Practical considerations in soft tissue sarcoma 3Sameer Rastogi
It deals with contemporary issues with the management of soft tissue sarcomas. It deals with almost every aspect of soft tissue sarcoma including radiology, pathology, treatment, follow up etc.
Practical considerations in soft tissue sarcoma 3Sameer Rastogi
It deals with contemporary issues with the management of soft tissue sarcomas. It deals with almost every aspect of soft tissue sarcoma including radiology, pathology, treatment, follow up etc.
Perspectives on the Treatment of Melanomaflasco_org
OBJECTIVES:
To understand the mechanisms of action of BRAF and MEK targeted therapy of melanoma.
To understand the mechanisms of action of currently approved immunotherapy drugs for melanoma.
To outline the recent phase III results of immunotherapy and targeted therapy for metastatic melanoma.
Updates on Electron Beam Therapy
I) Introduction
II) Central Axis Depth dose distribution
III) Dosimetric parametrics of electron beam
IV) Clinical Considerations of Electron beam therapy
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
- 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
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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.
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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.
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.
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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
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
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.
2. Out line of presentation:
A) Case on the presentation
B) Investigation Modalities
C) Staging
D) Managements
E) Prognostic factors
F) Follow up
G) Case critics
H) References
3. B) Investigations
1)History –Hx of nevi,personal Hx of melanoma
2)Physical Exam-special attention to loco
regional area & LN drainage.
• complete dermatologic examination is
recommended for all pts with newly
diagnosed melanoma
4. B)Investigations…
3)Biopsy
• Pts presenting with a suspicious pigmented
lesion should undergo fullthickness biopsy
preferably with 1-2mm negative margins.
• Any met site should be confirmed
pathologically(FNAC,biopsy) except brain met
5. B) Investigations…
Biopsy
The procedure should be:
-full-thickness biopsy of the entire lesion
- include the most suspicious area of the lesion
-narrow margin of grossly normal skin (1 to 2 mm)
-include portion of edge (transitions) of lesion to normal skin
to enable assessment of the junctional change
8. B) Investigations…
• Pathology report:
• NCCN Melanoma Panel recommend minimum
inclusion of:
-Breslow thickness
-ulceration status
-mitotic rate (#/mm2)
- deep and peripheral margin status (+ve or -ve)
- presence or absence of microsatellitosis
-pure desmoplasia if present
- total number of LNs examined & the presence or
absence of extranodal tumor extension
10. B) Investigation Modalities…
6) Sentinel LN biopsy(SNBx)
• In the past, standard recommendation was to perform
ELNDs for intermediate thickness melanoma(1-4mm)
• Current retrospective & prospective studies failed to
show any significant survival advantage of routine ELND
• New procedure (intraoperative lymphatic mapping &
SNBx) developed for surgical staging of clinically LN-ve
melanomas (in early 1990s)
• LN met is associated with higher risk of systemic disease
11. B) Investigation Modalities…
6) Sentinel LN biopsy(SNBx)
• SNBx detection rate using:
- both blue dye and radiocolloid =99%
-blue dye alone =87% ,P < .0001.
• Rate of positive SNBx in most series (typically for
melanomas >1 mm) is 15-25%.
12.
13. B) Investigation Modalities…
8) FNAC
• High index of
suspicion & liberal
use of FNA for
suspicious regional
nodes should be
encouraged.
14. B)Investigations…
• Stage I & II
– H & P
– Routine imaging/lab tests not recommended
– Imaging only to evaluate specific signs or symptoms
• Stage IIIA ( SLN +ve )
– Consider imaging for baseline staging ( category IIB)
– Imaging only to evaluate specific signs or symptoms
• Stage IIIB/C SLN +ve, III clinically +ve nodes, III clinical satellite or in tansit
– Imaging for baseline staging and to evaluate specific signs or symptoms ( CT,
PET or MRI )
• Stage IV
– Imaging for baseline staging and to evaluate specific signs or symptoms ( CT,
PET or MRI)
– LDH
– Testing for BRAF & other genetic analysis
• Stage IIIC & above
– Brian MRI as baseline
15.
