field reduction is typically used in the
postoperative setting. CTV margins for the reduced field(s) vary and can include about 2
cm on the operative bed or on the initial GTV.
(Baldini et al. found no recurrences in 36 patients with resection margins ≥1 cm compared to an
actuarial 10-year LR rate of 13% (4 of 38) for those with margins <1 cm.)
Perez and Brady’s 6TH
51. Are large CTV Expansions necessary ?
• 2 Prospective Randomised controlled trials are addressing this issue
• VORTEX Trial : Volume Of post-operative RadioTherapy given to
adult patients with eXtremity soft tissue sarcoma
• RTOG 0630 : A Phase II Trial of Image guided pre operative
Radiotherapy for Primary Soft tissue sarcomas of the extremity
52.
53. Results: Two hundred sixteen patients were randomized, 108 in each arm.
• Tumor/normal tissues were collected from 206 randomized and 301 registered
patients.
Median follow-up was 4.8yr (C and R).
The 5-year local recurrence free survival (LRFS) rates were; for C: 86% and for R:
84%.
For C the 5-year overall survival was 72% and for R 67%.
There were no statistical differences between the arms in late radiation toxicity
grade 2+ at 2 years.
Conclusion: There was no difference in limb function at 2 years between control and
research arms. Because of the small number of events it was not possible to state
whether or not the research arm was inferior for LRFS.
54.
55. Doses
• The standard dose for preoperative external-beam RT is 50 Gy
delivered in 2-Gy fractions. In the situation of positive margins, a
postoperative external-beam RT boost of 16 to 20 Gy (delivered in
1.8- to 2-Gy fractions) is sometimes delivered.
• For postoperative external-beam RT, treatment usually commences
about 4 to 6 weeks following surgery and once the wound is fully
healed. Recommended total doses are 60 to 66 Gy (delivered in 1.8- or
2-Gy fractions) for the case of negative margins and 66 to 68 Gy for
positive margins
Perez and Brady’s 6TH
56. Principles of Treatment Planning
• Basic tenets for treating the extremity are to “spare a strip” of the limb
circumference (to prevent subsequent lymphedema and pain), to avoid
treating the whole thickness of bone to high doses (to diminish risk of
fracture), and to avoid treating an entire joint to high doses (to
decrease joint stiffness).
• With IMRT, in order to achieve more dose conformality, the tradeoff is
that the volume of tissue that receives a low dose is increased; for
some of these cases, the entire circumference of the limb may receive
some low dose.
Perez and Brady’s 6TH
57. Radiation Therapy Toxicity
• Chronic Toxicity :
• Edema
• Subcutaneous fibrosis
• Decreased muscle
strength
• Decreased range of
motion and pain
• Bone fracture
• Peripheral nerve
damage
Acute Toxicities
• skin erythema and possible
desquamation in high-dose areas,
• problems with wound healing,
• localized alopecia,
• fatigue.
• Moist desquamation can be quite
uncomfortable,
Perez and Brady’s 6TH
58. Pre Operative Radiation Therapy
Advantages
• Smaller RT fields
• Lower RT doses
• Reduced treatment time
• Tumor down staging
• Radiobiological advantage
Disadvantages
• Higher risk of major wound
complications
Perez and Brady’s 6TH
59. Post Operative Radiation Therapy
Advantages
• Complete tumor specimen is
available for pathology review
for determination of histology
and margin status
• Lower risk of major wound
complications
Disadvantages
• Larger treatment volumes
• Higher doses
• More hypoxic tissue –
Radiobiological disadvantage
• High incidence of late toxicity
Perez and Brady’s 6TH
60. Chemotherapy
• There is no clear evidence showing that chemotherapy, adjuvant or neoadjuvant
showing significant improved OS or PFS.
• Drugs tried are
1) Doxorubicin
2) Ifosfamide
• Chemotherapy is effective only in
i. Rhabdomyosarcoma
ii. Ewing’s sarcoma.
ESMO 2018
62. Locally recurrent sarcomas
• Sarcomas have high local recurrence.
• The treatment modalities available are
1. Radical re-excision(amputation).
2. Limited resection with adjuvant RT(if previously not given).
• Brachytherapy is preferred over EBRT as it decreases dose to normal
tissues.
63. Metastatic disease
• Chemotherapy is the main modality for treating metastatic disease.
• Anthracycline based regimens were found to be effective.(doxorubicin
with ifosfamide and Mesna).
• Recent evidence showed gemcitabine in combination with docetaxel
showed increased survival.
P=0.005
P=0.009
66. Management of advanced/metastatic disease
• Metachronous (disease-free interval1 year), resectable lung metastases without extrapulmonary
disease are managed with surgery as standard treatment, if complete excision of all lesions is feasible.
• Standard ChT is based on anthracyclines as the first-line treatment [I, A]. Multi-agent ChT with
adequate-dose anthracyclines plus ifosfamide may be the treatment of choice, particularly in subtypes
sensitive to ifosfamide, when a tumour response is felt to be potentially advantageous and patient PS
is good [I, B]
• The combination of doxorubicin with an anti-PDGFRA agent, olaratumab, is option.
• Gemcitabine/docetaxel combination is not generally recommended as a first-line therapy for
advanced STS patients [I, D]
• Imatinib is standard medical therapy for those rare patients with dermatofibrosarcoma protuberans.
• Trabectedin is an option for second line and is approved for advanced previously treated STS.
• Pazopanib is an option in non-adipogenic STS.
• Eribulin is an option in patients with liposarcomas and LMS.
• Regorafenib is an option in doxorubicin-pretreated advanced, non-adipogenic STS patients.
• Crizotinib in inflammatory myofibroblastic tumours associated with ALK translocations.
Sunitinib and cediranib in alveolar soft part sarcoma, where the molecular target is as yet unclear and
Sunitinib in solitary fibrous tumours [IV, C]
ESMO 2018
69. Fallow up
Surgically-treated intermediate-/high-grade patients may be followed
every 3–4 months in the first 2–3 years, then twice a year up to the fifth
year, and once a year thereafter.
Low-grade sarcoma patients may be followed for local relapse every 4–
6months, with chest X-rays or CT scan at longer intervals in the first 3–
5 years, then annually.
ESMO 2018