16. D)Management of melanoma
• For management purpose cutaneous
melanomas are categorized as follows:
I)Localized disease with no evidence of
metastases (stage I-II)
II)Regional disease (stage III)
III)Distant metastatic disease (stage IV)
17. Metastatic melanoma
• Most met occurs after an interval from their original management for
clinically localized disease
• Interval for detection of distant met is shorter in pts initially presented
with high-stage disease.
• 60-80% of 1st met are local/regional sites including regional nodes.
• Most common 1st sites of visceral met are lung(10%) &liver(10%)
• Other visceral sites of met are brain, GI tract(especially small bowel) &
adrenal gland.
• New active systemic therapies for advanced melanoma are changing the
pts prognosis.
• Without treatment, or treatment with ineffective therapies, stage IV
melanoma were reported to have:
- median survival of 12 months
- survivals of 6 -9 months for those who presented with visceral
metastatic
18. D)Management of metastatic melanoma
• Options:
1) Palliative surgery
2) Palliative RT
3) Immune therapy
- Cytotoxic T lymphocyte antigen-4 (CTL-4) antibody
- Programmed cell death protein 1 (PD-1) antibody
-High dose IL-2
-Adoptive cell transfer therapy(ACT)
4) Targeted therapy
-BRAF/MEK mutation inhibitors
-KIT mutation inhibitors (imatinib )
5) Cytotoxic therapy
6) Clinical trials
19. D.1) Surgery for Distant Metastases (Stage IV)
• Cases in Which the Benefit of Surgery Is Clear
• Anemia due to occult bleeding from intestinal metastasis
• Bowel obstruction due to small bowel metastasis
• Cutaneous or subcutaneous metastasis with ulceration, pain,
or impending ulceration
• Lymph node metastasis with neurologic symptoms
• Symptomatic brain metastasis
• Life-threatening hemorrhage from metastasis
20. D.2) Immune Checkpoint Inhibitors
• The immune system is capable of identifying &
destroying malignant cells, called immunosurveillance.
• Conditions or events that compromise the immune
system can lead to cancer cells escaping
immunosurveillance
• Immunotherapies augmente the immune response to
overcome immune evasion mechanisms of cancer cells
21. D.2) Immune Checkpoint Inhibitors
• CTLA-4 & PD-1 are 2 receptors on T cells that upon ligand
binding trigger a signaling cascade that inhibits cell
activation, limiting the immune response
• Antibodies against these receptor removing the
inhibition of T-cell activation &releasing the brake on the
immune response.
• And this was recently recognized by 2018 Nobel Prize
award in Medicine to James Allison and Tasuku Honjo
for their research on CTLA-4 and PD-1
22.
23. D.2.1) Cytotoxic T lymphocyte antigen-4 (CTLA-4)
antibody
Ipilimumab
• monoclonal antibody against the immune checkpoint
receptor CTLA –4.
• Two phase III trials in pts with unresectable stage III/IV
melanoma support the use of ipilimumab .
• Results from these trials showed that ipilimumab improved
-response rates -OS
-response duration -PFS
• Most importantly, extended follow up showed that resulted in
long term survival(5 year OS):
- ipilimumab =18%
-dacarbazine)=9%
24. Ipilimumab +Dacarbazine vs Dacarbazine
502 pts untreated met
melanoma,
randomized in1:1 to
ipilimumab (10 mg /kg)
+ dacarbazine (850
mg/m2)
dacarbazine (850 mg/m2)
+placebo, given at weeks 1,
4, 7, and 10,
followed by dacarbazine
alone every 3 weeks
Pts with SD or
objective response
and no dose limiting
toxic effects received
ipilimumab or placebo
every 12 weeks
thereafter as
maintenance therapy
primary end point -OS
25. Ipilimumab +Dacarbazine vs Dacarbazine
Variable Ipilimumab +Dacarbazine Dacarbazine Remark
OS 11.2 months 9.1 months
1 yr survival 47.3% 36.3%
2 yr survival 28.5% 17.9%
3yr survival 20.8% 12.2% P<0.001
Grade 3/4 toxicity 56.3% 27.5% P<0.001
Conclusion
Ipilimumab (at a dose of 10 mg per kilogram) in
combination with dacarbazine
compared with dacarbazine plus placebo, improved
overall survival in patients with
previously untreated metastatic melanoma.
26.
27. D.2.2)programmed cell death protein 1 (PD-1) antibody
• Nivolumab
• Checkmate 037 compared nivolumab versus
investigator’s choice chemotherapy in pts with
unresectable stage III/IV melanoma who had previously
progressed on:
- ipilimumab
- BRAFV600 ihibitors, in BRAF mutation +ve
• Over 70% of pts in this trial had received two or more
prior systemic therapies.
• Results show nivolumab improved RR & duration
compared with chemotherapy.
28. Nivolumab vs Dacarbazine (without BRAF Mutation)
418 pts untreated met
melanoma with out BRAF
mutation randomly assigned
to:
Nivolumab (3
mg/kg ) every
2weeks
Dacarbazine
(1000 mg/m2
every 3weeks).
primary end point=OS
29. Nivolumab vs Dacarbazine (without BRAF Mutation)
Variable Nivolumab Dacarbazine Remarks
1 yr survival 72.9% 42.1% P<0.001
median PFS 5.1 months 2.2 months P<0.001
objective response rate 40% 13.9% P<0.001
grade 3 or 4 11.7% 17.6%
CONCLUSIONS
Nivolumab was associated with significant improvements in OS
& PFS, as compared with dacarbazine, among previously
untreate patients who had metastatic melanoma without a BRAF
mutation.
31. D.2) Immune Checkpoint Inhibitors
• The results of Checkmate 066 & 067 support &
recommended that nivolumab should be considered as
first-line therapy in pts with unresectable or metastatic
disease.
32. D.2.3) Anti-CTLA-4/Anti-PD-1 Combination Therapy
• CTLA-4 and PD-1 inhibitor combination therapies have
been investigated in a number of trials in unresectable
stage III/IV melanoma .
• There are ongoing clinical trials evaluating even lower
doses of ipilimumab in combinations in order to mitigate
the toxicity while still maintaining the synergy of the
combination.
33. D.2.3) Anti-CTLA-4/Anti-PD-1 Combination Therapy
• Among pts treated with nivolumab + ipilimumab
combination therapy, RR, PFS, and OS tend to increase
with increasing PD-L1 expression level
• But ,none of these analyses were able to identify PD-L1
expression threshold for selection of an anti-PD-1 agent.
• Nivolumab/ipilimumab combination improved RR &
outcomes compared with ipilimumab monotherapy for
all PD-L1 expression levels—including pts with very low
PD-L1 expression
34. Nivolumab + ipilimumab vs nivolumab
• 5-year survival outcomes reported
recently(update of survival outcomes from the
Checkmate 067 trial with a minimum of 5 years of
follow-up)
• 945 pts with unresectable ,previously not treated
stage III or IV melanoma in 1:1:1 ratio to:
-nivolumab alone
-nivolumab + ipilimumab
-ipilimumab alone
Primary end point=PFS & OS
35. At minimum of 60 months follow up
Variables Nivolumab + ipilimumab Nivolumab ipilimumab Remarks
Median OS 60 months 36.9months 19.9 months
5 yrs OS 52% 44% 26%
No sustained deterioration of health-related QOL
No new late toxic effects were noted.
5 yrs PFS 36% 29% 8%
36.
37.
38. Nivolumab + ipilimumab vs nivolumab
• CONCLUSIONS
• sustained long-term OS at 5 years was
observed in a greater percentage of pts
received nivolumab + ipilimumab or
nivolumab alone than pts received ipilimumab
alone, with no apparent loss of QOL.
39. D.3)BRAF-Targeted Therapies
• 50% met cutanous melanoma have activating mutation of
BRAF
• Most melanoma BRAF mutations occur at V600 (usually
V600E occasionally V600K)
• BRAF inhibitors shows clinical activity in met melanomas
with BRAF V600 mutation.
• Co-administration with MEK inhibitors potentiates the
effects
• FDA-approved :
-BRAF inhibitors= vemurafenib, dabrafenib and encorafenib
-MEK inhibitors=trametinib, cobimetinib, and binimetinib
40. Sequence of Immune Checkpoint Inhibitors
• Preliminary results from a randomized phase
II trial show ↑ toxicity but trends toward
improved RR and OS for pts treated with
nivolumab followed by ipilimumab compared
with pts who received these therapies in the
reverse order.
41. Sequence of Immune Checkpoint Inhibitors
• Given that responses to immune checkpoint inhibitors
can take longer to develop, BRAF-targeted therapy may
be preferred in cases where :
-symptomatic diseases
-rapidly progressing disease
-overall health of pt is deteriorating
• Other pts with asymptomatic metastatic melanoma may
be good candidates for immune checkpoint inhibitor
therapy.
43. Response assessment in immune therapy
• Main feature of therapy with anti–CTLA-4 antibodies is long
durability of tumor responses in pts with objective response
• Pts with met to lung & liver who initially received ipilimumab in
May of 2001,continues in response beyond 15 yrs
• So it is difficult to use RACIST criteria to asses responses b/c:
I)it can appear late after the therapy
II)can pass through a process of apparent clinical progression
(pseudo progression)
• For this reason we use alternative response assessment called
immune related response criteria
• Application of traditional RECIST criteria may lead to premature
discontinuation in a patient who will eventually respond to
treatment.
44.
45.
46. Toxicity of Immune Checkpoint Inhibitors
• are autoimmune in nature
• 3 most common AEs are:
1)Cutaneous toxicities (rash,pruritus,maculopapular rash &vitiligo),
2)Gastrointestinal toxicities (diarrhea/colitis)
3)Fatigue
• most common high-grade toxicities :
1)Endocrinopathies (adrenal insufficiency, hypo/hyperthyroidism)
2)pancreatitis (elevated lipase and amylase)
3) hepatic AEs (elevated ALT/AST, hepatitis)
• potentially life threatening high grade immune related toxicities:
1)Nephritis
2)Pneumonitis
3)myocarditis
48. D.4) Cytotoxic Therapy
• Melanoma is relatively chemotherapy-refractory tumor.
• mechanisms of resistance not well known but likely :
- Naturally resistant to apoptotic death
- DNA repair enzymes
- Efflux pumps for xenobiotics -highly expressed in melanoma than other ca
Chemotherapy is considered a 3rd /4th line treatment option in melanoma after:
1)clinical trials
2immune therapy
3)BRAF-targeted therapy(if indicated)
• Common cytotoxic agents being used in patients with metastatic melanoma
include :
-single agents =dacarbazine,temozolomide , fotemustine & Nab-paclitaxel
-combination CT- cisplatin, vinblastine, and dacarbazine (CVD)
- carboplatin+paclitaxel
- Dartmouth regimen (cisplatin,carmustine, dacarbazine, &tamoxifen).
49. EORTC 18032
• Temozolomide is at least as effective as dacarbazine in
metastatic disease
• 859 stage IV melanoma pts were randomized to
receive:
- PO temozolomide150 mg/m2/day for 7 days Q2 wks
- IV dacarbazine 1000 mg/m2 Q3 wks
- Median OS-temozolomide= 9.1 months
-dacarbazine 9.4 months
Response rate -temozolomide =14.5%
-dacarbazine =9.8%
50. Brain met Rx
Current treatment recommendation in pts with brain met from melanoma:
• All symptomatic brain met corticostoid should be administered initially
• Good PS with no/minimal systemic met;& solitary brain met-resection/SRS
• unresectable lesion or ≥5 small lesions=SRS
• Pts on immune therapy who are responding extracranially -continued
immunotherapy during RT
• Pts on BRAF , discontinued while on irradiation
• Palliative WBRT/hospice for:
-poor PS
-diffuse systemic disease
-more than 5 bulky lesions
-progressed on systemic therapy
51. E)Prognostic Factors
• Breslow thickness(↑thickness,bad prognosis)
• Ulceration (+ve bad prognosis)
• Mitotic rate(High mitotic rate)
• ↑level of invasion (Clark level)
• LVI & PNI
• presence of microscopic satellite
• tumor location(extrimeties better, H& N,trunk badprognosis)
• Age(young age good prognosis)
• Sex(Female better)
• LN status & number of +ve LNs
• Histology types(NM→ALM→SSM→LMM)
• Site of metastasis(CNS& visceral)
• Growth patterns(VGP)
• LDH value in stage IV(↑)